Sample records for target applications include

  1. Measuring and Reducing Off-Target Activities of Programmable Nucleases Including CRISPR-Cas9

    PubMed Central

    Koo, Taeyoung; Lee, Jungjoon; Kim, Jin-Soo

    2015-01-01

    Programmable nucleases, which include zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and RNA-guided engineered nucleases (RGENs) repurposed from the type II clustered, regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system are now widely used for genome editing in higher eukaryotic cells and whole organisms, revolutionising almost every discipline in biological research, medicine, and biotechnology. All of these nucleases, however, induce off-target mutations at sites homologous in sequence with on-target sites, limiting their utility in many applications including gene or cell therapy. In this review, we compare methods for detecting nuclease off-target mutations. We also review methods for profiling genome-wide off-target effects and discuss how to reduce or avoid off-target mutations. PMID:25985872

  2. In silico target prediction for elucidating the mode of action of herbicides including prospective validation.

    PubMed

    Chiddarwar, Rucha K; Rohrer, Sebastian G; Wolf, Antje; Tresch, Stefan; Wollenhaupt, Sabrina; Bender, Andreas

    2017-01-01

    The rapid emergence of pesticide resistance has given rise to a demand for herbicides with new mode of action (MoA). In the agrochemical sector, with the availability of experimental high throughput screening (HTS) data, it is now possible to utilize in silico target prediction methods in the early discovery phase to suggest the MoA of a compound via data mining of bioactivity data. While having been established in the pharmaceutical context, in the agrochemical area this approach poses rather different challenges, as we have found in this work, partially due to different chemistry, but even more so due to different (usually smaller) amounts of data, and different ways of conducting HTS. With the aim to apply computational methods for facilitating herbicide target identification, 48,000 bioactivity data against 16 herbicide targets were processed to train Laplacian modified Naïve Bayesian (NB) classification models. The herbicide target prediction model ("HerbiMod") is an ensemble of 16 binary classification models which are evaluated by internal, external and prospective validation sets. In addition to the experimental inactives, 10,000 random agrochemical inactives were included in the training process, which showed to improve the overall balanced accuracy of our models up to 40%. For all the models, performance in terms of balanced accuracy of≥80% was achieved in five-fold cross validation. Ranking target predictions was addressed by means of z-scores which improved predictivity over using raw scores alone. An external testset of 247 compounds from ChEMBL and a prospective testset of 394 compounds from BASF SE tested against five well studied herbicide targets (ACC, ALS, HPPD, PDS and PROTOX) were used for further validation. Only 4% of the compounds in the external testset lied in the applicability domain and extrapolation (and correct prediction) was hence impossible, which on one hand was surprising, and on the other hand illustrated the utilization of

  3. 34 CFR 645.21 - What assurances must an applicant include in an application?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... services and promote collaborations so that more students can be served. (b) An applicant for an Upward... target area in order to minimize the duplication of services and promote collaborations so that more... in the target area in order to minimize the duplication of services and promote collaborations so...

  4. Synthesis and bio-applications of targeted magnetic-fluorescent composite nanoparticles

    NASA Astrophysics Data System (ADS)

    Xia, Hui; Tong, Ruijie; Song, Yanling; Xiong, Fang; Li, Jiman; Wang, Shichao; Fu, Huihui; Wen, Jirui; Li, Dongze; Zeng, Ye; Zhao, Zhiwei; Wu, Jiang

    2017-04-01

    Magnetic-fluorescent nanoparticles have a tremendous potential in biology. As the benefits of these materials gained recognition, increasing attention has been given to the conjugation of magnetic-fluorescent nanoparticles with targeting ligands. The magnetic and fluorescent properties of nanoparticles offer several functionalities, including imaging, separation, and visualization, while the presence of a targeting ligand allows for selective cell and tissue targeting. In this review, methods for the synthesis of targeted magnetic-fluorescent nanoparticles are explored, and recent applications of these nanocomposites to the detection and separation of biomolecules, fluorescent and magnetic resonance imaging, and cancer diagnosis and treatment will be summarized. As these materials are further optimized, targeted magnetic-fluorescent nanoparticles hold great promise for the diagnosis and treatment of some diseases.

  5. Application of target costing in machining

    NASA Astrophysics Data System (ADS)

    Gopalakrishnan, Bhaskaran; Kokatnur, Ameet; Gupta, Deepak P.

    2004-11-01

    In today's intensely competitive and highly volatile business environment, consistent development of low cost and high quality products meeting the functionality requirements is a key to a company's survival. Companies continuously strive to reduce the costs while still producing quality products to stay ahead in the competition. Many companies have turned to target costing to achieve this objective. Target costing is a structured approach to determine the cost at which a proposed product, meeting the quality and functionality requirements, must be produced in order to generate the desired profits. It subtracts the desired profit margin from the company's selling price to establish the manufacturing cost of the product. Extensive literature review revealed that companies in automotive, electronic and process industries have reaped the benefits of target costing. However target costing approach has not been applied in the machining industry, but other techniques based on Geometric Programming, Goal Programming, and Lagrange Multiplier have been proposed for application in this industry. These models follow a forward approach, by first selecting a set of machining parameters, and then determining the machining cost. Hence in this study we have developed an algorithm to apply the concepts of target costing, which is a backward approach that selects the machining parameters based on the required machining costs, and is therefore more suitable for practical applications in process improvement and cost reduction. A target costing model was developed for turning operation and was successfully validated using practical data.

  6. A generalized target theory and its applications.

    PubMed

    Zhao, Lei; Mi, Dong; Hu, Bei; Sun, Yeqing

    2015-09-28

    Different radiobiological models have been proposed to estimate the cell-killing effects, which are very important in radiotherapy and radiation risk assessment. However, most applied models have their own scopes of application. In this work, by generalizing the relationship between "hit" and "survival" in traditional target theory with Yager negation operator in Fuzzy mathematics, we propose a generalized target model of radiation-induced cell inactivation that takes into account both cellular repair effects and indirect effects of radiation. The simulation results of the model and the rethinking of "the number of targets in a cell" and "the number of hits per target" suggest that it is only necessary to investigate the generalized single-hit single-target (GSHST) in the present theoretical frame. Analysis shows that the GSHST model can be reduced to the linear quadratic model and multitarget model in the low-dose and high-dose regions, respectively. The fitting results show that the GSHST model agrees well with the usual experimental observations. In addition, the present model can be used to effectively predict cellular repair capacity, radiosensitivity, target size, especially the biologically effective dose for the treatment planning in clinical applications.

  7. Advances in targeted proteomics and applications to biomedical research

    PubMed Central

    Shi, Tujin; Song, Ehwang; Nie, Song; Rodland, Karin D.; Liu, Tao; Qian, Wei-Jun; Smith, Richard D.

    2016-01-01

    Targeted proteomics technique has emerged as a powerful protein quantification tool in systems biology, biomedical research, and increasing for clinical applications. The most widely used targeted proteomics approach, selected reaction monitoring (SRM), also known as multiple reaction monitoring (MRM), can be used for quantification of cellular signaling networks and preclinical verification of candidate protein biomarkers. As an extension to our previous review on advances in SRM sensitivity herein we review recent advances in the method and technology for further enhancing SRM sensitivity (from 2012 to present), and highlighting its broad biomedical applications in human bodily fluids, tissue and cell lines. Furthermore, we also review two recently introduced targeted proteomics approaches, parallel reaction monitoring (PRM) and data-independent acquisition (DIA) with targeted data extraction on fast scanning high-resolution accurate-mass (HR/AM) instruments. Such HR/AM targeted quantification with monitoring all target product ions addresses SRM limitations effectively in specificity and multiplexing; whereas when compared to SRM, PRM and DIA are still in the infancy with a limited number of applications. Thus, for HR/AM targeted quantification we focus our discussion on method development, data processing and analysis, and its advantages and limitations in targeted proteomics. Finally, general perspectives on the potential of achieving both high sensitivity and high sample throughput for large-scale quantification of hundreds of target proteins are discussed. PMID:27302376

  8. Drug-Target Interactions: Prediction Methods and Applications.

    PubMed

    Anusuya, Shanmugam; Kesherwani, Manish; Priya, K Vishnu; Vimala, Antonydhason; Shanmugam, Gnanendra; Velmurugan, Devadasan; Gromiha, M Michael

    2018-01-01

    Identifying the interactions between drugs and target proteins is a key step in drug discovery. This not only aids to understand the disease mechanism, but also helps to identify unexpected therapeutic activity or adverse side effects of drugs. Hence, drug-target interaction prediction becomes an essential tool in the field of drug repurposing. The availability of heterogeneous biological data on known drug-target interactions enabled many researchers to develop various computational methods to decipher unknown drug-target interactions. This review provides an overview on these computational methods for predicting drug-target interactions along with available webservers and databases for drug-target interactions. Further, the applicability of drug-target interactions in various diseases for identifying lead compounds has been outlined. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Advances in targeted proteomics and applications to biomedical research

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

    Shi, Tujin; Song, Ehwang; Nie, Song

    Targeted proteomics technique has emerged as a powerful protein quantification tool in systems biology, biomedical research, and increasing for clinical applications. The most widely used targeted proteomics approach, selected reaction monitoring (SRM), also known as multiple reaction monitoring (MRM), can be used for quantification of cellular signaling networks and preclinical verification of candidate protein biomarkers. As an extension to our previous review on advances in SRM sensitivity (Shi et al., Proteomics, 12, 1074–1092, 2012) herein we review recent advances in the method and technology for further enhancing SRM sensitivity (from 2012 to present), and highlighting its broad biomedical applications inmore » human bodily fluids, tissue and cell lines. Furthermore, we also review two recently introduced targeted proteomics approaches, parallel reaction monitoring (PRM) and data-independent acquisition (DIA) with targeted data extraction on fast scanning high-resolution accurate-mass (HR/AM) instruments. Such HR/AM targeted quantification with monitoring all target product ions addresses SRM limitations effectively in specificity and multiplexing; whereas when compared to SRM, PRM and DIA are still in the infancy with a limited number of applications. Thus, for HR/AM targeted quantification we focus our discussion on method development, data processing and analysis, and its advantages and limitations in targeted proteomics. Finally, general perspectives on the potential of achieving both high sensitivity and high sample throughput for large-scale quantification of hundreds of target proteins are discussed.« less

  10. Cryostat including heater to heat a target

    DOEpatents

    Pehl, Richard H.; Madden, Norman W.; Malone, Donald F.

    1990-01-01

    A cryostat is provided which comprises a vacuum vessel; a target disposed within the vacuum vessel; a heat sink disposed within the vacuum vesssel for absorbing heat from the detector; a cooling mechanism for cooling the heat sink; a cryoabsorption mechanism for cryoabsorbing residual gas within the vacuum vessel; and a heater for maintaining the target above a temperature at which the residual gas is cryoabsorbed in the course of cryoabsorption of the residual gas by the cryoabsorption mechanism.

  11. Cryostat including heater to heat a target

    DOEpatents

    Pehl, R.H.; Madden, N.W.; Malone, D.F.

    1990-09-11

    A cryostat is provided which comprises a vacuum vessel; a target disposed within the vacuum vessel; a heat sink disposed within the vacuum vessel for absorbing heat from the detector; a cooling mechanism for cooling the heat sink; a cryoabsorption mechanism for cryoabsorbing residual gas within the vacuum vessel; and a heater for maintaining the target above a temperature at which the residual gas is cryoabsorbed in the course of cryoabsorption of the residual gas by the cryoabsorption mechanism. 2 figs.

  12. DecoyFinder: an easy-to-use python GUI application for building target-specific decoy sets.

    PubMed

    Cereto-Massagué, Adrià; Guasch, Laura; Valls, Cristina; Mulero, Miquel; Pujadas, Gerard; Garcia-Vallvé, Santiago

    2012-06-15

    Decoys are molecules that are presumed to be inactive against a target (i.e. will not likely bind to the target) and are used to validate the performance of molecular docking or a virtual screening workflow. The Directory of Useful Decoys database (http://dud.docking.org/) provides a free directory of decoys for use in virtual screening, though it only contains a limited set of decoys for 40 targets.To overcome this limitation, we have developed an application called DecoyFinder that selects, for a given collection of active ligands of a target, a set of decoys from a database of compounds. Decoys are selected if they are similar to active ligands according to five physical descriptors (molecular weight, number of rotational bonds, total hydrogen bond donors, total hydrogen bond acceptors and the octanol-water partition coefficient) without being chemically similar to any of the active ligands used as an input (according to the Tanimoto coefficient between MACCS fingerprints). To the best of our knowledge, DecoyFinder is the first application designed to build target-specific decoy sets. A complete description of the software is included on the application home page. A validation of DecoyFinder on 10 DUD targets is provided as Supplementary Table S1. DecoyFinder is freely available at http://URVnutrigenomica-CTNS.github.com/DecoyFinder.

  13. 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.

  14. 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

  15. Target and (Astro-)WISE technologies Data federations and its applications

    NASA Astrophysics Data System (ADS)

    Valentijn, E. A.; Begeman, K.; Belikov, A.; Boxhoorn, D. R.; Brinchmann, J.; McFarland, J.; Holties, H.; Kuijken, K. H.; Verdoes Kleijn, G.; Vriend, W.-J.; Williams, O. R.; Roerdink, J. B. T. M.; Schomaker, L. R. B.; Swertz, M. A.; Tsyganov, A.; van Dijk, G. J. W.

    2017-06-01

    After its first implementation in 2003 the Astro-WISE technology has been rolled out in several European countries and is used for the production of the KiDS survey data. In the multi-disciplinary Target initiative this technology, nicknamed WISE technology, has been further applied to a large number of projects. Here, we highlight the data handling of other astronomical applications, such as VLT-MUSE and LOFAR, together with some non-astronomical applications such as the medical projects Lifelines and GLIMPS; the MONK handwritten text recognition system; and business applications, by amongst others, the Target Holding. We describe some of the most important lessons learned and describe the application of the data-centric WISE type of approach to the Science Ground Segment of the Euclid satellite.

  16. In silico pharmacology for drug discovery: applications to targets and beyond

    PubMed Central

    Ekins, S; Mestres, J; Testa, B

    2007-01-01

    Computational (in silico) methods have been developed and widely applied to pharmacology hypothesis development and testing. These in silico methods include databases, quantitative structure-activity relationships, similarity searching, pharmacophores, homology models and other molecular modeling, machine learning, data mining, network analysis tools and data analysis tools that use a computer. Such methods have seen frequent use in the discovery and optimization of novel molecules with affinity to a target, the clarification of absorption, distribution, metabolism, excretion and toxicity properties as well as physicochemical characterization. The first part of this review discussed the methods that have been used for virtual ligand and target-based screening and profiling to predict biological activity. The aim of this second part of the review is to illustrate some of the varied applications of in silico methods for pharmacology in terms of the targets addressed. We will also discuss some of the advantages and disadvantages of in silico methods with respect to in vitro and in vivo methods for pharmacology research. Our conclusion is that the in silico pharmacology paradigm is ongoing and presents a rich array of opportunities that will assist in expediating the discovery of new targets, and ultimately lead to compounds with predicted biological activity for these novel targets. PMID:17549046

  17. Actinium-225 in targeted alpha-particle therapeutic applications

    PubMed Central

    Scheinberg, David A.; McDevit, Michael R.

    2017-01-01

    Alpha particle-emitting isotopes are being investigated in radioimmunotherapeutic applications because of their unparalleled cytotoxicity when targeted to cancer and their relative lack of toxicity towards untargeted normal tissue. Actinium-225 has been developed into potent targeting drug constructs and is in clinical use against acute myelogenous leukemia. The key properties of the alpha particles generated by 225Ac are the following: i) limited range in tissue of a few cell diameters; ii) high linear energy transfer leading to dense radiation damage along each alpha track; iii) a 10 day half-life; and iv) four net alpha particles emitted per decay. Targeting 225Ac-drug constructs have potential in the treatment of cancer. PMID:22202153

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

    NASA Astrophysics Data System (ADS)

    Vickers, Linda Diane

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

  19. TAPIR, a web server for the prediction of plant microRNA targets, including target mimics.

    PubMed

    Bonnet, Eric; He, Ying; Billiau, Kenny; Van de Peer, Yves

    2010-06-15

    We present a new web server called TAPIR, designed for the prediction of plant microRNA targets. The server offers the possibility to search for plant miRNA targets using a fast and a precise algorithm. The precise option is much slower but guarantees to find less perfectly paired miRNA-target duplexes. Furthermore, the precise option allows the prediction of target mimics, which are characterized by a miRNA-target duplex having a large loop, making them undetectable by traditional tools. The TAPIR web server can be accessed at: http://bioinformatics.psb.ugent.be/webtools/tapir. Supplementary data are available at Bioinformatics online.

  20. Colon-targeted delivery of live bacterial cell biotherapeutics including microencapsulated live bacterial cells

    PubMed Central

    Prakash, Satya; Malgorzata Urbanska, Aleksandra

    2008-01-01

    There has been an ample interest in delivery of therapeutic molecules using live cells. Oral delivery has been stipulated as best way to deliver live cells to humans for therapy. Colon, in particular, is a part of gastrointestinal (GI) tract that has been proposed to be an oral targeted site. The main objective of these oral therapy procedures is to deliver live cells not only to treat diseases like colorectal cancer, inflammatory bowel disease, and other GI tract diseases like intestinal obstruction and gastritis, but also to deliver therapeutic molecules for overall therapy in various diseases such as renal failure, coronary heart disease, hypertension, and others. This review provides a comprehensive summary of recent advancement in colon targeted live bacterial cell biotherapeutics. Current status of bacterial cell therapy, principles of artificial cells and its potentials in oral delivery of live bacterial cell biotherapeutics for clinical applications as well as biotherapeutic future perspectives are also discussed in our review. PMID:19707368

  1. Applications of CRISPR/Cas9 technology for targeted mutagenesis, gene replacement and stacking of genes in higher plants.

    PubMed

    Luo, Ming; Gilbert, Brian; Ayliffe, Michael

    2016-07-01

    Mutagenesis continues to play an essential role for understanding plant gene function and, in some instances, provides an opportunity for plant improvement. The development of gene editing technologies such as TALENs and zinc fingers has revolutionised the targeted mutation specificity that can now be achieved. The CRISPR/Cas9 system is the most recent addition to gene editing technologies and arguably the simplest requiring only two components; a small guide RNA molecule (sgRNA) and Cas9 endonuclease protein which complex to recognise and cleave a specific 20 bp target site present in a genome. Target specificity is determined by complementary base pairing between the sgRNA and target site sequence enabling highly specific, targeted mutation to be readily engineered. Upon target site cleavage, error-prone endogenous repair mechanisms produce small insertion/deletions at the target site usually resulting in loss of gene function. CRISPR/Cas9 gene editing has been rapidly adopted in plants and successfully undertaken in numerous species including major crop species. Its applications are not restricted to mutagenesis and target site cleavage can be exploited to promote sequence insertion or replacement by recombination. The multiple applications of this technology in plants are described.

  2. Novel medical therapeutics in glioblastomas, including targeted molecular therapies, current and future clinical trials.

    PubMed

    Quant, Eudocia C; Wen, Patrick Y

    2010-08-01

    The prognosis for glioblastoma is poor despite optimal therapy with surgery, radiation, and chemotherapy. New therapies that improve survival and quality of life are needed. Research has increased our understanding of the molecular pathways important for gliomagenesis and disease progression. Novel agents have been developed against these targets, including receptor tyrosine kinases, intracellular signaling molecules, epigenetic abnormalities, and tumor vasculature and microenvironment. This article reviews novel therapies for glioblastoma, with an emphasis on targeted agents. Copyright 2010 Elsevier Inc. All rights reserved.

  3. Chemical probes targeting epigenetic proteins: Applications beyond oncology

    PubMed Central

    Ackloo, Suzanne; Brown, Peter J.; Müller, Susanne

    2017-01-01

    ABSTRACT Epigenetic chemical probes are potent, cell-active, small molecule inhibitors or antagonists of specific domains in a protein; they have been indispensable for studying bromodomains and protein methyltransferases. The Structural Genomics Consortium (SGC), comprising scientists from academic and pharmaceutical laboratories, has generated most of the current epigenetic chemical probes. Moreover, the SGC has shared about 4 thousand aliquots of these probes, which have been used primarily for phenotypic profiling or to validate targets in cell lines or primary patient samples cultured in vitro. Epigenetic chemical probes have been critical tools in oncology research and have uncovered mechanistic insights into well-established targets, as well as identify new therapeutic starting points. Indeed, the literature primarily links epigenetic proteins to oncology, but applications in inflammation, viral, metabolic and neurodegenerative diseases are now being reported. We summarize the literature of these emerging applications and provide examples where existing probes might be used. PMID:28080202

  4. Acute Pesticide Illnesses Associated with Off-Target Pesticide Drift from Agricultural Applications: 11 States, 1998–2006

    PubMed Central

    Lee, Soo-Jeong; Mehler, Louise; Beckman, John; Diebolt-Brown, Brienne; Prado, Joanne; Lackovic, Michelle; Waltz, Justin; Mulay, Prakash; Schwartz, Abby; Mitchell, Yvette; Moraga-McHaley, Stephanie; Gergely, Rita

    2011-01-01

    Background: Pesticides are widely used in agriculture, and off-target pesticide drift exposes workers and the public to harmful chemicals. Objective: We estimated the incidence of acute illnesses from pesticide drift from outdoor agricultural applications and characterized drift exposure and illnesses. Methods: Data were obtained from the National Institute for Occupational Safety and Health’s Sentinel Event Notification System for Occupational Risks–Pesticides program and the California Department of Pesticide Regulation. Drift included off-target movement of pesticide spray, volatiles, and contaminated dust. Acute illness cases were characterized by demographics, pesticide and application variables, health effects, and contributing factors. Results: From 1998 through 2006, we identified 2,945 cases associated with agricultural pesticide drift from 11 states. Our findings indicate that 47% were exposed at work, 92% experienced low-severity illness, and 14% were children (< 15 years). The annual incidence ranged from 1.39 to 5.32 per million persons over the 9-year period. The overall incidence (in million person-years) was 114.3 for agricultural workers, 0.79 for other workers, 1.56 for nonoccupational cases, and 42.2 for residents in five agriculture-intensive counties in California. Soil applications with fumigants were responsible for the largest percentage (45%) of cases. Aerial applications accounted for 24% of cases. Common factors contributing to drift cases included weather conditions, improper seal of the fumigation site, and applicator carelessness near nontarget areas. Conclusions: Agricultural workers and residents in agricultural regions had the highest rate of pesticide poisoning from drift exposure, and soil fumigations were a major hazard, causing large drift incidents. Our findings highlight areas where interventions to reduce off-target drift could be focused. PMID:21642048

  5. Final report SI 08-SI-004: Fusion application targets

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

    Biener, J; Kucheyev, S O; Wang, M Y

    2010-12-03

    Complex target structures are necessary to take full advantage of the unique laboratory environment created by inertial confinement fusion experiments. For example, uses-of-ignition targets that contain a thin layer of a low density nanoporous material inside a spherical ablator shell allow placing dopants in direct contact with the DT fuel. The ideal foam for this application is a low-density hydrocarbon foam that is strong enough to survive wetting with cryogenic hydrogen, and low enough in density (density less than {approx}30 mg/cc) to not reduce the yield of the target. Here, we discuss the fabrication foam-lined uses-of-ignition targets, and the developmentmore » of low-density foams that can be used for this application. Much effort has been directed over the last 20 years toward the development of spherical foam targets for direct-drive and fast-ignition experiments. In these targets, the spherical foam shell is used to define the shape of the cryogenic DT fuel layer, or acts as a surrogate to simulate the cryogenic fuel layer. These targets are fabricated from relatively high-density aerogels (>100 mg/cc) and coated with a few micron thick permeation barrier. With exception of the above mentioned fast ignition targets, the wall of these targets is typically larger than 100 microns. In contrast, the fusion application targets for indirect-drive experiments on NIF will require a much thinner foam shell surrounded by a much thicker ablator shell. The design requirements for both types of targets are compared in Table 1. The foam shell targets for direct-drive experiments can be made in large quantities and with reasonably high yields using an encapsulation technique pioneered by Takagi et al. in the early 90's. In this approach, targets are made by first generating unsupported foam shells using a triple-orifice droplet generator, followed by coating the dried foam shells with a thin permeation barrier. However, this approach is difficult, if not impossible

  6. Internal Targeting and External Control: Phototriggered Targeting in Nanomedicine.

    PubMed

    Arrue, Lily; Ratjen, Lars

    2017-12-07

    The photochemical control of structure and reactivity bears great potential for chemistry, biology, and life sciences. A key feature of photochemistry is the spatiotemporal control over secondary events. Well-established applications of photochemistry in medicine are photodynamic therapy (PDT) and photopharmacology (PP). However, although both are highly localizable through the application of light, they lack cell- and tissue-specificity. The combination of nanomaterial-based drug delivery and targeting has the potential to overcome limitations for many established therapy concepts. Even more privileged seems the merger of nanomedicine and cell-specific targeting (internal targeting) controlled by light (external control), as it can potentially be applied to many different areas of medicine and pharmaceutical research, including the aforementioned PDT and PP. In this review a survey of the interface of photochemistry, medicine and targeted drug delivery is given, especially focusing on phototriggered targeting in nanomedicine. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. 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.

  8. Mathematical description of drug-target interactions: application to biologics that bind to targets with two binding sites.

    PubMed

    Gibiansky, Leonid; Gibiansky, Ekaterina

    2018-02-01

    The emerging discipline of mathematical pharmacology occupies the space between advanced pharmacometrics and systems biology. A characteristic feature of the approach is application of advance mathematical methods to study the behavior of biological systems as described by mathematical (most often differential) equations. One of the early application of mathematical pharmacology (that was not called this name at the time) was formulation and investigation of the target-mediated drug disposition (TMDD) model and its approximations. The model was shown to be remarkably successful, not only in describing the observed data for drug-target interactions, but also in advancing the qualitative and quantitative understanding of those interactions and their role in pharmacokinetic and pharmacodynamic properties of biologics. The TMDD model in its original formulation describes the interaction of the drug that has one binding site with the target that also has only one binding site. Following the framework developed earlier for drugs with one-to-one binding, this work aims to describe a rigorous approach for working with similar systems and to apply it to drugs that bind to targets with two binding sites. The quasi-steady-state, quasi-equilibrium, irreversible binding, and Michaelis-Menten approximations of the model are also derived. These equations can be used, in particular, to predict concentrations of the partially bound target (RC). This could be clinically important if RC remains active and has slow internalization rate. In this case, introduction of the drug aimed to suppress target activity may lead to the opposite effect due to RC accumulation.

  9. 30 CFR 250.1007 - What to include in applications.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... and risers; pressure-regulating devices (including back-pressure regulators); sensing devices with.... (ii) If you propose to use one or more pipeline risers for a tension leg platform or other floating platform, your application must include: (A) The design fatigue life of the riser, with calculations, and...

  10. 30 CFR 250.1007 - What to include in applications.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... and risers; pressure-regulating devices (including back-pressure regulators); sensing devices with.... (ii) If you propose to use one or more pipeline risers for a tension leg platform or other floating platform, your application must include: (A) The design fatigue life of the riser, with calculations, and...

  11. 30 CFR 250.1007 - What to include in applications.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... and risers; pressure-regulating devices (including back-pressure regulators); sensing devices with.... (ii) If you propose to use one or more pipeline risers for a tension leg platform or other floating platform, your application must include: (A) The design fatigue life of the riser, with calculations, and...

  12. Biomimetics: reconstitution of low-density lipoprotein for targeted drug delivery and related theranostic applications.

    PubMed

    Zhu, Chunlei; Xia, Younan

    2017-12-11

    Low-density lipoprotein (LDL), one of the four major groups of lipoproteins for lipid transport in vivo, is emerging as an attractive carrier for the targeted delivery of theranostic agents. In contrast to the synthetic systems, LDL particles are intrinsically biocompatible and biodegradable, together with reduced immunogenicity and natural capabilities to target cancerous cells and to escape from the recognition and elimination by the reticuloendothelial system. Enticed by these attributes, a number of strategies have been developed for reconstituting LDL particles, including conjugation to the apolipoprotein, insertion into the phospholipid layer, and loading into the core. Here we present a tutorial review on the development of reconstituted LDL (rLDL) particles for theranostic applications. We start with a brief introduction to LDL and LDL receptor, as well as the advantages of using rLDL particles as a natural and versatile platform for the targeted delivery of theranostic agents. After a discussion of commonly used strategies for the reconstitution of LDL, we highlight the applications of rLDL particles in the staging of disease progression, treatment of lesioned tissues, and delivery of photosensitizers for photodynamic cancer therapy. We finish this review with a perspective on the remaining challenges and future directions.

  13. 25 CFR 1000.66 - What must be included in the application?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... EDUCATION ACT Other Financial Assistance for Planning and Negotiation Grants for Non-BIA Programs Eligibility and Application Process § 1000.66 What must be included in the application? The application for a...

  14. 25 CFR 1000.66 - What must be included in the application?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... EDUCATION ACT Other Financial Assistance for Planning and Negotiation Grants for Non-BIA Programs Eligibility and Application Process § 1000.66 What must be included in the application? The application for a...

  15. 25 CFR 1000.66 - What must be included in the application?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... EDUCATION ACT Other Financial Assistance for Planning and Negotiation Grants for Non-BIA Programs Eligibility and Application Process § 1000.66 What must be included in the application? The application for a...

  16. 25 CFR 1000.66 - What must be included in the application?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... EDUCATION ACT Other Financial Assistance for Planning and Negotiation Grants for Non-BIA Programs Eligibility and Application Process § 1000.66 What must be included in the application? The application for a...

  17. Direct target NOTES: prospective applications for next generation robotic platforms.

    PubMed

    Atallah, S; Hodges, A; Larach, S W

    2018-05-01

    A new era in surgical robotics has centered on alternative access to anatomic targets and next generation designs include flexible, single-port systems which follow circuitous rather than straight pathways. Such systems maintain a small footprint and could be utilized for specialized operations based on direct organ target natural orifice transluminal endoscopic surgery (NOTES), of which transanal total mesorectal excision (taTME) is an important derivative. During two sessions, four direct target NOTES operations were conducted on a cadaveric model using a flexible robotic system to demonstrate proof-of-concept of the application of a next generation robotic system to specific types of NOTES operations, all of which required removal of a direct target organ through natural orifice access. These four operations were (a) robotic taTME, (b) robotic transvaginal hysterectomy in conjunction with (c) robotic transvaginal salpingo-oophorectomy, and in an ex vivo model, (d) trans-cecal appendectomy. Feasibility was demonstrated in all cases using the Flex ® Robotic System with Colorectal Drive. During taTME, the platform excursion was 17 cm along a non-linear path; operative time was 57 min for the transanal portion of the dissection. Robotic transvaginal hysterectomy was successfully completed in 78 min with transvaginal extraction of the uterus, although laparoscopic assistance was required. Robotic transvaginal unilateral salpingo-oophorectomy with transvaginal extraction of the ovary and fallopian tube was performed without laparoscopic assistance in 13.5 min. In an ex vivo model, a robotic trans-cecal appendectomy was also successfully performed for the purpose of demonstrating proof-of-concept only; this was completed in 24 min. A flexible robotic system has the potential to access anatomy along circuitous paths, making it a suitable platform for direct target NOTES. The conceptual operations posed could be considered suitable for next generation robotics once

  18. Barriers to Liposomal Gene Delivery: from Application Site to the Target.

    PubMed

    Saffari, Mostafa; Moghimi, Hamid Reza; Dass, Crispin R

    2016-01-01

    Gene therapy is a therapeutic approach to deliver genetic material into cells to alter their function in entire organism. One promising form of gene delivery system (DDS) is liposomes. The success of liposome-mediated gene delivery is a multifactorial issue and well-designed liposomal systems might lead to optimized gene transfection particularly in vivo. Liposomal gene delivery systems face different barriers from their site of application to their target, which is inside the cells. These barriers include presystemic obstacles (epithelial barriers), systemic barriers in blood circulation and cellular barriers. Epithelial barriers differ depending on the route of administration. Systemic barriers include enzymatic degradation, binding and opsonisation. Both of these barriers can act as limiting hurdles that genetic material and their vector should overcome before reaching the cells. Finally liposomes should overcome cellular barriers that include cell entrance, endosomal escape and nuclear uptake. These barriers and their impact on liposomal gene delivery will be discussed in this review.

  19. 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

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

    PubMed

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

    2017-06-01

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

  1. Treating spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis, to target: recommendations of an international task force

    PubMed Central

    Smolen, Josef S; Braun, Jürgen; Dougados, Maxime; Emery, Paul; FitzGerald, Oliver; Helliwell, Philip; Kavanaugh, Arthur; Kvien, Tore K; Landewé, Robert; Luger, Thomas; Mease, Philip; Olivieri, Ignazio; Reveille, John; Ritchlin, Christopher; Rudwaleit, Martin; Schoels, Monika; Sieper, Joachim; de Wit, Martinus; Baraliakos, Xenofon; Betteridge, Neil; Burgos-Vargas, Ruben; Collantes-Estevez, Eduardo; Deodhar, Atul; Elewaut, Dirk; Gossec, Laure; Jongkees, Merryn; Maccarone, Mara; Redlich, Kurt; van den Bosch, Filip; Wei, James Cheng-Chung; Winthrop, Kevin; van der Heijde, Désirée

    2014-01-01

    Background Therapeutic targets have been defined for diseases like diabetes, hypertension or rheumatoid arthritis and adhering to them has improved outcomes. Such targets are just emerging for spondyloarthritis (SpA). Objective To define the treatment target for SpA including ankylosing spondylitis and psoriatic arthritis (PsA) and develop recommendations for achieving the target, including a treat-to-target management strategy. Methods Based on results of a systematic literature review and expert opinion, a task force of expert physicians and patients developed recommendations which were broadly discussed and voted upon in a Delphi-like process. Level of evidence, grade and strength of the recommendations were derived by respective means. The commonalities between axial SpA, peripheral SpA and PsA were discussed in detail. Results Although the literature review did not reveal trials comparing a treat-to-target approach with another or no strategy, it provided indirect evidence regarding an optimised approach to therapy that facilitated the development of recommendations. The group agreed on 5 overarching principles and 11 recommendations; 9 of these recommendations related commonly to the whole spectrum of SpA and PsA, and only 2 were designed separately for axial SpA, peripheral SpA and PsA. The main treatment target, which should be based on a shared decision with the patient, was defined as remission, with the alternative target of low disease activity. Follow-up examinations at regular intervals that depend on the patient's status should safeguard the evolution of disease activity towards the targeted goal. Additional recommendations relate to extra-articular and extramusculoskeletal aspects and other important factors, such as comorbidity. While the level of evidence was generally quite low, the mean strength of recommendation was 9–10 (10: maximum agreement) for all recommendations. A research agenda was formulated. Conclusions The task force defined the

  2. Human microRNA target analysis and gene ontology clustering by GOmir, a novel stand-alone application

    PubMed Central

    Roubelakis, Maria G; Zotos, Pantelis; Papachristoudis, Georgios; Michalopoulos, Ioannis; Pappa, Kalliopi I; Anagnou, Nicholas P; Kossida, Sophia

    2009-01-01

    Background microRNAs (miRNAs) are single-stranded RNA molecules of about 20–23 nucleotides length found in a wide variety of organisms. miRNAs regulate gene expression, by interacting with target mRNAs at specific sites in order to induce cleavage of the message or inhibit translation. Predicting or verifying mRNA targets of specific miRNAs is a difficult process of great importance. Results GOmir is a novel stand-alone application consisting of two separate tools: JTarget and TAGGO. JTarget integrates miRNA target prediction and functional analysis by combining the predicted target genes from TargetScan, miRanda, RNAhybrid and PicTar computational tools as well as the experimentally supported targets from TarBase and also providing a full gene description and functional analysis for each target gene. On the other hand, TAGGO application is designed to automatically group gene ontology annotations, taking advantage of the Gene Ontology (GO), in order to extract the main attributes of sets of proteins. GOmir represents a new tool incorporating two separate Java applications integrated into one stand-alone Java application. Conclusion GOmir (by using up to five different databases) introduces miRNA predicted targets accompanied by (a) full gene description, (b) functional analysis and (c) detailed gene ontology clustering. Additionally, a reverse search initiated by a potential target can also be conducted. GOmir can freely be downloaded BRFAA. PMID:19534746

  3. Human microRNA target analysis and gene ontology clustering by GOmir, a novel stand-alone application.

    PubMed

    Roubelakis, Maria G; Zotos, Pantelis; Papachristoudis, Georgios; Michalopoulos, Ioannis; Pappa, Kalliopi I; Anagnou, Nicholas P; Kossida, Sophia

    2009-06-16

    microRNAs (miRNAs) are single-stranded RNA molecules of about 20-23 nucleotides length found in a wide variety of organisms. miRNAs regulate gene expression, by interacting with target mRNAs at specific sites in order to induce cleavage of the message or inhibit translation. Predicting or verifying mRNA targets of specific miRNAs is a difficult process of great importance. GOmir is a novel stand-alone application consisting of two separate tools: JTarget and TAGGO. JTarget integrates miRNA target prediction and functional analysis by combining the predicted target genes from TargetScan, miRanda, RNAhybrid and PicTar computational tools as well as the experimentally supported targets from TarBase and also providing a full gene description and functional analysis for each target gene. On the other hand, TAGGO application is designed to automatically group gene ontology annotations, taking advantage of the Gene Ontology (GO), in order to extract the main attributes of sets of proteins. GOmir represents a new tool incorporating two separate Java applications integrated into one stand-alone Java application. GOmir (by using up to five different databases) introduces miRNA predicted targets accompanied by (a) full gene description, (b) functional analysis and (c) detailed gene ontology clustering. Additionally, a reverse search initiated by a potential target can also be conducted. GOmir can freely be downloaded BRFAA.

  4. Preparation of a Versatile Bifunctional Zeolite for Targeted Imaging Applications

    PubMed Central

    Ndiege, Nicholas; Raidoo, Renugan; Schultz, Michael K.; Larsen, Sarah

    2011-01-01

    Bifunctional zeolite Y was prepared for use in targeted in vivo molecular imaging applications. The strategy involved functionalization of the external surface of zeolite Y with chloropropyltriethoxysilane followed by reaction with sodium azide to form azide-functionalized NaY, which is amenable to copper(1) catalyzed click chemistry. In this study, a model alkyne (4-pentyn-1-ol) was attached to the azide-terminated surface via click chemistry to demonstrate feasibility for attachment of molecular targeting vectors (e.g., peptides, aptamers) to the zeolite surface. The modified particle efficiently incorporates the imaging radioisotope gallium-68 (68Ga) into the pores of the azide-functionalized NaY zeolite to form a stable bifunctional molecular targeting vector. The result is a versatile “clickable” zeolite platform that can be tailored for future in vivo molecular targeting and imaging modalities. PMID:21306141

  5. 49 CFR 107.709 - Processing of an application for approval, including an application for renewal or modification.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Processing of an application for approval..., Registrations and Submissions § 107.709 Processing of an application for approval, including an application for... before the disposition of an application. (b) At any time during the processing of an application, the...

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

    PubMed

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

    2014-06-30

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

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

    PubMed

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

    2014-06-01

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

  8. Plasma Immersion Ion Implantation with Solid Targets for Space and Aerospace Applications

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

    Oliveira, R. M.; Goncalves, J. A. N.; Ueda, M.

    2009-01-05

    This paper describes successful results obtained by a new type of plasma source, named as Vaporization of Solid Targets (VAST), for treatment of materials for space and aerospace applications, by means of plasma immersion ion implantation and deposition (PIII and D). Here, the solid element is vaporized in a high pressure glow discharge, being further ionized and implanted/deposited in a low pressure cycle, with the aid of an extra electrode. First experiments in VAST were run using lithium as the solid target. Samples of silicon and aluminum alloy (2024) were immersed into highly ionized lithium plasma, whose density was measuredmore » by a double Langmuir probe. Measurements performed with scanning electron microscopy (SEM) showed clear modification of the cross-sectioned treated silicon samples. X-ray photoelectron spectroscopy (XPS) analysis revealed that lithium was implanted/deposited into/onto the surface of the silicon. Implantation depth profiles may vary according to the condition of operation of VAST. One direct application of this treatment concerns the protection against radiation damage for silicon solar cells. For the case of the aluminum alloy, X-ray diffraction analysis indicated the appearance of prominent new peaks. Surface modification of A12024 by lithium implantation/deposition can lower the coefficient of friction and improve the resistance to fatigue of this alloy. Recently, cadmium was vaporized and ionized in VAST. The main benefit of this element is associated with the improvement of corrosion resistance of metallic substrates. Besides lithium and cadmium, VAST allows to performing PIII and D with other species, leading to the modification of the near-surface of materials for distinct purposes, including applications in the space and aerospace areas.« less

  9. Application of Smoothing Techniques for Tracking Maneuvering Targets. Multiple Target Tracking in Clutter: New Approaches

    DTIC Science & Technology

    1992-07-01

    target state estimation is affected not only by the measurement noise but also by the uncertainty in the origins of the measurements. To improve the...to identify targets in the presence of anticipated background noise (including earth, lunar, star backgrounds, complicated spacecraft structures...each other. Futhermore, those frames are often degraded versions of the original scene due to blur and noise . Through the task of image registration

  10. Engineered Peptides for Applications in Cancer-Targeted Drug Delivery and Tumor Detection.

    PubMed

    Soudy, R; Byeon, N; Raghuwanshi, Y; Ahmed, S; Lavasanifar, A; Kaur, K

    2017-01-01

    Cancer-targeting peptides as ligands for targeted delivery of anticancer drugs or drug carriers have the potential to significantly enhance the selectivity and the therapeutic benefit of current chemotherapeutic agents. Identification of tumor-specific biomarkers like integrins, aminopeptidase N, and epidermal growth factor receptor as well as the popularity of phage display techniques along with synthetic combinatorial methods used for peptide design and structure optimization have fueled the advancement and application of peptide ligands for targeted drug delivery and tumor detection in cancer treatment, detection and guided therapy. Although considerable preclinical data have shown remarkable success in the use of tumor targeting peptides, peptides generally suffer from poor pharmacokinetics, enzymatic instability, and weak receptor affinity, and they need further structural modification before successful translation to clinics is possible. The current review gives an overview of the different engineering strategies that have been developed for peptide structure optimization to confer selectivity and stability. We also provide an update on the methods used for peptide ligand identification, and peptide- receptor interactions. Additionally, some applications for the use of peptides in targeted delivery of chemotherapeutics and diagnostics over the past 5 years are summarized. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. 40 CFR 725.355 - Information to be included in the TME application.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... or the environment as a result of the test marketing. The TME application must be in writing and must... the microorganism as a result of test marketing, including information regarding duration and route of... for Test Marketing § 725.355 Information to be included in the TME application. (a) To review a TME...

  12. Application of chemical biology in target identification and drug discovery.

    PubMed

    Zhu, Yue; Xiao, Ting; Lei, Saifei; Zhou, Fulai; Wang, Ming-Wei

    2015-09-01

    Drug discovery and development is vital to the well-being of mankind and sustainability of the pharmaceutical industry. Using chemical biology approaches to discover drug leads has become a widely accepted path partially because of the completion of the Human Genome Project. Chemical biology mainly solves biological problems through searching previously unknown targets for pharmacologically active small molecules or finding ligands for well-defined drug targets. It is a powerful tool to study how these small molecules interact with their respective targets, as well as their roles in signal transduction, molecular recognition and cell functions. There have been an increasing number of new therapeutic targets being identified and subsequently validated as a result of advances in functional genomics, which in turn led to the discovery of numerous active small molecules via a variety of high-throughput screening initiatives. In this review, we highlight some applications of chemical biology in the context of drug discovery.

  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. Application of Magnetized Target Fusion to High-Energy Space Propulsion

    NASA Technical Reports Server (NTRS)

    Thio, Y. C. F.; Schmidt, G. R.; Kirkpatrick, R. C.; Rodgers, Stephen L. (Technical Monitor)

    2001-01-01

    Most fusion propulsion concepts that have been investigated in the past employ some form of inertial or magnetic confinement. Although the prospective performance of these concepts is excellent, the fusion processes on which these concepts are based still require considerable development before they can be seriously considered for actual applications. Furthermore, these processes are encumbered by the need for sophisticated plasma and power handling systems that are generally quite inefficient and have historically resulted in large, massive spacecraft designs. Here we present a comparatively new approach, Magnetized Target Fusion (MTF), which offers a nearer-term avenue for realizing the tremendous performance benefits of fusion propulsion'. The key advantage of MTF is its less demanding requirements for driver energy and power processing. Additional features include: 1) very low system masses and volumes, 2) high gain and relatively low waste heat, 3) substantial utilization of energy from product neutrons, 4) efficient, low peak-power drivers based on existing pulsed power technology, and 5) very high Isp, specific power and thrust. MTF overcomes many of the problems associated with traditional fusion techniques, thus making it particularly attractive for space applications. Isp greater than 50,000 seconds and specific powers greater than 50 kilowatts/kilogram appear feasible using relatively near-term pulse power and plasma gun technology.

  15. Target-cancer-cell-specific activatable fluorescence imaging probes: rational design and in vivo applications.

    PubMed

    Kobayashi, Hisataka; Choyke, Peter L

    2011-02-15

    Conventional imaging methods, such as angiography, computed tomography (CT), magnetic resonance imaging (MRI), and radionuclide imaging, rely on contrast agents (iodine, gadolinium, and radioisotopes, for example) that are "always on." Although these indicators have proven clinically useful, their sensitivity is lacking because of inadequate target-to-background signal ratio. A unique aspect of optical imaging is that fluorescence probes can be designed to be activatable, that is, only "turned on" under certain conditions. These probes are engineered to emit signal only after binding a target tissue; this design greatly increases sensitivity and specificity in the detection of disease. Current research focuses on two basic types of activatable fluorescence probes. The first developed were conventional enzymatically activatable probes. These fluorescent molecules exist in the quenched state until activated by enzymatic cleavage, which occurs mostly outside of the cells. However, more recently, researchers have begun designing target-cell-specific activatable probes. These fluorophores exist in the quenched state until activated within targeted cells by endolysosomal processing, which results when the probe binds specific receptors on the cell surface and is subsequently internalized. In this Account, we present a review of the rational design and in vivo applications of target-cell-specific activatable probes. In engineering these probes, researchers have asserted control over a variety of factors, including photochemistry, pharmacological profile, and biological properties. Their progress has recently allowed the rational design and synthesis of target-cell-specific activatable fluorescence imaging probes, which can be conjugated to a wide variety of targeting molecules. Several different photochemical mechanisms have been utilized, each of which offers a unique capability for probe design. These include self-quenching, homo- and hetero-fluorescence resonance

  16. 30 CFR 250.1007 - What to include in applications.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... line pipe and risers; pressure-regulating devices (including back-pressure regulators); sensing devices... § 250.198), if applicable. (ii) If you propose to use one or more pipeline risers for a tension leg... riser, with calculations, and the fatigue point at which you would replace the riser; (B) The results of...

  17. Target-Pathogen: a structural bioinformatic approach to prioritize drug targets in pathogens.

    PubMed

    Sosa, Ezequiel J; Burguener, Germán; Lanzarotti, Esteban; Defelipe, Lucas; Radusky, Leandro; Pardo, Agustín M; Marti, Marcelo; Turjanski, Adrián G; Fernández Do Porto, Darío

    2018-01-04

    Available genomic data for pathogens has created new opportunities for drug discovery and development to fight them, including new resistant and multiresistant strains. In particular structural data must be integrated with both, gene information and experimental results. In this sense, there is a lack of an online resource that allows genome wide-based data consolidation from diverse sources together with thorough bioinformatic analysis that allows easy filtering and scoring for fast target selection for drug discovery. Here, we present Target-Pathogen database (http://target.sbg.qb.fcen.uba.ar/patho), designed and developed as an online resource that allows the integration and weighting of protein information such as: function, metabolic role, off-targeting, structural properties including druggability, essentiality and omic experiments, to facilitate the identification and prioritization of candidate drug targets in pathogens. We include in the database 10 genomes of some of the most relevant microorganisms for human health (Mycobacterium tuberculosis, Mycobacterium leprae, Klebsiella pneumoniae, Plasmodium vivax, Toxoplasma gondii, Leishmania major, Wolbachia bancrofti, Trypanosoma brucei, Shigella dysenteriae and Schistosoma Smanosoni) and show its applicability. New genomes can be uploaded upon request. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. Target-Pathogen: a structural bioinformatic approach to prioritize drug targets in pathogens

    PubMed Central

    Sosa, Ezequiel J; Burguener, Germán; Lanzarotti, Esteban; Radusky, Leandro; Pardo, Agustín M; Marti, Marcelo

    2018-01-01

    Abstract Available genomic data for pathogens has created new opportunities for drug discovery and development to fight them, including new resistant and multiresistant strains. In particular structural data must be integrated with both, gene information and experimental results. In this sense, there is a lack of an online resource that allows genome wide-based data consolidation from diverse sources together with thorough bioinformatic analysis that allows easy filtering and scoring for fast target selection for drug discovery. Here, we present Target-Pathogen database (http://target.sbg.qb.fcen.uba.ar/patho), designed and developed as an online resource that allows the integration and weighting of protein information such as: function, metabolic role, off-targeting, structural properties including druggability, essentiality and omic experiments, to facilitate the identification and prioritization of candidate drug targets in pathogens. We include in the database 10 genomes of some of the most relevant microorganisms for human health (Mycobacterium tuberculosis, Mycobacterium leprae, Klebsiella pneumoniae, Plasmodium vivax, Toxoplasma gondii, Leishmania major, Wolbachia bancrofti, Trypanosoma brucei, Shigella dysenteriae and Schistosoma Smanosoni) and show its applicability. New genomes can be uploaded upon request. PMID:29106651

  19. 78 FR 14121 - Notice of Availability of Funds and Solicitation for Grant Applications for Strategies Targeting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-04

    ... Solicitation for Grant Applications for Strategies Targeting Characteristics Common to Female Ex-Offenders... will be targeted to females, but must also be open to eligible male ex-offenders. Strategies Targeting Characteristics Common to Female Ex-Offenders grants [[Page 14122

  20. Selection of phage-displayed accessible recombinant targeted antibodies (SPARTA): methodology and applications.

    PubMed

    D'Angelo, Sara; Staquicini, Fernanda I; Ferrara, Fortunato; Staquicini, Daniela I; Sharma, Geetanjali; Tarleton, Christy A; Nguyen, Huynh; Naranjo, Leslie A; Sidman, Richard L; Arap, Wadih; Bradbury, Andrew Rm; Pasqualini, Renata

    2018-05-03

    We developed a potentially novel and robust antibody discovery methodology, termed selection of phage-displayed accessible recombinant targeted antibodies (SPARTA). This combines an in vitro screening step of a naive human antibody library against known tumor targets, with in vivo selections based on tumor-homing capabilities of a preenriched antibody pool. This unique approach overcomes several rate-limiting challenges to generate human antibodies amenable to rapid translation into medical applications. As a proof of concept, we evaluated SPARTA on 2 well-established tumor cell surface targets, EphA5 and GRP78. We evaluated antibodies that showed tumor-targeting selectivity as a representative panel of antibody-drug conjugates (ADCs) and were highly efficacious. Our results validate a discovery platform to identify and validate monoclonal antibodies with favorable tumor-targeting attributes. This approach may also extend to other diseases with known cell surface targets and affected tissues easily isolated for in vivo selection.

  1. Application of a Dynamic Programming Algorithm for Weapon Target Assignment

    DTIC Science & Technology

    2016-02-01

    25] A . Turan , “Techniques for the Allocation of Resources Under Uncertainty,” Middle Eastern Technical University, Ankara, Turkey, 2012. [26] K...UNCLASSIFIED UNCLASSIFIED Application of a Dynamic Programming Algorithm for Weapon Target Assignment Lloyd Hammond Weapons and...optimisation techniques to support the decision making process. This report documents the methodology used to identify, develop and assess a

  2. Manmade target extraction based on multistage decision and its application for change detection in polarimetric synthetic aperture radar image

    NASA Astrophysics Data System (ADS)

    Cong, Runmin; Han, Ping; Li, Chongyi; He, Jiaji; Zhang, Zaiji

    2016-09-01

    Targets of interest are different in various applications in which manmade targets, such as aircraft, ships, and buildings, are given more attention. Manmade target extraction methods using synthetic aperture radar (SAR) images are designed in response to various demands, which include civil uses, business purposes, and military industries. This plays an increasingly vital role in monitoring, military reconnaissance, and precision strikes. Achieving accurate and complete results through traditional methods is becoming more challenging because of the scattered complexity of polarization in polarimetric synthetic aperture radar (PolSAR) image. A multistage decision-based method is proposed composed of power decision, dominant scattering mechanism decision, and reflection symmetry decision. In addition, the theories of polarimetric contrast enhancement, generalized Y decomposition, and maximum eigenvalue ratio are applied to assist the decision. Fully PolSAR data are adopted to evaluate and verify the approach. Experimental results show that the method can achieve an effective result with a lower false alarm rate and clear contours. Finally, on this basis, a universal framework of change detection for manmade targets is presented as an application of our method. Two sets of measured data are also used to evaluate and verify the effectiveness of the change-detection algorithm.

  3. On the Impact of Localization and Density Control Algorithms in Target Tracking Applications for Wireless Sensor Networks

    PubMed Central

    Campos, Andre N.; Souza, Efren L.; Nakamura, Fabiola G.; Nakamura, Eduardo F.; Rodrigues, Joel J. P. C.

    2012-01-01

    Target tracking is an important application of wireless sensor networks. The networks' ability to locate and track an object is directed linked to the nodes' ability to locate themselves. Consequently, localization systems are essential for target tracking applications. In addition, sensor networks are often deployed in remote or hostile environments. Therefore, density control algorithms are used to increase network lifetime while maintaining its sensing capabilities. In this work, we analyze the impact of localization algorithms (RPE and DPE) and density control algorithms (GAF, A3 and OGDC) on target tracking applications. We adapt the density control algorithms to address the k-coverage problem. In addition, we analyze the impact of network density, residual integration with density control, and k-coverage on both target tracking accuracy and network lifetime. Our results show that DPE is a better choice for target tracking applications than RPE. Moreover, among the evaluated density control algorithms, OGDC is the best option among the three. Although the choice of the density control algorithm has little impact on the tracking precision, OGDC outperforms GAF and A3 in terms of tracking time. PMID:22969329

  4. Planar optical waveguide based sandwich assay sensors and processes for the detection of biological targets including protein markers, pathogens and cellular debris

    DOEpatents

    Martinez, Jennifer S [Santa Fe, NM; Swanson, Basil I [Los Alamos, NM; Grace, Karen M [Los Alamos, NM; Grace, Wynne K [Los Alamos, NM; Shreve, Andrew P [Santa Fe, NM

    2009-06-02

    An assay element is described including recognition ligands bound to a film on a single mode planar optical waveguide, the film from the group of a membrane, a polymerized bilayer membrane, and a self-assembled monolayer containing polyethylene glycol or polypropylene glycol groups therein and an assay process for detecting the presence of a biological target is described including injecting a biological target-containing sample into a sensor cell including the assay element, with the recognition ligands adapted for binding to selected biological targets, maintaining the sample within the sensor cell for time sufficient for binding to occur between selected biological targets within the sample and the recognition ligands, injecting a solution including a reporter ligand into the sensor cell; and, interrogating the sample within the sensor cell with excitation light from the waveguide, the excitation light provided by an evanescent field of the single mode penetrating into the biological target-containing sample to a distance of less than about 200 nanometers from the waveguide thereby exciting the fluorescent-label in any bound reporter ligand within a distance of less than about 200 nanometers from the waveguide and resulting in a detectable signal.

  5. 30 CFR 285.906 - What must my decommissioning application include?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What must my decommissioning application include? 285.906 Section 285.906 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR OFFSHORE RENEWABLE ENERGY ALTERNATE USES OF EXISTING FACILITIES ON THE OUTER CONTINENTAL SHELF...

  6. 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.

  7. 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

  8. Target-cancer cell specific activatable fluorescence imaging Probes: Rational Design and in vivo Applications

    PubMed Central

    Kobayashi, Hisataka; Choyke, Peter L.

    2010-01-01

    CONSPECTUS Conventional imaging methods, such as angiography, computed tomography, magnetic resonance imaging and radionuclide imaging, rely on contrast agents (iodine, gadolinium, radioisotopes) that are “always on”. While these agents have proven clinically useful, they are not sufficiently sensitive because of the inadequate target to background ratio. A unique aspect of optical imaging is that fluorescence probes can be designed to be activatable, i.e. only “turned on” under certain conditions. These probes can be designed to emit signal only after binding a target tissue, greatly increasing sensitivity and specificity in the detection of disease. There are two basic types of activatable fluorescence probes; 1) conventional enzymatically activatable probes, which exist in the quenched state until activated by enzymatic cleavage mostly outside of the cells, and 2) newly designed target-cell specific activatable probes, which are quenched until activated in targeted cells by endolysosomal processing that results when the probe binds specific cell-surface receptors and is subsequently internalized. Herein, we present a review of the rational design and in vivo applications of target-cell specific activatable probes. Designing these probes based on their photo-chemical (e.g. activation strategy), pharmacological (e.g. biodistribution), and biological (e.g. target specificity) properties has recently allowed the rational design and synthesis of target-cell specific activatable fluorescence imaging probes, which can be conjugated to a wide variety of targeting molecules. Several different photo-chemical mechanisms have been utilized, each of which offers a unique capability for probe design. These include: self-quenching, homo- and hetero-fluorescence resonance energy transfer (FRET), H-dimer formation and photon-induced electron transfer (PeT). In addition, the repertoire is further expanded by the option for reversibility or irreversibility of the signal

  9. Extending multi-tenant architectures: a database model for a multi-target support in SaaS applications

    NASA Astrophysics Data System (ADS)

    Rico, Antonio; Noguera, Manuel; Garrido, José Luis; Benghazi, Kawtar; Barjis, Joseph

    2016-05-01

    Multi-tenant architectures (MTAs) are considered a cornerstone in the success of Software as a Service as a new application distribution formula. Multi-tenancy allows multiple customers (i.e. tenants) to be consolidated into the same operational system. This way, tenants run and share the same application instance as well as costs, which are significantly reduced. Functional needs vary from one tenant to another; either companies from different sectors run different types of applications or, although deploying the same functionality, they do differ in the extent of their complexity. In any case, MTA leaves one major concern regarding the companies' data, their privacy and security, which requires special attention to the data layer. In this article, we propose an extended data model that enhances traditional MTAs in respect of this concern. This extension - called multi-target - allows MT applications to host, manage and serve multiple functionalities within the same multi-tenant (MT) environment. The practical deployment of this approach will allow SaaS vendors to target multiple markets or address different levels of functional complexity and yet commercialise just one single MT application. The applicability of the approach is demonstrated via a case study of a real multi-tenancy multi-target (MT2) implementation, called Globalgest.

  10. Application of Nanotechnology in the Targeted Release of Anticancer Drugs in Ovarian Cancer Treatment

    DTIC Science & Technology

    2007-12-01

    used in detection, diagnosis, and treatment of cancer . When loaded with chemotherapeutic agents, nanoparticle delivery to cancerous tissues...Targeted Release of Anticancer Drugs in Ovarian Cancer Treatment PRINCIPAL INVESTIGATOR: Colleen Feltmate, M.D. CONTRACTING ORGANIZATION...5a. CONTRACT NUMBER Application of Nanotechnology in the Targeted Release of Anticancer Drugs in Ovarian Cancer Treatment 5b. GRANT NUMBER

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

    NASA Astrophysics Data System (ADS)

    Miao, Hua; Guo, Xiaoming; Chen, Yu

    2014-11-01

    . Experimental results show that the improved automatic threshold processing has special application value for the recognition of dynamic target with low contrast.

  12. Pediatric, Adolescent, and Young Adult Thyroid Carcinoma Harbors Frequent and Diverse Targetable Genomic Alterations, Including Kinase Fusions

    PubMed Central

    Schrock, Alexa B.; Anderson, Peter M.; Morris, John C.; Heilmann, Andreas M.; Holmes, Oliver; Wang, Kai; Johnson, Adrienne; Waguespack, Steven G.; Ou, Sai‐Hong Ignatius; Khan, Saad; Fung, Kar‐Ming; Stephens, Philip J.; Erlich, Rachel L.; Miller, Vincent A.; Ross, Jeffrey S.; Ali, Siraj M.

    2017-01-01

    Background. Thyroid carcinoma, which is rare in pediatric patients (age 0–18 years) but more common in adolescent and young adult (AYA) patients (age 15–39 years), carries the potential for morbidity and mortality. Methods. Hybrid‐capture‐based comprehensive genomic profiling (CGP) was performed prospectively on 512 consecutively submitted thyroid carcinomas, including 58 from pediatric and AYA (PAYA) patients, to identify genomic alterations (GAs), including base substitutions, insertions/deletions, copy number alterations, and rearrangements. This PAYA data series includes 41 patients with papillary thyroid carcinoma (PTC), 3 with anaplastic thyroid carcinoma (ATC), and 14 with medullary thyroid carcinoma (MTC). Results. GAs were detected in 93% (54/58) of PAYA cases, with a mean of 1.4 GAs per case. In addition to BRAF V600E mutations, detected in 46% (19/41) of PAYA PTC cases and in 1 of 3 AYA ATC cases, oncogenic fusions involving RET, NTRK1, NTRK3, and ALK were detected in 37% (15/41) of PAYA PTC and 33% (1/3) of AYA ATC cases. Ninety‐three percent (13/14) of MTC patients harbored RET alterations, including 3 novel insertions/deletions in exons 6 and 11. Two of these MTC patients with novel alterations in RET experienced clinical benefit from vandetanib treatment. Conclusion. CGP identified diverse clinically relevant GAs in PAYA patients with thyroid carcinoma, including 83% (34/41) of PTC cases harboring activating kinase mutations or activating kinase rearrangements. These genomic observations and index cases exhibiting clinical benefit from targeted therapy suggest that young patients with advanced thyroid carcinoma can benefit from CGP and rationally matched targeted therapy. Implications for Practice. The detection of diverse clinically relevant genomic alterations in the majority of pediatric, adolescent, and young adult patients with thyroid carcinoma in this study suggests that comprehensive genomic profiling may be beneficial for young

  13. Design of ligand-targeted nanoparticles for enhanced cancer targeting

    NASA Astrophysics Data System (ADS)

    Stefanick, Jared F.

    Ligand-targeted nanoparticles are increasingly used as drug delivery vehicles for cancer therapy, yet have not consistently produced successful clinical outcomes. Although these inconsistencies may arise from differences in disease models and target receptors, nanoparticle design parameters can significantly influence therapeutic efficacy. By employing a multifaceted synthetic strategy to prepare peptide-targeted nanoparticles with high purity, reproducibility, and precisely controlled stoichiometry of functionalities, this work evaluates the roles of polyethylene glycol (PEG) coating, ethylene glycol (EG) peptide-linker length, peptide hydrophilicity, peptide density, and nanoparticle size on tumor targeting in a systematic manner. These parameters were analyzed in multiple disease models by targeting human epidermal growth factor receptor 2 (HER2) in breast cancer and very late antigen-4 (VLA-4) in multiple myeloma to demonstrate the widespread applicability of this approach. By increasing the hydrophilicity of the targeting peptide sequence and simultaneously optimizing the EG peptide-linker length, the in vitro cellular uptake of targeted liposomes was significantly enhanced. Specifically, including a short oligolysine chain adjacent to the targeting peptide sequence effectively increased cellular uptake ~80-fold using an EG6 peptide-linker compared to ~10-fold using an EG45 linker. In vivo, targeted liposomes prepared in a traditional manner lacking the oligolysine chain demonstrated similar biodistribution and tumor uptake to non-targeted liposomes. However, by including the oligolysine chain, targeted liposomes using an EG45 linker significantly improved tumor uptake ~8-fold over non-targeted liposomes, while the use of an EG6 linker decreased tumor accumulation and uptake, owing to differences in cellular uptake kinetics, clearance mechanisms, and binding site barrier effects. To further improve tumor targeting and enhance the selectivity of targeted

  14. Introduction to spallation physics and spallation-target design

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

    Russell, G.J.; Pitcher, E.J.; Daemen, L.L.

    1995-10-01

    When coupled with the spallation process in appropriate target materials, high-power accelerators can be used to produce large numbers of neutrons, thus providing an alternate method to the use of nuclear reactors for this purpose. Spallation offers exciting new possibilities for generating intense neutron fluxes for a variety of applications, including: (a) spallation-neutron sources for materials science research; (b) accelerator-based production of tritium; (c) accelerator-based transmutation of waste; (d) accelerator-based destruction of plutonium; and (e) radioisotope production for medical and energy applications. Target design plays a key role in these applications, with neutron production/leakage being strongly dependent on the incidentmore » particle type and energy, and target material and geometry.« less

  15. Collagen like peptide bioconjugates for targeted drug delivery applications

    NASA Astrophysics Data System (ADS)

    Luo, Tianzhi

    Collagen is the most abundant protein in mammals, and there has been long-standing interest in understanding and controlling collagen assembly in the design of new materials. Collagen-like peptides (CLP), also known as collagen-mimetic peptides (CMP), are short synthetic peptides which mimic the triple helical conformation of native collagens. In the past few decades, collagen like peptides and their conjugated hybrids have become a new class of biomaterials that possesses unique structures and properties. In addition to traditional applications of using CLPs to decipher the role of different amino acid residues and tripeptide motifs in stabilizing the collagen triple helix and mimicking collagen fibril formation, with the introduction of specific interactions including electrostatic interactions, pi-pi stacking interaction and metal-ligand coordination, a variety of artificial collagen-like peptides with well-defined sequences have been designed to create higher order assemblies with specific biological functions. The CLPs have also been widely used as bioactive domains or physical cross-linkers to fabricate hydrogels, which have shown potential to improve cell adhesion, proliferation and ECM macromolecule production. Despite this widespread use, the utilization of CLPs as domains in stimuli responsive bioconjugates represents a relatively new area for the development of functional polymeric materials. In this work, a new class of thermoresponsive diblock conjugates, containing collagen-like peptides and a thermoresponsive polymer, namely poly(diethylene glycol methyl ether methacrylate) (PDEGMEMA), is introduced. The CLP domain maintains its triple helix conformation after conjugation with the polymer. The engineered LCST of these conjugates has enabled temperature-induced assembly under aqueous conditions, at physiologically relevant temperatures, into well-defined vesicles with diameters of approximately 50-200 nm. The formation of nanostructures was driven by

  16. Applications of 211At and 223Ra in Targeted Alpha-Particle Radiotherapy

    PubMed Central

    Vaidyanathan, Ganesan; Zalutsky, Michael R.

    2012-01-01

    Targeted radiotherapy using agents tagged with α-emitting radionuclides is gaining traction with several clinical trials already undertaken or ongoing, and others in the advanced planning stage. The most commonly used α-emitting radionuclides are 213Bi, 211At, 223Ra and 225Ac. While each one of these has pros and cons, it can be argued that 211At probably is the most versatile based on its half life, decay scheme and chemistry. On the other hand, for targeting bone metastases, 223Ra is the ideal radionuclide because simple cationic radium can be used for this purpose. In this review, we will discuss the recent developments taken place in the application of 211At-labeled radiopharmaceuticals and give an overview of the current status of 223Ra for targeted α-particle radiotherapy. PMID:22202151

  17. 12 CFR 550.90 - What information must I include in my application?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 5 2011-01-01 2011-01-01 false What information must I include in my application? 550.90 Section 550.90 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY FIDUCIARY POWERS OF SAVINGS ASSOCIATIONS Obtaining Fiduciary Powers § 550.90 What information must I include...

  18. 12 CFR 550.90 - What information must I include in my application?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false What information must I include in my application? 550.90 Section 550.90 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY FIDUCIARY POWERS OF SAVINGS ASSOCIATIONS Obtaining Fiduciary Powers § 550.90 What information must I include...

  19. 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.

  20. Liquid crystals as on-demand, variable thickness targets for intense laser applications

    NASA Astrophysics Data System (ADS)

    Poole, Patrick L.; Andereck, C. David; Schumacher, Douglass W.

    2014-10-01

    Laser-based ion acceleration is currently studied for its applications to advanced imaging and cancer therapy, among others. Targets for these and other high-intensity laser experiments are often small metallic foils with few to sub-micron thicknesses, where the thickness determines the physics of the dominant acceleration mechanism. We have developed liquid crystal films that preserve the planar target geometry advantageous to ion acceleration schemes while providing on-demand thickness variation between 50 and 5000 nm. This thickness control is obtained in part by varying the temperature at which films are formed, which governs the phase (and hence molecular ordering) of the liquid crystal material. Liquid crystals typically have vapor pressures well below the 10-6 Torr operating pressures of intense laser target chambers, and films formed in air maintain their thickness during chamber evacuation. Additionally, the minute volume that comprises each film makes the cost of each target well below one cent, in stark contrast to many standard solid targets. We will discuss the details of liquid crystal film control and formation, as well as characterization experiments performed at the Scarlet laser facility. This work was performed with support from DARPA and NNSA.

  1. Treat-to-target trials in diabetes.

    PubMed

    Wangnoo, Subhash K; Sethi, Bipin; Sahay, Rakesh K; John, Mathew; Ghosal, Samit; Sharma, Surendra K

    2014-03-01

    Treat-to-target is a therapeutic concept that considers well defined and specific physiologic targets as aims in controlling the pathophysiology of the disease. It has been widely used in diseases that pathophysiology includes, chronic metabolic and physiological disturbances, namely rheumatic conditions, vascular medicine and diabetes. In diabetes, the availability of "gold-standard" quantitative measures like fasting plasma glucose and glycated hemoglobin make the application of treat-to-target trials especially pertinent. Treatment modalities which have used single therapeutic agents or combinations or in combination with a variety of titration algorithms and implementation protocols have broadened our understanding of diabetes management with specific reference to insulin initiation and maintenance. Treat-to-target trials have been used to investigate a wide variety of questions including efficacy, safety, effect of treatment on comorbidities and patient satisfaction, ideal mechanisms to implement insulin initiation etc. A more generalized acceptance and implementation of treat-to-target trials may finally revolutionize diabetes management by combining aspects of individual care with standard treatment protocols.

  2. Applications of polymeric micelles with tumor targeted in chemotherapy

    NASA Astrophysics Data System (ADS)

    Ding, Hui; Wang, Xiaojun; Zhang, Song; Liu, Xinli

    2012-11-01

    Polymeric micelles (PMs) have gained more progress as a carrier system with the quick development of biological and nanoparticle techniques. In particular, PMs with smart targeting can deliver anti-cancer drugs directly into tumor cells at a sustained rate. PMs with core-shell structure (with diameters of 10 100 nm) have been prepared by a variety of biodegradable and biocompatible polymers via a self-assembly process. The preparation of polymeric micelles with stimuli-responsive block copolymers or modification of target molecules on polymeric micelles' surface are able to significantly improve the efficiency of drug delivery. Polymeric micelles, which have been considered as a novel promising drug carrier for cancer therapeutics, are rapidly evolving and being introduced in an attempt to overcome several limitations of traditional chemotherapeutics, including water solubility, tumor-specific accumulation, anti-tumor efficacy, and non-specific toxicity. This review describes the preparation of polymeric micelles and the targeted modification which greatly enhance the effects of chemotherapeutic agents.

  3. Identification of Homeotic Target Genes in Drosophila Melanogaster Including Nervy, a Proto-Oncogene Homologue

    PubMed Central

    Feinstein, P. G.; Kornfeld, K.; Hogness, D. S.; Mann, R. S.

    1995-01-01

    In Drosophila, the specific morphological characteristics of each segment are determined by the homeotic genes that regulate the expression of downstream target genes. We used a subtractive hybridization procedure to isolate activated target genes of the homeotic gene Ultrabithorax (Ubx). In addition, we constructed a set of mutant genotypes that measures the regulatory contribution of individual homeotic genes to a complex target gene expression pattern. Using these mutants, we demonstrate that homeotic genes can regulate target gene expression at the start of gastrulation, suggesting a previously unknown role for the homeotic genes at this early stage. We also show that, in abdominal segments, the levels of expression for two target genes increase in response to high levels of Ubx, demonstrating that the normal down-regulation of Ubx in these segments is functional. Finally, the DNA sequence of cDNAs for one of these genes predicts a protein that is similar to a human proto-oncogene involved in acute myeloid leukemias. These results illustrate potentially general rules about the homeotic control of target gene expression and suggest that subtractive hybridization can be used to isolate interesting homeotic target genes. PMID:7498738

  4. Histone-Targeted Nucleic Acid Delivery for Tissue Regenerative Applications

    NASA Astrophysics Data System (ADS)

    Munsell, Erik V.

    Nucleic acid delivery has garnered significant attention as an innovative therapeutic approach for treating a wide variety of diseases. However, the design of non-viral delivery systems that negotiate efficient intracellular trafficking and nuclear entry represents a significant challenge. Overcoming these hurdles requires a combination of well-controlled materials approaches with techniques to understand and direct cellular delivery. Recent investigations have highlighted the roles histone tail sequences play in directing nuclear delivery and retention, as well as activating DNA transcription. We established the ability to recapitulate these natural histone tail activities within non-viral gene nanocarriers, driving gene transfer/expression by enabling effective navigation to the nucleus via retrograde vesicular trafficking. A unique finding of this histone-targeted approach was that nanocarriers gained enhanced access to the nucleus during mitosis. The work described in this dissertation builds off of these fundamental insights to facilitate the translation of this histone-targeted delivery approach toward regenerative medicine applications. During native tissue repair, actively proliferating mesenchymal stem cells (MSCs) respond to a complex series of growth factor signals that direct their differentiation. Accordingly, the investigations in this work focused on utilizing the histone-targeted nanocarriers to enhance osteogenic growth factor gene transfer in dividing MSCs leading to augmented MSC chondrogenic differentiation, an essential first step in skeletal tissue repair. Concurrently, additional studies focused on optimizing the histone-targeted nanocarrier design strategy to enable improved plasmid DNA (pDNA) binding stability and tunable harnessing of native cellular processing pathways for enhanced gene transfer. Overall, the work presented herein demonstrated substantial increases in growth factor expression following histone-targeted gene transfer. This

  5. 40 CFR 1045.205 - What must I include in my application?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 34 2012-07-01 2012-07-01 false What must I include in my application? 1045.205 Section 1045.205 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS CONTROL OF EMISSIONS FROM SPARK-IGNITION PROPULSION MARINE ENGINES AND VESSELS Certifying...

  6. 40 CFR 1045.205 - What must I include in my application?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 33 2011-07-01 2011-07-01 false What must I include in my application? 1045.205 Section 1045.205 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS CONTROL OF EMISSIONS FROM SPARK-IGNITION PROPULSION MARINE ENGINES AND VESSELS Certifying...

  7. 40 CFR 1045.205 - What must I include in my application?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 34 2013-07-01 2013-07-01 false What must I include in my application? 1045.205 Section 1045.205 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS CONTROL OF EMISSIONS FROM SPARK-IGNITION PROPULSION MARINE ENGINES AND VESSELS Certifying...

  8. 40 CFR 1045.205 - What must I include in my application?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 33 2014-07-01 2014-07-01 false What must I include in my application? 1045.205 Section 1045.205 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS CONTROL OF EMISSIONS FROM SPARK-IGNITION PROPULSION MARINE ENGINES AND VESSELS Certifying...

  9. 40 CFR 1045.205 - What must I include in my application?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false What must I include in my application? 1045.205 Section 1045.205 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS CONTROL OF EMISSIONS FROM SPARK-IGNITION PROPULSION MARINE ENGINES AND VESSELS Certifying...

  10. 40 CFR 59.623 - What must I include in my application?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) List the specifications of the test fuel to show that it falls within the required ranges specified in... application (including the test procedures, test parameters, and test fuels) to show you meet the requirements... PRODUCTS Control of Evaporative Emissions From New and In-Use Portable Fuel Containers Certifying Emission...

  11. 40 CFR 1037.205 - What must I include in my application?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... the application (including the test procedures, test parameters, and test fuels) to show you meet the... basic parameters of the vehicle's design and emission controls. List the fuel type on which your vehicles are designed to operate (for example, ultra low-sulfur diesel fuel). (b) Explain how the emission...

  12. 40 CFR 59.623 - What must I include in my application?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) List the specifications of the test fuel to show that it falls within the required ranges specified in... application (including the test procedures, test parameters, and test fuels) to show you meet the requirements... PRODUCTS Control of Evaporative Emissions From New and In-Use Portable Fuel Containers Certifying Emission...

  13. 40 CFR 1037.205 - What must I include in my application?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... the application (including the test procedures, test parameters, and test fuels) to show you meet the... basic parameters of the vehicle's design and emission controls. List the fuel type on which your vehicles are designed to operate (for example, ultra low-sulfur diesel fuel). (b) Explain how the emission...

  14. 40 CFR 59.623 - What must I include in my application?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) List the specifications of the test fuel to show that it falls within the required ranges specified in... application (including the test procedures, test parameters, and test fuels) to show you meet the requirements... PRODUCTS Control of Evaporative Emissions From New and In-Use Portable Fuel Containers Certifying Emission...

  15. 40 CFR 59.623 - What must I include in my application?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) List the specifications of the test fuel to show that it falls within the required ranges specified in... application (including the test procedures, test parameters, and test fuels) to show you meet the requirements... PRODUCTS Control of Evaporative Emissions From New and In-Use Portable Fuel Containers Certifying Emission...

  16. 40 CFR 59.623 - What must I include in my application?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) List the specifications of the test fuel to show that it falls within the required ranges specified in... application (including the test procedures, test parameters, and test fuels) to show you meet the requirements... PRODUCTS Control of Evaporative Emissions From New and In-Use Portable Fuel Containers Certifying Emission...

  17. 34 CFR 206.20 - What must be included in an application?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false What must be included in an application? 206.20 Section 206.20 Education Regulations of the Offices of the Department of Education OFFICE OF ELEMENTARY AND SECONDARY EDUCATION, DEPARTMENT OF EDUCATION SPECIAL EDUCATIONAL PROGRAMS FOR STUDENTS WHOSE FAMILIES ARE...

  18. Electroplating targets for production of unique PET radionuclides

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

    Bui, V.; Sheh, Y.; Finn, R.

    1994-12-31

    The past decade has witnessed the applications of Positron Emission Tomography (PET) evolving from a purely research endeavour to a procedure which has specific clinical applications in the areas of cardiology, neurology and oncology. The growth of PET has been facilitated by developments in medical instrumentation and radiopharmaceutical chemistry efforts. Included in this latter effort has been the low energy accelerator production and processing of unique PET radionuclides appropriate for the radiolabeling of biomolecules i.e. monoclonal antibodies and pepetides. The development and application of electroplated targets of antimony and copper for the production of iodine-124 and gallium-66 respectively, utilizing themore » Memorial Sloan-Kettering Cancer Center cyclotron are examples of target design and development applicable to many medical accelerators.« less

  19. Electroplated targets for production of unique PET radionuclides

    NASA Astrophysics Data System (ADS)

    Bui, V.; Sheh, Y.; Finn, R.; Francesconi, L.; Cai, S.; Schlyer, D.; Wieland, B.

    1995-12-01

    The past decade has witnessed the applications of positron emission tomography (PET) evolving from a purely research endeavor to a procedure which has specific clinical applications in the areas of cardiology, neurology and oncology. The growth of PET has been facilitated by developments in both medical instrumentation and radiopharmaceutical chemistry efforts. Included in this latter effort has been the low energy accelerator production and processing of unique PET radionuclides appropriate for the radiolabeling of biomolecules, i.e. monoclonal antibodies and peptides. The development and application of electroplated targets of antimony and copper for the production of iodine-124 and gallium-66 respectively, utilizing the Memorial Sloan-Kettering Cancer Center (MSKCC) cyclotron are examples of target design and development applicable to many medical accelerators.

  20. Spray pesticide applications in Mediterranean citrus orchards: Canopy deposition and off-target losses.

    PubMed

    Garcerá, Cruz; Moltó, Enrique; Chueca, Patricia

    2017-12-01

    Only a portion of the water volume sprayed is deposited on the target when applying plant protection products with air-assisted axial-fan airblast sprayers in high growing crops. A fraction of the off-target losses deposits on the ground, but droplets also drift away from the site. This work aimed at assessing the spray distribution to different compartments (tree canopy, ground and air) during pesticide applications in a Mediterranean citrus orchard. Standard cone nozzles (Teejet D3 DC35) and venturi drift reducing nozzles (Albuz TVI 80 03) were compared. Applications were performed with a conventional air-assisted sprayer, with a spray volume of around 3000lha -1 in a Navel orange orchard. Brilliant Sulfoflavine (BSF) was used as a tracer. Results showed that only around 46% of the applied spray was deposited on the target trees and around 4% of the spray was deposited on adjacent trees from adjoining rows independently of the nozzle type. Applications with standard nozzles produced more potential airborne spray drift (23%) than those with the drift reducing nozzles (17%) but fewer direct losses to the ground (22% vs. 27%). Indirect losses (sedimenting spray drift) to the ground of adjacent paths were around 7-9% in both cases. The important data set of spray distribution in the different compartments around sprayed orchard (air, ground, vegetation) generated in this work is highly useful as input source of exposure to take into account for the risk assessment in Mediterranean citrus scenario. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Shape and texture fused recognition of flying targets

    NASA Astrophysics Data System (ADS)

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

    2011-06-01

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

  2. Nanoparticle-based targeted therapeutics in head-and-neck cancer.

    PubMed

    Wu, Ting-Ting; Zhou, Shui-Hong

    2015-01-01

    Head-and-neck cancer is a major form of the disease worldwide. Treatment consists of surgery, radiation therapy and chemotherapy, but these have not resulted in improved survival rates over the past few decades. Versatile nanoparticles, with selective tumor targeting, are considered to have the potential to improve these poor outcomes. Application of nanoparticle-based targeted therapeutics has extended into many areas, including gene silencing, chemotherapeutic drug delivery, radiosensitization, photothermal therapy, and has shown much promise. In this review, we discuss recent advances in the field of nanoparticle-mediated targeted therapeutics for head-and-neck cancer, with an emphasis on the description of targeting points, including future perspectives.

  3. Controlling data transfers from an origin compute node to a target compute node

    DOEpatents

    Archer, Charles J [Rochester, MN; Blocksome, Michael A [Rochester, MN; Ratterman, Joseph D [Rochester, MN; Smith, Brian E [Rochester, MN

    2011-06-21

    Methods, apparatus, and products are disclosed for controlling data transfers from an origin compute node to a target compute node that include: receiving, by an application messaging module on the target compute node, an indication of a data transfer from an origin compute node to the target compute node; and administering, by the application messaging module on the target compute node, the data transfer using one or more messaging primitives of a system messaging module in dependence upon the indication.

  4. 40 CFR 1060.205 - What must I include in my application?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... procedures you used (see § 1060.501). (d) List the specifications of the test fuel to show that it falls... the application (including the test procedures, test parameters, and test fuels) to show you meet the... certification for gasoline or some other fuel type. List each distinguishable configuration in the emission...

  5. 40 CFR 1060.205 - What must I include in my application?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... procedures you used (see § 1060.501). (d) List the specifications of the test fuel to show that it falls... the application (including the test procedures, test parameters, and test fuels) to show you meet the... certification for gasoline or some other fuel type. List each distinguishable configuration in the emission...

  6. 40 CFR 1060.205 - What must I include in my application?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... procedures you used (see § 1060.501). (d) List the specifications of the test fuel to show that it falls... the application (including the test procedures, test parameters, and test fuels) to show you meet the... certification for gasoline or some other fuel type. List each distinguishable configuration in the emission...

  7. 40 CFR 1060.205 - What must I include in my application?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... procedures you used (see § 1060.501). (d) List the specifications of the test fuel to show that it falls... the application (including the test procedures, test parameters, and test fuels) to show you meet the... certification for gasoline or some other fuel type. List each distinguishable configuration in the emission...

  8. 40 CFR 1060.205 - What must I include in my application?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... procedures you used (see § 1060.501). (d) List the specifications of the test fuel to show that it falls... the application (including the test procedures, test parameters, and test fuels) to show you meet the... certification for gasoline or some other fuel type. List each distinguishable configuration in the emission...

  9. Antibody Drug Conjugates: Application of Quantitative Pharmacology in Modality Design and Target Selection.

    PubMed

    Sadekar, S; Figueroa, I; Tabrizi, M

    2015-07-01

    Antibody drug conjugates (ADCs) are a multi-component modality comprising of an antibody targeting a cell-specific antigen, a potent drug/payload, and a linker that can be processed within cellular compartments to release payload upon internalization. Numerous ADCs are being evaluated in both research and clinical settings within the academic and pharmaceutical industry due to their ability to selectively deliver potent payloads. Hence, there is a clear need to incorporate quantitative approaches during early stages of drug development for effective modality design and target selection. In this review, we describe a quantitative approach and framework for evaluation of the interplay between drug- and systems-dependent properties (i.e., target expression, density, localization, turnover, and affinity) in order to deliver a sufficient amount of a potent payload into the relevant target cells. As discussed, theoretical approaches with particular considerations given to various key properties for the target and modality suggest that delivery of the payload into particular effect cells to be more sensitive to antigen concentrations for targets with slow turnover rates as compared to those with faster internalization rates. Further assessments also suggest that increasing doses beyond the threshold of the target capacity (a function of target internalization and expression) may not impact the maximum amount of payload delivered to the intended effect cells. This article will explore the important application of quantitative sciences in selection of the target and design of ADC modalities.

  10. 34 CFR 222.185 - What additional information must be included in an emergency grant application?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false What additional information must be included in an... for A Grant § 222.185 What additional information must be included in an emergency grant application? In addition to the information specified in § 222.184, an application for an emergency grant must...

  11. Oligonucleotide Aptamers: New Tools for Targeted Cancer Therapy

    PubMed Central

    Sun, Hongguang; Zhu, Xun; Lu, Patrick Y; Rosato, Roberto R; Tan, Wen; Zu, Youli

    2014-01-01

    Aptamers are a class of small nucleic acid ligands that are composed of RNA or single-stranded DNA oligonucleotides and have high specificity and affinity for their targets. Similar to antibodies, aptamers interact with their targets by recognizing a specific three-dimensional structure and are thus termed “chemical antibodies.” In contrast to protein antibodies, aptamers offer unique chemical and biological characteristics based on their oligonucleotide properties. Hence, they are more suitable for the development of novel clinical applications. Aptamer technology has been widely investigated in various biomedical fields for biomarker discovery, in vitro diagnosis, in vivo imaging, and targeted therapy. This review will discuss the potential applications of aptamer technology as a new tool for targeted cancer therapy with emphasis on the development of aptamers that are able to specifically target cell surface biomarkers. Additionally, we will describe several approaches for the use of aptamers in targeted therapeutics, including aptamer-drug conjugation, aptamer-nanoparticle conjugation, aptamer-mediated targeted gene therapy, aptamer-mediated immunotherapy, and aptamer-mediated biotherapy. PMID:25093706

  12. Engineering nucleases for gene targeting: safety and regulatory considerations.

    PubMed

    Pauwels, Katia; Podevin, Nancy; Breyer, Didier; Carroll, Dana; Herman, Philippe

    2014-01-25

    Nuclease-based gene targeting (NBGT) represents a significant breakthrough in targeted genome editing since it is applicable from single-celled protozoa to human, including several species of economic importance. Along with the fast progress in NBGT and the increasing availability of customized nucleases, more data are available about off-target effects associated with the use of this approach. We discuss how NBGT may offer a new perspective for genetic modification, we address some aspects crucial for a safety improvement of the corresponding techniques and we also briefly relate the use of NBGT applications and products to the regulatory oversight. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. WE-H-BRA-03: Development of a Model to Include the Evolution of Resistant Tumor Subpopulations Into the Treatment Optimization Process for Schedules Involving Targeted Agents in Chemoradiation Therapy

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

    Grassberger, C; Paganetti, H

    Purpose: To develop a model that includes the process of resistance development into the treatment optimization process for schedules that include targeted therapies. Further, to validate the approach using clinical data and to apply the model to assess the optimal induction period with targeted agents before curative treatment with chemo-radiation in stage III lung cancer. Methods: Growth of the tumor and its subpopulations is modeled by Gompertzian growth dynamics, resistance induction as a stochastic process. Chemotherapy induced cell kill is modeled by log-cell kill dynamics, targeted agents similarly but restricted to the sensitive population. Radiation induced cell kill is assumedmore » to follow the linear-quadratic model. The validation patient data consist of a cohort of lung cancer patients treated with tyrosine kinase inhibitors that had longitudinal imaging data available. Results: The resistance induction model was successfully validated using clinical trial data from 49 patients treated with targeted agents. The observed recurrence kinetics, with tumors progressing from 1.4–63 months, result in tumor growth equaling a median volume doubling time of 92 days [34–248] and a median fraction of pre-existing resistance of 0.035 [0–0.22], in agreement with previous clinical studies. The model revealed widely varying optimal time points for the use of curative therapy, reaching from ∼1m to >6m depending on the patient’s growth rate and amount of pre-existing resistance. This demonstrates the importance of patient-specific treatment schedules when targeted agents are incorporated into the treatment. Conclusion: We developed a model including evolutionary dynamics of resistant sub-populations with traditional chemotherapy and radiation cell kill models. Fitting to clinical data yielded patient specific growth rates and resistant fraction in agreement with previous studies. Further application of the model demonstrated how proper timing of chemo

  14. Application of QSAR and shape pharmacophore modeling approaches for targeted chemical library design.

    PubMed

    Ebalunode, Jerry O; Zheng, Weifan; Tropsha, Alexander

    2011-01-01

    Optimization of chemical library composition affords more efficient identification of hits from biological screening experiments. The optimization could be achieved through rational selection of reagents used in combinatorial library synthesis. However, with a rapid advent of parallel synthesis methods and availability of millions of compounds synthesized by many vendors, it may be more efficient to design targeted libraries by means of virtual screening of commercial compound collections. This chapter reviews the application of advanced cheminformatics approaches such as quantitative structure-activity relationships (QSAR) and pharmacophore modeling (both ligand and structure based) for virtual screening. Both approaches rely on empirical SAR data to build models; thus, the emphasis is placed on achieving models of the highest rigor and external predictive power. We present several examples of successful applications of both approaches for virtual screening to illustrate their utility. We suggest that the expert use of both QSAR and pharmacophore models, either independently or in combination, enables users to achieve targeted libraries enriched with experimentally confirmed hit compounds.

  15. Difference in target definition using three different methods to include respiratory motion in radiotherapy of lung cancer.

    PubMed

    Sloth Møller, Ditte; Knap, Marianne Marquard; Nyeng, Tine Bisballe; Khalil, Azza Ahmed; Holt, Marianne Ingerslev; Kandi, Maria; Hoffmann, Lone

    2017-11-01

    Minimizing the planning target volume (PTV) while ensuring sufficient target coverage during the entire respiratory cycle is essential for free-breathing radiotherapy of lung cancer. Different methods are used to incorporate the respiratory motion into the PTV. Fifteen patients were analyzed. Respiration can be included in the target delineation process creating a respiratory GTV, denoted iGTV. Alternatively, the respiratory amplitude (A) can be measured based on the 4D-CT and A can be incorporated in the margin expansion. The GTV expanded by A yielded GTV + resp, which was compared to iGTV in terms of overlap. Three methods for PTV generation were compared. PTV del (delineated iGTV expanded to CTV plus PTV margin), PTV σ (GTV expanded to CTV and A was included as a random uncertainty in the CTV to PTV margin) and PTV ∑ (GTV expanded to CTV, succeeded by CTV linear expansion by A to CTV + resp, which was finally expanded to PTV ∑ ). Deformation of tumor and lymph nodes during respiration resulted in volume changes between the respiratory phases. The overlap between iGTV and GTV + resp showed that on average 7% of iGTV was outside the GTV + resp implying that GTV + resp did not capture the tumor during the full deformable respiration cycle. A comparison of the PTV volumes showed that PTV σ was smallest and PTV Σ largest for all patients. PTV σ was in mean 14% (31 cm 3 ) smaller than PTV del , while PTV del was 7% (20 cm 3 ) smaller than PTV Σ . PTV σ yields the smallest volumes but does not ensure coverage of tumor during the full respiratory motion due to tumor deformation. Incorporating the respiratory motion in the delineation (PTV del ) takes into account the entire respiratory cycle including deformation, but at the cost, however, of larger treatment volumes. PTV Σ should not be used, since it incorporates the disadvantages of both PTV del and PTV σ .

  16. Non-target screening to trace ozonation transformation products in a wastewater treatment train including different post-treatments.

    PubMed

    Schollée, Jennifer E; Bourgin, Marc; von Gunten, Urs; McArdell, Christa S; Hollender, Juliane

    2018-05-25

    Ozonation and subsequent post-treatments are increasingly implemented in wastewater treatment plants (WWTPs) for enhanced micropollutant abatement. While this technology is effective, micropollutant oxidation leads to the formation of ozonation transformation products (OTPs). Target and suspect screening provide information about known parent compounds and known OTPs, but for a more comprehensive picture, non-target screening is needed. Here, sampling was conducted at a full-scale WWTP to investigate OTP formation at four ozone doses (2, 3, 4, and 5 mg/L, ranging from 0.3 to 1.0 gO 3 /gDOC) and subsequent changes during five post-treatment steps (i.e., sand filter, fixed bed bioreactor, moving bed bioreactor, and two granular activated carbon (GAC) filters, relatively fresh and pre-loaded). Samples were measured with online solid-phase extraction coupled to liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS) using electrospray ionization (ESI) in positive and negative modes. Existing non-target screening workflows were adapted to (1) examine the formation of potential OTPs at four ozone doses and (2) compare the removal of OTPs among five post-treatments. In (1), data processing included principal component analysis (PCA) and chemical knowledge on possible oxidation reactions to prioritize non-target features likely to be OTPs. Between 394 and 1328 unique potential OTPs were detected in positive ESI for the four ozone doses tested; between 12 and 324 unique potential OTPs were detected in negative ESI. At a specific ozone dose of 0.5 gO 3 /gDOC, 27 parent compounds were identified and were related to 69 non-target features selected as potential OTPs. Two OTPs were confirmed with reference standards (venlafaxine N-oxide and chlorothiazide); 34 other potential OTPs were in agreement with literature data and/or reaction mechanisms. In (2), hierarchical cluster analysis (HCA) was applied on profiles detected in positive ESI mode across the

  17. [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.

  18. Subpixel target detection and enhancement in hyperspectral images

    NASA Astrophysics Data System (ADS)

    Tiwari, K. C.; Arora, M.; Singh, D.

    2011-06-01

    Hyperspectral data due to its higher information content afforded by higher spectral resolution is increasingly being used for various remote sensing applications including information extraction at subpixel level. There is however usually a lack of matching fine spatial resolution data particularly for target detection applications. Thus, there always exists a tradeoff between the spectral and spatial resolutions due to considerations of type of application, its cost and other associated analytical and computational complexities. Typically whenever an object, either manmade, natural or any ground cover class (called target, endmembers, components or class) gets spectrally resolved but not spatially, mixed pixels in the image result. Thus, numerous manmade and/or natural disparate substances may occur inside such mixed pixels giving rise to mixed pixel classification or subpixel target detection problems. Various spectral unmixing models such as Linear Mixture Modeling (LMM) are in vogue to recover components of a mixed pixel. Spectral unmixing outputs both the endmember spectrum and their corresponding abundance fractions inside the pixel. It, however, does not provide spatial distribution of these abundance fractions within a pixel. This limits the applicability of hyperspectral data for subpixel target detection. In this paper, a new inverse Euclidean distance based super-resolution mapping method has been presented that achieves subpixel target detection in hyperspectral images by adjusting spatial distribution of abundance fraction within a pixel. Results obtained at different resolutions indicate that super-resolution mapping may effectively aid subpixel target detection.

  19. Multishot Targeted PROPELLER Magnetic Resonance Imaging: Description of the Technique and Initial Applications

    PubMed Central

    Deng, Jie; Larson, Andrew C.

    2010-01-01

    Objectives To test the feasibility of combining inner-volume imaging (IVI) techniques with conventional multishot periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) techniques for targeted-PROPELLER magnetic resonance imaging. Materials and Methods Perpendicular section-selective gradients for spatially selective excitation and refocusing RF pulses were applied to limit the refocused field-of-view (FOV) along the phase-encoding direction for each rectangular blade image. We performed comparison studies in phantoms and normal volunteers by using targeted-PROPELLER methods for a wide range of imaging applications that commonly use turbo-spin-echo (TSE) approaches (brain, abdominal, vessel wall, cardiac). Results In these initial studies, we demonstrated the feasibility of using targeted-PROPELLER approaches to limit the imaging FOV thereby reducing the number of blades or permitting increased spatial resolution without commensurate increases in scan time. Both phantom and in vivo motion studies demonstrated the potential for more robust regional self-navigated motion correction compared with conventional full FOV PROPELLER methods. Conclusion We demonstrated that the reduced FOV targeted-PROPELLER technique offers the potential for reducing imaging time, increasing spatial resolution, and targeting specific areas for robust regional motion correction. PMID:19465860

  20. Targeted microbubbles: a novel application for the treatment of kidney stones.

    PubMed

    Ramaswamy, Krishna; Marx, Vanessa; Laser, Daniel; Kenny, Thomas; Chi, Thomas; Bailey, Michael; Sorensen, Mathew D; Grubbs, Robert H; Stoller, Marshall L

    2015-07-01

    Kidney stone disease is endemic. Extracorporeal shockwave lithotripsy was the first major technological breakthrough where focused shockwaves were used to fragment stones in the kidney or ureter. The shockwaves induced the formation of cavitation bubbles, whose collapse released energy at the stone, and the energy fragmented the kidney stones into pieces small enough to be passed spontaneously. Can the concept of microbubbles be used without the bulky machine? The logical progression was to manufacture these powerful microbubbles ex vivo and inject these bubbles directly into the collecting system. An external source can be used to induce cavitation once the microbubbles are at their target; the key is targeting these microbubbles to specifically bind to kidney stones. Two important observations have been established: (i) bisphosphonates attach to hydroxyapatite crystals with high affinity; and (ii) there is substantial hydroxyapatite in most kidney stones. The microbubbles can be equipped with bisphosphonate tags to specifically target kidney stones. These bubbles will preferentially bind to the stone and not surrounding tissue, reducing collateral damage. Ultrasound or another suitable form of energy is then applied causing the microbubbles to induce cavitation and fragment the stones. This can be used as an adjunct to ureteroscopy or percutaneous lithotripsy to aid in fragmentation. Randall's plaques, which also contain hydroxyapatite crystals, can also be targeted to pre-emptively destroy these stone precursors. Additionally, targeted microbubbles can aid in kidney stone diagnostics by virtue of being used as an adjunct to traditional imaging methods, especially useful in high-risk patient populations. This novel application of targeted microbubble technology not only represents the next frontier in minimally invasive stone surgery, but a platform technology for other areas of medicine. © 2014 The Authors BJU International © 2014 BJU International Published

  1. 30 CFR 280.12 - What must I include in my application or notification?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... application form (Form MMS-134) at least 30 days before the startup date for activities in the permit area. If... Director to arrange an acceptable deadline. The form includes names of persons; the type, location, purpose... other person(s) participating in the proposed research, including the sponsor; (3) The type of research...

  2. PhytoCRISP-Ex: a web-based and stand-alone application to find specific target sequences for CRISPR/CAS editing.

    PubMed

    Rastogi, Achal; Murik, Omer; Bowler, Chris; Tirichine, Leila

    2016-07-01

    With the emerging interest in phytoplankton research, the need to establish genetic tools for the functional characterization of genes is indispensable. The CRISPR/Cas9 system is now well recognized as an efficient and accurate reverse genetic tool for genome editing. Several computational tools have been published allowing researchers to find candidate target sequences for the engineering of the CRISPR vectors, while searching possible off-targets for the predicted candidates. These tools provide built-in genome databases of common model organisms that are used for CRISPR target prediction. Although their predictions are highly sensitive, the applicability to non-model genomes, most notably protists, makes their design inadequate. This motivated us to design a new CRISPR target finding tool, PhytoCRISP-Ex. Our software offers CRIPSR target predictions using an extended list of phytoplankton genomes and also delivers a user-friendly standalone application that can be used for any genome. The software attempts to integrate, for the first time, most available phytoplankton genomes information and provide a web-based platform for Cas9 target prediction within them with high sensitivity. By offering a standalone version, PhytoCRISP-Ex maintains an independence to be used with any organism and widens its applicability in high throughput pipelines. PhytoCRISP-Ex out pars all the existing tools by computing the availability of restriction sites over the most probable Cas9 cleavage sites, which can be ideal for mutant screens. PhytoCRISP-Ex is a simple, fast and accurate web interface with 13 pre-indexed and presently updating phytoplankton genomes. The software was also designed as a UNIX-based standalone application that allows the user to search for target sequences in the genomes of a variety of other species.

  3. Application of industrial scale genomics to discovery of therapeutic targets in heart failure.

    PubMed

    Mehraban, F; Tomlinson, J E

    2001-12-01

    In recent years intense activity in both academic and industrial sectors has provided a wealth of information on the human genome with an associated impressive increase in the number of novel gene sequences deposited in sequence data repositories and patent applications. This genomic industrial revolution has transformed the way in which drug target discovery is now approached. In this article we discuss how various differential gene expression (DGE) technologies are being utilized for cardiovascular disease (CVD) drug target discovery. Other approaches such as sequencing cDNA from cardiovascular derived tissues and cells coupled with bioinformatic sequence analysis are used with the aim of identifying novel gene sequences that may be exploited towards target discovery. Additional leverage from gene sequence information is obtained through identification of polymorphisms that may confer disease susceptibility and/or affect drug responsiveness. Pharmacogenomic studies are described wherein gene expression-based techniques are used to evaluate drug response and/or efficacy. Industrial-scale genomics supports and addresses not only novel target gene discovery but also the burgeoning issues in pharmaceutical and clinical cardiovascular medicine relative to polymorphic gene responses.

  4. An Evaluation of a Flight Deck Interval Management Algorithm Including Delayed Target Trajectories

    NASA Technical Reports Server (NTRS)

    Swieringa, Kurt A.; Underwood, Matthew C.; Barmore, Bryan; Leonard, Robert D.

    2014-01-01

    NASA's first Air Traffic Management (ATM) Technology Demonstration (ATD-1) was created to facilitate the transition of mature air traffic management technologies from the laboratory to operational use. The technologies selected for demonstration are the Traffic Management Advisor with Terminal Metering (TMA-TM), which provides precise timebased scheduling in the terminal airspace; Controller Managed Spacing (CMS), which provides controllers with decision support tools enabling precise schedule conformance; and Interval Management (IM), which consists of flight deck automation that enables aircraft to achieve or maintain precise in-trail spacing. During high demand operations, TMA-TM may produce a schedule and corresponding aircraft trajectories that include delay to ensure that a particular aircraft will be properly spaced from other aircraft at each schedule waypoint. These delayed trajectories are not communicated to the automation onboard the aircraft, forcing the IM aircraft to use the published speeds to estimate the target aircraft's estimated time of arrival. As a result, the aircraft performing IM operations may follow an aircraft whose TMA-TM generated trajectories have substantial speed deviations from the speeds expected by the spacing algorithm. Previous spacing algorithms were not designed to handle this magnitude of uncertainty. A simulation was conducted to examine a modified spacing algorithm with the ability to follow aircraft flying delayed trajectories. The simulation investigated the use of the new spacing algorithm with various delayed speed profiles and wind conditions, as well as several other variables designed to simulate real-life variability. The results and conclusions of this study indicate that the new spacing algorithm generally exhibits good performance; however, some types of target aircraft speed profiles can cause the spacing algorithm to command less than optimal speed control behavior.

  5. Development, evaluation, and application of sediment quality targets for assessing and managing contaminated sediments in Tampa Bay, Florida

    USGS Publications Warehouse

    MacDonald, D.D.; Carr, R.S.; Eckenrod, D.; Greening, H.; Grabe, S.; Ingersoll, C.G.; Janicki, S.; Janicki, T.; Lindskoog, R.A.; Long, E.R.; Pribble, R.; Sloane, G.; Smorong, D.E.

    2004-01-01

    Tampa Bay is a large, urban estuary that is located in west central Florida. Although water quality conditions represent an important concern in this estuary, information from numerous sources indicates that sediment contamination also has the potential to adversely affect aquatic organisms, aquatic-dependent wildlife, and human health. As such, protecting relatively uncontaminated areas of the bay from contamination and reducing the amount of toxic chemicals in contaminated sediments have been identified as high-priority sediment management objectives for Tampa Bay. To address concerns related to sediment contamination in the bay, an ecosystem-based framework for assessing and managing sediment quality conditions was developed that included identification of sediment quality issues and concerns, development of ecosystem goals and objectives, selection of ecosystem health indicators, establishment of metrics and targets for key indicators, and incorporation of key indicators, metrics, and targets into watershed management plans and decision-making processes. This paper describes the process that was used to select and evaluate numerical sediment quality targets (SQTs) for assessing and managing contaminated sediments. These SQTs included measures of sediment chemistry, whole-sediment and pore-water toxicity, and benthic invertebrate community structure. In addition, the paper describes how the SQTs were used to develop site-specific concentration-response models that describe how the frequency of adverse biological effects changes with increasing concentrations of chemicals of potential concern. Finally, a key application of the SQTs for defining sediment management areas is discussed.

  6. Termites as targets and models for biotechnology.

    PubMed

    Scharf, Michael E

    2015-01-07

    Termites have many unique evolutionary adaptations associated with their eusocial lifestyles. Recent omics research has created a wealth of new information in numerous areas of termite biology (e.g., caste polyphenism, lignocellulose digestion, and microbial symbiosis) with wide-ranging applications in diverse biotechnological niches. Termite biotechnology falls into two categories: (a) termite-targeted biotechnology for pest management purposes, and (b) termite-modeled biotechnology for use in various industrial applications. The first category includes several candidate termiticidal modes of action such as RNA interference, digestive inhibition, pathogen enhancement, antimicrobials, endocrine disruption, and primer pheromone mimicry. In the second category, termite digestomes are deep resources for host and symbiont lignocellulases and other enzymes with applications in a variety of biomass, industrial, and processing applications. Moving forward, one of the most important approaches for accelerating advances in both termite-targeted and termite-modeled biotechnology will be to consider host and symbiont together as a single functional unit.

  7. Thermal Insulation System for Non-Vacuum Applications Including a Multilayer Composite

    NASA Technical Reports Server (NTRS)

    Fesmire, James E. (Inventor)

    2017-01-01

    The thermal insulation system of the present invention is for non-vacuum applications and is specifically tailored to the ambient pressure environment with any level of humidity or moisture. The thermal insulation system includes a multilayered composite including i) at least one thermal insulation layer and at least one compressible barrier layer provided as alternating, successive layers, and ii) at least one reflective film provided on at least one surface of the thermal insulation layer and/or said compressible barrier layer. The different layers and materials and their combinations are designed to provide low effective thermal conductivity for the system by managing all modes of heat transfer. The thermal insulation system includes an optional outer casing surrounding the multilayered composite. The thermal insulation system is particularly suited for use in any sub-ambient temperature environment where moisture or its adverse effects are a concern. The thermal insulation system provides physical resilience against damaging mechanical effects including compression, flexure, impact, vibration, and thermal expansion/contraction.

  8. High power neutron production targets

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

    Wender, S.

    1996-06-01

    The author describes issues of concern in the design of targets and associated systems for high power neutron production facilities. The facilities include uses for neutron scattering, accelerator driven transmutation, accelerator production of tritium, short pulse spallation sources, and long pulse spallation sources. Each of these applications requires a source with different design needs and consequently different implementation in practise.

  9. Biotechnological applications of mobile group II introns and their reverse transcriptases: gene targeting, RNA-seq, and non-coding RNA analysis.

    PubMed

    Enyeart, Peter J; Mohr, Georg; Ellington, Andrew D; Lambowitz, Alan M

    2014-01-13

    Mobile group II introns are bacterial retrotransposons that combine the activities of an autocatalytic intron RNA (a ribozyme) and an intron-encoded reverse transcriptase to insert site-specifically into DNA. They recognize DNA target sites largely by base pairing of sequences within the intron RNA and achieve high DNA target specificity by using the ribozyme active site to couple correct base pairing to RNA-catalyzed intron integration. Algorithms have been developed to program the DNA target site specificity of several mobile group II introns, allowing them to be made into 'targetrons.' Targetrons function for gene targeting in a wide variety of bacteria and typically integrate at efficiencies high enough to be screened easily by colony PCR, without the need for selectable markers. Targetrons have found wide application in microbiological research, enabling gene targeting and genetic engineering of bacteria that had been intractable to other methods. Recently, a thermostable targetron has been developed for use in bacterial thermophiles, and new methods have been developed for using targetrons to position recombinase recognition sites, enabling large-scale genome-editing operations, such as deletions, inversions, insertions, and 'cut-and-pastes' (that is, translocation of large DNA segments), in a wide range of bacteria at high efficiency. Using targetrons in eukaryotes presents challenges due to the difficulties of nuclear localization and sub-optimal magnesium concentrations, although supplementation with magnesium can increase integration efficiency, and directed evolution is being employed to overcome these barriers. Finally, spurred by new methods for expressing group II intron reverse transcriptases that yield large amounts of highly active protein, thermostable group II intron reverse transcriptases from bacterial thermophiles are being used as research tools for a variety of applications, including qRT-PCR and next-generation RNA sequencing (RNA-seq). The

  10. Cooperative Robots to Observe Moving Targets: Review.

    PubMed

    Khan, Asif; Rinner, Bernhard; Cavallaro, Andrea

    2018-01-01

    The deployment of multiple robots for achieving a common goal helps to improve the performance, efficiency, and/or robustness in a variety of tasks. In particular, the observation of moving targets is an important multirobot application that still exhibits numerous open challenges, including the effective coordination of the robots. This paper reviews control techniques for cooperative mobile robots monitoring multiple targets. The simultaneous movement of robots and targets makes this problem particularly interesting, and our review systematically addresses this cooperative multirobot problem for the first time. We classify and critically discuss the control techniques: cooperative multirobot observation of multiple moving targets, cooperative search, acquisition, and track, cooperative tracking, and multirobot pursuit evasion. We also identify the five major elements that characterize this problem, namely, the coordination method, the environment, the target, the robot and its sensor(s). These elements are used to systematically analyze the control techniques. The majority of the studied work is based on simulation and laboratory studies, which may not accurately reflect real-world operational conditions. Importantly, while our systematic analysis is focused on multitarget observation, our proposed classification is useful also for related multirobot applications.

  11. Sensor Compromise Detection in Multiple-Target Tracking Systems

    PubMed Central

    Doucette, Emily A.; Curtis, Jess W.

    2018-01-01

    Tracking multiple targets using a single estimator is a problem that is commonly approached within a trusted framework. There are many weaknesses that an adversary can exploit if it gains control over the sensors. Because the number of targets that the estimator has to track is not known with anticipation, an adversary could cause a loss of information or a degradation in the tracking precision. Other concerns include the introduction of false targets, which would result in a waste of computational and material resources, depending on the application. In this work, we study the problem of detecting compromised or faulty sensors in a multiple-target tracker, starting with the single-sensor case and then considering the multiple-sensor scenario. We propose an algorithm to detect a variety of attacks in the multiple-sensor case, via the application of finite set statistics (FISST), one-class classifiers and hypothesis testing using nonparametric techniques. PMID:29466314

  12. Targeting Strategies for Multifunctional Nanoparticles in Cancer Imaging and Therapy

    PubMed Central

    Yu, Mi Kyung; Park, Jinho; Jon, Sangyong

    2012-01-01

    Nanomaterials offer new opportunities for cancer diagnosis and treatment. Multifunctional nanoparticles harboring various functions including targeting, imaging, therapy, and etc have been intensively studied aiming to overcome limitations associated with conventional cancer diagnosis and therapy. Of various nanoparticles, magnetic iron oxide nanoparticles with superparamagnetic property have shown potential as multifunctional nanoparticles for clinical translation because they have been used asmagnetic resonance imaging (MRI) constrast agents in clinic and their features could be easily tailored by including targeting moieties, fluorescence dyes, or therapeutic agents. This review summarizes targeting strategies for construction of multifunctional nanoparticles including magnetic nanoparticles-based theranostic systems, and the various surface engineering strategies of nanoparticles for in vivo applications. PMID:22272217

  13. 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.

  14. Molecular imaging with targeted contrast ultrasound.

    PubMed

    Piedra, Mark; Allroggen, Achim; Lindner, Jonathan R

    2009-01-01

    Molecular imaging with contrast-enhanced ultrasound uses targeted microbubbles that are retained in diseased tissue. The resonant properties of these microbubbles produce acoustic signals in an ultrasound field. The microbubbles are targeted to diseased tissue by using certain chemical constituents in the microbubble shell or by attaching disease-specific ligands such as antibodies to the microbubble. In this review, we discuss the applications of this technique to pathological states in the cerebrovascular system including atherosclerosis, tumor angiogenesis, ischemia, intravascular thrombus, and inflammation. Copyright 2009 S. Karger AG, Basel.

  15. Novel approaches for targeting the adenosine A2A receptor.

    PubMed

    Yuan, Gengyang; Gedeon, Nicholas G; Jankins, Tanner C; Jones, Graham B

    2015-01-01

    The adenosine A2A receptor (A2AR) represents a drug target for a wide spectrum of diseases. Approaches for targeting this membrane-bound protein have been greatly advanced by new stabilization techniques. The resulting X-ray crystal structures and subsequent analyses provide deep insight to the A2AR from both static and dynamic perspectives. Application of this, along with other biophysical methods combined with fragment-based drug design (FBDD), has become a standard approach in targeting A2AR. Complementarities of in silico screening based- and biophysical screening assisted- FBDD are likely to feature in future approaches in identifying novel ligands against this key receptor. This review describes evolution of the above approaches for targeting A2AR and highlights key modulators identified. It includes a review of: adenosine receptor structures, homology modeling, X-ray structural analysis, rational drug design, biophysical methods, FBDD and in silico screening. As a drug target, the A2AR is attractive as its function plays a role in a wide spectrum of diseases including oncologic, inflammatory, Parkinson's and cardiovascular diseases. Although traditional approaches such as high-throughput screening and homology model-based virtual screening (VS) have played a role in targeting A2AR, numerous shortcomings have generally restricted their applications to specific ligand families. Using stabilization methods for crystallization, X-ray structures of A2AR have greatly accelerated drug discovery and influenced development of biophysical-in silico hybrid screening methods. Application of these new methods to other ARs and G-protein-coupled receptors is anticipated in the future.

  16. Engineering RNA for Targeted siRNA Delivery and Medical Application

    PubMed Central

    Guo, Peixuan; Coban, Oana; Snead, Nick; Trebley, Joe; Hoeprich, Steve; Guo, Songchuan; Shu, Yi

    2010-01-01

    RNA engineering for nanotechnology and medical applications is an exciting emerging research field. RNA has intrinsically defined features on the nanometer scale and is a particularly interesting candidate for such applications due to its amazing diversity, flexibility and versatility in structure and function. Specifically, the current use of siRNA to silence target genes involved in disease has generated much excitement in the scientific community. The intrinsic ability to sequence-specifically down-regulate gene expression in a temporally- and spatially-controlled fashion has led to heightened interest and rapid development of siRNA-based therapeutics. Though methods for gene silencing with high efficacy and specificity have been achieved in vitro, the effective delivery of nucleic acids to specific cells in vivo has been a hurdle for RNA therapeutics. This review covers different RNA-based approaches for diagnosis, prevention and treatment of human disease, with a focus on the latest developments of nonviral carriers of siRNA for delivery in vivo. The applications and challenges of siRNA therapy, as well as potential solutions to these problems, the approaches for using phi29 pRNA-based vectors as polyvalent vehicles for specific delivery of siRNA, ribozymes, drugs or other therapeutic agents to specific cells for therapy will also be addressed. PMID:20230868

  17. [Progress in application of targeting viral vector regulated by microRNA in gene therapy: a review].

    PubMed

    Zhang, Guohai; Wang, Qizhao; Zhang, Jinghong; Xu, Ruian

    2010-06-01

    A safe and effective targeting viral vector is the key factor for successful clinical gene therapy. microRNA, a class of small, single-stranded endogenous RNAs, act as post-transcriptional regulators of gene expression. The discovery of these kind regulatory elements provides a new approach to regulate gene expression more accurately. In this review, we elucidated the principle of microRNA in regulation of targeting viral vector. The applications of microRNA in the fields of elimination contamination from replication competent virus, reduction of transgene-specific immunity, promotion of cancer-targeted gene therapy and development of live attenuated vaccines were also discussed.

  18. Time-reversal MUSIC imaging of extended targets.

    PubMed

    Marengo, Edwin A; Gruber, Fred K; Simonetti, Francesco

    2007-08-01

    This paper develops, within a general framework that is applicable to rather arbitrary electromagnetic and acoustic remote sensing systems, a theory of time-reversal "MUltiple Signal Classification" (MUSIC)-based imaging of extended (nonpoint-like) scatterers (targets). The general analysis applies to arbitrary remote sensing geometry and sheds light onto how the singular system of the scattering matrix relates to the geometrical and propagation characteristics of the entire transmitter-target-receiver system and how to use this effect for imaging. All the developments are derived within exact scattering theory which includes multiple scattering effects. The derived time-reversal MUSIC methods include both interior sampling, as well as exterior sampling (or enclosure) approaches. For presentation simplicity, particular attention is given to the time-harmonic case where the informational wave modes employed for target interrogation are purely spatial, but the corresponding generalization to broadband fields is also given. This paper includes computer simulations illustrating the derived theory and algorithms.

  19. BEAM ON TARGET MODEL Produces All Gamma Ray Burst Phenomena Including Afterglow

    NASA Astrophysics Data System (ADS)

    Greyber, H.

    2000-12-01

    While one must applaud the splendid research by L. Piro et al and L. Amati et al reported in SCIENCE recently, one must question, as M. Rees and S. Woolsey have done, their conclusion that a ``supranova model" is the only explanation for these new X-ray observations. In fact L. Piro was quoted as saying, ``Our data helps rule out the scenario where two neutron stars or black holes collide. We think GRBs result from something similar to a supernova explosion, but much more powerful." A relatively unknown physical model for GRBs, Greyber's Beam On Target model (BOT), dating back to the first CGRO observations, can plausibly explain the iron emission lines observed for GRB991216, and also the mass of the dense medium within a light-day of the GRB being roughly equivalent to at least one-tenth solar mass, as well as the initial shedding of material followed by the GRB event. When a galaxy forms under gravitational collapse in the presence of a primordial magnetic field, Mestel and Strittmatter demonstrated that, for finite Ohmic diffusion, a growing equatorial current loop is formed. Even if this stable ``Storage Ring" has only 10exp-9 of the total energy released during a typical galaxy's formation, the relativistic beam can possess 10exp58 ergs. The GRB ``fireball" occurs when a target star races across the powerful beam, blowing off target material as a hot, rapidly expanding plasma cloud, simulating an explosion. Since currents in space are known to be sometimes filamentary, sharp millisecond spikes can be expected in some GRBs. Proton and alpha particle nuclear reactions produce a gamma ray beam. Beam particles impinging on denser cloud material create an electromagnetic shower, producing X-ray, optical and radio radiation. Since the Storage Ring has an intense magnetic field around it, synchrotron radiation is expected. The beam, striking a highly evolved massive target star, produces the iron emission lines. H. D. Greyber, in ``After the Dark Ages:When Galaxies

  20. [Genome-editing: focus on the off-target effects].

    PubMed

    He, Xiubin; Gu, Feng

    2017-10-25

    Breakthroughs of genome-editing in recent years have paved the way to develop new therapeutic strategies. These genome-editing tools mainly include Zinc-finger nucleases (ZFNs), Transcription activator-like effector nucleases (TALENs), and clustered regulatory interspaced short palindromic repeat (CRISPR)/Cas-based RNA-guided DNA endonucleases. However, off-target effects are still the major issue in genome editing, and limit the application in gene therapy. Here, we summarized the cause and compared different detection methods of off-targets.

  1. 24 CFR 35.82 - Scope and applicability.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... applicability. This subpart applies to all transactions to sell or lease target housing, including subleases, with the exception of the following: (a) Sales of target housing at foreclosure. (b) Leases of target...) Renewals of existing leases in target housing in which the lessor has previously disclosed all information...

  2. 24 CFR 35.82 - Scope and applicability.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... applicability. This subpart applies to all transactions to sell or lease target housing, including subleases, with the exception of the following: (a) Sales of target housing at foreclosure. (b) Leases of target...) Renewals of existing leases in target housing in which the lessor has previously disclosed all information...

  3. 24 CFR 35.82 - Scope and applicability.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... applicability. This subpart applies to all transactions to sell or lease target housing, including subleases, with the exception of the following: (a) Sales of target housing at foreclosure. (b) Leases of target...) Renewals of existing leases in target housing in which the lessor has previously disclosed all information...

  4. 24 CFR 35.82 - Scope and applicability.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... applicability. This subpart applies to all transactions to sell or lease target housing, including subleases, with the exception of the following: (a) Sales of target housing at foreclosure. (b) Leases of target...) Renewals of existing leases in target housing in which the lessor has previously disclosed all information...

  5. 24 CFR 35.82 - Scope and applicability.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... applicability. This subpart applies to all transactions to sell or lease target housing, including subleases, with the exception of the following: (a) Sales of target housing at foreclosure. (b) Leases of target...) Renewals of existing leases in target housing in which the lessor has previously disclosed all information...

  6. 45 CFR 2516.410 - What must a community-based entity include in an application for a grant?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE SCHOOL-BASED SERVICE-LEARNING PROGRAMS Application Contents § 2516.410 What must a community-based entity include in an application for a grant? In order to... 45 Public Welfare 4 2014-10-01 2014-10-01 false What must a community-based entity include in an...

  7. 45 CFR 2516.410 - What must a community-based entity include in an application for a grant?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE SCHOOL-BASED SERVICE-LEARNING PROGRAMS Application Contents § 2516.410 What must a community-based entity include in an application for a grant? In order to... 45 Public Welfare 4 2013-10-01 2013-10-01 false What must a community-based entity include in an...

  8. 45 CFR 2516.410 - What must a community-based entity include in an application for a grant?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE SCHOOL-BASED SERVICE-LEARNING PROGRAMS Application Contents § 2516.410 What must a community-based entity include in an application for a grant? In order to... 45 Public Welfare 4 2012-10-01 2012-10-01 false What must a community-based entity include in an...

  9. Recent Advances in Superparamagnetic Iron Oxide Nanoparticles for Cellular Imaging and Targeted Therapy Research

    PubMed Central

    Wang, Yi-Xiang J.; Xuan, Shouhu; Port, Marc; Idee, Jean-Marc

    2013-01-01

    Advances of nanotechnology have led to the development of nanomaterials with both potential diagnostic and therapeutic applications. Among them, superparamagnetic iron oxide (SPIO) nanoparticles have received particular attention. Over the past decade, various SPIOs with unique physicochemical and biological properties have been designed by modifying the particle structure, size and coating. This article reviews the recent advances in preparing SPIOs with novel properties, the way these physicochemical properties of SPIOs influence their interaction with cells, and the development of SPIOs in liver and lymph nodes magnetic resonance imaging (MRI) contrast. Cellular uptake of SPIO can be exploited in a variety of potential clinical applications, including stem cell and inflammation cell tracking and intra-cellular drug delivery to cancerous cells which offers higher intra-cellular concentration. When SPIOs are used as carrier vehicle, additional advantages can be achieved including magnetic targeting and hyperthermia options, as well as monitoring with MRI. Other potential applications of SPIO include magnetofection and gene delivery, targeted retention of labeled stem cells, sentinel lymph nodes mapping, and magnetic force targeting and cell orientation for tissue engineering. PMID:23621536

  10. 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.

  11. Engineering liposomal nanoparticles for targeted gene therapy.

    PubMed

    Zylberberg, C; Gaskill, K; Pasley, S; Matosevic, S

    2017-08-01

    Recent mechanistic studies have attempted to deepen our understanding of the process by which liposome-mediated delivery of genetic material occurs. Understanding the interactions between lipid nanoparticles and cells is still largely elusive. Liposome-mediated delivery of genetic material faces systemic obstacles alongside entry into the cell, endosomal escape, lysosomal degradation and nuclear uptake. Rational design approaches for targeted delivery have been developed to reduce off-target effects and enhance transfection. These strategies, which have included the modification of lipid nanoparticles with target-specific ligands to enhance intracellular uptake, have shown significant promise at the proof-of-concept stage. Control of physical and chemical specifications of liposome composition, which includes lipid-to-DNA charge, size, presence of ester bonds, chain length and nature of ligand complexation, is integral to the performance of targeted liposomes as genetic delivery agents. Clinical advances are expected to rely on such systems in the therapeutic application of liposome nanoparticle-based gene therapy. Here, we discuss the latest breakthroughs in the development of targeted liposome-based agents for the delivery of genetic material, paying particular attention to new ligand and cationic lipid design as well as recent in vivo advances.

  12. 34 CFR 367.11 - What assurances must a DSA include in its application?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 2 2014-07-01 2013-07-01 true What assurances must a DSA include in its application? 367.11 Section 367.11 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION INDEPENDENT LIVING...

  13. 34 CFR 367.11 - What assurances must a DSA include in its application?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 2 2012-07-01 2012-07-01 false What assurances must a DSA include in its application? 367.11 Section 367.11 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION INDEPENDENT LIVING...

  14. 34 CFR 367.11 - What assurances must a DSA include in its application?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 2 2013-07-01 2013-07-01 false What assurances must a DSA include in its application? 367.11 Section 367.11 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION INDEPENDENT LIVING...

  15. 34 CFR 607.12 - What must be included in cooperative arrangement grant applications?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 3 2013-07-01 2013-07-01 false What must be included in cooperative arrangement grant applications? 607.12 Section 607.12 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION STRENGTHENING INSTITUTIONS PROGRAM How...

  16. 34 CFR 607.12 - What must be included in cooperative arrangement grant applications?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 3 2011-07-01 2011-07-01 false What must be included in cooperative arrangement grant applications? 607.12 Section 607.12 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION STRENGTHENING INSTITUTIONS PROGRAM How...

  17. 34 CFR 607.12 - What must be included in cooperative arrangement grant applications?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 3 2012-07-01 2012-07-01 false What must be included in cooperative arrangement grant applications? 607.12 Section 607.12 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION STRENGTHENING INSTITUTIONS PROGRAM How...

  18. 34 CFR 607.12 - What must be included in cooperative arrangement grant applications?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 3 2014-07-01 2014-07-01 false What must be included in cooperative arrangement grant applications? 607.12 Section 607.12 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION STRENGTHENING INSTITUTIONS PROGRAM How...

  19. 34 CFR 607.12 - What must be included in cooperative arrangement grant applications?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What must be included in cooperative arrangement grant applications? 607.12 Section 607.12 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION STRENGTHENING INSTITUTIONS PROGRAM How...

  20. Application of Hybrid Along-Track Interferometry/Displaced Phase Center Antenna Method for Moving Human Target Detection in Forest Environments

    DTIC Science & Technology

    2016-10-01

    ARL-TR-7846 ● OCT 2016 US Army Research Laboratory Application of Hybrid Along-Track Interferometry/ Displaced Phase Center...Research Laboratory Application of Hybrid Along-Track Interferometry/ Displaced Phase Center Antenna Method for Moving Human Target Detection...TYPE Technical Report 3. DATES COVERED (From - To) 2015–2016 4. TITLE AND SUBTITLE Application of Hybrid Along-Track Interferometry/ Displaced

  1. Application of molecular targeted therapies in the treatment of head and neck squamous cell carcinoma.

    PubMed

    Kozakiewicz, Paulina; Grzybowska-Szatkowska, Ludmiła

    2018-05-01

    Despite the development of standard therapies, including surgery, radiotherapy and chemotherapy, survival rates for head and neck squamous cell carcinoma (HNSCC) have not changed significantly over the past three decades. Complete recovery is achieved in <50% of patients. The treatment of advanced HNSCC frequently requires multimodality therapy and involves significant toxicity. The promising, novel treatment option for patients with HNSCC is molecular-targeted therapies. The best known targeted therapies include: Epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab, panitumumab, zalutumumab and nimotuzumab), EGFR tyrosine kinase inhibitors (gefitinib, erlotinib, lapatinib, afatinib and dacomitinib), vascular endothelial growth factor (VEGF) inhibitor (bevacizumab) or vascular endothelial growth factor receptor (VEGFR) inhibitors (sorafenib, sunitinib and vandetanib) and inhibitors of phosphatidylinositol 3-kinase/serine/threonine-specific protein kinase/mammalian target of rapamycin. There are also various inhibitors of other pathways and targets, which are promising and require evaluation in further studies.

  2. Simultaneous quantification of tumor uptake for targeted and non-targeted liposomes and their encapsulated contents by ICP-MS

    PubMed Central

    Cheng, Zhiliang; Zaki, Ajlan Al; Hui, James Z; Tsourkas, Andrew

    2012-01-01

    Liposomes are intensively being developed for biomedical applications including drug and gene delivery. However, targeted liposomal delivery in cancer treatment is a very complicated multi-step process. Unfavorable liposome biodistribution upon intravenous administration and membrane destabilization in blood circulation could result in only a very small fraction of cargo reaching the tumors. It would therefore be desirable to develop new quantitative strategies to track liposomal delivery systems to improve the therapeutic index and decrease systemic toxicity. Here, we developed a simple and non-radiative method to quantify the tumor uptake of targeted and non-targeted control liposomes as well as their encapsulated contents simultaneously. Specifically, four different chelated lanthanide metals were encapsulated or surface-conjugated onto tumor-targeted and non-targeted liposomes, respectively. The two liposome formulations were then injected into tumor-bearing mice simultaneously and their tumor delivery was determined quantitatively via inductively coupled plasma-mass spectroscopy (ICP-MS), allowing for direct comparisons. Tumor uptake of the liposomes themselves and their encapsulated contents were consistent with targeted and non-targeted liposome formulations that were injected individually. PMID:22882145

  3. Generalized Wideband Harmonic Imaging of Nonlinearly Loaded Scatterers: Theory, Analysis, and Application for Forward-Looking Radar Target Detection

    DTIC Science & Technology

    2014-09-01

    signal) operations; it is general enough so that it can accommodate high - power (large-signal) sensing as well—which may be needed to detect targets... Generalized Wideband Harmonic Imaging of Nonlinearly Loaded Scatterers: Theory, Analysis, and Application for Forward-Looking Radar Target...Research Laboratory Adelphi, MD 20783-1138 ARL-TR-7121 September 2014 Generalized Wideband Harmonic Imaging of Nonlinearly Loaded

  4. Chloride channels as drug targets

    PubMed Central

    Verkman, Alan S.; Galietta, Luis J. V.

    2013-01-01

    Chloride channels represent a relatively under-explored target class for drug discovery as elucidation of their identity and physiological roles has lagged behind that of many other drug targets. Chloride channels are involved in a wide range of biological functions, including epithelial fluid secretion, cell-volume regulation, neuroexcitation, smooth-muscle contraction and acidification of intracellular organelles. Mutations in several chloride channels cause human diseases, including cystic fibrosis, macular degeneration, myotonia, kidney stones, renal salt wasting and hyperekplexia. Chloride-channel modulators have potential applications in the treatment of some of these disorders, as well as in secretory diarrhoeas, polycystic kidney disease, osteoporosis and hypertension. Modulators of GABAA (γ-aminobutyric acid A) receptor chloride channels are in clinical use and several small-molecule chloride-channel modulators are in preclinical development and clinical trials. Here, we discuss the broad opportunities that remain in chloride-channel-based drug discovery. PMID:19153558

  5. Targeting kinase signaling pathways with constrained peptide scaffolds

    PubMed Central

    Hanold, Laura E.; Fulton, Melody D.; Kennedy, Eileen J.

    2017-01-01

    Kinases are amongst the largest families in the human proteome and serve as critical mediators of a myriad of cell signaling pathways. Since altered kinase activity is implicated in a variety of pathological diseases, kinases have become a prominent class of proteins for targeted inhibition. Although numerous small molecule and antibody-based inhibitors have already received clinical approval, several challenges may still exist with these strategies including resistance, target selection, inhibitor potency and in vivo activity profiles. Constrained peptide inhibitors have emerged as an alternative strategy for kinase inhibition. Distinct from small molecule inhibitors, peptides can provide a large binding surface area that allows them to bind shallow protein surfaces rather than defined pockets within the target protein structure. By including chemical constraints within the peptide sequence, additional benefits can be bestowed onto the peptide scaffold such as improved target affinity and target selectivity, cell permeability and proteolytic resistance. In this review, we highlight examples of diverse chemistries that are being employed to constrain kinase-targeting peptide scaffolds and highlight their application to modulate kinase signaling as well as their potential clinical implications. PMID:28185915

  6. SuperTarget goes quantitative: update on drug–target interactions

    PubMed Central

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

    2012-01-01

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

  7. 40 CFR 1051.725 - What must I include in my applications for certification?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false What must I include in my applications... certification: (1) A statement that, to the best of your belief, you will not have a negative balance of... 40506, July 13, 2005, as amended at 73 FR 59256, Oct. 8, 2008] ...

  8. 40 CFR 1051.725 - What must I include in my applications for certification?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 33 2011-07-01 2011-07-01 false What must I include in my applications... certification: (1) A statement that, to the best of your belief, you will not have a negative balance of... 40506, July 13, 2005, as amended at 73 FR 59256, Oct. 8, 2008] ...

  9. 40 CFR 1051.725 - What must I include in my applications for certification?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 34 2013-07-01 2013-07-01 false What must I include in my applications... certification: (1) A statement that, to the best of your belief, you will not have a negative balance of... 40506, July 13, 2005, as amended at 73 FR 59256, Oct. 8, 2008] ...

  10. 40 CFR 1051.725 - What must I include in my applications for certification?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 33 2014-07-01 2014-07-01 false What must I include in my applications... certification: (1) A statement that, to the best of your belief, you will not have a negative balance of... 40506, July 13, 2005, as amended at 73 FR 59256, Oct. 8, 2008] ...

  11. 40 CFR 1051.725 - What must I include in my applications for certification?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 34 2012-07-01 2012-07-01 false What must I include in my applications... certification: (1) A statement that, to the best of your belief, you will not have a negative balance of... 40506, July 13, 2005, as amended at 73 FR 59256, Oct. 8, 2008] ...

  12. Ultrasonic Nanobubbles Carrying Anti-PSMA Nanobody: Construction and Application in Prostate Cancer-Targeted Imaging.

    PubMed

    Fan, Xiaozhou; Wang, Luofu; Guo, Yanli; Tu, Zhui; Li, Lang; Tong, Haipeng; Xu, Yang; Li, Rui; Fang, Kejing

    2015-01-01

    To facilitate prostate cancer imaging using targeted molecules, we constructed ultrasonic nanobubbles coupled with specific anti-PSMA (prostate specific membrane antigen) nanobodies, and evaluated their in vitro binding capacity and in vivo imaging efficacy. The "targeted" nanobubbles, which were constructed via a biotin-streptavidin system, had an average diameter of 487.60 ± 33.55 nm and carried the anti-PSMA nanobody as demonstrated by immunofluorescence. Microscopy revealed targeted binding of nanobubbles in vitro to PSMA-positive cells. Additionally, ultrasonography indicators of nanobubble imaging (including arrival time, peak time, peak intensity and enhanced duration) were evaluated for the ultrasound imaging in three kinds of animal xenografts (LNCaP, C4-2 and MKN45), and showed that these four indicators of targeted nanobubbles exhibited significant differences from blank nanobubbles. Therefore, this study not only presents a novel approach to target prostate cancer ultrasonography, but also provides the basis and methods for constructing small-sized and high-efficient targeted ultrasound nanobubbles.

  13. Photoaffinity labeling in target- and binding-site identification

    PubMed Central

    Smith, Ewan; Collins, Ian

    2015-01-01

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

  14. A Model for the Application of Target-Controlled Intravenous Infusion for a Prolonged Immersive DMT Psychedelic Experience

    PubMed Central

    Gallimore, Andrew R.; Strassman, Rick J.

    2016-01-01

    The state of consciousness induced by N,N-dimethyltryptamine (DMT) is one of the most extraordinary of any naturally-occurring psychedelic substance. Users consistently report the complete replacement of normal subjective experience with a novel “alternate universe,” often densely populated with a variety of strange objects and other highly complex visual content, including what appear to be sentient “beings.” The phenomenology of the DMT state is of great interest to psychology and calls for rigorous academic enquiry. The extremely short duration of DMT effects—less than 20 min—militates against single dose administration as the ideal model for such enquiry. Using pharmacokinetic modeling and DMT blood sampling data, we demonstrate that the unique pharmacological characteristics of DMT, which also include a rapid onset and lack of acute tolerance to its subjective effects, make it amenable to administration by target-controlled intravenous infusion. This is a technology developed to maintain a stable brain concentration of anesthetic drugs during surgery. Simulations of our model demonstrate that this approach will allow research subjects to be induced into a stable and prolonged DMT experience, making it possible to carefully observe its psychological contents, and provide more extensive accounts for subsequent analyses. This model would also be valuable in performing functional neuroimaging, where subjects are required to remain under the influence of the drug for extended periods. Finally, target-controlled intravenous infusion of DMT may aid the development of unique psychotherapeutic applications of this psychedelic agent. PMID:27471468

  15. A Model for the Application of Target-Controlled Intravenous Infusion for a Prolonged Immersive DMT Psychedelic Experience.

    PubMed

    Gallimore, Andrew R; Strassman, Rick J

    2016-01-01

    The state of consciousness induced by N,N-dimethyltryptamine (DMT) is one of the most extraordinary of any naturally-occurring psychedelic substance. Users consistently report the complete replacement of normal subjective experience with a novel "alternate universe," often densely populated with a variety of strange objects and other highly complex visual content, including what appear to be sentient "beings." The phenomenology of the DMT state is of great interest to psychology and calls for rigorous academic enquiry. The extremely short duration of DMT effects-less than 20 min-militates against single dose administration as the ideal model for such enquiry. Using pharmacokinetic modeling and DMT blood sampling data, we demonstrate that the unique pharmacological characteristics of DMT, which also include a rapid onset and lack of acute tolerance to its subjective effects, make it amenable to administration by target-controlled intravenous infusion. This is a technology developed to maintain a stable brain concentration of anesthetic drugs during surgery. Simulations of our model demonstrate that this approach will allow research subjects to be induced into a stable and prolonged DMT experience, making it possible to carefully observe its psychological contents, and provide more extensive accounts for subsequent analyses. This model would also be valuable in performing functional neuroimaging, where subjects are required to remain under the influence of the drug for extended periods. Finally, target-controlled intravenous infusion of DMT may aid the development of unique psychotherapeutic applications of this psychedelic agent.

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

    PubMed

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

    2016-01-01

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

  17. Double-shell target fabrication workshop-2016 report

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

    Wang, Y. Morris; Oertel, John; Farrell, Michael

    On June 30, 2016, over 40 representatives from Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), General Atomics (GA), Laboratory for Laser Energetics (LLE), Schafer Corporation, and NNSA headquarter attended a double-shell (DS) target fabrication workshop at Livermore, California. Pushered-single-shell (PSS) and DS metalgas platforms potentially have a large impact on programmatic applications. The goal of this focused workshop is to bring together target fabrication scientists, physicists, and designers to brainstorm future PSS and DS target fabrication needs and strategies. This one-day workshop intends to give an overall view of historical information, recent approaches, and future research activitiesmore » at each participating organization. Five topical areas have been discussed that are vital to the success of future DS target fabrications, including inner metal shells, foam spheres, outer ablators, fill tube assembly, and metrology.« less

  18. 30 CFR 280.12 - What must I include in my application or notification?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... original and three copies of the permit application form (Form MMS-134) at least 30 days before the startup... includes names of persons; the type, location, purpose, and dates of activity; and environmental and other... the sponsor; (3) The type of research and a brief description of how you will conduct it; (4) A map...

  19. Quality of Graphite Target for Biological/Biomedical/Environmental Applications of 14C-Accelerator Mass Spectrometry

    PubMed Central

    2010-01-01

    Catalytic graphitization for 14C-accelerator mass spectrometry (14C-AMS) produced various forms of elemental carbon. Our high-throughput Zn reduction method (C/Fe = 1:5, 500 °C, 3 h) produced the AMS target of graphite-coated iron powder (GCIP), a mix of nongraphitic carbon and Fe3C. Crystallinity of the AMS targets of GCIP (nongraphitic carbon) was increased to turbostratic carbon by raising the C/Fe ratio from 1:5 to 1:1 and the graphitization temperature from 500 to 585 °C. The AMS target of GCIP containing turbostratic carbon had a large isotopic fractionation and a low AMS ion current. The AMS target of GCIP containing turbostratic carbon also yielded less accurate/precise 14C-AMS measurements because of the lower graphitization yield and lower thermal conductivity that were caused by the higher C/Fe ratio of 1:1. On the other hand, the AMS target of GCIP containing nongraphitic carbon had higher graphitization yield and better thermal conductivity over the AMS target of GCIP containing turbostratic carbon due to optimal surface area provided by the iron powder. Finally, graphitization yield and thermal conductivity were stronger determinants (over graphite crystallinity) for accurate/precise/high-throughput biological, biomedical, and environmental14C-AMS applications such as absorption, distribution, metabolism, elimination (ADME), and physiologically based pharmacokinetics (PBPK) of nutrients, drugs, phytochemicals, and environmental chemicals. PMID:20163100

  20. Linear and angular retroreflecting interferometric alignment target

    DOEpatents

    Maxey, L. Curtis

    2001-01-01

    The present invention provides a method and apparatus for measuring both the linear displacement and angular displacement of an object using a linear interferometer system and an optical target comprising a lens, a reflective surface and a retroreflector. The lens, reflecting surface and retroreflector are specifically aligned and fixed in optical connection with one another, creating a single optical target which moves as a unit that provides multi-axis displacement information for the object with which it is associated. This displacement information is useful in many applications including machine tool control systems and laser tracker systems, among others.

  1. Threat Assessment and Targeted Violence at Institutions of Higher Education: Implications for Policy and Practice Including Unique Considerations for Community Colleges

    ERIC Educational Resources Information Center

    Bennett, Laura; Bates, Michael

    2015-01-01

    This article provides an overview of the research on targeted violence, including campus violence, and the implications for policy and practice at institutions of higher education. Unique challenges of threat assessment in the community college setting are explored, and an overview of an effective threat assessment policy and team at William…

  2. The research and application of visual saliency and adaptive support vector machine in target tracking field.

    PubMed

    Chen, Yuantao; Xu, Weihong; Kuang, Fangjun; Gao, Shangbing

    2013-01-01

    The efficient target tracking algorithm researches have become current research focus of intelligent robots. The main problems of target tracking process in mobile robot face environmental uncertainty. They are very difficult to estimate the target states, illumination change, target shape changes, complex backgrounds, and other factors and all affect the occlusion in tracking robustness. To further improve the target tracking's accuracy and reliability, we present a novel target tracking algorithm to use visual saliency and adaptive support vector machine (ASVM). Furthermore, the paper's algorithm has been based on the mixture saliency of image features. These features include color, brightness, and sport feature. The execution process used visual saliency features and those common characteristics have been expressed as the target's saliency. Numerous experiments demonstrate the effectiveness and timeliness of the proposed target tracking algorithm in video sequences where the target objects undergo large changes in pose, scale, and illumination.

  3. 40 CFR 745.101 - Scope and applicability.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Scope and applicability. This subpart applies to all transactions to sell or lease target housing, including subleases, with the exception of the following: (a) Sales of target housing at foreclosure. (b) Leases of target housing that have been found to be lead-based paint free by an inspector certified under...

  4. 40 CFR 745.101 - Scope and applicability.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Scope and applicability. This subpart applies to all transactions to sell or lease target housing, including subleases, with the exception of the following: (a) Sales of target housing at foreclosure. (b) Leases of target housing that have been found to be lead-based paint free by an inspector certified under...

  5. 40 CFR 745.101 - Scope and applicability.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Scope and applicability. This subpart applies to all transactions to sell or lease target housing, including subleases, with the exception of the following: (a) Sales of target housing at foreclosure. (b) Leases of target housing that have been found to be lead-based paint free by an inspector certified under...

  6. 40 CFR 745.101 - Scope and applicability.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Scope and applicability. This subpart applies to all transactions to sell or lease target housing, including subleases, with the exception of the following: (a) Sales of target housing at foreclosure. (b) Leases of target housing that have been found to be lead-based paint free by an inspector certified under...

  7. 40 CFR 745.101 - Scope and applicability.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Scope and applicability. This subpart applies to all transactions to sell or lease target housing, including subleases, with the exception of the following: (a) Sales of target housing at foreclosure. (b) Leases of target housing that have been found to be lead-based paint free by an inspector certified under...

  8. Design criteria for a high energy Compton Camera and possible application to targeted cancer therapy

    NASA Astrophysics Data System (ADS)

    Conka Nurdan, T.; Nurdan, K.; Brill, A. B.; Walenta, A. H.

    2015-07-01

    The proposed research focuses on the design criteria for a Compton Camera with high spatial resolution and sensitivity, operating at high gamma energies and its possible application for molecular imaging. This application is mainly on the detection and visualization of the pharmacokinetics of tumor targeting substances specific for particular cancer sites. Expected high resolution (< 0.5 mm) permits monitoring the pharmacokinetics of labeled gene constructs in vivo in small animals with a human tumor xenograft which is one of the first steps in evaluating the potential utility of a candidate gene. The additional benefit of high sensitivity detection will be improved cancer treatment strategies in patients based on the use of specific molecules binding to cancer sites for early detection of tumors and identifying metastasis, monitoring drug delivery and radionuclide therapy for optimum cell killing at the tumor site. This new technology can provide high resolution, high sensitivity imaging of a wide range of gamma energies and will significantly extend the range of radiotracers that can be investigated and used clinically. The small and compact construction of the proposed camera system allows flexible application which will be particularly useful for monitoring residual tumor around the resection site during surgery. It is also envisaged as able to test the performance of new drug/gene-based therapies in vitro and in vivo for tumor targeting efficacy using automatic large scale screening methods.

  9. Serverification of Molecular Modeling Applications: The Rosetta Online Server That Includes Everyone (ROSIE)

    PubMed Central

    Conchúir, Shane Ó.; Der, Bryan S.; Drew, Kevin; Kuroda, Daisuke; Xu, Jianqing; Weitzner, Brian D.; Renfrew, P. Douglas; Sripakdeevong, Parin; Borgo, Benjamin; Havranek, James J.; Kuhlman, Brian; Kortemme, Tanja; Bonneau, Richard; Gray, Jeffrey J.; Das, Rhiju

    2013-01-01

    The Rosetta molecular modeling software package provides experimentally tested and rapidly evolving tools for the 3D structure prediction and high-resolution design of proteins, nucleic acids, and a growing number of non-natural polymers. Despite its free availability to academic users and improving documentation, use of Rosetta has largely remained confined to developers and their immediate collaborators due to the code’s difficulty of use, the requirement for large computational resources, and the unavailability of servers for most of the Rosetta applications. Here, we present a unified web framework for Rosetta applications called ROSIE (Rosetta Online Server that Includes Everyone). ROSIE provides (a) a common user interface for Rosetta protocols, (b) a stable application programming interface for developers to add additional protocols, (c) a flexible back-end to allow leveraging of computer cluster resources shared by RosettaCommons member institutions, and (d) centralized administration by the RosettaCommons to ensure continuous maintenance. This paper describes the ROSIE server infrastructure, a step-by-step ‘serverification’ protocol for use by Rosetta developers, and the deployment of the first nine ROSIE applications by six separate developer teams: Docking, RNA de novo, ERRASER, Antibody, Sequence Tolerance, Supercharge, Beta peptide design, NCBB design, and VIP redesign. As illustrated by the number and diversity of these applications, ROSIE offers a general and speedy paradigm for serverification of Rosetta applications that incurs negligible cost to developers and lowers barriers to Rosetta use for the broader biological community. ROSIE is available at http://rosie.rosettacommons.org. PMID:23717507

  10. Nanocarriers for cancer-targeted drug delivery.

    PubMed

    Kumari, Preeti; Ghosh, Balaram; Biswas, Swati

    2016-01-01

    Nanoparticles as drug delivery system have received much attention in recent years, especially for cancer treatment. In addition to improving the pharmacokinetics of the loaded poorly soluble hydrophobic drugs by solubilizing them in the hydrophobic compartments, nanoparticles allowed cancer specific drug delivery by inherent passive targeting phenomena and adopted active targeting strategies. For this reason, nanoparticles-drug formulations are capable of enhancing the safety, pharmacokinetic profiles and bioavailability of the administered drugs leading to improved therapeutic efficacy compared to conventional therapy. The focus of this review is to provide an overview of various nanoparticle formulations in both research and clinical applications with a focus on various chemotherapeutic drug delivery systems for the treatment of cancer. The use of various nanoparticles, including liposomes, polymeric nanoparticles, dendrimers, magnetic and other inorganic nanoparticles for targeted drug delivery in cancer is detailed.

  11. Ultrasonic Nanobubbles Carrying Anti-PSMA Nanobody: Construction and Application in Prostate Cancer-Targeted Imaging

    PubMed Central

    Guo, Yanli; Tu, Zhui; Li, Lang; Tong, Haipeng; Xu, Yang; Li, Rui; Fang, Kejing

    2015-01-01

    To facilitate prostate cancer imaging using targeted molecules, we constructed ultrasonic nanobubbles coupled with specific anti-PSMA (prostate specific membrane antigen) nanobodies, and evaluated their in vitro binding capacity and in vivo imaging efficacy. The “targeted” nanobubbles, which were constructed via a biotin-streptavidin system, had an average diameter of 487.60 ± 33.55 nm and carried the anti-PSMA nanobody as demonstrated by immunofluorescence. Microscopy revealed targeted binding of nanobubbles in vitro to PSMA-positive cells. Additionally, ultrasonography indicators of nanobubble imaging (including arrival time, peak time, peak intensity and enhanced duration) were evaluated for the ultrasound imaging in three kinds of animal xenografts (LNCaP, C4-2 and MKN45), and showed that these four indicators of targeted nanobubbles exhibited significant differences from blank nanobubbles. Therefore, this study not only presents a novel approach to target prostate cancer ultrasonography, but also provides the basis and methods for constructing small-sized and high-efficient targeted ultrasound nanobubbles. PMID:26111008

  12. Application of liposomes in drug development — focus on gastroenterological targets

    PubMed Central

    Zhang, Jian-Xin; Wang, Kun; Mao, Zheng-Fa; Fan, Xin; Jiang, De-Li; Chen, Min; Cui, Lei; Sun, Kang; Dang, Sheng-Chun

    2013-01-01

    Over the past decade, liposomes became a focal point in developing drug delivery systems. New liposomes, with novel lipid molecules or conjugates, and new formulations opened possibilities for safely and efficiently treating many diseases including cancers. New types of liposomes can prolong circulation time or specifically deliver drugs to therapeutic targets. This article concentrates on current developments in liposome based drug delivery systems for treating diseases of the gastrointestinal tract. We will review different types and uses of liposomes in the development of therapeutics for gastrointestinal diseases including inflammatory bowel diseases and colorectal cancer. PMID:23630417

  13. Cell targeting peptides as smart ligands for targeting of therapeutic or diagnostic agents: a systematic review.

    PubMed

    Mousavizadeh, Ali; Jabbari, Ali; Akrami, Mohammad; Bardania, Hassan

    2017-10-01

    Cell targeting peptides (CTP) are small peptides which have high affinity and specificity to a cell or tissue targets. They are typically identified by using phage display and chemical synthetic peptide library methods. CTPs have attracted considerable attention as a new class of ligands to delivery specifically therapeutic and diagnostic agents, because of the fact they have several advantages including easy synthesis, smaller physical sizes, lower immunogenicity and cytotoxicity and their simple and better conjugation to nano-carriers and therapeutic or diagnostic agents compared to conventional antibodies. In this systematic review, we will focus on the basic concepts concerning the use of cell-targeting peptides (CTPs), following the approaches of selecting them from peptide libraries. We discuss several developed strategies for cell-specific delivery of different cargos by CTPs, which are designed for drug delivery and diagnostic applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Target Fabrication Technology and New Functional Materials for Laser Fusion and Laser-Plasma Experiment

    NASA Astrophysics Data System (ADS)

    Nagai, Keiji; Norimatsu, Takayoshi; Izawa, Yasukazu

    Target fabrication technique is a key issue of laser fusion. We present a comprehensive, up-to-data compilation of laser fusion target fabrication and relating new materials. To achieve highly efficient laser implosion, organic and inorganic highly spherical millimeter-sized capsules and cryogenic hydrogen layers inside should be uniform in diameter and thickness within sub-micrometer ˜ nanometer error. Porous structured targets and molecular cluster targets are required for laser-plasma experiments and applications. Various technologies and new materials concerning above purposes are summarized including fast-ignition targets, equation-of-state measurement targets, high energy ion generation targets, etc.

  15. The application of an MPM-MFM method for simulating weapon-target interaction.

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

    Ma, X.; Zou, Q.; Zhang, D. Z.

    2005-01-01

    During the past two decades, Los Alamos National Laboratory (LANL) has developed computational algorithms and software for analysis of multiphase flow suitable for high-speed projectile penetration of metallic and nonmetallic materials, using a material point method (MPM)-multiphase flow method (MFM). Recently, ACTA has teamed with LANL to advance a computational algorithm for simulating complex weapon-target interaction for penetrating and exploding munitions, such as tank rounds and artillery shells, as well as non-exploding kinetic energy penetrators. This paper will outline the mathematical basis for the MPM-MFM method as implemented in LANL's CartaBlanca code. CartaBlanca, written entirely in Java using object-oriented design,more » is used to solve complex problems involving (a) failure and penetration of solids, (b) heat transfer, (c) phase change, (d) chemical reactions, and (e) multiphase flow. We will present its application to the penetration of a steel target by a tungsten cylinder and compare results with time-resolved experimental data published by Anderson, et. al., Int. J. Impact Engng., Vol. 16, No. 1, pp. 1-18, 1995.« less

  16. Nanomedicine strategies for targeting skin inflammation.

    PubMed

    Abdel-Mottaleb, Mona Ma; Try, Celine; Pellequer, Yann; Lamprecht, Alf

    2014-08-01

    Topical treatment of skin diseases is an attractive strategy as it receives high acceptance from patients, resulting in higher compliance and therapeutic outcomes. Recently, the use of variable nanocarriers for dermal application has been widely explored, as they offer several advantages compared with conventional topical preparations, including higher skin penetration, controlled and targeted drug delivery and the achievement of higher therapeutic effects. This article will focus on skin inflammation or dermatitis as it is one of the most common skin problems, describing the different types and causes of dermatitis, as well as the typical treatment regimens. The potential use of nanocarriers for targeting skin inflammation and the achievement of higher therapeutic effects using nanotechnology will be explored.

  17. Calibration Method for IATS and Application in Multi-Target Monitoring Using Coded Targets

    NASA Astrophysics Data System (ADS)

    Zhou, Yueyin; Wagner, Andreas; Wunderlich, Thomas; Wasmeier, Peter

    2017-06-01

    The technique of Image Assisted Total Stations (IATS) has been studied for over ten years and is composed of two major parts: one is the calibration procedure which combines the relationship between the camera system and the theodolite system; the other is the automatic target detection on the image by various methods of photogrammetry or computer vision. Several calibration methods have been developed, mostly using prototypes with an add-on camera rigidly mounted on the total station. However, these prototypes are not commercially available. This paper proposes a calibration method based on Leica MS50 which has two built-in cameras each with a resolution of 2560 × 1920 px: an overview camera and a telescope (on-axis) camera. Our work in this paper is based on the on-axis camera which uses the 30-times magnification of the telescope. The calibration consists of 7 parameters to estimate. We use coded targets, which are common tools in photogrammetry for orientation, to detect different targets in IATS images instead of prisms and traditional ATR functions. We test and verify the efficiency and stability of this monitoring method with multi-target.

  18. Robust autofocus algorithm for ISAR imaging of moving targets

    NASA Astrophysics Data System (ADS)

    Li, Jian; Wu, Renbiao; Chen, Victor C.

    2000-08-01

    A robust autofocus approach, referred to as AUTOCLEAN (AUTOfocus via CLEAN), is proposed for the motion compensation in ISAR (inverse synthetic aperture radar) imaging of moving targets. It is a parametric algorithm based on a very flexible data model which takes into account arbitrary range migration and arbitrary phase errors across the synthetic aperture that may be induced by unwanted radial motion of the target as well as propagation or system instability. AUTOCLEAN can be classified as a multiple scatterer algorithm (MSA), but it differs considerably from other existing MSAs in several aspects: (1) dominant scatterers are selected automatically in the two-dimensional (2-D) image domain; (2) scatterers may not be well-isolated or very dominant; (3) phase and RCS (radar cross section) information from each selected scatterer are combined in an optimal way; (4) the troublesome phase unwrapping step is avoided. AUTOCLEAN is computationally efficient and involves only a sequence of FFTs (fast Fourier Transforms). Another good feature associated with AUTOCLEAN is that its performance can be progressively improved by assuming a larger number of dominant scatterers for the target. Hence it can be easily configured for real-time applications including, for example, ATR (automatic target recognition) of non-cooperative moving targets, and for some other applications where the image quality is of the major concern but not the computational time including, for example, for the development and maintenance of low observable aircrafts. Numerical and experimental results have shown that AUTOCLEAN is a very robust autofocus tool for ISAR imaging.

  19. Analytic validation and real-time clinical application of an amplicon-based targeted gene panel for advanced cancer

    PubMed Central

    Wing, Michele R.; Reeser, Julie W.; Smith, Amy M.; Reeder, Matthew; Martin, Dorrelyn; Jewell, Benjamin M.; Datta, Jharna; Miya, Jharna; Monk, J. Paul; Mortazavi, Amir; Otterson, Gregory A.; Goldberg, Richard M.; VanDeusen, Jeffrey B.; Cole, Sharon; Dittmar, Kristin; Jaiswal, Sunny; Kinzie, Matthew; Waikhom, Suraj; Freud, Aharon G.; Zhou, Xiao-Ping; Chen, Wei; Bhatt, Darshna; Roychowdhury, Sameek

    2017-01-01

    Multiplex somatic testing has emerged as a strategy to test patients with advanced cancer. We demonstrate our analytic validation approach for a gene hotspot panel and real-time prospective clinical application for any cancer type. The TruSight Tumor 26 assay amplifies 85 somatic hotspot regions across 26 genes. Using cell line and tumor mixes, we observed that 100% of the 14,715 targeted bases had at least 1000x raw coverage. We determined the sensitivity (100%, 95% CI: 96-100%), positive predictive value (100%, 95% CI: 96-100%), reproducibility (100% concordance), and limit of detection (3% variant allele frequency at 1000x read depth) of this assay to detect single nucleotide variants and small insertions and deletions. Next, we applied the assay prospectively in a clinical tumor sequencing study to evaluate 174 patients with metastatic or advanced cancer, including frozen tumors, formalin-fixed tumors, and enriched peripheral blood mononuclear cells in hematologic cancers. We reported one or more somatic mutations in 89 (53%) of the sequenced tumors (167 passing quality filters). Forty-three of these patients (26%) had mutations that would enable eligibility for targeted therapies. This study demonstrates the validity and feasibility of applying TruSight Tumor 26 for pan-cancer testing using multiple specimen types. PMID:29100271

  20. Video Guidance Sensors Using Remotely Activated Targets

    NASA Technical Reports Server (NTRS)

    Bryan, Thomas C.; Howard, Richard T.; Book, Michael L.

    2004-01-01

    Four updated video guidance sensor (VGS) systems have been proposed. As described in a previous NASA Tech Briefs article, a VGS system is an optoelectronic system that provides guidance for automated docking of two vehicles. The VGS provides relative position and attitude (6-DOF) information between the VGS and its target. In the original intended application, the two vehicles would be spacecraft, but the basic principles of design and operation of the system are applicable to aircraft, robots, objects maneuvered by cranes, or other objects that may be required to be aligned and brought together automatically or under remote control. In the first two of the four VGS systems as now proposed, the tracked vehicle would include active targets that would light up on command from the tracking vehicle, and a video camera on the tracking vehicle would be synchronized with, and would acquire images of, the active targets. The video camera would also acquire background images during the periods between target illuminations. The images would be digitized and the background images would be subtracted from the illuminated-target images. Then the position and orientation of the tracked vehicle relative to the tracking vehicle would be computed from the known geometric relationships among the positions of the targets in the image, the positions of the targets relative to each other and to the rest of the tracked vehicle, and the position and orientation of the video camera relative to the rest of the tracking vehicle. The major difference between the first two proposed systems and prior active-target VGS systems lies in the techniques for synchronizing the flashing of the active targets with the digitization and processing of image data. In the prior active-target VGS systems, synchronization was effected, variously, by use of either a wire connection or the Global Positioning System (GPS). In three of the proposed VGS systems, the synchronizing signal would be generated on, and

  1. Development of practice and consensus-based strategies including a treat-to-target approach for the management of moderate and severe juvenile dermatomyositis in Germany and Austria.

    PubMed

    Hinze, Claas H; Oommen, Prasad T; Dressler, Frank; Urban, Andreas; Weller-Heinemann, Frank; Speth, Fabian; Lainka, Elke; Brunner, Jürgen; Fesq, Heike; Foell, Dirk; Müller-Felber, Wolfgang; Neudorf, Ulrich; Rietschel, Christoph; Schwarz, Tobias; Schara, Ulrike; Haas, Johannes-Peter

    2018-06-25

    Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy in childhood and a major cause of morbidity among children with pediatric rheumatic diseases. The management of JDM is very heterogeneous. The JDM working group of the Society for Pediatric Rheumatology (GKJR) aims to define consensus- and practice-based strategies in order to harmonize diagnosis, treatment and monitoring of JDM. The JDM working group was established in 2015 consisting of 23 pediatric rheumatologists, pediatric neurologists and dermatologists with expertise in the management of JDM. Current practice patterns of management in JDM had previously been identified via an online survey among pediatric rheumatologists and neurologists. Using a consensus process consisting of online surveys and a face-to-face consensus conference statements were defined regarding the diagnosis, treatment and monitoring of JDM. During the conference consensus was achieved via nominal group technique. Voting took place using an electronic audience response system, and at least 80% consensus was required for individual statements. Overall 10 individual statements were developed, finally reaching a consensus of 92 to 100% regarding (1) establishing a diagnosis, (2) case definitions for the application of the strategies (moderate and severe JDM), (3) initial diagnostic testing, (4) monitoring and documentation, (5) treatment targets within the context of a treat-to-target strategy, (6) supportive therapies, (7) explicit definition of a treat-to-target strategy, (8) various glucocorticoid regimens, including intermittent intravenous methylprednisolone pulse and high-dose oral glucocorticoid therapies with tapering, (9) initial glucocorticoid-sparing therapy and (10) management of refractory disease. Using a consensus process among JDM experts, statements regarding the management of JDM were defined. These statements and the strategies aid in the management of patients with moderate and severe JDM.

  2. ELECTRICAL TECHNIQUES FOR ENGINEERING APPLICATIONS.

    USGS Publications Warehouse

    Bisdorf, Robert J.

    1985-01-01

    Surface electrical geophysical methods have been used in such engineering applications as locating and delineating shallow gravel deposits, depth to bedrock, faults, clay zones, and other geological phenomena. Other engineering applications include determining water quality, tracing ground water contaminant plumes and locating dam seepages. Various methods and electrode arrays are employed to solve particular geological problems. The sensitivity of a particular method or electrode array depends upon the physics on which the method is based, the array geometry, the electrical contrast between the target and host materials, and the depth to the target. Each of the available electrical methods has its own particular advantages and applications which the paper discusses.

  3. An integrated molecular analysis of lung adenocarcinomas identifies potential therapeutic targets among TTF1-negative tumors including DNA repair proteins and Nrf2

    PubMed Central

    Cardnell, Robert J.G.; Behrens, Carmen; Diao, Lixia; Fan, YouHong; Tang, Ximing; Tong, Pan; John D., Minna; Mills, Gordon B.; Heymach, John V.; Wistuba, Ignacio I.; Wang, Jing; Byers., Lauren A.

    2015-01-01

    Purpose Thyroid transcription factor-1 (TTF1) immunohistochemistry (IHC) is used clinically to differentiate primary lung adenocarcinomas (LUAD) from squamous lung cancers and metastatic adenocarcinomas from other primary sites. However, a subset of LUAD (15-20%) does not express TTF1 and TTF1-negative patients have worse clinical outcomes. As there are no established targeted agents with activity in TTF1-negative LUAD, we performed an integrated molecular analysis to identify potential therapeutic targets. Experimental Design Using two clinical LUAD cohorts (274 tumors), one from our institution (PROSPECT) and the TCGA, we interrogated proteomic profiles (by reverse-phase protein array (RPPA)), gene expression, and mutational data. Drug response data from 74 cell lines were used to validate potential therapeutic agents. Results Strong correlations were observed between TTF1 IHC and TTF1 measurements by RPPA (Rho=0.57, p<0.001) and gene expression (NKX2-1, Rho=0.61, p<0.001). Established driver mutations (e.g. BRAF and EGFR) were associated with high TTF1 expression. In contrast, TTF1-negative LUAD had a higher frequency of inactivating KEAP1 mutations (p=0.001). Proteomic profiling identified increased expression of DNA repair proteins (e.g., Chk1 and the DNA repair score) and suppressed PI3K/MAPK signaling among TTF1-negative tumors, with differences in total proteins confirmed at the mRNA level. Cell line analysis showed drugs targeting DNA repair to be more active in TTF1-low cell lines. Conclusions Combined genomic and proteomic analyses demonstrated infrequent alteration of validated lung cancer targets (including the absence of BRAF mutations in TTF1-negative LUAD), but identified novel potential targets for TTF1-negative LUAD includingKEAP1/Nrf2 and DNA repair pathways. PMID:25878335

  4. 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.

  5. Fragile X Syndrome and Targeted Treatment Trials

    PubMed Central

    Lauterborn, Julie; Au, Jacky; Berry-Kravis, Elizabeth

    2014-01-01

    Work in recent years has revealed an abundance of possible new treatment targets for fragile X syndrome (FXS). The use of animal models, including the fragile X knockout mouse which manifests a phenotype very similar to FXS in humans, has resulted in great strides in this direction of research. The lack of Fragile X Mental Retardation Protein (FMRP) in FXS causes dysregulation and usually overexpression of a number of its target genes, which can cause imbalances of neurotransmission and deficits in synaptic plasticity. The use of metabotropic glutamate receptor (mGluR) blockers and gamma amino-butyric acid (GABA) agonists have been shown to be efficacious in reversing cellular and behavioral phenotypes, and restoring proper brain connectivity in the mouse and fly models. Proposed new pharmacological treatments and educational interventions are discussed in this chapter. In combination, these various targeted treatments show promising preliminary results in mitigating or even reversing the neurobiological abnormalities caused by loss of FMRP, with possible translational applications to other neurodevelopmental disorders including autism. PMID:22009360

  6. Fragile X syndrome and targeted treatment trials.

    PubMed

    Hagerman, Randi; Lauterborn, Julie; Au, Jacky; Berry-Kravis, Elizabeth

    2012-01-01

    Work in recent years has revealed an abundance of possible new treatment targets for fragile X syndrome (FXS). The use of animal models, including the fragile X knockout mouse which manifests a phenotype very similar to FXS in humans, has resulted in great strides in this direction of research. The lack of Fragile X Mental Retardation Protein (FMRP) in FXS causes dysregulation and usually overexpression of a number of its target genes, which can cause imbalances of neurotransmission and deficits in synaptic plasticity. The use of metabotropic glutamate receptor (mGluR) blockers and gamma amino-butyric acid (GABA) agonists have been shown to be efficacious in reversing cellular and behavioral phenotypes, and restoring proper brain connectivity in the mouse and fly models. Proposed new pharmacological treatments and educational interventions are discussed in this chapter. In combination, these various targeted treatments show promising preliminary results in mitigating or even reversing the neurobiological abnormalities caused by loss of FMRP, with possible translational applications to other neurodevelopmental disorders including autism.

  7. Infrared target simulation environment for pattern recognition applications

    NASA Astrophysics Data System (ADS)

    Savakis, Andreas E.; George, Nicholas

    1994-07-01

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

  8. Common IED exploitation target set ontology

    NASA Astrophysics Data System (ADS)

    Russomanno, David J.; Qualls, Joseph; Wowczuk, Zenovy; Franken, Paul; Robinson, William

    2010-04-01

    The Common IED Exploitation Target Set (CIEDETS) ontology provides a comprehensive semantic data model for capturing knowledge about sensors, platforms, missions, environments, and other aspects of systems under test. The ontology also includes representative IEDs; modeled as explosives, camouflage, concealment objects, and other background objects, which comprise an overall threat scene. The ontology is represented using the Web Ontology Language and the SPARQL Protocol and RDF Query Language, which ensures portability of the acquired knowledge base across applications. The resulting knowledge base is a component of the CIEDETS application, which is intended to support the end user sensor test and evaluation community. CIEDETS associates a system under test to a subset of cataloged threats based on the probability that the system will detect the threat. The associations between systems under test, threats, and the detection probabilities are established based on a hybrid reasoning strategy, which applies a combination of heuristics and simplified modeling techniques. Besides supporting the CIEDETS application, which is focused on efficient and consistent system testing, the ontology can be leveraged in a myriad of other applications, including serving as a knowledge source for mission planning tools.

  9. Ion beam inertial confinement target

    DOEpatents

    Bangerter, Roger O.; Meeker, Donald J.

    1985-01-01

    A target for implosion by ion beams composed of a spherical shell of frozen DT surrounded by a low-density, low-Z pusher shell seeded with high-Z material, and a high-density tamper shell. The target has various applications in the inertial confinement technology. For certain applications, if desired, a low-density absorber shell may be positioned intermediate the pusher and tamper shells.

  10. Compound Structure-Independent Activity Prediction in High-Dimensional Target Space.

    PubMed

    Balfer, Jenny; Hu, Ye; Bajorath, Jürgen

    2014-08-01

    Profiling of compound libraries against arrays of targets has become an important approach in pharmaceutical research. The prediction of multi-target compound activities also represents an attractive task for machine learning with potential for drug discovery applications. Herein, we have explored activity prediction in high-dimensional target space. Different types of models were derived to predict multi-target activities. The models included naïve Bayesian (NB) and support vector machine (SVM) classifiers based upon compound structure information and NB models derived on the basis of activity profiles, without considering compound structure. Because the latter approach can be applied to incomplete training data and principally depends on the feature independence assumption, SVM modeling was not applicable in this case. Furthermore, iterative hybrid NB models making use of both activity profiles and compound structure information were built. In high-dimensional target space, NB models utilizing activity profile data were found to yield more accurate activity predictions than structure-based NB and SVM models or hybrid models. An in-depth analysis of activity profile-based models revealed the presence of correlation effects across different targets and rationalized prediction accuracy. Taken together, the results indicate that activity profile information can be effectively used to predict the activity of test compounds against novel targets. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Therapeutic potential of peptide toxins that target ion channels.

    PubMed

    Beraud, Evelyne; Chandy, K George

    2011-10-01

    Traditional healthcare systems in China, India, Greece and the Middle East have for centuries exploited venomous creatures as a resource for medicines. This review focuses on one class of pharmacologically active compounds from venom, namely peptide toxins that target ion channels. We highlight their therapeutic potential and the specific channels they target. The field of therapeutic application is vast, including pain, inflammation, cancer, neurological disorders, cardioprotection, and autoimmune diseases. One of these peptides is in clinical use, and many others are in various stages of pre-clinical and clinical development.

  12. Missing the target: including perspectives of women with overweight and obesity to inform stigma‐reduction strategies

    PubMed Central

    Himmelstein, M. S.; Gorin, A. A.; Suh, Y. J.

    2017-01-01

    Summary Objective Pervasive weight stigma and discrimination have led to ongoing calls for efforts to reduce this bias. Despite increasing research on stigma‐reduction strategies, perspectives of individuals who have experienced weight stigma have rarely been included to inform this research. The present study conducted a systematic examination of women with high body weight to assess their perspectives about a broad range of strategies to reduce weight‐based stigma. Methods Women with overweight or obesity (N = 461) completed an online survey in which they evaluated the importance, feasibility and potential impact of 35 stigma‐reduction strategies in diverse settings. Participants (91.5% who reported experiencing weight stigma) also completed self‐report measures assessing experienced and internalized weight stigma. Results Most participants assigned high importance to all stigma‐reduction strategies, with school‐based and healthcare approaches accruing the highest ratings. Adding weight stigma to existing anti‐harassment workplace training was rated as the most impactful and feasible strategy. The family environment was viewed as an important intervention target, regardless of participants' experienced or internalized stigma. Conclusion These findings underscore the importance of including people with stigmatized identities in stigma‐reduction research; their insights provide a necessary and valuable contribution that can inform ways to reduce weight‐based inequities and prioritize such efforts. PMID:28392929

  13. Physical property control in core/shell inorganic nanostructures for fluorescence and magnetic targeting applications

    NASA Astrophysics Data System (ADS)

    Roberts, Stephen K.

    Nanomaterials show immense promise for the future in numerous areas of application. Properties that are unique from the bulk material and are tunable allow for innovation in material design. This thesis will focus on controlling the physical properties of core/shell nanostructures to enhance the utility of the materials. The first focus is on the impact of different solvent mixtures during the shell growth phase of SILAR based core/shell quantum dot synthesis is studied. Gaining insight into the mechanism for SILAR growth of core/shell nanoparticles allows improved synthetic yields and precursor binding, providing enhanced control to synthesis of core/shell nanoparticles. The second focus of this thesis is exploring the use of magnetic nanoparticles for magnetic drug targeting for cardiovascular conditions. Magnetic targeting for drug delivery enables increased local drug concentration, while minimizing non-specific interactions. In order to be effective for magnetic targeting, it must be shown that low magnetic strength is sufficient to capture flowing nanoparticles. By demonstrating the binding of a therapeutic agent to the surface at medicinal levels, the viability for use as a nanoparticle drug delivery system is improved.

  14. Alternative divertor target concepts for next step fusion devices

    NASA Astrophysics Data System (ADS)

    Mazul, I. V.

    2016-12-01

    The operational conditions of a divertor target in the next steps of fusion devices are more severe in comparison with ITER. The current divertor designs and technologies have a limited application concerning these conditions, and so new design concepts/technologies are required. The main reasons which practically prevent the use of the traditional motionless solid divertor target are analyzed. We describe several alternative divertor target concepts in this paper. The comparative analysis of these concepts (including the advantages and the drawbacks) is made and the prospects for their practical implementation are prioritized. The concept of the swept divertor target with a liquid metal interlayer between the moving armour and motionless heat-sink is presented in more detail. The critical issues of this design are listed and outlined, and the possible experiments are presented.

  15. Phenothiazinium based photosensitisers--photodynamic agents with a multiplicity of cellular targets and clinical applications.

    PubMed

    Harris, F; Chatfield, L K; Phoenix, D A

    2005-08-01

    PhBPs show selectivity for tumour and microbial cells, which appears to be based on electrostatic interactions between the positive charge generally carried by these molecules and the negative charge found on the outer surface of these target cells. In some cases, a site of action for photoactivated PhBPs is the outer membrane/envelope of the target cell. Such action can involve the modification of membrane lipid and/or lipopolysaccharide, and the inactivation of essential proteins and enzymes, with these effects usually leading to cell lysis and death. However, more often, PhBPs are internalised by target cells, promoted by a variety of factors, including low pH and enzymatic reduction, and upon photoactivation, internalised, PhBPs are able to inflict damage on a number of intracellular targets. In tumour cells, PhBPs can photodamage DNA and the membranes of organelles, thereby inducing necrosis and/or apoptosis. In bacterial cells, whilst DNA is generally a primary target of PhBPs, these compounds can exhibit multiple sites of action within a given cell and show different sites of action between different bacterial species. This variable targeting makes PhBPs attractive propositions as alternatives to conventional antibiotics in that the emergence of bacterial strains with acquired resistance to these compounds appears to be highly unlikely.

  16. Target attribute-based false alarm rejection in small infrared target detection

    NASA Astrophysics Data System (ADS)

    Kim, Sungho

    2012-11-01

    Infrared search and track is an important research area in military applications. Although there are a lot of works on small infrared target detection methods, we cannot apply them in real field due to high false alarm rate caused by clutters. This paper presents a novel target attribute extraction and machine learning-based target discrimination method. Eight kinds of target features are extracted and analyzed statistically. Learning-based classifiers such as SVM and Adaboost are developed and compared with conventional classifiers for real infrared images. In addition, the generalization capability is also inspected for various infrared clutters.

  17. The drug target genes show higher evolutionary conservation than non-target genes.

    PubMed

    Lv, Wenhua; Xu, Yongdeng; Guo, Yiying; Yu, Ziqi; Feng, Guanglong; Liu, Panpan; Luan, Meiwei; Zhu, Hongjie; Liu, Guiyou; Zhang, Mingming; Lv, Hongchao; Duan, Lian; Shang, Zhenwei; Li, Jin; Jiang, Yongshuai; Zhang, Ruijie

    2016-01-26

    Although evidence indicates that drug target genes share some common evolutionary features, there have been few studies analyzing evolutionary features of drug targets from an overall level. Therefore, we conducted an analysis which aimed to investigate the evolutionary characteristics of drug target genes. We compared the evolutionary conservation between human drug target genes and non-target genes by combining both the evolutionary features and network topological properties in human protein-protein interaction network. The evolution rate, conservation score and the percentage of orthologous genes of 21 species were included in our study. Meanwhile, four topological features including the average shortest path length, betweenness centrality, clustering coefficient and degree were considered for comparison analysis. Then we got four results as following: compared with non-drug target genes, 1) drug target genes had lower evolutionary rates; 2) drug target genes had higher conservation scores; 3) drug target genes had higher percentages of orthologous genes and 4) drug target genes had a tighter network structure including higher degrees, betweenness centrality, clustering coefficients and lower average shortest path lengths. These results demonstrate that drug target genes are more evolutionarily conserved than non-drug target genes. We hope that our study will provide valuable information for other researchers who are interested in evolutionary conservation of drug targets.

  18. Artificial neural network study on organ-targeting peptides

    NASA Astrophysics Data System (ADS)

    Jung, Eunkyoung; Kim, Junhyoung; Choi, Seung-Hoon; Kim, Minkyoung; Rhee, Hokyoung; Shin, Jae-Min; Choi, Kihang; Kang, Sang-Kee; Lee, Nam Kyung; Choi, Yun-Jaie; Jung, Dong Hyun

    2010-01-01

    We report a new approach to studying organ targeting of peptides on the basis of peptide sequence information. The positive control data sets consist of organ-targeting peptide sequences identified by the peroral phage-display technique for four organs, and the negative control data are prepared from random sequences. The capacity of our models to make appropriate predictions is validated by statistical indicators including sensitivity, specificity, enrichment curve, and the area under the receiver operating characteristic (ROC) curve (the ROC score). VHSE descriptor produces statistically significant training models and the models with simple neural network architectures show slightly greater predictive power than those with complex ones. The training and test set statistics indicate that our models could discriminate between organ-targeting and random sequences. We anticipate that our models will be applicable to the selection of organ-targeting peptides for generating peptide drugs or peptidomimetics.

  19. Novel self-healing materials chemistries for targeted applications

    NASA Astrophysics Data System (ADS)

    Wilson, Gerald O.

    Self-healing materials of the type developed by White and co-workers [1] were designed to autonomically heal themselves when damaged, thereby extending the lifetime of various applications in which such material systems are employed. The system was based on urea-formaldehyde microcapsules containing dicyclopentadiene (DCPD) and Grubbs' catalyst particles embedded together in an epoxy matrix. When a crack propagates through the material, it ruptures the microcapsules, releasing DCPD into the crack plane, where it comes in contact and reacts with the catalyst to initiate a ring opening metathesis polymerization (ROMP), bonding the crack and restoring structural continuity. The present work builds on this concept in several ways. Firstly, it expands the scope and versatility of the ROMP self-healing chemistry by incorporation into epoxy vinyl ester matrices. Major technical challenges in this application include protection of the catalyst from deactivation by aggressive curing agents, and optimization of the concentration of healing agents in the matrix. Secondly, new ruthenium catalysts are evaluated for application in ROMP-based self-healing materials. The use of alternative derivatives of Grubbs' catalyst gave rise to self-healing systems with improved healing efficiencies and thermal properties. Evaluation of the stability of these new catalysts to primary amine curing agents used in the curing of common epoxy matrices also led to the discovery and characterization of new ruthenium catalysts which exhibited ROMP initiation kinetics superior to those of first and second generation Grubbs' catalysts. Finally, free radical polymerization was evaluated for application in the development of bio-compatible self-healing materials. [1] White, S. R.; Sottos, N. R.; Geubelle, P. R.; Moore, J. S.; Kessler, M. R.; Sriram, S. R.; Brown, E. N.; Viswanathan, S. Nature 2001, 409, 794.

  20. Effect of Patient Set-up and Respiration motion on Defining Biological Targets for Image-Guided Targeted Radiotherapy

    NASA Astrophysics Data System (ADS)

    McCall, Keisha C.

    Identification and monitoring of sub-tumor targets will be a critical step for optimal design and evaluation of cancer therapies in general and biologically targeted radiotherapy (dose-painting) in particular. Quantitative PET imaging may be an important tool for these applications. Currently radiotherapy planning accounts for tumor motion by applying geometric margins. These margins create a motion envelope to encompass the most probable positions of the tumor, while also maintaining the appropriate tumor control and normal tissue complication probabilities. This motion envelope is effective for uniform dose prescriptions where the therapeutic dose is conformed to the external margins of the tumor. However, much research is needed to establish the equivalent margins for non-uniform fields, where multiple biological targets are present and each target is prescribed its own dose level. Additionally, the size of the biological targets and close proximity make it impractical to apply planning margins on the sub-tumor level. Also, the extent of high dose regions must be limited to avoid excessive dose to the surrounding tissue. As such, this research project is an investigation of the uncertainty within quantitative PET images of moving and displaced dose-painting targets, and an investigation of the residual errors that remain after motion management. This included characterization of the changes in PET voxel-values as objects are moved relative to the discrete sampling interval of PET imaging systems (SPECIFIC AIM 1). Additionally, the repeatability of PET distributions and the delineating dose-painting targets were measured (SPECIFIC AIM 2). The effect of imaging uncertainty on the dose distributions designed using these images (SPECIFIC AIM 3) has also been investigated. This project also included analysis of methods to minimize motion during PET imaging and reduce the dosimetric impact of motion/position-induced imaging uncertainty (SPECIFIC AIM 4).

  1. A precisely targeted application strategy of dipping young cucumber fruit in fungicide to control cucumber gray mold.

    PubMed

    He, Leiming; Cui, Kaidi; Song, Yufei; Zhang, Zhengqun; Li, Beixing; Mu, Wei; Liu, Feng

    2018-04-27

    Gray mold is a ubiquitous destructive plant disease worldwide. To avoid the shortcomings of conventional spraying systems for controlling this disease, such as high selection pressure on Botrytis cinerea for resistance and fungicide waste resulting from spray drift, a precisely targeted application strategy of dipping young cucumber fruit in a mixture of fungicide and forchlorfenuron (plant growth regulator, PGR) during the bloom period to control cucumber gray mold was developed in the current study. Without leaving above-limit residues in cucumber fruits, dipping in fludioxonil at 30 mg liter -1 provided a greater efficacy (85.4%) against cucumber gray mold than did spraying at 100 mg liter -1 (76.4%). Importantly, fludioxonil mixed with forchlorfenuron from 25 to 35 mg liter -1 increased the yield of cucumbers by 26.2%-36.7% compared to dipping fruit only in forchlorfenuron. The increased yield may be a benefit of controlling gray mold. Dipping fruit in fungicides and PGRs seems to be a potential precisely targeted application strategy to not only control cucumber gray mold effectively but also, through the action of PGRs, to increase the cucumber yield. This novel application method is believed to have a bright prospect in cucumber production in Chinese solar greenhouses. This article is protected by copyright. All rights reserved.

  2. Targeting the RAS oncogene

    PubMed Central

    Takashima, Asami

    2013-01-01

    Introduction The Ras proteins (K-Ras, N-Ras, H-Ras) are GTPases that function as molecular switches for a variety of critical cellular activities and their function is tightly and temporally regulated in normal cells. Oncogenic mutations in the RAS genes, which create constitutively-active Ras proteins, can result in uncontrolled proliferation or survival in tumor cells. Areas covered The paper discusses three therapeutic approaches targeting the Ras pathway in cancer: 1) Ras itself, 2) Ras downstream pathways, and 3) synthetic lethality. The most adopted approach is targeting Ras downstream signaling, and specifically the PI3K-AKT-mTOR and Raf-MEK pathways, as they are frequently major oncogenic drivers in cancers with high Ras signaling. Although direct targeting of Ras has not been successful clinically, newer approaches being investigated in preclinical studies, such as RNA interference-based and synthetic lethal approaches, promise great potential for clinical application. Expert opinion The challenges of current and emerging therapeutics include the lack of “tumor specificity” and their limitation to those cancers which are “dependent” upon aberrant Ras signaling for survival. While the newer approaches have the potential to overcome these limitations, they also highlight the importance of robust preclinical studies and bidirectional translational research for successful clinical development of Ras-related targeted therapies. PMID:23360111

  3. Postsynthetic Tuning of Metal-Organic Frameworks for Targeted Applications.

    PubMed

    Islamoglu, Timur; Goswami, Subhadip; Li, Zhanyong; Howarth, Ashlee J; Farha, Omar K; Hupp, Joseph T

    2017-04-18

    Metal-organic frameworks (MOFs) are periodic, hybrid, atomically well-defined porous materials that typically form by self-assembly and consist of inorganic nodes (metal ions or clusters) and multitopic organic linkers. MOFs as a whole offer many intriguing properties, including ultrahigh porosity, tunable chemical functionality, and low density. These properties point to numerous potential applications, including gas storage, chemical separations, catalysis, light harvesting, and chemical sensing, to name a few. Reticular chemistry, or the linking of molecular building blocks into predetermined network structures, has been employed to synthesize thousands of MOFs. Given the vast library of candidate nodes and linkers, the number of potentially synthetically accessible MOFs is enormous. Nevertheless, a powerful complementary approach to obtain specific structures with desired chemical functionality is to modify known MOFs after synthesis. This approach is particularly useful when incorporation of particular chemical functionalities via direct synthesis is challenging or impossible. The challenges may stem from limited stability or solubility of precursors, unwanted secondary reactivity of precursors, or incompatibility of functional groups with the conditions needed for direct synthesis. MOFs can be postsynthetically modified by replacing the metal nodes and/or organic linkers or via functionalization of the metal nodes and/or organic linkers. Here we describe some of our efforts toward the development and application of postsynthetic strategies for imparting desired chemical functionalities in MOFs of known topology. The techniques include methods for functionalizing MOF nodes, i.e., solvent-assisted ligand incorporation (SALI) and atomic layer deposition in MOFs (AIM) as well as a method to replace structural linkers, termed solvent-assisted linker exchange (SALE), also known as postsynthethic exchange (PSE). For each functionalization strategy, we first describe

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

    PubMed

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

    2012-01-01

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

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

    PubMed

    Lee, Kyoungyeul; Lee, Minho; Kim, Dongsup

    2017-12-28

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

  6. Antibody derivatization and conjugation strategies: application in preparation of stealth immunoliposome to target chemotherapeutics to tumor.

    PubMed

    Manjappa, Arehalli S; Chaudhari, Kiran R; Venkataraju, Makam P; Dantuluri, Prudhviraju; Nanda, Biswarup; Sidda, Chennakesavulu; Sawant, Krutika K; Murthy, Rayasa S Ramachandra

    2011-02-28

    A great deal of effort has been made over the years to develop liposomes that have targeting vectors (oligosaccharides, peptides, proteins and vitamins) attached to the bilayer surface. Most studies have focused on antibody conjugates since procedures for producing highly specific monoclonal antibodies are well established. Antibody conjugated liposomes have recently attracted a great deal of interest, principally because of their potential use as targeted drug delivery systems and in diagnostic applications. A number of methods have been reported for coupling antibodies to the surface of stealth liposomes. The objective of this review is to enumerate various strategies which are employed in the modification and conjugation of antibodies to the surface of stealth liposomes. This review also describes various derivatization techniques of lipids prior and after their use in the preparation of liposomes. The use of single chain variable fragments and affibodies as targeting ligands in the preparation of immunoliposomes is also discussed. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Enrichment of target sequences for next-generation sequencing applications in research and diagnostics.

    PubMed

    Altmüller, Janine; Budde, Birgit S; Nürnberg, Peter

    2014-02-01

    Abstract Targeted re-sequencing such as gene panel sequencing (GPS) has become very popular in medical genetics, both for research projects and in diagnostic settings. The technical principles of the different enrichment methods have been reviewed several times before; however, new enrichment products are constantly entering the market, and researchers are often puzzled about the requirement to take decisions about long-term commitments, both for the enrichment product and the sequencing technology. This review summarizes important considerations for the experimental design and provides helpful recommendations in choosing the best sequencing strategy for various research projects and diagnostic applications.

  8. 13 CFR 123.401 - What types of mitigation measures can your business include in an application for a pre-disaster...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... can your business include in an application for a pre-disaster mitigation loan? 123.401 Section 123.401 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Pre-Disaster... a pre-disaster mitigation loan? To be included in a pre-disaster mitigation loan application, each...

  9. Targeting Membrane-Bound Viral RNA Synthesis Reveals Potent Inhibition of Diverse Coronaviruses Including the Middle East Respiratory Syndrome Virus

    PubMed Central

    Bergström, Tomas; Kann, Nina; Adamiak, Beata; Hannoun, Charles; Kindler, Eveline; Jónsdóttir, Hulda R.; Muth, Doreen; Kint, Joeri; Forlenza, Maria; Müller, Marcel A.; Drosten, Christian; Thiel, Volker; Trybala, Edward

    2014-01-01

    Coronaviruses raise serious concerns as emerging zoonotic viruses without specific antiviral drugs available. Here we screened a collection of 16671 diverse compounds for anti-human coronavirus 229E activity and identified an inhibitor, designated K22, that specifically targets membrane-bound coronaviral RNA synthesis. K22 exerts most potent antiviral activity after virus entry during an early step of the viral life cycle. Specifically, the formation of double membrane vesicles (DMVs), a hallmark of coronavirus replication, was greatly impaired upon K22 treatment accompanied by near-complete inhibition of viral RNA synthesis. K22-resistant viruses contained substitutions in non-structural protein 6 (nsp6), a membrane-spanning integral component of the viral replication complex implicated in DMV formation, corroborating that K22 targets membrane bound viral RNA synthesis. Besides K22 resistance, the nsp6 mutants induced a reduced number of DMVs, displayed decreased specific infectivity, while RNA synthesis was not affected. Importantly, K22 inhibits a broad range of coronaviruses, including Middle East respiratory syndrome coronavirus (MERS–CoV), and efficient inhibition was achieved in primary human epithelia cultures representing the entry port of human coronavirus infection. Collectively, this study proposes an evolutionary conserved step in the life cycle of positive-stranded RNA viruses, the recruitment of cellular membranes for viral replication, as vulnerable and, most importantly, druggable target for antiviral intervention. We expect this mode of action to serve as a paradigm for the development of potent antiviral drugs to combat many animal and human virus infections. PMID:24874215

  10. 13 CFR 123.401 - What types of mitigation measures can your business include in an application for a pre-disaster...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... can your business include in an application for a pre-disaster mitigation loan? 123.401 Section 123.401 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Pre-Disaster Mitigation Loans § 123.401 What types of mitigation measures can your business include in an application for...

  11. 13 CFR 123.401 - What types of mitigation measures can your business include in an application for a pre-disaster...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... can your business include in an application for a pre-disaster mitigation loan? 123.401 Section 123.401 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Pre-Disaster Mitigation Loans § 123.401 What types of mitigation measures can your business include in an application for...

  12. 13 CFR 123.401 - What types of mitigation measures can your business include in an application for a pre-disaster...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... can your business include in an application for a pre-disaster mitigation loan? 123.401 Section 123.401 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Pre-Disaster Mitigation Loans § 123.401 What types of mitigation measures can your business include in an application for...

  13. 13 CFR 123.401 - What types of mitigation measures can your business include in an application for a pre-disaster...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... can your business include in an application for a pre-disaster mitigation loan? 123.401 Section 123.401 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Pre-Disaster Mitigation Loans § 123.401 What types of mitigation measures can your business include in an application for...

  14. TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models.

    PubMed

    Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

    2016-05-01

    Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com .

  15. TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models

    NASA Astrophysics Data System (ADS)

    Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

    2016-05-01

    Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com.

  16. METABOLOMICS IN SMALL FISH TOXICOLOGY AND OTHER ENVIRONMENTAL APPLICATIONS

    EPA Science Inventory

    Although lagging behind applications targeted to human endpoints, metabolomics offers great potential in environmental applications, including ecotoxicology. Indeed, the advantages of metabolomics (relative to other 'omic techniques) may be more tangible in ecotoxicology because...

  17. Nuclear reactor target assemblies, nuclear reactor configurations, and methods for producing isotopes, modifying materials within target material, and/or characterizing material within a target material

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

    Toth, James J.; Wall, Donald; Wittman, Richard S.

    Target assemblies are provided that can include a uranium-comprising annulus. The assemblies can include target material consisting essentially of non-uranium material within the volume of the annulus. Reactors are disclosed that can include one or more discrete zones configured to receive target material. At least one uranium-comprising annulus can be within one or more of the zones. Methods for producing isotopes within target material are also disclosed, with the methods including providing neutrons to target material within a uranium-comprising annulus. Methods for modifying materials within target material are disclosed as well as are methods for characterizing material within a targetmore » material.« less

  18. Increased hematocrit after applications of conducted energy weapons (including TASER(®) devices) to Sus scrofa.

    PubMed

    Jauchem, James R

    2011-01-01

    Conducted energy weapons (CEWs) are used by law enforcement personnel to incapacitate individuals quickly and effectively, without intending to cause lethality. CEWs have been deployed for relatively long or repeated exposures in some cases. In laboratory animal models, central venous hematocrit has increased significantly after CEW exposure. Even limited applications (e.g., three 5-sec applications) resulted in statistically significant increases in hematocrit. Preexposure hematocrit was significantly higher in nonsurvivors versus survivors after more extreme CEW applications. The purpose of this technical note is to address specific questions that may be generated when examining these results. Comparisons among results of CEW applications, other electrical muscle stimulation, and exercise/voluntary muscle contraction are included. The anesthetized swine appears to be an acceptable animal model for studying changes in hematocrit and associated red blood cell changes. Potential detrimental effects of increased hematocrit, and considerations during law enforcement use, are discussed. 2010 American Academy of Forensic Sciences. Published 2010. This article is a U.S. Government work and is in the public domain in the U.S.A.

  19. Planar optical waveguide based sandwich assay sensors and processes for the detection of biological targets including early detection of cancers

    DOEpatents

    Martinez, Jennifer S [Santa Fe, NM; Swanson, Basil I [Los Alamos, NM; Shively, John E [Arcadia, CA; Li, Lin [Monrovia, CA

    2009-06-02

    An assay element is described including recognition ligands adapted for binding to carcinoembryonic antigen (CEA) bound to a film on a single mode planar optical waveguide, the film from the group of a membrane, a polymerized bilayer membrane, and a self-assembled monolayer containing polyethylene glycol or polypropylene glycol groups therein and an assay process for detecting the presence of CEA is described including injecting a possible CEA-containing sample into a sensor cell including the assay element, maintaining the sample within the sensor cell for time sufficient for binding to occur between CEA present within the sample and the recognition ligands, injecting a solution including a reporter ligand into the sensor cell; and, interrogating the sample within the sensor cell with excitation light from the waveguide, the excitation light provided by an evanescent field of the single mode penetrating into the biological target-containing sample to a distance of less than about 200 nanometers from the waveguide thereby exciting any bound reporter ligand within a distance of less than about 200 nanometers from the waveguide and resulting in a detectable signal.

  20. AEGIS Automated Targeting for the MSL ChemCam Instrument

    NASA Astrophysics Data System (ADS)

    Estlin, T.; Anderson, R. C.; Blaney, D. L.; Bornstein, B.; Burl, M. C.; Castano, R.; Gaines, D.; Judd, M.; Thompson, D. R.; Wiens, R. C.

    2013-12-01

    The Autonomous Exploration for Gathering Increased Science (AEGIS) system enables automated science data collection by a planetary rover. AEGIS has been in use on the Mars Exploration Rover (MER) mission Opportunity rover since 2010 to provide onboard targeting of the MER Panoramic Camera based on scientist-specified objectives. AEGIS is now being applied for use with the Mars Science Laboratory (MSL) mission ChemCam spectrometer. ChemCam uses a Laser Induced Breakdown Spectrometer (LIBS) to analyze the elemental composition of rocks and soil from up to seven meters away. ChemCam's tightly-focused laser beam (350-550 um) enables targeting of very fine-scale terrain features. AEGIS is being applied in two ways to help ChemCam collect valuable science data. The first application is to enable automated targeting of ChemCam during or after or in the middle of long drives. The majority of ChemCam measurements are collected by allowing the science team to select specific targets in rover images. However this requires the rover to stay in the same area while images are downlinked, analyzed for targets, and new commands uplinked. The only data that can be acquired without this communication cycle is via blind targeting, where measurements are often of soil patches vs. instead of more valuable targets such as rocks with specific properties. AEGIS is being applied to automatically analyze images onboard and select targets for ChemCam analysis. This approach allows the rover to autonomously select and sequence targeted measurements in an opportunistic fashion at different points along the rover's drive path. Rock targets can be prioritized for measurement based on various geologically relevant features, including size, shape and albedo. A second application is to enable intelligent pointing refinement of ChemCam when acquiring data of small targets, such as veins or concretions that are only a few millimeters wide. Due to backlash and other pointing challenges, it can often

  1. Biomedical Applications of Organometal-Peptide Conjugates

    NASA Astrophysics Data System (ADS)

    Metzler-Nolte, Nils

    Peptides are well suited as targeting vectors for the directed delivery of metal-based drugs or probes for biomedical investigations. This chapter describes synthetic strategies for the preparation of conjugates of medically interesting peptides with covalently bound metal complexes. Peptides that were used include neuropeptides (enkephalin, neuropeptide Y, neurotensin), uptake peptides (TAT and poly-Arg), and intracellular localization sequences. To these peptides, a whole variety of transition metal complexes has been attached in recent years by solid-phase peptide synthesis (SPPS) techniques. The metal complex can be attached to the peptide on the resin as part of the SPPS scheme. Alternatively, the metal complex may be attached to the peptide as a postsynthetic modification. Advantages as well as disadvantages for either strategy are discussed. Biomedical applications include radiopharmaceutical applications, anticancer and antibacterial activity, metal-peptide conjugates as targeted CO-releasing molecules, and metal-peptide conjugates in biosensor applications.

  2. Use of an activated beta-catenin to identify Wnt pathway target genes in caenorhabditis elegans, including a subset of collagen genes expressed in late larval development.

    PubMed

    Jackson, Belinda M; Abete-Luzi, Patricia; Krause, Michael W; Eisenmann, David M

    2014-04-16

    The Wnt signaling pathway plays a fundamental role during metazoan development, where it regulates diverse processes, including cell fate specification, cell migration, and stem cell renewal. Activation of the beta-catenin-dependent/canonical Wnt pathway up-regulates expression of Wnt target genes to mediate a cellular response. In the nematode Caenorhabditis elegans, a canonical Wnt signaling pathway regulates several processes during larval development; however, few target genes of this pathway have been identified. To address this deficit, we used a novel approach of conditionally activated Wnt signaling during a defined stage of larval life by overexpressing an activated beta-catenin protein, then used microarray analysis to identify genes showing altered expression compared with control animals. We identified 166 differentially expressed genes, of which 104 were up-regulated. A subset of the up-regulated genes was shown to have altered expression in mutants with decreased or increased Wnt signaling; we consider these genes to be bona fide C. elegans Wnt pathway targets. Among these was a group of six genes, including the cuticular collagen genes, bli-1 col-38, col-49, and col-71. These genes show a peak of expression in the mid L4 stage during normal development, suggesting a role in adult cuticle formation. Consistent with this finding, reduction of function for several of the genes causes phenotypes suggestive of defects in cuticle function or integrity. Therefore, this work has identified a large number of putative Wnt pathway target genes during larval life, including a small subset of Wnt-regulated collagen genes that may function in synthesis of the adult cuticle.

  3. Small Molecule Sequential Dual-Targeting Theragnostic Strategy (SMSDTTS): from Preclinical Experiments towards Possible Clinical Anticancer Applications

    PubMed Central

    Li, Junjie; Oyen, Raymond; Verbruggen, Alfons; Ni, Yicheng

    2013-01-01

    Hitting the evasive tumor cells proves challenging in targeted cancer therapies. A general and unconventional anticancer approach namely small molecule sequential dual-targeting theragnostic strategy (SMSDTTS) has recently been introduced with the aims to target and debulk the tumor mass, wipe out the residual tumor cells, and meanwhile enable cancer detectability. This dual targeting approach works in two steps for systemic delivery of two naturally derived drugs. First, an anti-tubulin vascular disrupting agent, e.g., combretastatin A4 phosphate (CA4P), is injected to selectively cut off tumor blood supply and to cause massive necrosis, which nevertheless always leaves peripheral tumor residues. Secondly, a necrosis-avid radiopharmaceutical, namely 131I-hypericin (131I-Hyp), is administered the next day, which accumulates in intratumoral necrosis and irradiates the residual cancer cells with beta particles. Theoretically, this complementary targeted approach may biologically and radioactively ablate solid tumors and reduce the risk of local recurrence, remote metastases, and thus cancer mortality. Meanwhile, the emitted gamma rays facilitate radio-scintigraphy to detect tumors and follow up the therapy, hence a simultaneous theragnostic approach. SMSDTTS has now shown promise from multicenter animal experiments and may demonstrate unique anticancer efficacy in upcoming preliminary clinical trials. In this short review article, information about the two involved agents, the rationale of SMSDTTS, its preclinical antitumor efficacy, multifocal targetability, simultaneous theragnostic property, and toxicities of the dose regimens are summarized. Meanwhile, possible drawbacks, practical challenges and future improvement with SMSDTTS are discussed, which hopefully may help to push forward this strategy from preclinical experiments towards possible clinical applications. PMID:23412554

  4. Small Molecule Sequential Dual-Targeting Theragnostic Strategy (SMSDTTS): from Preclinical Experiments towards Possible Clinical Anticancer Applications.

    PubMed

    Li, Junjie; Oyen, Raymond; Verbruggen, Alfons; Ni, Yicheng

    2013-01-01

    Hitting the evasive tumor cells proves challenging in targeted cancer therapies. A general and unconventional anticancer approach namely small molecule sequential dual-targeting theragnostic strategy (SMSDTTS) has recently been introduced with the aims to target and debulk the tumor mass, wipe out the residual tumor cells, and meanwhile enable cancer detectability. This dual targeting approach works in two steps for systemic delivery of two naturally derived drugs. First, an anti-tubulin vascular disrupting agent, e.g., combretastatin A4 phosphate (CA4P), is injected to selectively cut off tumor blood supply and to cause massive necrosis, which nevertheless always leaves peripheral tumor residues. Secondly, a necrosis-avid radiopharmaceutical, namely (131)I-hypericin ((131)I-Hyp), is administered the next day, which accumulates in intratumoral necrosis and irradiates the residual cancer cells with beta particles. Theoretically, this complementary targeted approach may biologically and radioactively ablate solid tumors and reduce the risk of local recurrence, remote metastases, and thus cancer mortality. Meanwhile, the emitted gamma rays facilitate radio-scintigraphy to detect tumors and follow up the therapy, hence a simultaneous theragnostic approach. SMSDTTS has now shown promise from multicenter animal experiments and may demonstrate unique anticancer efficacy in upcoming preliminary clinical trials. In this short review article, information about the two involved agents, the rationale of SMSDTTS, its preclinical antitumor efficacy, multifocal targetability, simultaneous theragnostic property, and toxicities of the dose regimens are summarized. Meanwhile, possible drawbacks, practical challenges and future improvement with SMSDTTS are discussed, which hopefully may help to push forward this strategy from preclinical experiments towards possible clinical applications.

  5. Magnetic field pattern synthesis and its application in targeted drug delivery: Design and implementation.

    PubMed

    Hajiaghajani, Amirhossein; Abdolali, Ali

    2018-05-01

    In cancer therapy, magnetic drug targeting is considered as an effective treatment to reduce chemotherapy's side effects. The accurate design and shaping of magnetic fields are crucial for healthy cells to be immune from chemotherapeutics. In this paper, arbitrary 2-dimensional spatial patterns of magnetic fields from DC to megahertz are represented in terms of spatial Fourier spectra with sinusoidal eigenfunctions. Realization of each spatial frequency was investigated by a set of elliptical coils. Therefore, it is shown that the desired pattern was synthesized by simultaneous use of coil sets. Currents running on each set were obtained via fast and straightforward analytical Fourier series calculation. Experimentally scanned sample patterns were in close agreement with full wave analysis. Discussions include the evaluation of the Fourier series approximation error and cross-polarization of produced magnetic fields. It was observed that by employing the controlled magnetic field produced by the proposed setup, we were able to steer therapeutic particles toward the right or left half-spheres of the breast, with an efficiency of 90%. Such a pattern synthesizer may be employed in numerous human arteries as well as other bioelectromagnetic patterning applications, e.g., wireless power transfer, magnetic innervation, and tomography. Bioelectromagnetics. 39:325-338, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  6. The influence of sterilization on nitrogen-included ultrananocrystalline diamond for biomedical applications.

    PubMed

    Tong, Wei; Tran, Phong A; Turnley, Ann M; Aramesh, Morteza; Prawer, Steven; Brandt, Milan; Fox, Kate

    2016-04-01

    Diamond has shown great potential in different biomedical applications, but the effects of sterilization on its properties have not been investigated. Here, we studied the influence of five sterilization techniques (solvent cleaning, oxygen plasma, UV irradiation, autoclave and hydrogen peroxide) on nitrogen-included ultrananocrystalline diamond. The chemical modification of the diamond surface was evaluated using X-ray photoelectron spectroscopy and water contact angle measurements. Different degrees of surface oxidation and selective sp(2) bonded carbon etching were found following all sterilization techniques, resulting in an increase of hydrophilicity. Higher viabilities of in vitro mouse 3T3 fibroblasts and rat cortical neuron cells were observed on oxygen plasma, autoclave and hydrogen peroxide sterilized diamond, which correlated with their higher hydrophilicity. By examination of apatite formation in simulated body fluid, in vivo bioactivity was predicted to be best on those surfaces which have been oxygen plasma treated and lowest on those which have been exposed to UV irradiation. The charge injection properties were also altered by the sterilization process and there appears to be a correlation between these changes and the degree of oxygen termination of the surface. We find that the modification brought by autoclave, oxygen plasma and hydrogen peroxide were most consistent with the use of N-UNCD in biological applications as compared to samples sterilized by solvent cleaning or UV exposure or indeed non-sterilized. A two-step process of sterilization by hydrogen peroxide following oxygen plasma treatment was then suggested. However, the final choice of sterilization technique will depend on the intended end application. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Single-Command Approach and Instrument Placement by a Robot on a Target

    NASA Technical Reports Server (NTRS)

    Huntsberger, Terrance; Cheng, Yang

    2005-01-01

    AUTOAPPROACH is a computer program that enables a mobile robot to approach a target autonomously, starting from a distance of as much as 10 m, in response to a single command. AUTOAPPROACH is used in conjunction with (1) software that analyzes images acquired by stereoscopic cameras aboard the robot and (2) navigation and path-planning software that utilizes odometer readings along with the output of the image-analysis software. Intended originally for application to an instrumented, wheeled robot (rover) in scientific exploration of Mars, AUTOAPPROACH could be adapted to terrestrial applications, notably including the robotic removal of land mines and other unexploded ordnance. A human operator generates the approach command by selecting the target in images acquired by the robot cameras. The approach path consists of multiple legs. Feature points are derived from images that contain the target and are thereafter tracked to correct odometric errors and iteratively refine estimates of the position and orientation of the robot relative to the target on successive legs. The approach is terminated when the robot attains the position and orientation required for placing a scientific instrument at the target. The workspace of the robot arm is then autonomously checked for self/terrain collisions prior to the deployment of the scientific instrument onto the target.

  8. Inheritable Silencing of Endogenous Genes by Hit-and-Run Targeted Epigenetic Editing.

    PubMed

    Amabile, Angelo; Migliara, Alessandro; Capasso, Paola; Biffi, Mauro; Cittaro, Davide; Naldini, Luigi; Lombardo, Angelo

    2016-09-22

    Gene silencing is instrumental to interrogate gene function and holds promise for therapeutic applications. Here, we repurpose the endogenous retroviruses' silencing machinery of embryonic stem cells to stably silence three highly expressed genes in somatic cells by epigenetics. This was achieved by transiently expressing combinations of engineered transcriptional repressors that bind to and synergize at the target locus to instruct repressive histone marks and de novo DNA methylation, thus ensuring long-term memory of the repressive epigenetic state. Silencing was highly specific, as shown by genome-wide analyses, sharply confined to the targeted locus without spreading to nearby genes, resistant to activation induced by cytokine stimulation, and relieved only by targeted DNA demethylation. We demonstrate the portability of this technology by multiplex gene silencing, adopting different DNA binding platforms and interrogating thousands of genomic loci in different cell types, including primary T lymphocytes. Targeted epigenome editing might have broad application in research and medicine. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. Spectral Target Detection using Schroedinger Eigenmaps

    NASA Astrophysics Data System (ADS)

    Dorado-Munoz, Leidy P.

    Applications of optical remote sensing processes include environmental monitoring, military monitoring, meteorology, mapping, surveillance, etc. Many of these tasks include the detection of specific objects or materials, usually few or small, which are surrounded by other materials that clutter the scene and hide the relevant information. This target detection process has been boosted lately by the use of hyperspectral imagery (HSI) since its high spectral dimension provides more detailed spectral information that is desirable in data exploitation. Typical spectral target detectors rely on statistical or geometric models to characterize the spectral variability of the data. However, in many cases these parametric models do not fit well HSI data that impacts the detection performance. On the other hand, non-linear transformation methods, mainly based on manifold learning algorithms, have shown a potential use in HSI transformation, dimensionality reduction and classification. In target detection, non-linear transformation algorithms are used as preprocessing techniques that transform the data to a more suitable lower dimensional space, where the statistical or geometric detectors are applied. One of these non-linear manifold methods is the Schroedinger Eigenmaps (SE) algorithm that has been introduced as a technique for semi-supervised classification. The core tool of the SE algorithm is the Schroedinger operator that includes a potential term that encodes prior information about the materials present in a scene, and enables the embedding to be steered in some convenient directions in order to cluster similar pixels together. A completely novel target detection methodology based on SE algorithm is proposed for the first time in this thesis. The proposed methodology does not just include the transformation of the data to a lower dimensional space but also includes the definition of a detector that capitalizes on the theory behind SE. The fact that target pixels and

  10. Characterization of single chain antibody targets through yeast two hybrid

    PubMed Central

    2010-01-01

    Background Due to their unique ability to bind their targets with high fidelity, antibodies are used widely not only in biomedical research, but also in many clinical applications. Recombinant antibodies, including single chain variable fragments (scFv), are gaining momentum because they allow powerful in vitro selection and manipulation without loss of function. Regardless of the ultimate application or type of antibody used, precise understanding of the interaction between the antibody's binding site and its specific target epitope(s) is of great importance. However, such data is frequently difficult to obtain. Results We describe an approach that allows detailed characterization of a given antibody's target(s) using the yeast two-hybrid system. Several recombinant scFv were used as bait and screened against highly complex cDNA libraries. Systematic sequencing of all retained clones and statistical analysis allowed efficient ranking of the prey fragments. Multiple alignment of the obtained cDNA fragments provided a selected interacting domain (SID), efficiently narrowing the epitope-containing region. Interactions between antibodies and their respective targets were characterized for several scFv. For AA2 and ROF7, two conformation-specific sensors that exclusively bind the activated forms of the small GTPases Rab6 and Rab1 respectively, only fragments expressing the entire target protein's core region were retained. This strongly suggested interaction with a non-linear epitope. For two other scFv, TA10 and SF9, which recognize the large proteins giantin and non-muscle myosin IIA, respectively, precise antibody-binding regions within the target were defined. Finally, for some antibodies, secondary targets within and across species could be revealed. Conclusions Our method, utilizing the yeast two-hybrid technology and scFv as bait, is a simple yet powerful approach for the detailed characterization of antibody targets. It allows precise domain mapping for linear

  11. Inertial Confinement fusion targets

    NASA Technical Reports Server (NTRS)

    Hendricks, C. D.

    1982-01-01

    Inertial confinement fusion (ICF) targets are made as simple flat discs, as hollow shells or as complicated multilayer structures. Many techniques were devised for producing the targets. Glass and metal shells are made by using drop and bubble techniques. Solid hydrogen shells are also produced by adapting old methods to the solution of modern problems. Some of these techniques, problems, and solutions are discussed. In addition, the applications of many of the techniques to fabrication of ICF targets is presented.

  12. Application of real-time single camera SLAM technology for image-guided targeting in neurosurgery

    NASA Astrophysics Data System (ADS)

    Chang, Yau-Zen; Hou, Jung-Fu; Tsao, Yi Hsiang; Lee, Shih-Tseng

    2012-10-01

    In this paper, we propose an application of augmented reality technology for targeting tumors or anatomical structures inside the skull. The application is a combination of the technologies of MonoSLAM (Single Camera Simultaneous Localization and Mapping) and computer graphics. A stereo vision system is developed to construct geometric data of human face for registration with CT images. Reliability and accuracy of the application is enhanced by the use of fiduciary markers fixed to the skull. The MonoSLAM keeps track of the current location of the camera with respect to an augmented reality (AR) marker using the extended Kalman filter. The fiduciary markers provide reference when the AR marker is invisible to the camera. Relationship between the markers on the face and the augmented reality marker is obtained by a registration procedure by the stereo vision system and is updated on-line. A commercially available Android based tablet PC equipped with a 320×240 front-facing camera was used for implementation. The system is able to provide a live view of the patient overlaid by the solid models of tumors or anatomical structures, as well as the missing part of the tool inside the skull.

  13. Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration

    PubMed Central

    Gu, Wenyi; Wu, Chengtie; Chen, Jiezhong; Xiao, Yin

    2013-01-01

    Nanotechnology is a vigorous research area and one of its important applications is in biomedical sciences. Among biomedical applications, targeted drug delivery is one of the most extensively studied subjects. Nanostructured particles and scaffolds have been widely studied for increasing treatment efficacy and specificity of present treatment approaches. Similarly, this technique has been used for treating bone diseases including bone regeneration. In this review, we have summarized and highlighted the recent advancement of nanostructured particles and scaffolds for the treatment of cancer bone metastasis, osteosarcoma, bone infections and inflammatory diseases, osteoarthritis, as well as for bone regeneration. Nanoparticles used to deliver deoxyribonucleic acid and ribonucleic acid molecules to specific bone sites for gene therapies are also included. The investigation of the implications of nanoparticles in bone diseases have just begun, and has already shown some promising potential. Further studies have to be conducted, aimed specifically at assessing targeted delivery and bioactive scaffolds to further improve their efficacy before they can be used clinically. PMID:23836972

  14. Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration.

    PubMed

    Gu, Wenyi; Wu, Chengtie; Chen, Jiezhong; Xiao, Yin

    2013-01-01

    Nanotechnology is a vigorous research area and one of its important applications is in biomedical sciences. Among biomedical applications, targeted drug delivery is one of the most extensively studied subjects. Nanostructured particles and scaffolds have been widely studied for increasing treatment efficacy and specificity of present treatment approaches. Similarly, this technique has been used for treating bone diseases including bone regeneration. In this review, we have summarized and highlighted the recent advancement of nanostructured particles and scaffolds for the treatment of cancer bone metastasis, osteosarcoma, bone infections and inflammatory diseases, osteoarthritis, as well as for bone regeneration. Nanoparticles used to deliver deoxyribonucleic acid and ribonucleic acid molecules to specific bone sites for gene therapies are also included. The investigation of the implications of nanoparticles in bone diseases have just begun, and has already shown some promising potential. Further studies have to be conducted, aimed specifically at assessing targeted delivery and bioactive scaffolds to further improve their efficacy before they can be used clinically.

  15. Target-responsive DNA hydrogel mediated "stop-flow" microfluidic paper-based analytic device for rapid, portable and visual detection of multiple targets.

    PubMed

    Wei, Xiaofeng; Tian, Tian; Jia, Shasha; Zhu, Zhi; Ma, Yanli; Sun, Jianjun; Lin, Zhenyu; Yang, Chaoyong James

    2015-04-21

    A versatile point-of-care assay platform was developed for simultaneous detection of multiple targets based on a microfluidic paper-based analytic device (μPAD) using a target-responsive hydrogel to mediate fluidic flow and signal readout. An aptamer-cross-linked hydrogel was used as a target-responsive flow regulator in the μPAD. In the absence of a target, the hydrogel is formed in the flow channel, stopping the flow in the μPAD and preventing the colored indicator from traveling to the final observation spot, thus yielding a "signal off" readout. In contrast, in the presence of a target, no hydrogel is formed because of the preferential interaction of target and aptamer. This allows free fluidic flow in the μPAD, carrying the indicator to the observation spot and producing a "signal on" readout. The device is inexpensive to fabricate, easy to use, and disposable after detection. Testing results can be obtained within 6 min by the naked eye via a simple loading operation without the need for any auxiliary equipment. Multiple targets, including cocaine, adenosine, and Pb(2+), can be detected simultaneously, even in complex biological matrices such as urine. The reported method offers simple, low cost, rapid, user-friendly, point-of-care testing, which will be useful in many applications.

  16. Targeted therapy using nanotechnology: focus on cancer

    PubMed Central

    Sanna, Vanna; Pala, Nicolino; Sechi, Mario

    2014-01-01

    Recent advances in nanotechnology and biotechnology have contributed to the development of engineered nanoscale materials as innovative prototypes to be used for biomedical applications and optimized therapy. Due to their unique features, including a large surface area, structural properties, and a long circulation time in blood compared with small molecules, a plethora of nanomaterials has been developed, with the potential to revolutionize the diagnosis and treatment of several diseases, in particular by improving the sensitivity and recognition ability of imaging contrast agents and by selectively directing bioactive agents to biological targets. Focusing on cancer, promising nanoprototypes have been designed to overcome the lack of specificity of conventional chemotherapeutic agents, as well as for early detection of precancerous and malignant lesions. However, several obstacles, including difficulty in achieving the optimal combination of physicochemical parameters for tumor targeting, evading particle clearance mechanisms, and controlling drug release, prevent the translation of nanomedicines into therapy. In spite of this, recent efforts have been focused on developing functionalized nanoparticles for delivery of therapeutic agents to specific molecular targets overexpressed on different cancer cells. In particular, the combination of targeted and controlled-release polymer nanotechnologies has resulted in a new programmable nanotherapeutic formulation of docetaxel, namely BIND-014, which recently entered Phase II clinical testing for patients with solid tumors. BIND-014 has been developed to overcome the limitations facing delivery of nanoparticles to many neoplasms, and represents a validated example of targeted nanosystems with the optimal biophysicochemical properties needed for successful tumor eradication. PMID:24531078

  17. TargetSpy: a supervised machine learning approach for microRNA target prediction.

    PubMed

    Sturm, Martin; Hackenberg, Michael; Langenberger, David; Frishman, Dmitrij

    2010-05-28

    , suggesting that it may be applicable to a broad range of species. Moreover, we have demonstrated that the application of machine learning techniques in combination with upcoming deep sequencing data results in a powerful microRNA target site prediction tool http://www.targetspy.org.

  18. TargetSpy: a supervised machine learning approach for microRNA target prediction

    PubMed Central

    2010-01-01

    in human and drosophila, suggesting that it may be applicable to a broad range of species. Moreover, we have demonstrated that the application of machine learning techniques in combination with upcoming deep sequencing data results in a powerful microRNA target site prediction tool http://www.targetspy.org. PMID:20509939

  19. The implementation of flipped classroom model in CIE in the environment of non-target language

    NASA Astrophysics Data System (ADS)

    Xiao, Renfei; Mustofa, Ali; Zhang, Fang; Su, Xiaoxue

    2018-01-01

    This paper sets a theoretical framework that it’s both feasible and indispensable of flipping classroom in Chinese International Education (CIE) in the non-target language environments. There are mainly three sections included: 1) what is flipped classroom and why it becomes inevitable existence; 2) why should we flip the classroom in CIE environments, especially in non-target language environments; 3) take Pusat Bahasa Mandarin Universitas Negeri Surabaya as an instance to discuss the application of flipped classroom in non-target language environments.

  20. Drug-repositioning opportunities for cancer therapy: novel molecular targets for known compounds.

    PubMed

    Würth, Roberto; Thellung, Stefano; Bajetto, Adriana; Mazzanti, Michele; Florio, Tullio; Barbieri, Federica

    2016-01-01

    Drug repositioning is gaining increasing attention in drug discovery because it represents a smart way to exploit new molecular targets of a known drug or target promiscuity among diverse diseases, for medical uses different from the one originally considered. In this review, we focus on known non-oncological drugs with new therapeutic applications in oncology, explaining the rationale behind this approach and providing practical evidence. Moving from incompleteness of the knowledge of drug-target interactions, particularly for older molecules, we highlight opportunities for repurposing compounds as cancer therapeutics, underling the biologically and clinically relevant affinities for new targets. Ideal candidates for repositioning can contribute to the therapeutically unmet need for more-efficient anticancer agents, including drugs that selectively target cancer stem cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Incorporating Target Priorities in the Sensor Tasking Reward Function

    NASA Astrophysics Data System (ADS)

    Gehly, S.; Bennett, J.

    2016-09-01

    Orbital debris tracking poses many challenges, most fundamentally the need to track a large number of objects from a limited number of sensors. The use of information theoretic sensor allocation provides a means to efficiently collect data on the multitarget system. An additional need of the community is the ability to specify target priorities, driven both by user needs and environmental factors such as collision warnings. This research develops a method to incorporate target priorities in the sensor tasking reward function, allowing for several applications in different tasking modes such as catalog maintenance, calibration, and collision monitoring. A set of numerical studies is included to demonstrate the functionality of the method.

  2. From Bioengineering to CRISPR/Cas9 – A Personal Retrospective of 20 Years of Research in Programmable Genome Targeting

    PubMed Central

    Jeltsch, Albert

    2018-01-01

    Genome targeting of restriction enzymes and DNA methyltransferases has many important applications including genome and epigenome editing. 15–20 years ago, my group was involved in the development of approaches for programmable genome targeting, aiming to connect enzymes with an oligodeoxynucleotide (ODN), which could form a sequence-specific triple helix at the genomic target site. Importantly, the target site of such enzyme-ODN conjugate could be varied simply by altering the ODN sequence promising great applicative values. However, this approach was facing many problems including the preparation and purification of the enzyme-ODN conjugates, their efficient delivery into cells, slow kinetics of triple helix formation and the requirement of a poly-purine target site sequence. Hence, for several years genome and epigenome editing approaches mainly were based on Zinc fingers and TAL proteins as targeting devices. More recently, CRISPR/Cas systems were discovered, which use a bound RNA for genome targeting that forms an RNA/DNA duplex with one DNA strand of the target site. These systems combine all potential advantages of the once imagined enzyme-ODN conjugates and avoid all main disadvantageous. Consequently, the application of CRISPR/Cas in genome and epigenome editing has exploded in recent years. We can draw two important conclusions from this example of research history. First, evolution still is the better bioengineer than humans and, whenever tested in parallel, natural solutions outcompete engineered ones. Second, CRISPR/Cas system were discovered in pure, curiosity driven, basic research, highlighting that it is basic, bottom-up research paving the way for fundamental innovation. PMID:29434619

  3. New frontiers in gene targeting and cloning: success, application and challenges in domestic animals and human embryonic stem cells.

    PubMed

    Denning, Chris; Priddle, Helen

    2003-07-01

    Until recently, precise modification of the animal genome by gene targeting was restricted to the mouse because germline competent embryonic stem cells are not available in any other mammalian species. Nuclear transfer (NT) technology now provides an alternative route for cell-based transgenesis in domestic species, offering new opportunities in genetic modification. Livestock that produce human therapeutic proteins in their milk, have organs suitable for xenotransplantation, or that could provide resistance to diseases such as spongiform encephalopathies have been produced by NT from engineered, cultured somatic cells. However, improvements in the efficiency of somatic cell gene targeting and a greater understanding of the reprogramming events that occur during NT are required for the routine application of what is currently an inefficient process. The ability to reprogramme and genetically manipulate cells will also be crucial for full exploitation of human embryonic stem (hES) cells, which offer unparalleled opportunities in human health and biotechnology. Particularly pertinent are directed differentiation of hES lines to specific cell lineages, production of cells that evade the patient's immune system and ensuring the safety of ensuing transplants. This review will discuss some of the successes, applications and challenges facing gene targeting in livestock and hES cells.

  4. Virtual target tracking (VTT) as applied to mobile satellite communication networks

    NASA Astrophysics Data System (ADS)

    Amoozegar, Farid

    1999-08-01

    Traditionally, target tracking has been used for aerospace applications, such as, tracking highly maneuvering targets in a cluttered environment for missile-to-target intercept scenarios. Although the speed and maneuvering capability of current aerospace targets demand more efficient algorithms, many complex techniques have already been proposed in the literature, which primarily cover the defense applications of tracking methods. On the other hand, the rapid growth of Global Communication Systems, Global Information Systems (GIS), and Global Positioning Systems (GPS) is creating new and more diverse challenges for multi-target tracking applications. Mobile communication and computing can very well appreciate a huge market for Cellular Communication and Tracking Devices (CCTD), which will be tracking networked devices at the cellular level. The objective of this paper is to introduce a new concept, i.e., Virtual Target Tracking (VTT) for commercial applications of multi-target tracking algorithms and techniques as applied to mobile satellite communication networks. It would be discussed how Virtual Target Tracking would bring more diversity to target tracking research.

  5. Towards large scale multi-target tracking

    NASA Astrophysics Data System (ADS)

    Vo, Ba-Ngu; Vo, Ba-Tuong; Reuter, Stephan; Lam, Quang; Dietmayer, Klaus

    2014-06-01

    Multi-target tracking is intrinsically an NP-hard problem and the complexity of multi-target tracking solutions usually do not scale gracefully with problem size. Multi-target tracking for on-line applications involving a large number of targets is extremely challenging. This article demonstrates the capability of the random finite set approach to provide large scale multi-target tracking algorithms. In particular it is shown that an approximate filter known as the labeled multi-Bernoulli filter can simultaneously track one thousand five hundred targets in clutter on a standard laptop computer.

  6. Targeted nanosystems: Advances in targeted dendrimers for cancer therapy.

    PubMed

    Yang, Hu

    2016-02-01

    Dendrimers possess discrete highly compact nanostructures constituted of successive branched layers. Soon after the inception of dendrimers, recognition of their tunable structures and biologically favorable properties provoked a great enthusiasm in delving deeply into the utility of dendrimers for biomedical and pharmaceutical applications. One of the most important nanotechnology applications is the development of nanomedicines for targeted cancer therapies. Tremendous success in targeted therapies has been achieved with the use of dendrimer-based nanomedicines. This article provides a concise review on latest advances in the utility of dendrimers in immunotherapies and hormone therapies. Much basic and clinical research has been done since the invention of dendrimers, which are highly branched nano-sized molecules with the ability to act as carriers in nanomedicine. In this concise review article, the authors highlighted the current use of dendrimers in immunotherapies and hormone therapies in the fight against cancers. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Development and validation of the Italian version of the Mobile Application Rating Scale and its generalisability to apps targeting primary prevention.

    PubMed

    Domnich, Alexander; Arata, Lucia; Amicizia, Daniela; Signori, Alessio; Patrick, Bernard; Stoyanov, Stoyan; Hides, Leanne; Gasparini, Roberto; Panatto, Donatella

    2016-07-07

    A growing body of literature affirms the usefulness of mobile technologies, including mobile applications (apps), in the primary prevention field. The quality of health apps, which today number in the thousands, is a crucial parameter, as it may affect health-related decision-making and outcomes among app end-users. The mobile application rating scale (MARS) has recently been developed to evaluate the quality of such apps, and has shown good psychometric properties. Since there is no standardised tool for assessing the apps available in Italian app stores, the present study developed and validated an Italian version of MARS in apps targeting primary prevention. The original 23-item version of the MARS assesses mobile app quality in four objective quality dimensions (engagement, functionality, aesthetics, information) and one subjective dimension. Validation of this tool involved several steps; the universalist approach to achieving equivalence was adopted. Following two backward translations, a reconciled Italian version of MARS was produced and compared with the original scale. On the basis of sample size estimation, 48 apps from three major app stores were downloaded; the first 5 were used for piloting, while the remaining 43 were used in the main study in order to assess the psychometric properties of the scale. The apps were assessed by two raters, each working independently. The psychometric properties of the final version of the scale was assessed including the inter-rater reliability, internal consistency, convergent, divergent and concurrent validities. The intralingual equivalence of the Italian version of the MARS was confirmed by the authors of the original scale. A total of 43 apps targeting primary prevention were tested. The MARS displayed acceptable psychometric properties. The MARS total score showed an excellent level of both inter-rater agreement (intra-class correlation coefficient of .96) and internal consistency (Cronbach's α of .90 and .91

  8. Quantifying on- and off-target genome editing.

    PubMed

    Hendel, Ayal; Fine, Eli J; Bao, Gang; Porteus, Matthew H

    2015-02-01

    Genome editing with engineered nucleases is a rapidly growing field thanks to transformative technologies that allow researchers to precisely alter genomes for numerous applications including basic research, biotechnology, and human gene therapy. While the ability to make precise and controlled changes at specified sites throughout the genome has grown tremendously in recent years, we still lack a comprehensive and standardized battery of assays for measuring the different genome editing outcomes created at endogenous genomic loci. Here we review the existing assays for quantifying on- and off-target genome editing and describe their utility in advancing the technology. We also highlight unmet assay needs for quantifying on- and off-target genome editing outcomes and discuss their importance for the genome editing field. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. A structural biology perspective on bioactive small molecules and their plant targets.

    PubMed

    Kumari, Selva; van der Hoorn, Renier A L

    2011-10-01

    Structural biology efforts in recent years have generated numerous co-crystal structures of bioactive small molecules interacting with their plant targets. These studies include the targets of various phytohormones, pathogen-derived effectors, herbicides and other bioactive compounds. Here we discuss that this collection of structures contains excellent examples of nine collective observations: molecular glues, allostery, inhibitors, molecular mimicry, promiscuous binding sites, unexpected electron densities, natural selection at atomic resolution, and applications in structure-guided mutagenesis and small molecule design. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. The Research and Applications of Quantum Dots as Nano-Carriers for Targeted Drug Delivery and Cancer Therapy

    NASA Astrophysics Data System (ADS)

    Zhao, Mei-Xia; Zhu, Bing-Jie

    2016-04-01

    Quantum dots (QDs), nano-carriers for drugs, can help realize the targeting of drugs, and improve the bioavailability of drugs in biological fields. And, a QD nano-carrier system for drugs has the potential to realize early detection, monitoring, and localized treatments of specific disease sites. In addition, QD nano-carrier systems for drugs can improve stability of drugs, lengthen circulation time in vivo, enhance targeted absorption, and improve the distribution and metabolism process of drugs in organization. So, the development of QD nano-carriers for drugs has become a hotspot in the fields of nano-drug research in recent years. In this paper, we review the advantages and applications of the QD nano-carriers for drugs in biological fields.

  11. A programmable method for massively parallel targeted sequencing

    PubMed Central

    Hopmans, Erik S.; Natsoulis, Georges; Bell, John M.; Grimes, Susan M.; Sieh, Weiva; Ji, Hanlee P.

    2014-01-01

    We have developed a targeted resequencing approach referred to as Oligonucleotide-Selective Sequencing. In this study, we report a series of significant improvements and novel applications of this method whereby the surface of a sequencing flow cell is modified in situ to capture specific genomic regions of interest from a sample and then sequenced. These improvements include a fully automated targeted sequencing platform through the use of a standard Illumina cBot fluidics station. Targeting optimization increased the yield of total on-target sequencing data 2-fold compared to the previous iteration, while simultaneously increasing the percentage of reads that could be mapped to the human genome. The described assays cover up to 1421 genes with a total coverage of 5.5 Megabases (Mb). We demonstrate a 10-fold abundance uniformity of greater than 90% in 1 log distance from the median and a targeting rate of up to 95%. We also sequenced continuous genomic loci up to 1.5 Mb while simultaneously genotyping SNPs and genes. Variants with low minor allele fraction were sensitively detected at levels of 5%. Finally, we determined the exact breakpoint sequence of cancer rearrangements. Overall, this approach has high performance for selective sequencing of genome targets, configuration flexibility and variant calling accuracy. PMID:24782526

  12. Method calibration of the model 13145 infrared target projectors

    NASA Astrophysics Data System (ADS)

    Huang, Jianxia; Gao, Yuan; Han, Ying

    2014-11-01

    The SBIR Model 13145 Infrared Target Projectors ( The following abbreviation Evaluation Unit ) used for characterizing the performances of infrared imaging system. Test items: SiTF, MTF, NETD, MRTD, MDTD, NPS. Infrared target projectors includes two area blackbodies, a 12 position target wheel, all reflective collimator. It provide high spatial frequency differential targets, Precision differential targets imaged by infrared imaging system. And by photoelectricity convert on simulate signal or digital signal. Applications software (IR Windows TM 2001) evaluate characterizing the performances of infrared imaging system. With regards to as a whole calibration, first differently calibration for distributed component , According to calibration specification for area blackbody to calibration area blackbody, by means of to amend error factor to calibration of all reflective collimator, radiance calibration of an infrared target projectors using the SR5000 spectral radiometer, and to analyze systematic error. With regards to as parameter of infrared imaging system, need to integrate evaluation method. According to regulation with -GJB2340-1995 General specification for military thermal imaging sets -testing parameters of infrared imaging system, the results compare with results from Optical Calibration Testing Laboratory . As a goal to real calibration performances of the Evaluation Unit.

  13. Application of passive imaging polarimetry in the discrimination and detection of different color targets of identical shapes using color-blind imaging sensors

    NASA Astrophysics Data System (ADS)

    El-Saba, A. M.; Alam, M. S.; Surpanani, A.

    2006-05-01

    Important aspects of automatic pattern recognition systems are their ability to efficiently discriminate and detect proper targets with low false alarms. In this paper we extend the applications of passive imaging polarimetry to effectively discriminate and detect different color targets of identical shapes using color-blind imaging sensor. For this case of study we demonstrate that traditional color-blind polarization-insensitive imaging sensors that rely only on the spatial distribution of targets suffer from high false detection rates, especially in scenarios where multiple identical shape targets are present. On the other hand we show that color-blind polarization-sensitive imaging sensors can successfully and efficiently discriminate and detect true targets based on their color only. We highlight the main advantages of using our proposed polarization-encoded imaging sensor.

  14. Off-target effects of sulforaphane include the derepression of long terminal repeats through histone acetylation events.

    PubMed

    Baier, Scott R; Zbasnik, Richard; Schlegel, Vicki; Zempleni, Janos

    2014-06-01

    Sulforaphane is a naturally occurring isothiocyanate in cruciferous vegetables. Sulforaphane inhibits histone deacetylases, leading to the transcriptional activation of genes including tumor suppressor genes. The compound has attracted considerable attention in the chemoprevention of prostate cancer. Here we tested the hypothesis that sulforaphane is not specific for tumor suppressor genes but also activates loci such as long terminal repeats (LTRs), which might impair genome stability. Studies were conducted using chemically pure sulforaphane in primary human IMR-90 fibroblasts and in broccoli sprout feeding studies in healthy adults. Sulforaphane (2.0 μM) caused an increase in LTR transcriptional activity in cultured cells. Consumption of broccoli sprouts (34, 68 or 102 g) by human volunteers caused a dose dependent elevation in LTR mRNA in circulating leukocytes, peaking at more than a 10-fold increase. This increase in transcript levels was associated with an increase in histone H3 K9 acetylation marks in LTR 15 in peripheral blood mononuclear cells from subjects consuming sprouts. Collectively, this study suggests that sulforaphane has off-target effects that warrant further investigation when recommending high levels of sulforaphane intake, despite its promising activities in chemoprevention. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. 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.

  16. Audiovisual synchrony enhances BOLD responses in a brain network including multisensory STS while also enhancing target-detection performance for both modalities

    PubMed Central

    Marchant, Jennifer L; Ruff, Christian C; Driver, Jon

    2012-01-01

    The brain seeks to combine related inputs from different senses (e.g., hearing and vision), via multisensory integration. Temporal information can indicate whether stimuli in different senses are related or not. A recent human fMRI study (Noesselt et al. [2007]: J Neurosci 27:11431–11441) used auditory and visual trains of beeps and flashes with erratic timing, manipulating whether auditory and visual trains were synchronous or unrelated in temporal pattern. A region of superior temporal sulcus (STS) showed higher BOLD signal for the synchronous condition. But this could not be related to performance, and it remained unclear if the erratic, unpredictable nature of the stimulus trains was important. Here we compared synchronous audiovisual trains to asynchronous trains, while using a behavioral task requiring detection of higher-intensity target events in either modality. We further varied whether the stimulus trains had predictable temporal pattern or not. Synchrony (versus lag) between auditory and visual trains enhanced behavioral sensitivity (d') to intensity targets in either modality, regardless of predictable versus unpredictable patterning. The analogous contrast in fMRI revealed BOLD increases in several brain areas, including the left STS region reported by Noesselt et al. [2007: J Neurosci 27:11431–11441]. The synchrony effect on BOLD here correlated with the subject-by-subject impact on performance. Predictability of temporal pattern did not affect target detection performance or STS activity, but did lead to an interaction with audiovisual synchrony for BOLD in inferior parietal cortex. PMID:21953980

  17. 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.

  18. Prediction methodologies for target scene generation in the aerothermal targets analysis program (ATAP)

    NASA Astrophysics Data System (ADS)

    Hudson, Douglas J.; Torres, Manuel; Dougherty, Catherine; Rajendran, Natesan; Thompson, Rhoe A.

    2003-09-01

    The Air Force Research Laboratory (AFRL) Aerothermal Targets Analysis Program (ATAP) is a user-friendly, engineering-level computational tool that features integrated aerodynamics, six-degree-of-freedom (6-DoF) trajectory/motion, convective and radiative heat transfer, and thermal/material response to provide an optimal blend of accuracy and speed for design and analysis applications. ATAP is sponsored by the Kinetic Kill Vehicle Hardware-in-the-Loop Simulator (KHILS) facility at Eglin AFB, where it is used with the CHAMP (Composite Hardbody and Missile Plume) technique for rapid infrared (IR) signature and imagery predictions. ATAP capabilities include an integrated 1-D conduction model for up to 5 in-depth material layers (with options for gaps/voids with radiative heat transfer), fin modeling, several surface ablation modeling options, a materials library with over 250 materials, options for user-defined materials, selectable/definable atmosphere and earth models, multiple trajectory options, and an array of aerodynamic prediction methods. All major code modeling features have been validated with ground-test data from wind tunnels, shock tubes, and ballistics ranges, and flight-test data for both U.S. and foreign strategic and theater systems. Numerous applications include the design and analysis of interceptors, booster and shroud configurations, window environments, tactical missiles, and reentry vehicles.

  19. 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

  20. Liquid Biopsies in the Screening of Oncogenic Mutations in NSCLC and its Application in Targeted Therapy.

    PubMed

    Tang, Jason H; Chia, David

    2015-01-01

    Non-small cell lung cancer (NSCLC) still dominates cancer-related deaths in America. Despite this, new discoveries and advancements in technology are helping with the detection and treatment of NSCLC. The discovery of circulating tumor DNA in blood and other biofluids is essential for the creation of a DNA biomarker. Limitations in technology and sequencing have stunted assay development, but with recent advancements in the next-generation sequencing, droplet digital PCR, and EFIRM, the detection of mutations in biofluids has become possible with reasonable sensitivity and specificity. These methods have been applied to the detection of mutations in NSCLC by measuring the levels of circulating tumor DNA. ALK fusion genes along with mutations in EGFR and KRAS have been shown to correlate to tumor size and metastasis. These methods allow for noninvasive, affordable, and efficient diagnoses of oncogenic mutations that overcome the issues of traditional biopsies. These issues include tumor heterogeneity and early detection of cancers with asymptomatic early stages. Early detection and treatment remain the best way to ensure survival. This review aims to describe these new technologies along with their application in mutation detection in NSCLC in order to proactively utilize targeted anticancer therapy.

  1. Application of an Efficient Gene Targeting System Linking Secondary Metabolites to their Biosynthetic Genes in Aspergillus terreus

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

    Guo, Chun-Jun; Knox, Benjamin P.; Sanchez, James F.

    2013-07-19

    Nonribosomal peptides (NRPs) are natural products biosynthesized by NRP synthetases. A kusA-, pyrG- mutant strain of Aspergillusterreus NIH 2624 was developed that greatly facilitated the gene targeting efficiency in this organism. Application of this tool allowed us to link four major types of NRP related secondary metabolites to their responsible genes in A. terreus. In addition, an NRP related melanin synthetase was also identified in this species.

  2. Aptamer-conjugated nanomaterials and their applications

    PubMed Central

    Yang, Liu; Ye, Mao; Yang, Ronghua; Fu, Ting; Chen, Yan; Wang, Kemin

    2011-01-01

    The combination of aptamers with novel nanomaterials, including nanomaterial-based aptamer bioconjugates. has attracted considerable interest and has led to a wide variety of applications. In this review, we discuss how a variety of nanomaterials, including gold, silica and magnetic nanoparticles, as well as carbon nanotubes, hydrogels, liposomes and micelles, have been used to functionalize aptamers for a variety of applications. These aptamer functionalized materials have led to advances in amplified biosensing, cancer cell-specific recognition, high-efficiency separation, and targeted drug delivery. PMID:22016112

  3. Non-target effect of continuous application of chlorpyrifos on soil microbes, nematodes and its persistence under sub-humid tropical rice-rice cropping system.

    PubMed

    Kumar, Upendra; Berliner, J; Adak, Totan; Rath, Prakash C; Dey, Avro; Pokhare, Somnath S; Jambhulkar, Nitiprasad N; Panneerselvam, P; Kumar, Anjani; Mohapatra, Shyamranjan D

    2017-01-01

    Application of pesticide in agricultural fields is "unnecessary evil" for non-target microflora and fauna. Hence, to identify the safer pesticide molecules against non-target microbes, a long-term pesticide experiment was initiated at National Rice Research Institute, Cuttack, India. In the present study, the effect of continuous application of chlorpyrifos (0.5kgha -1 ) in rice fields on non-target groups of soil microbes and nematodes was studied for seven seasons (four wet and three dry seasons) during 2009-2013. Treatments were arranged in a randomized complete block design with four replications of chlorpyrifos-treated (0.5kg a.i. ha -1 ) (CT) and untreated control (UT) plots. During seven seasons of experimentation, regular application of chlorpyrifos had no significant effect on population of heterotrophic aerobic, anaerobic, oligotrophic and copiotrophic bacteria in CT compared to UT, whereas, population of asymbiotic aerobic nitrogen fixer, nitrifiers, denitrifiers, gram positive and spore-forming bacteria were significantly reduced by nearly 0.25-2 fold in CT than UT. However, comparatively less deviation in population of actinomycetes, fungi, phosphate solubilizing and sulfur oxidizing bacteria were observed in CT than UT. Significant interactions were found between effects of chlorpyrifos with time in population dynamics of microbes. In plant parasitic nematode species, Meloidogyne graminicola (RRKN) and Hirschmanniella spp. (RRN), were significantly lower (p<0.01) in CT compared to UT after first year onwards. The overall observation of five years data indicated that the RRKN population showed a decreasing trend (R 2 =0.644) whereas RRN showed increasing trend (R 2 =0.932) in CT. The drastic chlorpyrifos dissipation was noticed after 15 days of application from the initial residue of 0.25mgkg -1 soil, which indicated that chlorpyrifos residue in rice field soil was not persistent and its half-life was found to be 4.02 days. Overall, the present

  4. New targeted therapies for indolent B-cell malignancies in older patients.

    PubMed

    Krem, Maxwell M; Gopal, Ajay K

    2015-01-01

    Molecularly targeted agents have become an established component of the treatment of indolent B-cell malignancies (iNHL). iNHL disproportionately affects older adults, so treatments that have excellent tolerability and efficacy across multiple lines of therapy are in demand. The numbers and classes of targeted therapies for iNHL have proliferated rapidly in recent years; classes of agents that show promise for older patients with iNHL include anti-CD20 antibodies, phosphatidyl-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway inhibitors, immunomodulators, proteasome inhibitors, epigenetic modulators, and immunotherapies. Here, we review the proposed mechanisms of action, efficacy, and tolerability of novel agents for iNHL, with an emphasis on their applicability to older patients.

  5. 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.

  6. Microsatellites as targets of natural selection.

    PubMed

    Haasl, Ryan J; Payseur, Bret A

    2013-02-01

    The ability to survey polymorphism on a genomic scale has enabled genome-wide scans for the targets of natural selection. Theory that connects patterns of genetic variation to evidence of natural selection most often assumes a diallelic locus and no recurrent mutation. Although these assumptions are suitable to selection that targets single nucleotide variants, fundamentally different types of mutation generate abundant polymorphism in genomes. Moreover, recent empirical results suggest that mutationally complex, multiallelic loci including microsatellites and copy number variants are sometimes targeted by natural selection. Given their abundance, the lack of inference methods tailored to the mutational peculiarities of these types of loci represents a notable gap in our ability to interrogate genomes for signatures of natural selection. Previous theoretical investigations of mutation-selection balance at multiallelic loci include assumptions that limit their application to inference from empirical data. Focusing on microsatellites, we assess the dynamics and population-level consequences of selection targeting mutationally complex variants. We develop general models of a multiallelic fitness surface, a realistic model of microsatellite mutation, and an efficient simulation algorithm. Using these tools, we explore mutation-selection-drift equilibrium at microsatellites and investigate the mutational history and selective regime of the microsatellite that causes Friedreich's ataxia. We characterize microsatellite selective events by their duration and cost, note similarities to sweeps from standing point variation, and conclude that it is premature to label microsatellites as ubiquitous agents of efficient adaptive change. Together, our models and simulation algorithm provide a powerful framework for statistical inference, which can be used to test the neutrality of microsatellites and other multiallelic variants.

  7. Microsatellites as Targets of Natural Selection

    PubMed Central

    Haasl, Ryan J.; Payseur, Bret A.

    2013-01-01

    The ability to survey polymorphism on a genomic scale has enabled genome-wide scans for the targets of natural selection. Theory that connects patterns of genetic variation to evidence of natural selection most often assumes a diallelic locus and no recurrent mutation. Although these assumptions are suitable to selection that targets single nucleotide variants, fundamentally different types of mutation generate abundant polymorphism in genomes. Moreover, recent empirical results suggest that mutationally complex, multiallelic loci including microsatellites and copy number variants are sometimes targeted by natural selection. Given their abundance, the lack of inference methods tailored to the mutational peculiarities of these types of loci represents a notable gap in our ability to interrogate genomes for signatures of natural selection. Previous theoretical investigations of mutation-selection balance at multiallelic loci include assumptions that limit their application to inference from empirical data. Focusing on microsatellites, we assess the dynamics and population-level consequences of selection targeting mutationally complex variants. We develop general models of a multiallelic fitness surface, a realistic model of microsatellite mutation, and an efficient simulation algorithm. Using these tools, we explore mutation-selection-drift equilibrium at microsatellites and investigate the mutational history and selective regime of the microsatellite that causes Friedreich’s ataxia. We characterize microsatellite selective events by their duration and cost, note similarities to sweeps from standing point variation, and conclude that it is premature to label microsatellites as ubiquitous agents of efficient adaptive change. Together, our models and simulation algorithm provide a powerful framework for statistical inference, which can be used to test the neutrality of microsatellites and other multiallelic variants. PMID:23104080

  8. Developmental validation of a custom panel including 273 SNPs for forensic application using Ion Torrent PGM.

    PubMed

    Zhang, Suhua; Bian, Yingnan; Chen, Anqi; Zheng, Hancheng; Gao, Yuzhen; Hou, Yiping; Li, Chengtao

    2017-03-01

    Utilizing massively parallel sequencing (MPS) technology for SNP testing in forensic genetics is becoming attractive because of the shortcomings of STR markers, such as their high mutation rates and disadvantages associated with the current PCR-CE method as well as its limitations regarding multiplex capabilities. MPS offers the potential to genotype hundreds to thousands of SNPs from multiple samples in a single experimental run. In this study, we designed a customized SNP panel that includes 273 forensically relevant identity SNPs chosen from SNPforID, IISNP, and the HapMap database as well as previously related studies and evaluated the levels of genotyping precision, sequence coverage, sensitivity and SNP performance using the Ion Torrent PGM. In a concordant study of the custom MPS-SNP panel, only four MPS callings were missing due to coverage reads that were too low (<20), whereas the others were fully concordant with Sanger's sequencing results across the two control samples, that is, 9947A and 9948. The analyses indicated a balanced coverage among the included loci, with the exception of the 16 SNPs that were used to detect an inconsistent allele balance and/or lower coverage reads among 50 tested individuals from the Chinese HAN population and the above controls. With the exception of the 16 poorly performing SNPs, the sequence coverage obtained was extensive for the bulk of the SNPs, and only three Y-SNPs (rs16980601, rs11096432, rs3900) showed a mean coverage below 1000. Analyses of the dilution series of control DNA 9948 yielded reproducible results down to 1ng of DNA input. In addition, we provide an analysis tool for automated data quality control and genotyping checks, and we conclude that the SNP targets are polymorphic and independent in the Chinese HAN population. In summary, the evaluation of the sensitivity, accuracy and genotyping performance provides strong support for the application of MPS technology in forensic SNP analysis, and the assay

  9. 34 CFR 429.20 - What must an application include?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... ADULT EDUCATION, DEPARTMENT OF EDUCATION BILINGUAL VOCATIONAL MATERIALS, METHODS, AND TECHNIQUES PROGRAM... part must— (a) Describe the qualifications of staff responsible for the project; and (b) Provide that... supervision of the applicant. (Approved by the Office of Management and Budget under control number 1830-0013...

  10. 34 CFR 429.20 - What must an application include?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... ADULT EDUCATION, DEPARTMENT OF EDUCATION BILINGUAL VOCATIONAL MATERIALS, METHODS, AND TECHNIQUES PROGRAM... part must— (a) Describe the qualifications of staff responsible for the project; and (b) Provide that... supervision of the applicant. (Approved by the Office of Management and Budget under control number 1830-0013...

  11. Surface-modified gold nanorods for specific cell targeting

    NASA Astrophysics Data System (ADS)

    Wang, Chan-Ung; Arai, Yoshie; Kim, Insun; Jang, Wonhee; Lee, Seonghyun; Hafner, Jason H.; Jeoung, Eunhee; Jung, Deokho; Kwon, Youngeun

    2012-05-01

    Gold nanoparticles (GNPs) have unique properties that make them highly attractive materials for developing functional reagents for various biomedical applications including photothermal therapy, targeted drug delivery, and molecular imaging. For in vivo applications, GNPs need to be prepared with very little or negligible cytotoxicitiy. Most GNPs are, however, prepared using growth-directing surfactants such as cetyl trimethylammonium bromide (CTAB), which are known to have considerable cytotoxicity. In this paper, we describe an approach to remove CTAB to a non-toxic concentration. We optimized the conditions for surface modification with methoxypolyethylene glycol thiol (mPEG), which replaced CTAB and formed a protective layer on the surface of gold nanorods (GNRs). The cytotoxicities of pristine and surface-modified GNRs were measured in primary human umbilical vein endothelial cells and human cell lines derived from hepatic carcinoma cells, embryonic kidney cells, and thyroid papillary carcinoma cells. Cytotoxicity assays revealed that treating cells with GNRs did not significantly affect cell viability except for thyroid papillary carcinoma cells. Thyroid cancer cells were more susceptible to residual CTAB, so CTAB had to be further removed by dialysis in order to use GNRs for thyroid cell targeting. PEGylated GNRs are further modified to present monoclonal antibodies that recognize a specific surface marker, Na-I symporter, for thyroid cells. Antibody-conjugated GNRs specifically targeted human thyroid cells in vitro.

  12. Tandem application of ligand-based virtual screening and G4-OAS assay to identify novel G-quadruplex-targeting chemotypes.

    PubMed

    Musumeci, Domenica; Amato, Jussara; Zizza, Pasquale; Platella, Chiara; Cosconati, Sandro; Cingolani, Chiara; Biroccio, Annamaria; Novellino, Ettore; Randazzo, Antonio; Giancola, Concetta; Pagano, Bruno; Montesarchio, Daniela

    2017-05-01

    G-quadruplex (G4) structures are key elements in the regulation of cancer cell proliferation and their targeting is deemed to be a promising strategy in anticancer therapy. A tandem application of ligand-based virtual screening (VS) calculations together with the experimental G-quadruplex on Oligo Affinity Support (G4-OAS) assay was employed to discover novel G4-targeting compounds. The interaction of the selected compounds with the investigated G4 in solution was analysed through a series of biophysical techniques and their biological activity investigated by immunofluorescence and MTT assays. A focused library of 60 small molecules, designed as putative G4 groove binders, was identified through the VS. The G4-OAS experimental screening led to the selection of 7 ligands effectively interacting with the G4-forming human telomeric DNA. Evaluation of the biological activity of the selected compounds showed that 3 ligands of this sub-library induced a marked telomere-localized DNA damage response in human tumour cells. The combined application of virtual and experimental screening tools proved to be a successful strategy to identify new bioactive chemotypes able to target the telomeric G4 DNA. These compounds may represent useful leads for the development of more potent and selective G4 ligands. Expanding the repertoire of the available G4-targeting chemotypes with improved physico-chemical features, in particular aiming at the discovery of novel, selective G4 telomeric ligands, can help in developing effective anti-cancer drugs with fewer side effects. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Chemical Structural Novelty: On-Targets and Off-Targets

    PubMed Central

    Yera, Emmanuel R.; Cleves, Ann. E.; Jain, Ajay N.

    2011-01-01

    Drug structures may be quantitatively compared based on 2D topological structural considerations and based on 3D characteristics directly related to binding. A framework for combining multiple similarity computations is presented along with its systematic application to 358 drugs with overlapping pharmacology. Given a new molecule along with a set of molecules sharing some biological effect, a single score based on comparison to the known set is produced, reflecting either 2D similarity, 3D similarity, or their combination. For prediction of primary targets, the benefit of 3D over 2D was relatively small, but for prediction of off-targets, the added benefit was large. In addition to assessing prediction, the relationship between chemical similarity and pharmacological novelty was studied. Drug pairs that shared high 3D similarity but low 2D similarity (i.e. a novel scaffold) were shown to be much more likely to exhibit pharmacologically relevant differences in terms of specific protein target modulation. PMID:21916467

  14. Micro-channel-based high specific power lithium target

    NASA Astrophysics Data System (ADS)

    Mastinu, P.; Martın-Hernández, G.; Praena, J.; Gramegna, F.; Prete, G.; Agostini, P.; Aiello, A.; Phoenix, B.

    2016-11-01

    A micro-channel-based heat sink has been produced and tested. The device has been developed to be used as a Lithium target for the LENOS (Legnaro Neutron Source) facility and for the production of radioisotope. Nevertheless, applications of such device can span on many areas: cooling of electronic devices, diode laser array, automotive applications etc. The target has been tested using a proton beam of 2.8MeV energy and delivering total power shots from 100W to 1500W with beam spots varying from 5mm2 to 19mm2. Since the target has been designed to be used with a thin deposit of lithium and since lithium is a low-melting-point material, we have measured that, for such application, a specific power of about 3kW/cm2 can be delivered to the target, keeping the maximum surface temperature not exceeding 150° C.

  15. Identifying mechanism-of-action targets for drugs and probes

    PubMed Central

    Gregori-Puigjané, Elisabet; Setola, Vincent; Hert, Jérôme; Crews, Brenda A.; Irwin, John J.; Lounkine, Eugen; Marnett, Lawrence; Roth, Bryan L.; Shoichet, Brian K.

    2012-01-01

    Notwithstanding their key roles in therapy and as biological probes, 7% of approved drugs are purported to have no known primary target, and up to 18% lack a well-defined mechanism of action. Using a chemoinformatics approach, we sought to “de-orphanize” drugs that lack primary targets. Surprisingly, targets could be easily predicted for many: Whereas these targets were not known to us nor to the common databases, most could be confirmed by literature search, leaving only 13 Food and Drug Administration—approved drugs with unknown targets; the number of drugs without molecular targets likely is far fewer than reported. The number of worldwide drugs without reasonable molecular targets similarly dropped, from 352 (25%) to 44 (4%). Nevertheless, there remained at least seven drugs for which reasonable mechanism-of-action targets were unknown but could be predicted, including the antitussives clemastine, cloperastine, and nepinalone; the antiemetic benzquinamide; the muscle relaxant cyclobenzaprine; the analgesic nefopam; and the immunomodulator lobenzarit. For each, predicted targets were confirmed experimentally, with affinities within their physiological concentration ranges. Turning this question on its head, we next asked which drugs were specific enough to act as chemical probes. Over 100 drugs met the standard criteria for probes, and 40 did so by more stringent criteria. A chemical information approach to drug-target association can guide therapeutic development and reveal applications to probe biology, a focus of much current interest. PMID:22711801

  16. Application of Biodegradable Nanoparticles in Liver Targeting of Tacrolimus

    NASA Astrophysics Data System (ADS)

    Affifi, Nagia N.; Heikal, Ola A.; Hanafi, Rasha S.; Tammam, Salma N.

    2011-06-01

    Tacrolimus is a potent immunosuppressant used in liver transplantation to avoid graft rejection. Tacrolimus has a narrow therapeutic index and variable pharmacokinetics, making dose adjustment and therapeutic drug monitoring a complicated task. Increasing the occurrence of adverse effects, especially nephrotoxicity are another concerns. In graft rejection, antigen presentation occurs in the graft and lymphatics. Therefore, by targeting tacrolimus to the liver and spleen, graft survival could be achieved with a decrease in nephrotoxicity. Poly(lactide) tacrolimus nanoparticles (PLA-TAC-NP) were formulated and characterized with the aim of targeting tacrolimus to the liver and spleen and therefore decreasing its nephrotoxicity. To evaluate the targeting efficiency of PLA-TAC-NP, rats were divided into two groups. They were intravenously injected either PLA-TAC-NP or free tacrolimus. At assigned time intervals, blood, liver, spleen and kidney samples were collected from each rat. Drug extraction and HPLC analysis were used to evaluate tacrolimus tissue distribution and consequently the targeting efficiency of the prepared PLA-TAC-NP. PLA-TAC-NP proved their success in targeting liver and spleen, by showing significantly higher drug amounts compared to the rats injected with free tacrolimus. PLA-TAC-NP increased tacrolimus concentration in the liver 24 fold and in the spleen 1.94 fold whereas tacrolimus concentration in the kidneys decreased by 7.12 fold. Transmission electron microscopy (TEM) was used to examine a liver section, obtained from a rat that has received PLA-TAC-NP. TEM images showed PLA-TAC-NP in a Kupffer cell and in the liver sinusoids. Therefore, PLA-TAC-NP are promising drug delivery systems for achieving localized immunosuppression and minimizing nephrotoxicity in liver transplant patients.

  17. Challenges of Sustaining the International Space Station through 2020 and Beyond: Including Epistemic Uncertainty in Reassessing Confidence Targets

    NASA Technical Reports Server (NTRS)

    Anderson, Leif; Carter-Journet, Katrina; Box, Neil; DiFilippo, Denise; Harrington, Sean; Jackson, David; Lutomski, Michael

    2012-01-01

    This paper introduces an analytical approach, Probability and Confidence Trade-space (PACT), which can be used to assess uncertainty in International Space Station (ISS) hardware sparing necessary to extend the life of the vehicle. There are several key areas under consideration in this research. We investigate what sparing confidence targets may be reasonable to ensure vehicle survivability and for completion of science on the ISS. The results of the analysis will provide a methodological basis for reassessing vehicle subsystem confidence targets. An ongoing annual analysis currently compares the probability of existing spares exceeding the total expected unit demand of the Orbital Replacement Unit (ORU) in functional hierarchies approximating the vehicle subsystems. In cases where the functional hierarchies availability does not meet subsystem confidence targets, the current sparing analysis further identifies which ORUs may require additional spares to extend the life of the ISS. The resulting probability is dependent upon hardware reliability estimates. However, the ISS hardware fleet carries considerable epistemic uncertainty (uncertainty in the knowledge of the true hardware failure rate), which does not currently factor into the annual sparing analysis. The existing confidence targets may be conservative. This paper will also discuss how confidence targets may be relaxed based on the inclusion of epistemic uncertainty for each ORU. The paper will conclude with strengths and limitations for implementing the analytical approach in sustaining the ISS through end of life, 2020 and beyond.

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

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

    PubMed Central

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

    2009-01-01

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

  20. Applications for the MATILDA robotic platform

    NASA Astrophysics Data System (ADS)

    Munkeby, Steve H.; Jones, Don; Bugg, George; Smith, Kathryn

    2002-07-01

    Most robotic platforms have, up to this point, been designed with emphasis placed on improving mobility technologies. Minimal emphasis has been placed on payloads and mission execution. Using a top-down approach, Mesa Associates, Inc. identified specific UGV mission applications and structured its MATILDA platform using these applications for vehicle mobility and motion control requirements. Specific applications identified for the MATILDA platform include: Target surveillance, explosive device neutralization, material pickup and transport, weapon transport and firing, and law enforcement. Current performance results, lessons-learned, technical hurdles, and future applications are examined.

  1. Emerging preclinical pharmacological targets for Parkinson's disease

    PubMed Central

    More, Sandeep Vasant; Choi, Dong-Kug

    2016-01-01

    Parkinson's disease (PD) is a progressive neurological condition caused by the degeneration of dopaminergic neurons in the basal ganglia. It is the most prevalent form of Parkinsonism, categorized by cardinal features such as bradykinesia, rigidity, tremors, and postural instability. Due to the multicentric pathology of PD involving inflammation, oxidative stress, excitotoxicity, apoptosis, and protein aggregation, it has become difficult to pin-point a single therapeutic target and evaluate its potential application. Currently available drugs for treating PD provide only symptomatic relief and do not decrease or avert disease progression resulting in poor patient satisfaction and compliance. Significant amount of understanding concerning the pathophysiology of PD has offered a range of potential targets for PD. Several emerging targets including AAV-hAADC gene therapy, phosphodiesterase-4, potassium channels, myeloperoxidase, acetylcholinesterase, MAO-B, dopamine, A2A, mGlu5, and 5-HT-1A/1B receptors are in different stages of clinical development. Additionally, alternative interventions such as deep brain stimulation, thalamotomy, transcranial magnetic stimulation, and gamma knife surgery, are also being developed for patients with advanced PD. As much as these therapeutic targets hold potential to delay the onset and reverse the disease, more targets and alternative interventions need to be examined in different stages of PD. In this review, we discuss various emerging preclinical pharmacological targets that may serve as a new promising neuroprotective strategy that could actually help alleviate PD and its symptoms. PMID:26988916

  2. Tracking Multiple Video Targets with an Improved GM-PHD Tracker

    PubMed Central

    Zhou, Xiaolong; Yu, Hui; Liu, Honghai; Li, Youfu

    2015-01-01

    Tracking multiple moving targets from a video plays an important role in many vision-based robotic applications. In this paper, we propose an improved Gaussian mixture probability hypothesis density (GM-PHD) tracker with weight penalization to effectively and accurately track multiple moving targets from a video. First, an entropy-based birth intensity estimation method is incorporated to eliminate the false positives caused by noisy video data. Then, a weight-penalized method with multi-feature fusion is proposed to accurately track the targets in close movement. For targets without occlusion, a weight matrix that contains all updated weights between the predicted target states and the measurements is constructed, and a simple, but effective method based on total weight and predicted target state is proposed to search the ambiguous weights in the weight matrix. The ambiguous weights are then penalized according to the fused target features that include spatial-colour appearance, histogram of oriented gradient and target area and further re-normalized to form a new weight matrix. With this new weight matrix, the tracker can correctly track the targets in close movement without occlusion. For targets with occlusion, a robust game-theoretical method is used. Finally, the experiments conducted on various video scenarios validate the effectiveness of the proposed penalization method and show the superior performance of our tracker over the state of the art. PMID:26633422

  3. Glioblastoma multiforme targeted therapy: The Chlorotoxin story.

    PubMed

    Cohen-Inbar, Or; Zaaroor, Menashe

    2016-11-01

    Glioblastoma multiforme (GBM) is the most common malignant primary brain neoplasm having a mean survival of <24months. Scorpion toxins are considered promising cancer drug candidates, primarily due to the discovery of hlorotoxin, derived from the venom of the Israeli yellow scorpion. This intriguing short peptide of only 36 amino-acids length and tight configuration, possess the ability to bind to GBM cells in a grade-related manner with ∼100% of GBM cells staining positive and no cross reactivity to normal brain. Chlorotoxin has an anti-angiogenic effect as well. Molecular targets for Chlorotoxin include voltage gated chloride channels (GCC), calcium-dependent phospholipid-binding protein Annexin-2, and the inducible extracellular enzyme Matrix Metalloproteinase-2 (MMP-2). Of all its targets, MMP-2 seems to bear the most anti-neoplastic potential. Chlorotoxin is a promising tumortargeting peptide. Its small size and compact shape are convenient for intracranial delivery. We present a short discussion on Chlorotoxin. The structure, biological activity, molecular targets and possible clinical role of Chlorotoxin are discussed. Chlorotoxin can be utilized as a targeting domain as well, attaching different effector functions to it. Clinical applications in GBM therapy, intraoperative imaging, nano-probes and nano-vectors based technology; targeted chemotherapy and immunotherapy are discussed as well. Chlorotoxin is likely to play a significant role in effective GBM immunotherapy in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Enhancing and targeting nucleic acid delivery by magnetic force.

    PubMed

    Plank, Christian; Anton, Martina; Rudolph, Carsten; Rosenecker, Joseph; Krötz, Florian

    2003-08-01

    Insufficient contact of inherently highly active nucleic acid delivery systems with target cells is a primary reason for their often observed limited efficacy. Physical methods of targeting can overcome this limitation and reduce the risk of undesired side effects due to non-target site delivery. The authors and others have developed a novel means of physical targeting, exploiting magnetic force acting on nucleic acid vectors associated with magnetic particles in order to mediate the rapid contact of vectors with target cells. Here, the principles of magnetic drug and nucleic acid delivery are reviewed, and the facts and potentials of the technique for research and therapeutic applications are discussed. Magnetically enhanced nucleic acid delivery - magnetofection - is universally applicable to viral and non-viral vectors, is extraordinarily rapid, simple and yields saturation level transfection at low dose in vitro. The method is useful for site-specific vector targeting in vivo. Exploiting the full potential of the technique requires an interdisciplinary research effort in magnetic field physics, magnetic particle chemistry, pharmaceutical formulation and medical application.

  5. Target R and D for high power proton beam applications

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

    Fabich, A.

    High power targets are one of the major issues in an accelerator complex for future HEP physic studies. The paper will review status of studies worldwide. It will focus on the status of the MERIT mercury-jet target experiment at CERN.

  6. Targeted Nanomaterials for Phototherapy

    PubMed Central

    Chitgupi, Upendra; Qin, Yiru; Lovell, Jonathan F.

    2017-01-01

    Phototherapies involve the irradiation of target tissues with light. To further enhance selectivity and potency, numerous molecularly targeted photosensitizers and photoactive nanoparticles have been developed. Active targeting typically involves harnessing the affinity between a ligand and a cell surface receptor for improved accumulation in the targeted tissue. Targeting ligands including peptides, proteins, aptamers and small molecules have been explored for phototherapy. In this review, recent examples of targeted nanomaterials used in phototherapy are summarized. PMID:29071178

  7. A Targeting Microbubble for Ultrasound Molecular Imaging

    PubMed Central

    Yeh, James Shue-Min; Sennoga, Charles A.; McConnell, Ellen; Eckersley, Robert; Tang, Meng-Xing; Nourshargh, Sussan; Seddon, John M.; Haskard, Dorian O.; Nihoyannopoulos, Petros

    2015-01-01

    Rationale Microbubbles conjugated with targeting ligands are used as contrast agents for ultrasound molecular imaging. However, they often contain immunogenic (strept)avidin, which impedes application in humans. Although targeting bubbles not employing the biotin-(strept)avidin conjugation chemistry have been explored, only a few reached the stage of ultrasound imaging in vivo, none were reported/evaluated to show all three of the following properties desired for clinical applications: (i) low degree of non-specific bubble retention in more than one non-reticuloendothelial tissue; (ii) effective for real-time imaging; and (iii) effective for acoustic quantification of molecular targets to a high degree of quantification. Furthermore, disclosures of the compositions and methodologies enabling reproduction of the bubbles are often withheld. Objective To develop and evaluate a targeting microbubble based on maleimide-thiol conjugation chemistry for ultrasound molecular imaging. Methods and Results Microbubbles with a previously unreported generic (non-targeting components) composition were grafted with anti-E-selectin F(ab’)2 using maleimide-thiol conjugation, to produce E-selectin targeting microbubbles. The resulting targeting bubbles showed high specificity to E-selectin in vitro and in vivo. Non-specific bubble retention was minimal in at least three non-reticuloendothelial tissues with inflammation (mouse heart, kidneys, cremaster). The bubbles were effective for real-time ultrasound imaging of E-selectin expression in the inflamed mouse heart and kidneys, using a clinical ultrasound scanner. The acoustic signal intensity of the targeted bubbles retained in the heart correlated strongly with the level of E-selectin expression (|r|≥0.8), demonstrating a high degree of non-invasive molecular quantification. Conclusions Targeting microbubbles for ultrasound molecular imaging, based on maleimide-thiol conjugation chemistry and the generic composition described

  8. Non-target organism effects tests on Vip3A and their application to the ecological risk assessment for cultivation of MIR162 maize.

    PubMed

    Raybould, Alan; Vlachos, Demetra

    2011-06-01

    Transgenic crops producing insecticidal proteins from Bacillus thuringiensis (Bt) provide economic, environmental and health benefits by maintaining or increasing crop yields with fewer applications of insecticide. To sustain these benefits, it is important to delay the evolution of insect resistance to the proteins, and to ensure that the proteins do not harm non-target organisms, particularly those that may control secondary pests that would otherwise flourish because of reduced insecticide applications. Vip3A is a Bt vegetative insecticidal protein that is active against lepidopterous pests. It has a different mode of action from other proteins for control of Lepidoptera in current Bt crops, and when combined with these proteins, it should help to delay the evolution of pest resistance to Bt crops. This paper presents data on the effects of Vip3A on non-target organisms, and an ecological risk assessment of MIR162 maize, which expresses Vip3Aa20. Laboratory studies indicate few adverse effects of Vip3A to non-target organisms: 11 of 12 species tested showed no adverse effects when exposed to high concentrations of Vip3A relative to estimated exposures resulting from cultivation of MIR162 maize. Daphnia magna exposed to Vip3Aa20 were unaffected in terms of survival or fecundity, but grew slightly more slowly than unexposed controls. The data indicate that cultivation of MIR162 maize poses negligible risk to non-target organisms, and that crops producing Vip3A are unlikely to adversely affect biological control organisms such that benefits from reduced insecticide applications are lost.

  9. Effective treatment of glioblastoma requires crossing the blood–brain barrier and targeting tumors including cancer stem cells: The promise of nanomedicine

    PubMed Central

    Kim, Sang-Soo; Harford, Joe B.; Pirollo, Kathleen F.; Chang, Esther H.

    2015-01-01

    Glioblastoma multiforme (GBM) is the most aggressive and lethal type of brain tumor. Both therapeutic resistance and restricted permeation of drugs across the blood–brain barrier (BBB) play a major role in the poor prognosis of GBM patients. Accumulated evidence suggests that in many human cancers, including GBM, therapeutic resistance can be attributed to a small fraction of cancer cells known as cancer stem cells (CSCs). CSCs have been shown to have stem cell-like properties that enable them to evade traditional cytotoxic therapies, and so new CSC-directed anti-cancer therapies are needed. Nanoparticles have been designed to selectively deliver payloads to relevant target cells in the body, and there is considerable interest in the use of nanoparticles for CSC-directed anti-cancer therapies. Recent advances in the field of nanomedicine offer new possibilities for overcoming CSC-mediated therapeutic resistance and thus significantly improving management of GBM. In this review, we will examine the current nanomedicine approaches for targeting CSCs and their therapeutic implications. The inhibitory effect of various nanoparticle-based drug delivery system towards CSCs in GBM tumors is the primary focus of this review. PMID:26116770

  10. Detection and identification of human targets in radar data

    NASA Astrophysics Data System (ADS)

    Gürbüz, Sevgi Z.; Melvin, William L.; Williams, Douglas B.

    2007-04-01

    Radar offers unique advantages over other sensors, such as visual or seismic sensors, for human target detection. Many situations, especially military applications, prevent the placement of video cameras or implantment seismic sensors in the area being observed, because of security or other threats. However, radar can operate far away from potential targets, and functions during daytime as well as nighttime, in virtually all weather conditions. In this paper, we examine the problem of human target detection and identification using single-channel, airborne, synthetic aperture radar (SAR). Human targets are differentiated from other detected slow-moving targets by analyzing the spectrogram of each potential target. Human spectrograms are unique, and can be used not just to identify targets as human, but also to determine features about the human target being observed, such as size, gender, action, and speed. A 12-point human model, together with kinematic equations of motion for each body part, is used to calculate the expected target return and spectrogram. A MATLAB simulation environment is developed including ground clutter, human and non-human targets for the testing of spectrogram-based detection and identification algorithms. Simulations show that spectrograms have some ability to detect and identify human targets in low noise. An example gender discrimination system correctly detected 83.97% of males and 91.11% of females. The problems and limitations of spectrogram-based methods in high clutter environments are discussed. The SNR loss inherent to spectrogram-based methods is quantified. An alternate detection and identification method that will be used as a basis for future work is proposed.

  11. A manifold learning approach to target detection in high-resolution hyperspectral imagery

    NASA Astrophysics Data System (ADS)

    Ziemann, Amanda K.

    Imagery collected from airborne platforms and satellites provide an important medium for remotely analyzing the content in a scene. In particular, the ability to detect a specific material within a scene is of high importance to both civilian and defense applications. This may include identifying "targets" such as vehicles, buildings, or boats. Sensors that process hyperspectral images provide the high-dimensional spectral information necessary to perform such analyses. However, for a d-dimensional hyperspectral image, it is typical for the data to inherently occupy an m-dimensional space, with m << d. In the remote sensing community, this has led to a recent increase in the use of manifold learning, which aims to characterize the embedded lower-dimensional, non-linear manifold upon which the hyperspectral data inherently lie. Classic hyperspectral data models include statistical, linear subspace, and linear mixture models, but these can place restrictive assumptions on the distribution of the data; this is particularly true when implementing traditional target detection approaches, and the limitations of these models are well-documented. With manifold learning based approaches, the only assumption is that the data reside on an underlying manifold that can be discretely modeled by a graph. The research presented here focuses on the use of graph theory and manifold learning in hyperspectral imagery. Early work explored various graph-building techniques with application to the background model of the Topological Anomaly Detection (TAD) algorithm, which is a graph theory based approach to anomaly detection. This led towards a focus on target detection, and in the development of a specific graph-based model of the data and subsequent dimensionality reduction using manifold learning. An adaptive graph is built on the data, and then used to implement an adaptive version of locally linear embedding (LLE). We artificially induce a target manifold and incorporate it into

  12. 29 CFR 2570.34 - Information to be included in every exemption application.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... knowledge and belief, the representations made in such statement are true and correct. (c) An application... with the matters discussed in this application and, to the best of my knowledge and belief, the representations made in this application are true and correct. (ii) This declaration must be dated and signed by...

  13. 13 CFR 123.402 - Can your business include its relocation as a mitigation measure in an application for a pre...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... relocation as a mitigation measure in an application for a pre-disaster mitigation loan? 123.402 Section 123.402 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Pre-Disaster Mitigation Loans § 123.402 Can your business include its relocation as a mitigation measure in an application...

  14. 13 CFR 123.402 - Can your business include its relocation as a mitigation measure in an application for a pre...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... relocation as a mitigation measure in an application for a pre-disaster mitigation loan? 123.402 Section 123.402 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Pre-Disaster Mitigation Loans § 123.402 Can your business include its relocation as a mitigation measure in an application...

  15. 13 CFR 123.402 - Can your business include its relocation as a mitigation measure in an application for a pre...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... relocation as a mitigation measure in an application for a pre-disaster mitigation loan? 123.402 Section 123.402 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Pre-Disaster Mitigation Loans § 123.402 Can your business include its relocation as a mitigation measure in an application...

  16. 13 CFR 123.402 - Can your business include its relocation as a mitigation measure in an application for a pre...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... relocation as a mitigation measure in an application for a pre-disaster mitigation loan? 123.402 Section 123.402 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Pre-Disaster Mitigation Loans § 123.402 Can your business include its relocation as a mitigation measure in an application...

  17. 75 FR 28280 - Deadline for Submission of Applications To Be Included on the Roll of Western Shoshone...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-20

    ... Included on the Roll of Western Shoshone Identifiable Group of Indians for Judgment Fund Distribution... Western Shoshone Identifiable Group of Indians in Docket No. 326-K. DATES: Applications must be received... the judgment funds awarded by the Indian Claims Commission to the Western Shoshone Identifiable Group...

  18. New Methods for Targeted Alpha Radiotherapy

    NASA Astrophysics Data System (ADS)

    Robertson, J. David

    2014-03-01

    Targeted radiotherapies based on alpha emitters are a promising alternative to beta emitting radionuclides. Because of their much shorter range, targeted α-radiotherapy (TAT) agents have great potential for application to small, disseminated tumors and micro metastases and treatment of hematological malignancies consisting of individual, circulating neoplastic cells. A promising approach to TAT is the use of the in vivo α-generator radionuclides 223 = 11.4 d) and 225Ac 1/2 = 10.0 d). In addition to their longer half-lives, these two isotopes have the potential of dramatically increasing the therapeutic efficacy of TAT as they each emit four α particles in their decay chain. This principle has recently been exploited in the development of Xofigo®, the first TAT agent approved for clinical use by the U.S. FDA. Xofigo, formulated as 223RaCl2, is used for treatment of metastatic bone cancer in men with castration-resistant prostate cancer. TAT with 223Ra works, however, only in the case of bone cancer because radium, as a chemical analogue of calcium, efficiently targets bone. In order to bring the benefits of TAT with 223Ra or 225Ac to other tumor types, a new delivery method must be devised. Retaining the in vivo α generator radionuclides at the target site through the decay process is one of the major challenges associated with the development of TAT. Because the recoil energy of the daughter radionuclides from the α-emission is ~ 100 keV - a value which is four orders of magnitude greater than the energy of a covalent bond - the daughters will not remain bound to the bioconjugate at the targeting site. Various approaches have been attempted to achieve retention of the α-generator daughter radionuclides at the target site, including incorporation of the in vivo generator into liposomes and fullerenes. Unfortunately, to date single wall liposomes and fullerenes are able to retain less than 10% of the daughter radionuclides. We have recently demonstrated that a

  19. Combined targeting of lentiviral vectors and positioning of transduced cells by magnetic nanoparticles

    PubMed Central

    Hofmann, Andreas; Wenzel, Daniela; Becher, Ulrich M.; Freitag, Daniel F.; Klein, Alexandra M.; Eberbeck, Dietmar; Schulte, Maike; Zimmermann, Katrin; Bergemann, Christian; Gleich, Bernhard; Roell, Wilhelm; Weyh, Thomas; Trahms, Lutz; Nickenig, Georg; Fleischmann, Bernd K.; Pfeifer, Alexander

    2009-01-01

    Targeting of viral vectors is a major challenge for in vivo gene delivery, especially after intravascular application. In addition, targeting of the endothelium itself would be of importance for gene-based therapies of vascular disease. Here, we used magnetic nanoparticles (MNPs) to combine cell transduction and positioning in the vascular system under clinically relevant, nonpermissive conditions, including hydrodynamic forces and hypothermia. The use of MNPs enhanced transduction efficiency of endothelial cells and enabled direct endothelial targeting of lentiviral vectors (LVs) by magnetic force, even in perfused vessels. In addition, application of external magnetic fields to mice significantly changed LV/MNP biodistribution in vivo. LV/MNP-transduced cells exhibited superparamagnetic behavior as measured by magnetorelaxometry, and they were efficiently retained by magnetic fields. The magnetic interactions were strong enough to position MNP-containing endothelial cells at the intima of vessels under physiological flow conditions. Importantly, magnetic positioning of MNP-labeled cells was also achieved in vivo in an injury model of the mouse carotid artery. Intravascular gene targeting can be combined with positioning of the transduced cells via nanomagnetic particles, thereby combining gene- and cell-based therapies. PMID:19118196

  20. Combined targeting of lentiviral vectors and positioning of transduced cells by magnetic nanoparticles.

    PubMed

    Hofmann, Andreas; Wenzel, Daniela; Becher, Ulrich M; Freitag, Daniel F; Klein, Alexandra M; Eberbeck, Dietmar; Schulte, Maike; Zimmermann, Katrin; Bergemann, Christian; Gleich, Bernhard; Roell, Wilhelm; Weyh, Thomas; Trahms, Lutz; Nickenig, Georg; Fleischmann, Bernd K; Pfeifer, Alexander

    2009-01-06

    Targeting of viral vectors is a major challenge for in vivo gene delivery, especially after intravascular application. In addition, targeting of the endothelium itself would be of importance for gene-based therapies of vascular disease. Here, we used magnetic nanoparticles (MNPs) to combine cell transduction and positioning in the vascular system under clinically relevant, nonpermissive conditions, including hydrodynamic forces and hypothermia. The use of MNPs enhanced transduction efficiency of endothelial cells and enabled direct endothelial targeting of lentiviral vectors (LVs) by magnetic force, even in perfused vessels. In addition, application of external magnetic fields to mice significantly changed LV/MNP biodistribution in vivo. LV/MNP-transduced cells exhibited superparamagnetic behavior as measured by magnetorelaxometry, and they were efficiently retained by magnetic fields. The magnetic interactions were strong enough to position MNP-containing endothelial cells at the intima of vessels under physiological flow conditions. Importantly, magnetic positioning of MNP-labeled cells was also achieved in vivo in an injury model of the mouse carotid artery. Intravascular gene targeting can be combined with positioning of the transduced cells via nanomagnetic particles, thereby combining gene- and cell-based therapies.

  1. Legume Lectins: Proteins with Diverse Applications

    PubMed Central

    Lagarda-Diaz, Irlanda; Guzman-Partida, Ana Maria; Vazquez-Moreno, Luz

    2017-01-01

    Lectins are a diverse class of proteins distributed extensively in nature. Among these proteins; legume lectins display a variety of interesting features including antimicrobial; insecticidal and antitumor activities. Because lectins recognize and bind to specific glycoconjugates present on the surface of cells and intracellular structures; they can serve as potential target molecules for developing practical applications in the fields of food; agriculture; health and pharmaceutical research. This review presents the current knowledge of the main structural characteristics of legume lectins and the relationship of structure to the exhibited specificities; provides an overview of their particular antimicrobial; insecticidal and antitumor biological activities and describes possible applications based on the pattern of recognized glyco-targets. PMID:28604616

  2. SECOND TARGET STATION MODERATOR PERFORMANCE WITH A ROTATING TARGET

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

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

    2016-01-01

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

  3. Targeting c-Met in Cancer by MicroRNAs: Potential Therapeutic Applications in Hepatocellular Carcinoma.

    PubMed

    Karagonlar, Zeynep F; Korhan, Peyda; Atabey, Neşe

    2015-11-01

    Preclinical Research Cancer is one of the world's deadliest diseases, with very low survival rates and increased occurrence in the future. Successfully developed target-based therapies have significantly changed cancer treatment. However, primary and/or acquired resistance in the tumor is a major challenge in current therapies and novel combinational therapies are required. RNA interference-mediated gene inactivation, alone or in combination with other current therapies, provides novel promising therapeutics that can improve cure rate and overcome resistance mechanisms to conventional therapeutics. Hepatocyte Growth Factor/c-Met signaling is one of the most frequently dysregulated pathways in human cancers and abnormal c-Met activation is correlated with poor clinical outcomes and drug resistance in hepatocellular carcinoma (HCC). In recent years, a growing number of studies have identified several inhibitors and microRNAs (miRNAs), specifically targeting c-Met in various cancers, including HCC. In this review, we discuss current knowledge regarding miRNAs, focusing on their involvement in cancer and their potential as research tools and therapeutics. Then, we focus on the potential use of c-Met targeting miRNAs for suppressing aberrant c-Met signaling in HCC treatment. © 2015 Wiley Periodicals, Inc.

  4. FIBER LASER CONSTRUCTION AND THEORY INCLUDING FIBER BRAGG GRATINGS Photonic Crystal Fibers (PCFs) and applications of gas filled PCFs

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

    Sutton, Jacob O.

    The principles used in fiber lasers have been around for a while but it is only within the past few years that fiber lasers have become commercially available and used in high power laser applications. This paper will focus on the basic design principles of fiber lasers, including fiber Bragg gratings, principles of operation, and forms of non-linear effects. It will describe the type and associated doping of the fiber used and difficult designs used to guide energy from the pump to the active medium. Topics covered include fiber laser design, fiber Bragg gratings, materials used, differences in quantum energymore » loss, thermo-optical effects, stimulated Raman scattering, Brillouin scattering, photonic crystal fibers and applications of gas filled Photonic Crystal Fibers (PCFs). Thanks to fiber lasers, the energy required to produce high power lasers has greatly dropped and as such we can now produce kW power using a standard 120V 15A circuit. High power laser applications are always requiring more power. The fiber laser can now deliver the greater power that these applications demand. Future applications requiring more power than can be combined using standard materials or configurations will need to be developed to overcome the high energy density and high non-linear optical scattering effects present during high power operations.« less

  5. Application of three-dimensional printing for colon targeted drug delivery systems

    PubMed Central

    Charbe, Nitin B.; McCarron, Paul A.; Lane, Majella E.; Tambuwala, Murtaza M.

    2017-01-01

    Orally administered solid dosage forms currently dominate over all other dosage forms and routes of administrations. However, human gastrointestinal tract (GIT) poses a number of obstacles to delivery of the drugs to the site of interest and absorption in the GIT. Pharmaceutical scientists worldwide have been interested in colon drug delivery for several decades, not only for the delivery of the drugs for the treatment of colonic diseases such as ulcerative colitis and colon cancer but also for delivery of therapeutic proteins and peptides for systemic absorption. Despite extensive research in the area of colon targeted drug delivery, we have not been able to come up with an effective way of delivering drugs to the colon. The current tablets designed for colon drug release depend on either pH-dependent or time-delayed release formulations. During ulcerative colitis the gastric transit time and colon pH-levels is constantly changing depending on whether the patient is having a relapse or under remission. Hence, the current drug delivery system to the colon is based on one-size-fits-all. Fails to effectively deliver the drugs locally to the colon for colonic diseases and delivery of therapeutic proteins and peptides for systemic absorption from the colon. Hence, to overcome the current issues associated with colon drug delivery, we need to provide the patients with personalized tablets which are specifically designed to match the individual's gastric transit time depending on the disease state. Three-dimensional (3D) printing (3DP) technology is getting cheaper by the day and bespoke manufacturing of 3D-printed tablets could provide the solutions in the form of personalized colon drug delivery system. This review provides a bird's eye view of applications and current advances in pharmaceutical 3DP with emphasis on the development of colon targeted drug delivery systems. PMID:28929046

  6. Application of three-dimensional printing for colon targeted drug delivery systems.

    PubMed

    Charbe, Nitin B; McCarron, Paul A; Lane, Majella E; Tambuwala, Murtaza M

    2017-01-01

    Orally administered solid dosage forms currently dominate over all other dosage forms and routes of administrations. However, human gastrointestinal tract (GIT) poses a number of obstacles to delivery of the drugs to the site of interest and absorption in the GIT. Pharmaceutical scientists worldwide have been interested in colon drug delivery for several decades, not only for the delivery of the drugs for the treatment of colonic diseases such as ulcerative colitis and colon cancer but also for delivery of therapeutic proteins and peptides for systemic absorption. Despite extensive research in the area of colon targeted drug delivery, we have not been able to come up with an effective way of delivering drugs to the colon. The current tablets designed for colon drug release depend on either pH-dependent or time-delayed release formulations. During ulcerative colitis the gastric transit time and colon pH-levels is constantly changing depending on whether the patient is having a relapse or under remission. Hence, the current drug delivery system to the colon is based on one-size-fits-all. Fails to effectively deliver the drugs locally to the colon for colonic diseases and delivery of therapeutic proteins and peptides for systemic absorption from the colon. Hence, to overcome the current issues associated with colon drug delivery, we need to provide the patients with personalized tablets which are specifically designed to match the individual's gastric transit time depending on the disease state. Three-dimensional (3D) printing (3DP) technology is getting cheaper by the day and bespoke manufacturing of 3D-printed tablets could provide the solutions in the form of personalized colon drug delivery system. This review provides a bird's eye view of applications and current advances in pharmaceutical 3DP with emphasis on the development of colon targeted drug delivery systems.

  7. Centredale Manor Superfund Site in Rhode Island included on EPA List of Targeted for Immediate Attention

    EPA Pesticide Factsheets

    Today, the U.S. Environmental Protection Agency released the list of Superfund sites that Administrator Pruitt has targeted for immediate and intense attention. The Centredale Manor Restoration Project superfund site is one of the 21 sites on the list.

  8. Signaling completion of a message transfer from an origin compute node to a target compute node

    DOEpatents

    Blocksome, Michael A [Rochester, MN; Parker, Jeffrey J [Rochester, MN

    2011-05-24

    Signaling completion of a message transfer from an origin node to a target node includes: sending, by an origin DMA engine, an RTS message, the RTS message specifying an application message for transfer to the target node from the origin node; receiving, by the origin DMA engine, a remote get message containing a data descriptor for the message and a completion notification descriptor, the completion notification descriptor specifying a local direct put transfer operation for transferring data locally on the origin node; inserting, by the origin DMA engine in an injection FIFO buffer, the data descriptor followed by the completion notification descriptor; transferring, by the origin DMA engine to the target node, the message in dependence upon the data descriptor; and notifying, by the origin DMA engine, the application that transfer of the message is complete in dependence upon the completion notification descriptor.

  9. Current progress on aptamer-targeted oligonucleotide therapeutics

    PubMed Central

    Dassie, Justin P; Giangrande, Paloma H

    2014-01-01

    Exploiting the power of the RNAi pathway through the use of therapeutic siRNA drugs has remarkable potential for treating a vast array of human disease conditions. However, difficulties in delivery of these and similar nucleic acid-based pharmacological agents to appropriate organs or tissues, remains a major impediment to their broad clinical application. Synthetic nucleic acid ligands (aptamers) have emerged as effective delivery vehicles for therapeutic oligonucleotides, including siRNAs. In this review, we summarize recent attractive developments in creatively employing cell-internalizing aptamers to deliver therapeutic oligonucleotides (e.g., siRNAs, miRNAs, anti-miRs and antisense oligos) to target cells. We also discuss advancements in aptamer-siRNA chimera technology, as well as, aptamer-functionalized nanoparticles for siRNA delivery. In addition, the challenges and future prospects of aptamer-targeted oligonucleotide drugs for clinical translation are further highlighted. PMID:24304250

  10. Applicator for in-vitro ultrasound-activated targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Gerold, B.; Gourevich, D.; Volovick, A.; Xu, D.; Arditti, F.; Prentice, P.; Cochran, S.; Gnaim, J.; Medan, Y.; Wang, L.; Melzer, A.

    2012-10-01

    Reducing toxicity and improving uptake of cancer drugs in tumors are important goals of targeted drug delivery (TDD). Ultrasonic drug release from various encapsulants has been a focus of many research groups. However, a single standard ultrasonic device, viable for use by biologists, is not currently present in the market. The device reported here is designed to allow investigation of the impact of ultrasound on cellular uptake and cell viability in-vitro. In it, single-element transducers with different operating frequencies are mounted below a standard 96-well plate. The plate is moved above the transducers, such that each line of wells can be sonicated at a different frequency. To assess the device, 96-well plates were seeded with cells and sonicated using different ultrasonic parameters, with and without doxorubicin. Cell viability was measured by colorimetric MTT assay and the uptake of doxorubicin by cells was also determined. The device proved to be highly viable in preliminary tests; it demonstrated that change in ultrasonic parameters produces different effect on cells. For example, increase in uptake of doxorubicin was demonstrated following ultrasound application. The growing interest in ultrasound-activated TDD emphasizes the need for standardization of the ultrasound device and the one reported here may offer some indications of how that may be achieved. It is planned to further improve the prototype by increasing the number of ultrasonic frequencies and degrees of freedom for each transducer.

  11. 30 CFR 250.1727 - What information must I include in my final application to remove a platform or other facility?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ....125. If you are proposing to use explosives, provide three copies of the application. If you are not proposing to use explosives, provide two copies of the application. Include the following information in the... use; (2) If you are using explosives, the following: (i) Type of explosives; (ii) Number and sizes of...

  12. 30 CFR 250.1727 - What information must I include in my final application to remove a platform or other facility?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... listed in § 250.125. If you are proposing to use explosives, provide three copies of the application. If you are not proposing to use explosives, provide two copies of the application. Include the following... will use; (2) If you are using explosives, the following: (i) Type of explosives; (ii) Number and sizes...

  13. 30 CFR 250.1727 - What information must I include in my final application to remove a platform or other facility?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ....125. If you are proposing to use explosives, provide three copies of the application. If you are not proposing to use explosives, provide two copies of the application. Include the following information in the... use; (2) If you are using explosives, the following: (i) Type of explosives; (ii) Number and sizes of...

  14. 30 CFR 250.1727 - What information must I include in my final application to remove a platform or other facility?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ....125. If you are proposing to use explosives, provide three copies of the application. If you are not proposing to use explosives, provide two copies of the application. Include the following information in the... use; (2) If you are using explosives, the following: (i) Type of explosives; (ii) Number and sizes of...

  15. SAR and LIDAR fusion: experiments and applications

    NASA Astrophysics Data System (ADS)

    Edwards, Matthew C.; Zaugg, Evan C.; Bradley, Joshua P.; Bowden, Ryan D.

    2013-05-01

    In recent years ARTEMIS, Inc. has developed a series of compact, versatile Synthetic Aperture Radar (SAR) systems which have been operated on a variety of small manned and unmanned aircraft. The multi-frequency-band SlimSAR has demonstrated a variety of capabilities including maritime and littoral target detection, ground moving target indication, polarimetry, interferometry, change detection, and foliage penetration. ARTEMIS also continues to build upon the radar's capabilities through fusion with other sensors, such as electro-optical and infrared camera gimbals and light detection and ranging (LIDAR) devices. In this paper we focus on experiments and applications employing SAR and LIDAR fusion. LIDAR is similar to radar in that it transmits a signal which, after being reflected or scattered by a target area, is recorded by the sensor. The differences are that a LIDAR uses a laser as a transmitter and optical sensors as a receiver, and the wavelengths used exhibit a very different scattering phenomenology than the microwaves used in radar, making SAR and LIDAR good complementary technologies. LIDAR is used in many applications including agriculture, archeology, geo-science, and surveying. Some typical data products include digital elevation maps of a target area and features and shapes extracted from the data. A set of experiments conducted to demonstrate the fusion of SAR and LIDAR data include a LIDAR DEM used in accurately processing the SAR data of a high relief area (mountainous, urban). Also, feature extraction is used in improving geolocation accuracy of the SAR and LIDAR data.

  16. Magnetic microgels for drug targeting applications: Physical-chemical properties and cytotoxicity evaluation

    NASA Astrophysics Data System (ADS)

    Turcu, Rodica; Craciunescu, Izabell; Garamus, Vasil M.; Janko, Christina; Lyer, Stefan; Tietze, Rainer; Alexiou, Christoph; Vekas, Ladislau

    2015-04-01

    Magnetoresponsive microgels with high saturation magnetization values have been obtained by a strategy based on the miniemulsion method using high colloidal stability organic carrier ferrofluid as primary material. Hydrophobic nanoparticles Fe3O4/oleic acid are densely packed into well-defined spherical nanoparticle clusters coated with polymers with sizes in the range 40-350 nm. Physical-chemical characteristics of magnetic microgels were investigated by TEM, SAXS, XPS and VSM measurements with the focus on the structure-properties relationship. The impact of magnetic microgels loaded with anticancer drug mitoxantrone (MTO) on the non-adherent human T cell leukemia line Jurkat was investigated in multiparameter flow cytometry. We showed that both MTO and microgel-loaded MTO penetrate into cells and both induce apoptosis and later secondary necrosis in a time- and dose dependent manner. In contrast, microgels without MTO are not cytotoxic in the corresponding concentrations. Our results show that MTO-loaded microgels are promising structures for application in magnetic drug targeting.

  17. Magnetically attached sputter targets

    DOEpatents

    Makowiecki, Daniel M.; McKernan, Mark A.

    1994-01-01

    An improved method and assembly for attaching sputtering targets to cathode assemblies of sputtering systems which includes a magnetically permeable material. The magnetically permeable material is imbedded in a target base that is brazed, welded, or soldered to the sputter target, or is mechanically retained in the target material. Target attachment to the cathode is achieved by virtue of the permanent magnets and/or the pole pieces in the cathode assembly that create magnetic flux lines adjacent to the backing plate, which strongly attract the magnetically permeable material in the target assembly.

  18. A review of mobile applications to help adolescent and young adult cancer patients

    PubMed Central

    Wesley, Kimberly M; Fizur, Philip J

    2015-01-01

    Objective To review research articles utilizing mobile applications with adolescent and young adult (AYA) cancer patients. Materials and methods We identified articles via online searches and reference lists (eg, PsycInfo, PubMed). Articles were reviewed by two study team members for target population, stated purpose, technological utilization, sample size, demographic characteristics, and outcome data. Strengths and weaknesses of each study were described. Results Of 19 identified manuscripts, six met full inclusion criteria for this review (four smartphone applications and two tablet applications). One additional article that included an application not specific to oncology but included AYA patients with cancer within the target sample was also reviewed. Uses of these applications included symptom tracking, pain management, monitoring of eating habits following bone marrow transplant, monitoring of mucositis, and improving medication management. Utility results from pilot studies are presented. Conclusion Mobile applications are growing in number and increasingly available to AYAs with and without chronic illness. These applications may prove useful in helping to support AYAs throughout their cancer treatment and beyond. However, few applications provide empirical data supporting their utility. Numerous strengths and benefits of these applications include increased accessibility to educational resources and self-management strategies, more frequent physical and emotional symptom tracking, and increased access to peer support. Despite these strengths, numerous limitations are identified, highlighting the need for future research in this area. PMID:26316835

  19. Development of Bone Targeting Drugs.

    PubMed

    Stapleton, Molly; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J; Mackenzie, William G; Mason, Robert W; Orii, Tadao; Tomatsu, Shunji

    2017-06-23

    The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca 2+ . The strategies for designing such targeting moieties can involve synthetic and/or biological components including negatively-charged amino acid peptides or bisphosphonates. Efficient delivery of bone-specific drugs provides significant impact in the treatment of skeletal related disorders including infectious diseases (osteoarthritis, osteomyelitis, etc.), osteoporosis, and metabolic skeletal dysplasia. Despite recent advances, however, both delivering the drug to its target without losing activity and avoiding adverse local effects remain a challenge. In this review, we investigate the current development of bone-targeting moieties, their efficacy and limitations, and discuss future directions for the development of these specific targeted treatments.

  20. Development of Bone Targeting Drugs

    PubMed Central

    Stapleton, Molly; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J.; Mackenzie, William G.; Mason, Robert W.; Orii, Tadao; Tomatsu, Shunji

    2017-01-01

    The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca2+. The strategies for designing such targeting moieties can involve synthetic and/or biological components including negatively-charged amino acid peptides or bisphosphonates. Efficient delivery of bone-specific drugs provides significant impact in the treatment of skeletal related disorders including infectious diseases (osteoarthritis, osteomyelitis, etc.), osteoporosis, and metabolic skeletal dysplasia. Despite recent advances, however, both delivering the drug to its target without losing activity and avoiding adverse local effects remain a challenge. In this review, we investigate the current development of bone-targeting moieties, their efficacy and limitations, and discuss future directions for the development of these specific targeted treatments. PMID:28644392

  1. Identification of tissue-specific targeting peptide

    NASA Astrophysics Data System (ADS)

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

    2012-11-01

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

  2. Nuclear Security: Target Analysis-rev

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

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

    2014-03-01

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

  3. Rapid computational identification of the targets of protein kinase inhibitors.

    PubMed

    Rockey, William M; Elcock, Adrian H

    2005-06-16

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

  4. Small-Molecule Binding Aptamers: Selection Strategies, Characterization, and Applications

    PubMed Central

    Ruscito, Annamaria; DeRosa, Maria C.

    2016-01-01

    Aptamers are single-stranded, synthetic oligonucleotides that fold into 3-dimensional shapes capable of binding non-covalently with high affinity and specificity to a target molecule. They are generated via an in vitro process known as the Systematic Evolution of Ligands by EXponential enrichment, from which candidates are screened and characterized, and then used in various applications. These applications range from therapeutic uses to biosensors for target detection. Aptamers for small molecule targets such as toxins, antibiotics, molecular markers, drugs, and heavy metals will be the focus of this review. Their accurate detection is needed for the protection and wellbeing of humans and animals. However, the small molecular weights of these targets, including the drastic size difference between the target and the oligonucleotides, make it challenging to select, characterize, and apply aptamers for their detection. Thus, recent (since 2012) notable advances in small molecule aptamers, which have overcome some of these challenges, are presented here, while defining challenges that still exist are discussed. PMID:27242994

  5. Small molecules targeting heterotrimeric G proteins.

    PubMed

    Ayoub, Mohammed Akli

    2018-05-05

    G protein-coupled receptors (GPCRs) represent the largest family of cell surface receptors regulating many human and animal physiological functions. Their implication in human pathophysiology is obvious with almost 30-40% medical drugs commercialized today directly targeting GPCRs as molecular entities. However, upon ligand binding GPCRs signal inside the cell through many key signaling, adaptor and regulatory proteins, including various classes of heterotrimeric G proteins. Therefore, G proteins are considered interesting targets for the development of pharmacological tools that are able to modulate their interaction with the receptors, as well as their activation/deactivation processes. In this review, old attempts and recent advances in the development of small molecules that directly target G proteins will be described with an emphasis on their utilization as pharmacological tools to dissect the mechanisms of activation of GPCR-G protein complexes. These molecules constitute a further asset for research in the "hot" areas of GPCR biology, areas such as multiple G protein coupling/signaling, GPCR-G protein preassembly, and GPCR functional selectivity or bias. Moreover, this review gives a particular focus on studies in vitro and in vivo supporting the potential applications of such small molecules in various GPCR/G protein-related diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Folic acid-functionalized up-conversion nanoparticles: toxicity studies in vivo and in vitro and targeted imaging applications

    NASA Astrophysics Data System (ADS)

    Sun, Lining; Wei, Zuwu; Chen, Haige; Liu, Jinliang; Guo, Jianjian; Cao, Ming; Wen, Tieqiao; Shi, Liyi

    2014-07-01

    Folate receptors (FRs) are overexpressed on a variety of human cancer cells and tissues, including cancers of the breast, ovaries, endometrium, and brain. This over-expression of FRs can be used to target folate-linked imaging specifically to FR-expressing tumors. Fluorescence is emerging as a powerful new modality for molecular imaging in both the diagnosis and treatment of disease. Combining innovative molecular biology and chemistry, we prepared three kinds of folate-targeted up-conversion nanoparticles as imaging agents (UCNC-FA: UCNC-Er-FA, UCNC-Tm-FA, and UCNC-Er,Tm-FA). In vivo and in vitro toxicity studies showed that these nanoparticles have both good biocompatibility and low toxicity. Moreover, the up-conversion luminescence imaging indicated that they have good targeting to HeLa cells and can therefore serve as potential fluorescent contrast agents.Folate receptors (FRs) are overexpressed on a variety of human cancer cells and tissues, including cancers of the breast, ovaries, endometrium, and brain. This over-expression of FRs can be used to target folate-linked imaging specifically to FR-expressing tumors. Fluorescence is emerging as a powerful new modality for molecular imaging in both the diagnosis and treatment of disease. Combining innovative molecular biology and chemistry, we prepared three kinds of folate-targeted up-conversion nanoparticles as imaging agents (UCNC-FA: UCNC-Er-FA, UCNC-Tm-FA, and UCNC-Er,Tm-FA). In vivo and in vitro toxicity studies showed that these nanoparticles have both good biocompatibility and low toxicity. Moreover, the up-conversion luminescence imaging indicated that they have good targeting to HeLa cells and can therefore serve as potential fluorescent contrast agents. Electronic supplementary information (ESI) available: Up-conversion luminescence spectra of UCNC-Er and UCNC-Er-FA, UCNC-Tm and UCNC-Tm-FA. Confocal luminescence imaging data collected as a series along the Z optical axis. See DOI: 10.1039/c4nr02312a

  7. Biocompatible PEGylated gold nanorods as colored contrast agents for targeted in vivo cancer applications

    NASA Astrophysics Data System (ADS)

    Kopwitthaya, Atcha; Yong, Ken-Tye; Hu, Rui; Roy, Indrajit; Ding, Hong; Vathy, Lisa A.; Bergey, Earl J.; Prasad, Paras N.

    2010-08-01

    In this contribution, we report the use of a PEGylated gold nanorods formulation as a colored dye for tumor labeling in vivo. We have demonstrated that the nanorod-targeted tumor site can be easily differentiated from the background tissues by the 'naked eye' without the need of sophisticated imaging instruments. In addition to tumor labeling, we have also performed in vivo toxicity and biodistribution studies of PEGylated gold nanorods in vivo by using BALB/c mice as the model. In vivo toxicity studies indicated no mortality or adverse effects or weight changes in BALB/c mice treated with PEGylated gold nanorods. This finding will provide useful guidelines in the future development of diagnostic probes for cancer diagnosis, optically guided tumor surgery, and lymph node mapping applications.

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

    PubMed

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

    2011-04-01

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

  9. Integrin Targeted MR Imaging

    PubMed Central

    Tan, Mingqian; Lu, Zheng-Rong

    2011-01-01

    Magnetic resonance imaging (MRI) is a powerful medical diagnostic imaging modality for integrin targeted imaging, which uses the magnetic resonance of tissue water protons to display tissue anatomic structures with high spatial resolution. Contrast agents are often used in MRI to highlight specific regions of the body and make them easier to visualize. There are four main classes of MRI contrast agents based on their different contrast mechanisms, including T1, T2, chemical exchange saturation transfer (CEST) agents, and heteronuclear contrast agents. Integrins are an important family of heterodimeric transmembrane glycoproteins that function as mediators of cell-cell and cell-extracellular matrix interactions. The overexpressed integrins can be used as the molecular targets for designing suitable integrin targeted contrast agents for MR molecular imaging. Integrin targeted contrast agent includes a targeting agent specific to a target integrin, a paramagnetic agent and a linker connecting the targeting agent with the paramagnetic agent. Proper selection of targeting agents is critical for targeted MRI contrast agents to effectively bind to integrins for in vivo imaging. An ideal integrin targeted MR contrast agent should be non-toxic, provide strong contrast enhancement at the target sites and can be completely excreted from the body after MR imaging. An overview of integrin targeted MR contrast agents based on small molecular and macromolecular Gd(III) complexes, lipid nanoparticles and superparamagnetic nanoparticles is provided for MR molecular imaging. By using proper delivery systems for loading sufficient Gd(III) chelates or superparamagnetic nanoparticles, effective molecular imaging of integrins with MRI has been demonstrated in animal models. PMID:21547154

  10. Improved decision making for prioritizing tumor targeting antibodies in human xenografts: Utility of fluorescence imaging to verify tumor target expression, antibody binding and optimization of dosage and application schedule.

    PubMed

    Dobosz, Michael; Haupt, Ute; Scheuer, Werner

    2017-01-01

    Preclinical efficacy studies of antibodies targeting a tumor-associated antigen are only justified when the expression of the relevant antigen has been demonstrated. Conventionally, antigen expression level is examined by immunohistochemistry of formalin-fixed paraffin-embedded tumor tissue section. This method represents the diagnostic "gold standard" for tumor target evaluation, but is affected by a number of factors, such as epitope masking and insufficient antigen retrieval. As a consequence, variances and discrepancies in histological staining results can occur, which may influence decision-making and therapeutic outcome. To overcome these problems, we have used different fluorescence-labeled therapeutic antibodies targeting human epidermal growth factor receptor (HER) family members and insulin-like growth factor-1 receptor (IGF1R) in combination with fluorescence imaging modalities to determine tumor antigen expression, drug-target interaction, and biodistribution and tumor saturation kinetics in non-small cell lung cancer xenografts. For this, whole-body fluorescence intensities of labeled antibodies, applied as a single compound or antibody mixture, were measured in Calu-1 and Calu-3 tumor-bearing mice, then ex vivo multispectral tumor tissue analysis at microscopic resolution was performed. With the aid of this simple and fast imaging method, we were able to analyze the tumor cell receptor status of HER1-3 and IGF1R, monitor the antibody-target interaction and evaluate the receptor binding sites of anti-HER2-targeting antibodies. Based on this, the most suitable tumor model, best therapeutic antibody, and optimal treatment dosage and application schedule was selected. Predictions drawn from obtained imaging data were in excellent concordance with outcome of conducted preclinical efficacy studies. Our results clearly demonstrate the great potential of combined in vivo and ex vivo fluorescence imaging for the preclinical development and characterization of

  11. Discovering Targets of Non-enzymatic Acylation by Thioester Reactivity Profiling | Center for Cancer Research

    Cancer.gov

    The cover image illuminates the non-enzymatic “ghost writers” of lysine acylation. Meier et al. detail the development of a chemoproteomic strategy that harnesses thioester reactivity to discover candidate cellular targets of non-enzymatic acylation. Application of this approach reveals that glycolytic enzymes can be strongly inhibited by reactive thioesters, including the

  12. Bypassing Protein Corona Issue on Active Targeting: Zwitterionic Coatings Dictate Specific Interactions of Targeting Moieties and Cell Receptors.

    PubMed

    Safavi-Sohi, Reihaneh; Maghari, Shokoofeh; Raoufi, Mohammad; Jalali, Seyed Amir; Hajipour, Mohammad J; Ghassempour, Alireza; Mahmoudi, Morteza

    2016-09-07

    Surface functionalization strategies for targeting nanoparticles (NP) to specific organs, cells, or organelles, is the foundation for new applications of nanomedicine to drug delivery and biomedical imaging. Interaction of NPs with biological media leads to the formation of a biomolecular layer at the surface of NPs so-called as "protein corona". This corona layer can shield active molecules at the surface of NPs and cause mistargeting or unintended scavenging by the liver, kidney, or spleen. To overcome this corona issue, we have designed biotin-cysteine conjugated silica NPs (biotin was employed as a targeting molecule and cysteine was used as a zwitterionic ligand) to inhibit corona-induced mistargeting and thus significantly enhance the active targeting capability of NPs in complex biological media. To probe the targeting yield of our engineered NPs, we employed both modified silicon wafer substrates with streptavidin (i.e., biotin receptor) to simulate a target and a cell-based model platform using tumor cell lines that overexpress biotin receptors. In both cases, after incubation with human plasma (thus forming a protein corona), cellular uptake/substrate attachment of the targeted NPs with zwitterionic coatings were significantly higher than the same NPs without zwitterionic coating. Our results demonstrated that NPs with a zwitterionic surface can considerably facilitate targeting yield of NPs and provide a promising new type of nanocarriers in biological applications.

  13. Magnetically attached sputter targets

    DOEpatents

    Makowiecki, D.M.; McKernan, M.A.

    1994-02-15

    An improved method and assembly for attaching sputtering targets to cathode assemblies of sputtering systems which includes a magnetically permeable material is described. The magnetically permeable material is imbedded in a target base that is brazed, welded, or soldered to the sputter target, or is mechanically retained in the target material. Target attachment to the cathode is achieved by virtue of the permanent magnets and/or the pole pieces in the cathode assembly that create magnetic flux lines adjacent to the backing plate, which strongly attract the magnetically permeable material in the target assembly. 11 figures.

  14. Evaluation of targeted exome sequencing for 28 protein-based blood group systems, including the homologous gene systems, for blood group genotyping.

    PubMed

    Schoeman, Elizna M; Lopez, Genghis H; McGowan, Eunike C; Millard, Glenda M; O'Brien, Helen; Roulis, Eileen V; Liew, Yew-Wah; Martin, Jacqueline R; McGrath, Kelli A; Powley, Tanya; Flower, Robert L; Hyland, Catherine A

    2017-04-01

    Blood group single nucleotide polymorphism genotyping probes for a limited range of polymorphisms. This study investigated whether massively parallel sequencing (also known as next-generation sequencing), with a targeted exome strategy, provides an extended blood group genotype and the extent to which massively parallel sequencing correctly genotypes in homologous gene systems, such as RH and MNS. Donor samples (n = 28) that were extensively phenotyped and genotyped using single nucleotide polymorphism typing, were analyzed using the TruSight One Sequencing Panel and MiSeq platform. Genes for 28 protein-based blood group systems, GATA1, and KLF1 were analyzed. Copy number variation analysis was used to characterize complex structural variants in the GYPC and RH systems. The average sequencing depth per target region was 66.2 ± 39.8. Each sample harbored on average 43 ± 9 variants, of which 10 ± 3 were used for genotyping. For the 28 samples, massively parallel sequencing variant sequences correctly matched expected sequences based on single nucleotide polymorphism genotyping data. Copy number variation analysis defined the Rh C/c alleles and complex RHD hybrids. Hybrid RHD*D-CE-D variants were correctly identified, but copy number variation analysis did not confidently distinguish between D and CE exon deletion versus rearrangement. The targeted exome sequencing strategy employed extended the range of blood group genotypes detected compared with single nucleotide polymorphism typing. This single-test format included detection of complex MNS hybrid cases and, with copy number variation analysis, defined RH hybrid genes along with the RHCE*C allele hitherto difficult to resolve by variant detection. The approach is economical compared with whole-genome sequencing and is suitable for a red blood cell reference laboratory setting. © 2017 AABB.

  15. Targeted eco-pharmacovigilance for ketoprofen in the environment: Need, strategy and challenge.

    PubMed

    Wang, Jun; Zhao, Shu-Qi; Zhang, Meng-Ya; He, Bing-Shu

    2018-03-01

    Implementing "targeted" eco-pharmacovigilance(EPV) which focuses on individual or specific pharmaceuticals on a prioritised basis is a feasible, economical and customized approach to reduce the environmental concentrations and risks of pharmaceuticals. Non-steroidal anti-inflammatory drugs(NSAIDs) remaining in environment are a kind of priority hazard substances, due to a notable case that diclofenac residues caused the loss of more than 99% of vultures across the Indian sub-continent. Ketoprofen, as another widely used NSAID with comparable or even higher global consumption than diclofenac, in the environment has been shown to present a potential risk to non-target terrestrial and aquatic species. Based on the review of 85 articles reporting the analyses of ketoprofen residues in environment since 2010, we found that this NSAID frequently present in various environmental compartments around the world. Therefore, it is urgent to implement EPV targeting ketoprofen pollution. Here, we provide some recommendations for implementing the targeted EPV for ketoprofen, including: Closely monitoring ketoprofen in the natural environment; Reducing the residues of ketoprofen through source control; Encouraging urine source separation and treatment; Limiting the application of veterinary ketoprofen; Designing and constituting a framework system of targeted EPV. But some challenges, such as ambiguity in the accountability of the main bodies responsible for continued monitoring of ketoprofen residues, the lack of optimized urine source separation scenarios and procedure, the need for detailed design and application schemes of the framework system of targeted EPV, etc. should be addressed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Value-focused framework for defining landscape-scale conservation targets

    USGS Publications Warehouse

    Romañach, Stephanie; Benscoter, Allison M.; Brandt, Laura A.

    2016-01-01

    Conservation of natural resources can be challenging in a rapidly changing world and require collaborative efforts for success. Conservation planning is the process of deciding how to protect, conserve, and enhance or minimize loss of natural and cultural resources. Establishing conservation targets (also called indicators or endpoints), the measurable expressions of desired resource conditions, can help with site-specific up to landscape-scale conservation planning. Using conservation targets and tracking them through time can deliver benefits such as insight into ecosystem health and providing early warnings about undesirable trends. We describe an approach using value-focused thinking to develop statewide conservation targets for Florida. Using such an approach allowed us to first identify stakeholder objectives and then define conservation targets to meet those objectives. Stakeholders were able to see how their shared efforts fit into the broader conservation context, and also anticipate the benefits of multi-agency and -organization collaboration. We developed an iterative process for large-scale conservation planning that included defining a shared framework for the process, defining the conservation targets themselves, as well as developing management and monitoring strategies for evaluation of their effectiveness. The process we describe is applicable to other geographies where multiple parties are seeking to implement collaborative, large-scale biological planning.

  17. Camouflage target detection via hyperspectral imaging plus information divergence measurement

    NASA Astrophysics Data System (ADS)

    Chen, Yuheng; Chen, Xinhua; Zhou, Jiankang; Ji, Yiqun; Shen, Weimin

    2016-01-01

    Target detection is one of most important applications in remote sensing. Nowadays accurate camouflage target distinction is often resorted to spectral imaging technique due to its high-resolution spectral/spatial information acquisition ability as well as plenty of data processing methods. In this paper, hyper-spectral imaging technique together with spectral information divergence measure method is used to solve camouflage target detection problem. A self-developed visual-band hyper-spectral imaging device is adopted to collect data cubes of certain experimental scene before spectral information divergences are worked out so as to discriminate target camouflage and anomaly. Full-band information divergences are measured to evaluate target detection effect visually and quantitatively. Information divergence measurement is proved to be a low-cost and effective tool for target detection task and can be further developed to other target detection applications beyond spectral imaging technique.

  18. Abasic pivot substitution harnesses target specificity of RNA interference

    PubMed Central

    Lee, Hye-Sook; Seok, Heeyoung; Lee, Dong Ha; Ham, Juyoung; Lee, Wooje; Youm, Emilia Moonkyung; Yoo, Jin Seon; Lee, Yong-Seung; Jang, Eun-Sook; Chi, Sung Wook

    2015-01-01

    Gene silencing via RNA interference inadvertently represses hundreds of off-target transcripts. Because small interfering RNAs (siRNAs) can function as microRNAs, avoiding miRNA-like off-target repression is a major challenge. Functional miRNA–target interactions are known to pre-require transitional nucleation, base pairs from position 2 to the pivot (position 6). Here, by substituting nucleotide in pivot with abasic spacers, which prevent base pairing and alleviate steric hindrance, we eliminate miRNA-like off-target repression while preserving on-target activity at ∼80–100%. Specifically, miR-124 containing dSpacer pivot substitution (6pi) loses seed-mediated transcriptome-wide target interactions, repression activity and biological function, whereas other conventional modifications are ineffective. Application of 6pi allows PCSK9 siRNA to efficiently lower plasma cholesterol concentration in vivo, and abolish potentially deleterious off-target phenotypes. The smallest spacer, C3, also shows the same improvement in target specificity. Abasic pivot substitution serves as a general means to harness the specificity of siRNA experiments and therapeutic applications. PMID:26679372

  19. Novel application of brain-targeting polyphenol compounds in sleep deprivation-induced cognitive dysfunction

    PubMed Central

    Zhao, Wei; Wang, Jun; Bi, Weina; Ferruzzi, Mario; Yemul, Shrishailam; Freire, Daniel; Mazzola, Paolo; Ho, Lap; Dubner, Lauren; Pasinetti, Giulio Maria

    2016-01-01

    Sleep deprivation produces deficits in hippocampal synaptic plasticity and hippocampal-dependent memory storage. Recent evidence suggests that sleep deprivation disrupts memory consolidation through multiple mechanisms, including the down-regulation of the cAMP-response element-binding protein (CREB) and of mammalian target of rapamycin (mTOR) signaling. In this study, we tested the effects of a Bioactive Dietary Polyphenol Preparation (BDPP), comprised of grape seed polyphenol extract, Concord grape juice, and resveratrol, on the attenuation of sleep deprivation-induced cognitive impairment. We found that BDPP significantly improves sleep deprivation-induced contextual memory deficits, possibly through the activation of CREB and mTOR signaling pathways. We also identified brain-available polyphenol metabolites from BDPP, among which quercetin-3-O-glucuronide activates CREB signaling and malvidin-3-O-glucoside activates mTOR signaling. In combination, quercetin and malvidin-glucoside significantly attenuated sleep deprivation-induced cognitive impairment in -a mouse model of acute sleep deprivation. Our data suggests the feasibility of using select brain-targeting polyphenol compounds derived from BDPP as potential therapeutic agents in promoting resilience against sleep deprivation-induced cognitive dysfunction. PMID:26235983

  20. Signaling completion of a message transfer from an origin compute node to a target compute node

    DOEpatents

    Blocksome, Michael A [Rochester, MN

    2011-02-15

    Signaling completion of a message transfer from an origin node to a target node includes: sending, by an origin DMA engine, an RTS message, the RTS message specifying an application message for transfer to the target node from the origin node; receiving, by the origin DMA engine, a remote get message containing a data descriptor for the message and a completion notification descriptor, the completion notification descriptor specifying a local memory FIFO data transfer operation for transferring data locally on the origin node; inserting, by the origin DMA engine in an injection FIFO buffer, the data descriptor followed by the completion notification descriptor; transferring, by the origin DMA engine to the target node, the message in dependence upon the data descriptor; and notifying, by the origin DMA engine, the application that transfer of the message is complete in dependence upon the completion notification descriptor.

  1. Reverse screening methods to search for the protein targets of chemopreventive compounds

    NASA Astrophysics Data System (ADS)

    Huang, Hongbin; Zhang, Guigui; Zhou, Yuquan; Lin, Chenru; Chen, Suling; Lin, Yutong; Mai, Shangkang; Huang, Zunnan

    2018-05-01

    This article is a systematic review of reverse screening methods used to search for the protein targets of chemopreventive compounds or drugs. Typical chemopreventive compounds include components of traditional Chinese medicine, natural compounds and Food and Drug Administration (FDA)-approved drugs. Such compounds are somewhat selective but are predisposed to bind multiple protein targets distributed throughout diverse signaling pathways in human cells. In contrast to conventional virtual screening, which identifies the ligands of a targeted protein from a compound database, reverse screening is used to identify the potential targets or unintended targets of a given compound from a large number of receptors by examining their known ligands or crystal structures. This method, also known as in silico or computational target fishing, is highly valuable for discovering the target receptors of query molecules from terrestrial or marine natural products, exploring the molecular mechanisms of chemopreventive compounds, finding alternative indications of existing drugs by drug repositioning, and detecting adverse drug reactions and drug toxicity. Reverse screening can be divided into three major groups: shape screening, pharmacophore screening and reverse docking. Several large software packages, such as Schrödinger and Discovery Studio; typical software/network services such as ChemMapper, PharmMapper, idTarget and INVDOCK; and practical databases of known target ligands and receptor crystal structures, such as ChEMBL, BindingDB and the Protein Data Bank (PDB), are available for use in these computational methods. Different programs, online services and databases have different applications and constraints. Here, we conducted a systematic analysis and multilevel classification of the computational programs, online services and compound libraries available for shape screening, pharmacophore screening and reverse docking to enable non-specialist users to quickly learn and

  2. Reverse Screening Methods to Search for the Protein Targets of Chemopreventive Compounds.

    PubMed

    Huang, Hongbin; Zhang, Guigui; Zhou, Yuquan; Lin, Chenru; Chen, Suling; Lin, Yutong; Mai, Shangkang; Huang, Zunnan

    2018-01-01

    This article is a systematic review of reverse screening methods used to search for the protein targets of chemopreventive compounds or drugs. Typical chemopreventive compounds include components of traditional Chinese medicine, natural compounds and Food and Drug Administration (FDA)-approved drugs. Such compounds are somewhat selective but are predisposed to bind multiple protein targets distributed throughout diverse signaling pathways in human cells. In contrast to conventional virtual screening, which identifies the ligands of a targeted protein from a compound database, reverse screening is used to identify the potential targets or unintended targets of a given compound from a large number of receptors by examining their known ligands or crystal structures. This method, also known as in silico or computational target fishing, is highly valuable for discovering the target receptors of query molecules from terrestrial or marine natural products, exploring the molecular mechanisms of chemopreventive compounds, finding alternative indications of existing drugs by drug repositioning, and detecting adverse drug reactions and drug toxicity. Reverse screening can be divided into three major groups: shape screening, pharmacophore screening and reverse docking. Several large software packages, such as Schrödinger and Discovery Studio; typical software/network services such as ChemMapper, PharmMapper, idTarget, and INVDOCK; and practical databases of known target ligands and receptor crystal structures, such as ChEMBL, BindingDB, and the Protein Data Bank (PDB), are available for use in these computational methods. Different programs, online services and databases have different applications and constraints. Here, we conducted a systematic analysis and multilevel classification of the computational programs, online services and compound libraries available for shape screening, pharmacophore screening and reverse docking to enable non-specialist users to quickly learn

  3. Reverse Screening Methods to Search for the Protein Targets of Chemopreventive Compounds

    PubMed Central

    Huang, Hongbin; Zhang, Guigui; Zhou, Yuquan; Lin, Chenru; Chen, Suling; Lin, Yutong; Mai, Shangkang; Huang, Zunnan

    2018-01-01

    This article is a systematic review of reverse screening methods used to search for the protein targets of chemopreventive compounds or drugs. Typical chemopreventive compounds include components of traditional Chinese medicine, natural compounds and Food and Drug Administration (FDA)-approved drugs. Such compounds are somewhat selective but are predisposed to bind multiple protein targets distributed throughout diverse signaling pathways in human cells. In contrast to conventional virtual screening, which identifies the ligands of a targeted protein from a compound database, reverse screening is used to identify the potential targets or unintended targets of a given compound from a large number of receptors by examining their known ligands or crystal structures. This method, also known as in silico or computational target fishing, is highly valuable for discovering the target receptors of query molecules from terrestrial or marine natural products, exploring the molecular mechanisms of chemopreventive compounds, finding alternative indications of existing drugs by drug repositioning, and detecting adverse drug reactions and drug toxicity. Reverse screening can be divided into three major groups: shape screening, pharmacophore screening and reverse docking. Several large software packages, such as Schrödinger and Discovery Studio; typical software/network services such as ChemMapper, PharmMapper, idTarget, and INVDOCK; and practical databases of known target ligands and receptor crystal structures, such as ChEMBL, BindingDB, and the Protein Data Bank (PDB), are available for use in these computational methods. Different programs, online services and databases have different applications and constraints. Here, we conducted a systematic analysis and multilevel classification of the computational programs, online services and compound libraries available for shape screening, pharmacophore screening and reverse docking to enable non-specialist users to quickly learn

  4. Generalized “Satisfaction of Search”: Adverse Influences on Dual-Target Search Accuracy

    PubMed Central

    Fleck, Mathias S.; Samei, Ehsan; Mitroff, Stephen R.

    2013-01-01

    The successful detection of a target in a radiological search can reduce the detectability of a second target, a phenomenon termed satisfaction of search (SOS). Given the potential consequences, here we investigate the generality of SOS with the goal of simultaneously informing radiology, cognitive psychology, and nonmedical searches such as airport luggage screening. Ten experiments utilizing nonmedical searches and untrained searchers suggest that SOS is affected by a diverse array of factors, including (1) the relative frequency of different target types, (2) external pressures (reward and time), and (3) expectations about the number of targets present. Collectively, these experiments indicate that SOS arises when searchers have a biased expectation about the low likelihood of specific targets or events, and when they are under pressure to perform efficiently. This first demonstration of SOS outside of radiology implicates a general heuristic applicable to many kinds of searches. In an example like airport luggage screening, the current data suggest that the detection of an easy-to-spot target (e.g., a water bottle) might reduce detection of a hard-to-spot target (e.g., a box cutter). PMID:20350044

  5. The search for drug-targetable diagnostic, prognostic and predictive biomarkers in chronic graft-versus-host disease.

    PubMed

    Ren, Hong-Gang; Adom, Djamilatou; Paczesny, Sophie

    2018-05-01

    Chronic graft-versus-host disease (cGVHD) continues to be the leading cause of late morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which is an increasingly applied curative method for both benign and malignant hematologic disorders. Biomarker identification is crucial for the development of noninvasive and cost-effective cGVHD diagnostic, prognostic, and predictive test for use in clinic. Furthermore, biomarkers may help to gain a better insight on ongoing pathophysiological processes. The recent widespread application of omics technologies including genomics, transcriptomics, proteomics and cytomics provided opportunities to discover novel biomarkers. Areas covered: This review focuses on biomarkers identified through omics that play a critical role in target identification for drug development, and that were verified in at least two independent cohorts. It also summarizes the current status on omics tools used to identify these useful cGVHD targets. We briefly list the biomarkers identified and verified so far. We further address challenges associated to their exploitation and application in the management of cGVHD patients. Finally, insights on biomarkers that are drug targetable and represent potential therapeutic targets are discussed. Expert commentary: We focus on biomarkers that play an essential role in target identification.

  6. Synthetic membrane-targeted antibiotics.

    PubMed

    Vooturi, S K; Firestine, S M

    2010-01-01

    Antimicrobial resistance continues to evolve and presents serious challenges in the therapy of both nosocomial and community-acquired infections. The rise of resistant strains like methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus (VRSA) and vancomycin-resistant enterococci (VRE) suggests that antimicrobial resistance is an inevitable evolutionary response to antimicrobial use. This highlights the tremendous need for antibiotics against new bacterial targets. Agents that target the integrity of bacterial membrane are relatively novel in the clinical armamentarium. Daptomycin, a lipopeptide is a classical example of membrane-bound antibiotic. Nature has also utilized this tactic. Antimicrobial peptides (AMPs), which are found in all kingdoms, function primarily by permeabilizing the bacterial membrane. AMPs have several advantages over existing antibiotics including a broad spectrum of activity, rapid bactericidal activity, no cross-resistance with the existing antibiotics and a low probability for developing resistance. Currently, a small number of peptides have been developed for clinical use but therapeutic applications are limited because of poor bioavailability and high manufacturing cost. However, their broad specificity, potent activity and lower probability for resistance have spurred the search for synthetic mimetics of antimicrobial peptides as membrane-active antibiotics. In this review, we will discuss the different classes of synthetic membrane-bound antibiotics published since 2004.

  7. Chapter 17. Extension of endogenous primers as a tool to detect micro-RNA targets.

    PubMed

    Vatolin, Sergei; Weil, Robert J

    2008-01-01

    Mammalian cells express a large number of small, noncoding RNAs, including micro-RNAs (miRNAs), that can regulate both the level of a target mRNA and the protein produced by the target mRNA. Recognition of miRNA targets is a complicated process, as a single target mRNA may be regulated by several miRNAs. The potential for combinatorial miRNA-mediated regulation of miRNA targets complicates diagnostic and therapeutic applications of miRNAs. Despite significant progress in understanding the biology of miRNAs and advances in computational predictions of miRNA targets, methods that permit direct physical identification of miRNA-mRNA complexes in eukaryotic cells are still required. Several groups have utilized coimmunoprecipitation of RNA associated with a protein(s) that is part of the RNA silencing macromolecular complex. This chapter describes a detailed but straightforward strategy that identifies miRNA targets based on the assumption that small RNAs base paired with a complementary target mRNA can be used as a primer to synthesize cDNA that may be used for cloning, identification, and functional analysis.

  8. RAC-tagging: Recombineering And Cas9-assisted targeting for protein tagging and conditional analyses

    PubMed Central

    Baker, Oliver; Gupta, Ashish; Obst, Mandy; Zhang, Youming; Anastassiadis, Konstantinos; Fu, Jun; Stewart, A. Francis

    2016-01-01

    A fluent method for gene targeting to establish protein tagged and ligand inducible conditional loss-of-function alleles is described. We couple new recombineering applications for one-step cloning of gRNA oligonucleotides and rapid generation of short-arm (~1 kb) targeting constructs with the power of Cas9-assisted targeting to establish protein tagged alleles in embryonic stem cells at high efficiency. RAC (Recombineering And Cas9)-tagging with Venus, BirM, APEX2 and the auxin degron is facilitated by a recombineering-ready plasmid series that permits the reuse of gene-specific reagents to insert different tags. Here we focus on protein tagging with the auxin degron because it is a ligand-regulated loss-of-function strategy that is rapid and reversible. Furthermore it includes the additional challenge of biallelic targeting. Despite high frequencies of monoallelic RAC-targeting, we found that simultaneous biallelic targeting benefits from long-arm (>4 kb) targeting constructs. Consequently an updated recombineering pipeline for fluent generation of long arm targeting constructs is also presented. PMID:27216209

  9. Anomalies in target-controlled infusion: an analysis after 20 years of clinical use.

    PubMed

    Engbers, F H M; Dahan, A

    2018-05-01

    Although target-controlled infusion has been in use for more than two decades, its benefits are being obscured by anomalies in clinical practice caused by a number of important problems. These include: a variety of pharmacokinetic models available in open target-controlled infusion systems, which often confuse the user; the extrapolation of anthropomorphic data which provokes anomalous adjustments of dosing by such systems; and the uncertainty of regulatory requirements for the application of target-controlled infusion which causes uncontrolled exploitation of drugs and pharmacokinetic models in target-controlled infusion devices. Comparison of performance of pharmacokinetic models is complex and mostly inconclusive. However, a specific behaviour of a model in a target-controlled infusion system that is neither intended nor supported by scientific data can be considered an artefact or anomaly. Several of these anomalies can be identified in the current commercially available target-controlled infusion systems and are discussed in this review. © 2018 The Association of Anaesthetists of Great Britain and Ireland.

  10. Targeted Quantitation of Proteins by Mass Spectrometry

    PubMed Central

    2013-01-01

    Quantitative measurement of proteins is one of the most fundamental analytical tasks in a biochemistry laboratory, but widely used immunochemical methods often have limited specificity and high measurement variation. In this review, we discuss applications of multiple-reaction monitoring (MRM) mass spectrometry, which allows sensitive, precise quantitative analyses of peptides and the proteins from which they are derived. Systematic development of MRM assays is permitted by databases of peptide mass spectra and sequences, software tools for analysis design and data analysis, and rapid evolution of tandem mass spectrometer technology. Key advantages of MRM assays are the ability to target specific peptide sequences, including variants and modified forms, and the capacity for multiplexing that allows analysis of dozens to hundreds of peptides. Different quantitative standardization methods provide options that balance precision, sensitivity, and assay cost. Targeted protein quantitation by MRM and related mass spectrometry methods can advance biochemistry by transforming approaches to protein measurement. PMID:23517332

  11. Targeted quantitation of proteins by mass spectrometry.

    PubMed

    Liebler, Daniel C; Zimmerman, Lisa J

    2013-06-04

    Quantitative measurement of proteins is one of the most fundamental analytical tasks in a biochemistry laboratory, but widely used immunochemical methods often have limited specificity and high measurement variation. In this review, we discuss applications of multiple-reaction monitoring (MRM) mass spectrometry, which allows sensitive, precise quantitative analyses of peptides and the proteins from which they are derived. Systematic development of MRM assays is permitted by databases of peptide mass spectra and sequences, software tools for analysis design and data analysis, and rapid evolution of tandem mass spectrometer technology. Key advantages of MRM assays are the ability to target specific peptide sequences, including variants and modified forms, and the capacity for multiplexing that allows analysis of dozens to hundreds of peptides. Different quantitative standardization methods provide options that balance precision, sensitivity, and assay cost. Targeted protein quantitation by MRM and related mass spectrometry methods can advance biochemistry by transforming approaches to protein measurement.

  12. NASTRAN thermal analyzer: Theory and application including a guide to modeling engineering problems, volume 1. [thermal analyzer manual

    NASA Technical Reports Server (NTRS)

    Lee, H. P.

    1977-01-01

    The NASTRAN Thermal Analyzer Manual describes the fundamental and theoretical treatment of the finite element method, with emphasis on the derivations of the constituent matrices of different elements and solution algorithms. Necessary information and data relating to the practical applications of engineering modeling are included.

  13. Applications of chemogenomic library screening in drug discovery.

    PubMed

    Jones, Lyn H; Bunnage, Mark E

    2017-04-01

    The allure of phenotypic screening, combined with the industry preference for target-based approaches, has prompted the development of innovative chemical biology technologies that facilitate the identification of new therapeutic targets for accelerated drug discovery. A chemogenomic library is a collection of selective small-molecule pharmacological agents, and a hit from such a set in a phenotypic screen suggests that the annotated target or targets of that pharmacological agent may be involved in perturbing the observable phenotype. In this Review, we describe opportunities for chemogenomic screening to considerably expedite the conversion of phenotypic screening projects into target-based drug discovery approaches. Other applications are explored, including drug repositioning, predictive toxicology and the discovery of novel pharmacological modalities.

  14. Effects of Application of Social Marketing Theory and the Health Belief Model in Promoting Cervical Cancer Screening among Targeted Women in Sisaket Province, Thailand.

    PubMed

    Wichachai, Suparp; Songserm, Nopparat; Akakul, Theerawut; Kuasiri, Chanapong

    2016-01-01

    Cervical cancer is a major public health problem in Thailand, being ranked second only to breast cancer. Thai women have been reported to have a low rate of cervical cancer screening (27.7% of the 80% goal of WHO). We therefore aimed to apply the social marketing theory and health belief model in promoting cervical cancer screening in Kanthararom District, Sisaket Province. A total of 92 from 974 targeted women aged 3060 years were randomly divided into two groups. The experimental group underwent application of social marketing theory and a health belief model program promoting cervical cancer screening while the control group received normal services. Two research tools were used: (1) application of social marketing theory and health belief model program and (2) questionnaire used to evaluate perceptions of cervical cancer. Descriptive and inferential statistics including paired sample ttest and independent ttest were used to analyze the data. After the program had been used, the mean score of perception of cervical cancer of experimental group was at a higher level (x=4.09; S.D. =0.30), than in the control group (x=3.82; S.D. =0.20) with statistical significance (p<0.001). This research demonstrated an appropriate communication process in behavioral modification to prevent cervical cancer. It can be recommended that this program featuring social marketing and the health belief model be used to promote cervical cancer screening in targeted women and it can be promoted as a guideline for other health services, especially in health promotion and disease prevention.

  15. Functional DNA-Containing Nanomaterials: Cellular Applications in Biosensing, Imaging, and Targeted Therapy

    PubMed Central

    2015-01-01

    Conspectus DNA performs a vital function as a carrier of genetic code, but in the field of nanotechnology, DNA molecules can catalyze chemical reactions in the cell, that is, DNAzymes, or bind with target-specific ligands, that is, aptamers. These functional DNAs with different modifications have been developed for sensing, imaging, and therapeutic systems. Thus, functional DNAs hold great promise for future applications in nanotechnology and bioanalysis. However, these functional DNAs face challenges, especially in the field of biomedicine. For example, functional DNAs typically require the use of cationic transfection reagents to realize cellular uptake. Such reagents enter the cells, increasing the difficulty of performing bioassays in vivo and potentially damaging the cell’s nucleus. To address this obstacle, nanomaterials, such as metallic, carbon, silica, or magnetic materials, have been utilized as DNA carriers or assistants. In this Account, we describe selected examples of functional DNA-containing nanomaterials and their applications from our recent research and those of others. As models, we have chosen to highlight DNA/nanomaterial complexes consisting of gold nanoparticles, graphene oxides, and aptamer–micelles, and we illustrate the potential of such complexes in biosensing, imaging, and medical diagnostics. Under proper conditions, multiple ligand–receptor interactions, decreased steric hindrance, and increased surface roughness can be achieved from a high density of DNA that is bound to the surface of nanomaterials, resulting in a higher affinity for complementary DNA and other targets. In addition, this high density of DNA causes a high local salt concentration and negative charge density, which can prevent DNA degradation. For example, DNAzymes assembled on gold nanoparticles can effectively catalyze chemical reactions even in living cells. And it has been confirmed that DNA–nanomaterial complexes can enter cells more easily than free

  16. Functional DNA-containing nanomaterials: cellular applications in biosensing, imaging, and targeted therapy.

    PubMed

    Liang, Hao; Zhang, Xiao-Bing; Lv, Yifan; Gong, Liang; Wang, Ruowen; Zhu, Xiaoyan; Yang, Ronghua; Tan, Weihong

    2014-06-17

    CONSPECTUS: DNA performs a vital function as a carrier of genetic code, but in the field of nanotechnology, DNA molecules can catalyze chemical reactions in the cell, that is, DNAzymes, or bind with target-specific ligands, that is, aptamers. These functional DNAs with different modifications have been developed for sensing, imaging, and therapeutic systems. Thus, functional DNAs hold great promise for future applications in nanotechnology and bioanalysis. However, these functional DNAs face challenges, especially in the field of biomedicine. For example, functional DNAs typically require the use of cationic transfection reagents to realize cellular uptake. Such reagents enter the cells, increasing the difficulty of performing bioassays in vivo and potentially damaging the cell's nucleus. To address this obstacle, nanomaterials, such as metallic, carbon, silica, or magnetic materials, have been utilized as DNA carriers or assistants. In this Account, we describe selected examples of functional DNA-containing nanomaterials and their applications from our recent research and those of others. As models, we have chosen to highlight DNA/nanomaterial complexes consisting of gold nanoparticles, graphene oxides, and aptamer-micelles, and we illustrate the potential of such complexes in biosensing, imaging, and medical diagnostics. Under proper conditions, multiple ligand-receptor interactions, decreased steric hindrance, and increased surface roughness can be achieved from a high density of DNA that is bound to the surface of nanomaterials, resulting in a higher affinity for complementary DNA and other targets. In addition, this high density of DNA causes a high local salt concentration and negative charge density, which can prevent DNA degradation. For example, DNAzymes assembled on gold nanoparticles can effectively catalyze chemical reactions even in living cells. And it has been confirmed that DNA-nanomaterial complexes can enter cells more easily than free single

  17. Application of Targeted Mass Spectrometry for the Quantification of Sirtuins in the Central Nervous System

    NASA Astrophysics Data System (ADS)

    Jayasena, T.; Poljak, A.; Braidy, N.; Zhong, L.; Rowlands, B.; Muenchhoff, J.; Grant, R.; Smythe, G.; Teo, C.; Raftery, M.; Sachdev, P.

    2016-10-01

    Sirtuin proteins have a variety of intracellular targets, thereby regulating multiple biological pathways including neurodegeneration. However, relatively little is currently known about the role or expression of the 7 mammalian sirtuins in the central nervous system. Western blotting, PCR and ELISA are the main techniques currently used to measure sirtuin levels. To achieve sufficient sensitivity and selectivity in a multiplex-format, a targeted mass spectrometric assay was developed and validated for the quantification of all seven mammalian sirtuins (SIRT1-7). Quantification of all peptides was by multiple reaction monitoring (MRM) using three mass transitions per protein-specific peptide, two specific peptides for each sirtuin and a stable isotope labelled internal standard. The assay was applied to a variety of samples including cultured brain cells, mammalian brain tissue, CSF and plasma. All sirtuin peptides were detected in the human brain, with SIRT2 being the most abundant. Sirtuins were also detected in human CSF and plasma, and guinea pig and mouse tissues. In conclusion, we have successfully applied MRM mass spectrometry for the detection and quantification of sirtuin proteins in the central nervous system, paving the way for more quantitative and functional studies.

  18. Deaf mobile application accessibility requirements

    NASA Astrophysics Data System (ADS)

    Nathan, Shelena Soosay; Hussain, Azham; Hashim, Nor Laily

    2016-08-01

    Requirement for deaf mobile applications need to be analysed to ensure the disabilities need are instilled into the mobile applications developed for them. Universal design is understandable to comply every user needs, however specific disability is argued by the authors to have different need and requirements. These differences are among the reasons for these applications being developed to target for a specific group of people, however they are less usable and later abandoned. This study focuses on deriving requirements that are needed by the deaf in their mobile applications that are meant specifically for them. Studies on previous literature was conducted it can be concluded that graphic, text, multimedia and sign language interpreter are among mostly required features to be included in their mobile application to ensure the applications are usable for this community.

  19. Targeted gene flow for conservation.

    PubMed

    Kelly, Ella; Phillips, Ben L

    2016-04-01

    Anthropogenic threats often impose strong selection on affected populations, causing rapid evolutionary responses. Unfortunately, these adaptive responses are rarely harnessed for conservation. We suggest that conservation managers pay close attention to adaptive processes and geographic variation, with an eye to using them for conservation goals. Translocating pre-adapted individuals into recipient populations is currently considered a potentially important management tool in the face of climate change. Targeted gene flow, which involves moving individuals with favorable traits to areas where these traits would have a conservation benefit, could have a much broader application in conservation. Across a species' range there may be long-standing geographic variation in traits or variation may have rapidly developed in response to a threatening process. Targeted gene flow could be used to promote natural resistance to threats to increase species resilience. We suggest that targeted gene flow is a currently underappreciated strategy in conservation that has applications ranging from the management of invasive species and their impacts to controlling the impact and virulence of pathogens. © 2015 Society for Conservation Biology.

  20. 45 CFR 2516.400 - What must a State or Indian tribe include in an application for a grant?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE SCHOOL-BASED SERVICE-LEARNING PROGRAMS Application... following: (a) A three-year strategic plan for promoting service-learning through programs under this part... include a description of how the SEA will coordinate its service-learning plan with the State Plan under...

  1. 45 CFR 2516.400 - What must a State or Indian tribe include in an application for a grant?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE SCHOOL-BASED SERVICE-LEARNING PROGRAMS Application... following: (a) A three-year strategic plan for promoting service-learning through programs under this part... include a description of how the SEA will coordinate its service-learning plan with the State Plan under...

  2. Human target acquisition performance

    NASA Astrophysics Data System (ADS)

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

    2012-06-01

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

  3. Engineering aspects of the application of structural materials in the 5 MW-ESS-mercury-target

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

    Guttek, B.

    1996-06-01

    A main problem of the ESS-Hg-target development and the design of the components of its primary Hg-circuit is the choice of structural materials. As designing, calculations and experiments with elected materials take time and are very costy, a preview on their successful application has to be done before as detailed as possible. One aspect on this is to have the knowledge of characteristics values of the structural material candidates under the occuring mechanical and thermal loads, irradiation, corrosion and erosion. Another point is the technology of engineering concerning the manufacturing, welding, surface treatment, and quality control of such parts andmore » components under the demand to reach maximum lifetime.« less

  4. Target-directed Dynamic Combinatorial Chemistry: A Study on Potentials and Pitfalls as Exemplified on a Bacterial Target.

    PubMed

    Frei, Priska; Pang, Lijuan; Silbermann, Marleen; Eriş, Deniz; Mühlethaler, Tobias; Schwardt, Oliver; Ernst, Beat

    2017-08-25

    Target-directed dynamic combinatorial chemistry (DCC) is an emerging technique for the efficient identification of inhibitors of pharmacologically relevant targets. In this contribution, we present an application for a bacterial target, the lectin FimH, a crucial virulence factor of uropathogenic E. coli being the main cause of urinary tract infections. A small dynamic library of acylhydrazones was formed from aldehydes and hydrazides and equilibrated at neutral pH in presence of aniline as nucleophilic catalyst. The major success factors turned out to be an accordingly adjusted ratio of scaffolds and fragments, an adequate sample preparation prior to HPLC analysis, and the data processing. Only then did the ranking of the dynamic library constituents correlate well with affinity data. Furthermore, as a support of DCC applications especially to larger libraries, a new protocol for improved hit identification was established. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Targets and processes for fabricating same

    DOEpatents

    Cowan, Thomas [Dresden, DE; Malekos, Steven [Reno, NV; Korgan, Grant [Reno, NV; Adams, Jesse [Reno, NV; Sentoku, Yasuhiko [Reno, NV; Le Galloudec, Nathalie [Reno, NV; Fuchs, Julien [Paris, FR

    2012-07-24

    In particular embodiments, the present disclosure provides targets including a metal layer and defining a hollow inner surface. The hollow inner surface has an internal apex. The distance between at least two opposing points of the internal apex is less than about 15 .mu.m. In particular examples, the distance is less than about 1 .mu.m. Particular implementations of the targets are free standing. The targets have a number of disclosed shaped, including cones, pyramids, hemispheres, and capped structures. The present disclosure also provides arrays of such targets. Also provided are methods of forming targets, such as the disclosed targets, using lithographic techniques, such as photolithographic techniques. In particular examples, a target mold is formed from a silicon wafer and then one or more sides of the mold are coated with a target material, such as one or more metals.

  6. Targets and processes for fabricating same

    DOEpatents

    Adams, Jesse D; Malekos, Steven; Le Galloudec, Nathalie; Korgan, Grant; Cowan, Thomas; Sentoku, Yasuhiko

    2016-05-17

    In particular embodiments, the present disclosure provides targets including a metal layer and defining a hollow inner surface. The hollow inner surface has an internal apex. The distance between at least two opposing points of the internal apex is less than about 15 .mu.m. In particular examples, the distance is less than about 1 .mu.m. Particular implementations of the targets are free standing. The targets have a number of disclosed shaped, including cones, pyramids, hemispheres, and capped structures. The present disclosure also provides arrays of such targets. Also provided are methods of forming targets, such as the disclosed targets, using lithographic techniques, such as photolithographic techniques. In particular examples, a target mold is formed from a silicon wafer and then one or more sides of the mold are coated with a target material, such as one or more metals.

  7. Targets and processes for fabricating same

    DOEpatents

    Cowna, Thomas; Malekos, Steven; Korgan, Grant; Adams, Jesse; Sentoku, Yasuhiko; LeGalloudec, Nathalie

    2014-06-10

    In particular embodiments, the present disclosure provides targets including a metal layer and defining a hollow inner surface. The hollow inner surface has an internal apex. The distance between at least two opposing points of the internal apex is less than about 15 .mu.m. In particular examples, the distance is less than about 1 .mu.m. Particular implementations of the targets are free standing. The targets have a number of disclosed shaped, including cones, pyramids, hemispheres, and capped structures. The present disclosure also provides arrays of such targets. Also provided are methods of forming targets, such as the disclosed targets, using lithographic techniques, such as photolithographic techniques. In particular examples, a target mold is formed from a silicon wafer and then one or more sides of the mold are coated with a target material, such as one or more metals.

  8. AAVSO Target Tool: A Web-Based Service for Tracking Variable Star Observations (Abstract)

    NASA Astrophysics Data System (ADS)

    Burger, D.; Stassun, K. G.; Barnes, C.; Kafka, S.; Beck, S.; Li, K.

    2018-06-01

    (Abstract only) The AAVSO Target Tool is a web-based interface for bringing stars in need of observation to the attention of AAVSOís network of amateur and professional astronomers. The site currently tracks over 700 targets of interest, collecting data from them on a regular basis from AAVSOís servers and sorting them based on priority. While the target tool does not require a login, users can obtain visibility times for each target by signing up and entering a telescope location. Other key features of the site include filtering by AAVSO observing section, sorting by different variable types, formatting the data for printing, and exporting the data to a CSV file. The AAVSO Target Tool builds upon seven years of experience developing web applications for astronomical data analysis, most notably on Filtergraph (Burger, D., et al. 2013, Astronomical Data Analysis Software and Systems XXII, Astronomical Society of the Pacific, San Francisco, 399), and is built using the web2py web framework based on the python programming language. The target tool is available at http://filtergraph.com/aavso.

  9. Seedling root targets

    Treesearch

    Diane L. Haase

    2011-01-01

    Roots are critical to seedling performance after outplanting. Although root quality is not as quick and simple to measure as shoot quality, target root characteristics should be included in any seedling quality assessment program. This paper provides a brief review of root characteristics most commonly targeted for operational seedling production. These are: root mass...

  10. 34 CFR 611.2 - What management plan must be included in a Teacher Quality Enhancement Grants Program application?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... TEACHER QUALITY ENHANCEMENT GRANTS PROGRAM General Provisions § 611.2 What management plan must be... 34 Education 3 2010-07-01 2010-07-01 false What management plan must be included in a Teacher Quality Enhancement Grants Program application? 611.2 Section 611.2 Education Regulations of the Offices...

  11. Selenium and Iron Oxide Nanocomposites for Magnetically-Targeted Anti-Cancer Applications.

    PubMed

    Hauksdóttir, Halla Laufey; Webster, Thomas J

    2018-03-01

    introduces a brand new composite nanoparticle consisting of iron oxide and selenium which should be further studied for a wide range of magnetically targeted anticancer applications.

  12. A new target ligand Ser-Glu for PEPT1-overexpressing cancer imaging.

    PubMed

    Dai, Tongcheng; Li, Na; Zhang, Lingzhi; Zhang, Yuanxing; Liu, Qin

    2016-01-01

    Nanoparticles functionalized with active target ligands have been widely used for tumor-specific diagnosis and therapy. The target ligands include antibodies, peptides, proteins, small molecules, and nucleic acid aptamers. Here, we utilize dipeptide Ser-Glu (DIP) as a new ligand to functionalize polymer-based fluorescent nanoparticles (NPs) for pancreatic cancer target imaging. We demonstrate that in the first step, Ser-Glu-conjugated NPs (NPs-DIP) efficiently bind to AsPC-1 and in the following NPs-DIP are internalized into AsPC-1 in vitro. The peptide transporter 1 inhibition experiment reveals that the targeting effects mainly depend on the specific binding of DIP to peptide transporter 1, which is remarkably upregulated in pancreatic cancer cells compared with varied normal cells. Furthermore, NPs-DIP specifically accumulate in the site of pancreatic tumor xenograft and are further internalized into the tumor cells in vivo after intravenous administration, indicating that DIP successfully enhanced nanoparticles internalization efficacy into tumor cells in vivo. This work establishes Ser-Glu to be a new tumor-targeting ligand and provides a promising tool for future tumor diagnostic or therapeutic applications.

  13. Effects of major parameters of nanoparticles on their physical and chemical properties and recent application of nanodrug delivery system in targeted chemotherapy.

    PubMed

    Zhang, Jing; Tang, Hua; Liu, Zefa; Chen, Baoan

    2017-01-01

    Chemotherapy is still one of the main cancer therapy treatments, but the curative effect of chemotherapy is relatively low, as such the development of a new cancer treatment is highly desirable. The gradual maturation of nanotechnology provides an innovative perspective not only for cancer therapy but also for many other applications. There are a diverse variety of nanoparticles available, and choosing the appropriate carriers according to the demand is the key issue. The performance of nanoparticles is affected by many parameters, mainly size, shape, surface charge, and toxicity. Using nanoparticles as the carriers to realize passive targeting and active targeting can improve the efficacy of chemotherapy drugs significantly, reduce the mortality rate of cancer patients, and improve the quality of life of patients. In recent years, there has been extensive research on nanocarriers. In this review, the effects of several major parameters of nanoparticles on their physical and chemical properties are reviewed, and then the recent progress in the application of several commonly used nanoparticles is presented.

  14. Off-target Effects in CRISPR/Cas9-mediated Genome Engineering

    PubMed Central

    Zhang, Xiao-Hui; Tee, Louis Y; Wang, Xiao-Gang; Huang, Qun-Shan; Yang, Shi-Hua

    2015-01-01

    CRISPR/Cas9 is a versatile genome-editing technology that is widely used for studying the functionality of genetic elements, creating genetically modified organisms as well as preclinical research of genetic disorders. However, the high frequency of off-target activity (≥50%)—RGEN (RNA-guided endonuclease)-induced mutations at sites other than the intended on-target site—is one major concern, especially for therapeutic and clinical applications. Here, we review the basic mechanisms underlying off-target cutting in the CRISPR/Cas9 system, methods for detecting off-target mutations, and strategies for minimizing off-target cleavage. The improvement off-target specificity in the CRISPR/Cas9 system will provide solid genotype–phenotype correlations, and thus enable faithful interpretation of genome-editing data, which will certainly facilitate the basic and clinical application of this technology. PMID:26575098

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

    PubMed

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

    2014-09-01

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

  16. Incoherent imaging of radar targets

    NASA Astrophysics Data System (ADS)

    van Ommen, A.; van der Spek, G. A.

    1986-05-01

    Theory suggests that, if a target can be modeled as a rigid constellation of point scatterers, the RCS pattern over a certain aspect change can be used to produce a one-dimensional image. The results for actual measured RCS patterns, however, are not promising. This is illustrated by processing on 4 s of echo data obtained from a Boeing 737 in straight flight, during which its aspect change is 2 deg. The conclusion might be that, for the application considered, aircraft cannot be modeled as a rigid constellation of point scatterers; this is partly due to the treatment of a three-dimensional target as a line target.

  17. 30 CFR 250.1726 - When must I submit an initial platform removal application and what must it include?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 2 2011-07-01 2011-07-01 false When must I submit an initial platform removal application and what must it include? 250.1726 Section 250.1726 Mineral Resources BUREAU OF OCEAN ENERGY... disposal plans; (d) Plans to protect marine life and the environment during decommissioning operations...

  18. Microfluidic bead-based diodes with targeted circular microchannels for low Reynolds number applications.

    PubMed

    Sochol, Ryan D; Lu, Albert; Lei, Jonathan; Iwai, Kosuke; Lee, Luke P; Lin, Liwei

    2014-05-07

    Self-regulating fluidic components are critical to the advancement of microfluidic processors for chemical and biological applications, such as sample preparation on chip, point-of-care molecular diagnostics, and implantable drug delivery devices. Although researchers have developed a wide range of components to enable flow rectification in fluidic systems, engineering microfluidic diodes that function at the low Reynolds number (Re) flows and smaller scales of emerging micro/nanofluidic platforms has remained a considerable challenge. Recently, researchers have demonstrated microfluidic diodes that utilize high numbers of suspended microbeads as dynamic resistive elements; however, using spherical particles to block fluid flow through rectangular microchannels is inherently limited. To overcome this issue, here we present a single-layer microfluidic bead-based diode (18 μm in height) that uses a targeted circular-shaped microchannel for the docking of a single microbead (15 μm in diameter) to rectify fluid flow under low Re conditions. Three-dimensional simulations and experimental results revealed that adjusting the docking channel geometry and size to better match the suspended microbead greatly increased the diodicity (Di) performance. Arraying multiple bead-based diodes in parallel was found to adversely affect system efficacy, while arraying multiple diodes in series was observed to enhance device performance. In particular, systems consisting of four microfluidic bead-based diodes with targeted circular-shaped docking channels in series revealed average Di's ranging from 2.72 ± 0.41 to 10.21 ± 1.53 corresponding to Re varying from 0.1 to 0.6.

  19. 14 CFR 399.62 - Target dates in hearing cases.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Target dates in hearing cases. 399.62... Target dates in hearing cases. (a) Applicability. This section applies to initial and recommended.... (b) Issuance of target dates. In cases to which this section applies, the Board or the administrative...

  20. 14 CFR 399.62 - Target dates in hearing cases.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Target dates in hearing cases. 399.62... Target dates in hearing cases. (a) Applicability. This section applies to initial and recommended.... (b) Issuance of target dates. In cases to which this section applies, the Board or the administrative...

  1. 14 CFR 399.62 - Target dates in hearing cases.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Target dates in hearing cases. 399.62... Target dates in hearing cases. (a) Applicability. This section applies to initial and recommended.... (b) Issuance of target dates. In cases to which this section applies, the Board or the administrative...

  2. 14 CFR 399.62 - Target dates in hearing cases.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 false Target dates in hearing cases. 399.62... Target dates in hearing cases. (a) Applicability. This section applies to initial and recommended.... (b) Issuance of target dates. In cases to which this section applies, the Board or the administrative...

  3. 14 CFR 399.62 - Target dates in hearing cases.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Target dates in hearing cases. 399.62... Target dates in hearing cases. (a) Applicability. This section applies to initial and recommended.... (b) Issuance of target dates. In cases to which this section applies, the Board or the administrative...

  4. 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.

  5. Large-signal model of the bilayer graphene field-effect transistor targeting radio-frequency applications: Theory versus experiment

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

    Pasadas, Francisco, E-mail: Francisco.Pasadas@uab.cat; Jiménez, David

    2015-12-28

    Bilayer graphene is a promising material for radio-frequency transistors because its energy gap might result in a better current saturation than the monolayer graphene. Because the great deal of interest in this technology, especially for flexible radio-frequency applications, gaining control of it requires the formulation of appropriate models for the drain current, charge, and capacitance. In this work, we have developed them for a dual-gated bilayer graphene field-effect transistor. A drift-diffusion mechanism for the carrier transport has been considered coupled with an appropriate field-effect model taking into account the electronic properties of the bilayer graphene. Extrinsic resistances have been includedmore » considering the formation of a Schottky barrier at the metal-bilayer graphene interface. The proposed model has been benchmarked against experimental prototype transistors, discussing the main figures of merit targeting radio-frequency applications.« less

  6. Aptamers: Active Targeting Ligands for Cancer Diagnosis and Therapy

    PubMed Central

    Wu, Xu; Chen, Jiao; Wu, Min; Zhao, Julia Xiaojun

    2015-01-01

    Aptamers, including DNA, RNA and peptide aptamers, are a group of promising recognition units that can specifically bind to target molecules and cells. Due to their excellent specificity and high affinity to targets, aptamers have attracted great attention in various fields in which selective recognition units are required. They have been used in biosensing, drug delivery, disease diagnosis and therapy (especially for cancer treatment). In this review, we summarized recent applications of DNA and RNA aptamers in cancer theranostics. The specific binding ability of aptamers to cancer-related markers and cancer cells ensured their high performance for early diagnosis of cancer. Meanwhile, the efficient targeting ability of aptamers to cancer cells and tissues provided a promising way to deliver imaging agents and drugs for cancer imaging and therapy. Furthermore, with the development of nanoscience and nanotechnology, the conjugation of aptamers with functional nanomaterials paved an exciting way for the fabrication of theranostic agents for different types of cancers, which might be a powerful tool for cancer treatment. PMID:25699094

  7. Pilots' Attention Distributions Between Chasing a Moving Target and a Stationary Target.

    PubMed

    Li, Wen-Chin; Yu, Chung-San; Braithwaite, Graham; Greaves, Matthew

    2016-12-01

    Attention plays a central role in cognitive processing; ineffective attention may induce accidents in flight operations. The objective of the current research was to examine military pilots' attention distributions between chasing a moving target and a stationary target. In the current research, 37 mission-ready F-16 pilots participated. Subjects' eye movements were collected by a portable head-mounted eye-tracker during tactical training in a flight simulator. The scenarios of chasing a moving target (air-to-air) and a stationary target (air-to-surface) consist of three operational phases: searching, aiming, and lock-on to the targets. The findings demonstrated significant differences in pilots' percentage of fixation during the searching phase between air-to-air (M = 37.57, SD = 5.72) and air-to-surface (M = 33.54, SD = 4.68). Fixation duration can indicate pilots' sustained attention to the trajectory of a dynamic target during air combat maneuvers. Aiming at the stationary target resulted in larger pupil size (M = 27,105, SD = 6565), reflecting higher cognitive loading than aiming at the dynamic target (M = 23,864, SD = 8762). Pilots' visual behavior is not only closely related to attention distribution, but also significantly associated with task characteristics. Military pilots demonstrated various visual scan patterns for searching and aiming at different types of targets based on the research settings of a flight simulator. The findings will facilitate system designers' understanding of military pilots' cognitive processes during tactical operations. They will assist human-centered interface design to improve pilots' situational awareness. The application of an eye-tracking device integrated with a flight simulator is a feasible and cost-effective intervention to improve the efficiency and safety of tactical training.Li W-C, Yu C-S, Braithwaite G, Greaves M. Pilots' attention distributions between chasing a moving target and a stationary target. Aerosp Med

  8. Magnetized Target Fusion

    NASA Technical Reports Server (NTRS)

    Griffin, Steven T.

    2002-01-01

    Magnetized target fusion (MTF) is under consideration as a means of building a low mass, high specific impulse, and high thrust propulsion system for interplanetary travel. This unique combination is the result of the generation of a high temperature plasma by the nuclear fusion process. This plasma can then be deflected by magnetic fields to provide thrust. Fusion is initiated by a small traction of the energy generated in the magnetic coils due to the plasma's compression of the magnetic field. The power gain from a fusion reaction is such that inefficiencies due to thermal neutrons and coil losses can be overcome. Since the fusion reaction products are directly used for propulsion and the power to initiate the reaction is directly obtained from the thrust generation, no massive power supply for energy conversion is required. The result should be a low engine mass, high specific impulse and high thrust system. The key is to successfully initiate fusion as a proof-of-principle for this application. Currently MSFC is implementing MTF proof-of-principle experiments. This involves many technical details and ancillary investigations. Of these, selected pertinent issues include the properties, orientation and timing of the plasma guns and the convergence and interface development of the "pusher" plasma. Computer simulations of the target plasma's behavior under compression and the convergence and mixing of the gun plasma are under investigation. This work is to focus on the gun characterization and development as it relates to plasma initiation and repeatability.

  9. Targeting epigenetic regulations in cancer

    PubMed Central

    Ning, Bo; Li, Wenyuan; Zhao, Wei; Wang, Rongfu

    2016-01-01

    Epigenetic regulation of gene expression is a dynamic and reversible process with DNA methylation, histone modifications, and chromatin remodeling. Recently, groundbreaking studies have demonstrated the importance of DNA and chromatin regulatory proteins from different aspects, including stem cell, development, and tumor genesis. Abnormal epigenetic regulation is frequently associated with diseases and drugs targeting DNA methylation and histone acetylation have been approved for cancer therapy. Although the network of epigenetic regulation is more complex than people expect, new potential druggable chromatin-associated proteins are being discovered and tested for clinical application. Here we review the key proteins that mediate epigenetic regulations through DNA methylation, the acetylation and methylation of histones, and the reader proteins that bind to modified histones. We also discuss cancer associations and recent progress of pharmacological development of these proteins. PMID:26508480

  10. Design of a bioactive small molecule that targets r(AUUCU) repeats in spinocerebellar ataxia 10.

    PubMed

    Yang, Wang-Yong; Gao, Rui; Southern, Mark; Sarkar, Partha S; Disney, Matthew D

    2016-06-01

    RNA is an important target for chemical probes of function and lead therapeutics; however, it is difficult to target with small molecules. One approach to tackle this problem is to identify compounds that target RNA structures and utilize them to multivalently target RNA. Here we show that small molecules can be identified to selectively bind RNA base pairs by probing a library of RNA-focused small molecules. A small molecule that selectively binds AU base pairs informed design of a dimeric compound (2AU-2) that targets the pathogenic RNA, expanded r(AUUCU) repeats, that causes spinocerebellar ataxia type 10 (SCA10) in patient-derived cells. Indeed, 2AU-2 (50 nM) ameliorates various aspects of SCA10 pathology including improvement of mitochondrial dysfunction, reduced activation of caspase 3, and reduction of nuclear foci. These studies provide a first-in-class chemical probe to study SCA10 RNA toxicity and potentially define broadly applicable compounds targeting RNA AU base pairs in cells.

  11. Proton Energy Optimization and Spatial Distribution Analysis from a Thickness Study Using Liquid Crystal Targets

    NASA Astrophysics Data System (ADS)

    Willis, Christopher; Poole, Patrick; Schumacher, Douglas; Freeman, Richard; van Woerkom, Linn

    2016-10-01

    Laser-accelerated ions from thin targets have been widely studied for applications including secondary radiation sources and cancer therapy, with recent studies trending towards thinner targets which can provide improved ion energies and yields. Here we discuss results from an experiment on the Scarlet laser at OSU using variable thickness liquid crystal targets. On this experiment, the spatial and spectral distributions of accelerated ions were measured along target normal and laser axes at varying thicknesses from 150nm to 2000nm at a laser intensity of 1 ×1020W /cm2 . Maximum ion energy was observed for targets in the 600 - 800nm thickness range, with proton energies reaching 24MeV . The ions were further characterized using radiochromic film, revealing an unusual spatial distribution on many laser shots. Here, the peak ion yield falls in an annular ring surrounding the target normal, with an increasing divergence angle as a function of ion energy. Details of these spatial and spectral ion distributions will be presented, including spectral deconvolution of the RCF data, revealing additional trends in the accelerated ion distributions. Supported by the DARPA PULSE program through a Grant from AMRDEC, and by the NNSA under contract DE-NA0001976.

  12. Polarimetric LIDAR with FRI sampling for target characterization

    NASA Astrophysics Data System (ADS)

    Wijerathna, Erandi; Creusere, Charles D.; Voelz, David; Castorena, Juan

    2017-09-01

    Polarimetric LIDAR is a significant tool for current remote sensing applications. In addition, measurement of the full waveform of the LIDAR echo provides improved ranging and target discrimination, although, data storage volume in this approach can be problematic. In the work presented here, we investigated the practical issues related to the implementation of a full waveform LIDAR system to identify polarization characteristics of multiple targets within the footprint of the illumination beam. This work was carried out on a laboratory LIDAR testbed that features a flexible arrangement of targets and the ability to change the target polarization characteristics. Targets with different retardance characteristics were illuminated with a linearly polarized laser beam and the return pulse intensities were analyzed by rotating a linear analyzer polarizer in front of a high-speed detector. Additionally, we explored the applicability and the limitations of applying a sparse sampling approach based on Finite Rate of Innovations (FRI) to compress and recover the characteristic parameters of the pulses reflected from the targets. The pulse parameter values extracted by the FRI analysis were accurate and we successfully distinguished the polarimetric characteristics and the range of multiple targets at different depths within the same beam footprint. We also demonstrated the recovery of an unknown target retardance value from the echoes by applying a Mueller matrix system model.

  13. Recent advances in dendrimer-based nanovectors for tumor-targeted drug and gene delivery

    PubMed Central

    Kesharwani, Prashant; Iyer, Arun K.

    2015-01-01

    Advances in the application of nanotechnology in medicine have given rise to multifunctional smart nanocarriers that can be engineered with tunable physicochemical characteristics to deliver one or more therapeutic agent(s) safely and selectively to cancer cells, including intracellular organelle-specific targeting. Dendrimers having properties resembling biomolecules, with well-defined 3D nanopolymeric architectures, are emerging as a highly attractive class of drug and gene delivery vector. The presence of numerous peripheral functional groups on hyperbranched dendrimers affords efficient conjugation of targeting ligands and biomarkers that can recognize and bind to receptors overexpressed on cancer cells for tumor-cell-specific delivery. The present review compiles the recent advances in dendrimer-mediated drug and gene delivery to tumors by passive and active targeting principles with illustrative examples. PMID:25555748

  14. Driver genes in non-small cell lung cancer: Characteristics, detection methods, and targeted therapies

    PubMed Central

    He, Bing; Zhang, Hu-Qin

    2017-01-01

    Lung cancer is one of the most common causes of cancer-related death in the world. The large number of lung cancer cases is non-small cell lung cancer (NSCLC), which approximately accounting for 75% of lung cancer. Over the past years, our comprehensive knowledge about the molecular biology of NSCLC has been rapidly enriching, which has promoted the discovery of driver genes in NSCLC and directed FDA-approved targeted therapies. Of course, the targeted therapies based on driver genes provide a more exact option for advanced non-small cell lung cancer, improving the survival rate of patients. Now, we will review the landscape of driver genes in NSCLC including the characteristics, detection methods, the application of target therapy and challenges. PMID:28915704

  15. Specifically targeted delivery of protein to phagocytic macrophages

    PubMed Central

    Yu, Min; Chen, Zeming; Guo, Wenjun; Wang, Jin; Feng, Yupeng; Kong, Xiuqi; Hong, Zhangyong

    2015-01-01

    Macrophages play important roles in the pathogenesis of various diseases, and are important potential therapeutic targets. Furthermore, macrophages are key antigen-presenting cells and important in vaccine design. In this study, we report on the novel formulation (bovine serum albumin [BSA]-loaded glucan particles [GMP-BSA]) based on β-glucan particles from cell walls of baker’s yeast for the targeted delivery of protein to macrophages. Using this formulation, chitosan, tripolyphosphate, and alginate were used to fabricate colloidal particles with the model protein BSA via electrostatic interactions, which were caged and incorporated BSA very tightly within the β-glucan particle shells. The prepared GMP-BSA exhibited good protein-release behavior and avoided protein leakage. The particles were also highly specific to phagocytic macrophages, such as Raw 264.7 cells, primary bone marrow-derived macrophages, and peritoneal exudate macrophages, whereas the particles were not taken up by nonphagocytic cells, including NIH3T3, AD293, HeLa, and Caco-2. We hypothesize that these tightly encapsulated protein-loaded glucan particles deliver various types of proteins to macrophages with notably high selectivity, and may have broad applications in targeted drug delivery or vaccine design against macrophages. PMID:25784802

  16. Reliable detection of Bacillus anthracis, Francisella tularensis and Yersinia pestis by using multiplex qPCR including internal controls for nucleic acid extraction and amplification.

    PubMed

    Janse, Ingmar; Hamidjaja, Raditijo A; Bok, Jasper M; van Rotterdam, Bart J

    2010-12-08

    Several pathogens could seriously affect public health if not recognized timely. To reduce the impact of such highly pathogenic micro-organisms, rapid and accurate diagnostic tools are needed for their detection in various samples, including environmental samples. Multiplex real-time PCRs were designed for rapid and reliable detection of three major pathogens that have the potential to cause high morbidity and mortality in humans: B. anthracis, F. tularensis and Y. pestis. The developed assays detect three pathogen-specific targets, including at least one chromosomal target, and one target from B. thuringiensis which is used as an internal control for nucleic acid extraction from refractory spores as well as successful DNA amplification. Validation of the PCRs showed a high analytical sensitivity, specificity and coverage of diverse pathogen strains. The multiplex qPCR assays that were developed allow the rapid detection of 3 pathogen-specific targets simultaneously, without compromising sensitivity. The application of B. thuringiensis spores as internal controls further reduces false negative results. This ensures highly reliable detection, while template consumption and laboratory effort are kept at a minimum.

  17. Reliable detection of Bacillus anthracis, Francisella tularensis and Yersinia pestis by using multiplex qPCR including internal controls for nucleic acid extraction and amplification

    PubMed Central

    2010-01-01

    Background Several pathogens could seriously affect public health if not recognized timely. To reduce the impact of such highly pathogenic micro-organisms, rapid and accurate diagnostic tools are needed for their detection in various samples, including environmental samples. Results Multiplex real-time PCRs were designed for rapid and reliable detection of three major pathogens that have the potential to cause high morbidity and mortality in humans: B. anthracis, F. tularensis and Y. pestis. The developed assays detect three pathogen-specific targets, including at least one chromosomal target, and one target from B. thuringiensis which is used as an internal control for nucleic acid extraction from refractory spores as well as successful DNA amplification. Validation of the PCRs showed a high analytical sensitivity, specificity and coverage of diverse pathogen strains. Conclusions The multiplex qPCR assays that were developed allow the rapid detection of 3 pathogen-specific targets simultaneously, without compromising sensitivity. The application of B. thuringiensis spores as internal controls further reduces false negative results. This ensures highly reliable detection, while template consumption and laboratory effort are kept at a minimum PMID:21143837

  18. Quantification of non-coding RNA target localization diversity and its application in cancers.

    PubMed

    Cheng, Lixin; Leung, Kwong-Sak

    2018-04-01

    Subcellular localization is pivotal for RNAs and proteins to implement biological functions. The localization diversity of protein interactions has been studied as a crucial feature of proteins, considering that the protein-protein interactions take place in various subcellular locations. Nevertheless, the localization diversity of non-coding RNA (ncRNA) target proteins has not been systematically studied, especially its characteristics in cancers. In this study, we provide a new algorithm, non-coding RNA target localization coefficient (ncTALENT), to quantify the target localization diversity of ncRNAs based on the ncRNA-protein interaction and protein subcellular localization data. ncTALENT can be used to calculate the target localization coefficient of ncRNAs and measure how diversely their targets are distributed among the subcellular locations in various scenarios. We focus our study on long non-coding RNAs (lncRNAs), and our observations reveal that the target localization diversity is a primary characteristic of lncRNAs in different biotypes. Moreover, we found that lncRNAs in multiple cancers, differentially expressed cancer lncRNAs, and lncRNAs with multiple cancer target proteins are prone to have high target localization diversity. Furthermore, the analysis of gastric cancer helps us to obtain a better understanding that the target localization diversity of lncRNAs is an important feature closely related to clinical prognosis. Overall, we systematically studied the target localization diversity of the lncRNAs and uncovered its association with cancer.

  19. Mohawk Tannery Hazardous Waste Site in New Hampshire included on EPA List of Targeted for Immediate Attention

    EPA Pesticide Factsheets

    Today, the U.S. Environmental Protection Agency released the list of Superfund sites that Administrator Pruitt has targeted for immediate and intense attention. The former Mohawk Tannery facility (a.k.a. Granite State Leathers) is one of the 21 sites on th

  20. Improved target detection by IR dual-band image fusion

    NASA Astrophysics Data System (ADS)

    Adomeit, U.; Ebert, R.

    2009-09-01

    Dual-band thermal imagers acquire information simultaneously in both the 8-12 μm (long-wave infrared, LWIR) and the 3-5 μm (mid-wave infrared, MWIR) spectral range. Compared to single-band thermal imagers they are expected to have several advantages in military applications. These advantages include the opportunity to use the best band for given atmospheric conditions (e. g. cold climate: LWIR, hot and humid climate: MWIR), the potential to better detect camouflaged targets and an improved discrimination between targets and decoys. Most of these advantages have not yet been verified and/or quantified. It is expected that image fusion allows better exploitation of the information content available with dual-band imagers especially with respect to detection of targets. We have developed a method for dual-band image fusion based on the apparent temperature differences in the two bands. This method showed promising results in laboratory tests. In order to evaluate its performance under operational conditions we conducted a field trial in an area with high thermal clutter. In such areas, targets are hardly to detect in single-band images because they vanish in the clutter structure. The image data collected in this field trial was used for a perception experiment. This perception experiment showed an enhanced target detection range and reduced false alarm rate for the fused images compared to the single-band images.

  1. Advancing the sensitivity of selected reaction monitoring-based targeted quantitative proteomics

    PubMed Central

    Shi, Tujin; Su, Dian; Liu, Tao; Tang, Keqi; Camp, David G.; Qian, Wei-Jun; Smith, Richard D.

    2012-01-01

    Selected reaction monitoring (SRM)—also known as multiple reaction monitoring (MRM)—has emerged as a promising high-throughput targeted protein quantification technology for candidate biomarker verification and systems biology applications. A major bottleneck for current SRM technology, however, is insufficient sensitivity for e.g., detecting low-abundance biomarkers likely present at the low ng/mL to pg/mL range in human blood plasma or serum, or extremely low-abundance signaling proteins in cells or tissues. Herein we review recent advances in methods and technologies, including front-end immunoaffinity depletion, fractionation, selective enrichment of target proteins/peptides including posttranslational modifications (PTMs), as well as advances in MS instrumentation which have significantly enhanced the overall sensitivity of SRM assays and enabled the detection of low-abundance proteins at low to sub- ng/mL level in human blood plasma or serum. General perspectives on the potential of achieving sufficient sensitivity for detection of pg/mL level proteins in plasma are also discussed. PMID:22577010

  2. Tumor-targeting peptides from combinatorial libraries*

    PubMed Central

    Liu, Ruiwu; Li, Xiaocen; Xiao, Wenwu; Lam, Kit S.

    2018-01-01

    Cancer is one of the major and leading causes of death worldwide. Two of the greatest challenges infighting cancer are early detection and effective treatments with no or minimum side effects. Widespread use of targeted therapies and molecular imaging in clinics requires high affinity, tumor-specific agents as effective targeting vehicles to deliver therapeutics and imaging probes to the primary or metastatic tumor sites. Combinatorial libraries such as phage-display and one-bead one-compound (OBOC) peptide libraries are powerful approaches in discovering tumor-targeting peptides. This review gives an overview of different combinatorial library technologies that have been used for the discovery of tumor-targeting peptides. Examples of tumor-targeting peptides identified from each combinatorial library method will be discussed. Published tumor-targeting peptide ligands and their applications will also be summarized by the combinatorial library methods and their corresponding binding receptors. PMID:27210583

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

    PubMed

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

    2017-01-01

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

  4. Self-assembled peptide-based nanostructures: Smart nanomaterials toward targeted drug delivery.

    PubMed

    Habibi, Neda; Kamaly, Nazila; Memic, Adnan; Shafiee, Hadi

    2016-02-01

    Self-assembly of peptides can yield an array of well-defined nanostructures that are highly attractive nanomaterials for many biomedical applications such as drug delivery. Some of the advantages of self-assembled peptide nanostructures over other delivery platforms include their chemical diversity, biocompatibility, high loading capacity for both hydrophobic and hydrophilic drugs, and their ability to target molecular recognition sites. Furthermore, these self-assembled nanostructures could be designed with novel peptide motifs, making them stimuli-responsive and achieving triggered drug delivery at disease sites. The goal of this work is to present a comprehensive review of the most recent studies on self-assembled peptides with a focus on their "smart" activity for formation of targeted and responsive drug-delivery carriers.

  5. Groundwater Quality Assessment Plan: Dickson County Landfill, Dickson County, Tennessee, including Application for Authorization for Class V Underground Injection Well

    EPA Pesticide Factsheets

    Contains site investigation plan & data for assessment of groundwater quality at Dickson County Landfill, Dickson, Tennessee, with figures, tables, appendices, November 1994, including Application for Authorization for Class V Underground Injection Well.

  6. Classifying transcription factor targets and discovering relevant biological features

    PubMed Central

    Holloway, Dustin T; Kon, Mark; DeLisi, Charles

    2008-01-01

    Background An important goal in post-genomic research is discovering the network of interactions between transcription factors (TFs) and the genes they regulate. We have previously reported the development of a supervised-learning approach to TF target identification, and used it to predict targets of 104 transcription factors in yeast. We now include a new sequence conservation measure, expand our predictions to include 59 new TFs, introduce a web-server, and implement an improved ranking method to reveal the biological features contributing to regulation. The classifiers combine 8 genomic datasets covering a broad range of measurements including sequence conservation, sequence overrepresentation, gene expression, and DNA structural properties. Principal Findings (1) Application of the method yields an amplification of information about yeast regulators. The ratio of total targets to previously known targets is greater than 2 for 11 TFs, with several having larger gains: Ash1(4), Ino2(2.6), Yaf1(2.4), and Yap6(2.4). (2) Many predicted targets for TFs match well with the known biology of their regulators. As a case study we discuss the regulator Swi6, presenting evidence that it may be important in the DNA damage response, and that the previously uncharacterized gene YMR279C plays a role in DNA damage response and perhaps in cell-cycle progression. (3) A procedure based on recursive-feature-elimination is able to uncover from the large initial data sets those features that best distinguish targets for any TF, providing clues relevant to its biology. An analysis of Swi6 suggests a possible role in lipid metabolism, and more specifically in metabolism of ceramide, a bioactive lipid currently being investigated for anti-cancer properties. (4) An analysis of global network properties highlights the transcriptional network hubs; the factors which control the most genes and the genes which are bound by the largest set of regulators. Cell-cycle and growth related

  7. Tritium target manufacturing for use in accelerators

    NASA Astrophysics Data System (ADS)

    Bach, P.; Monnin, C.; Van Rompay, M.; Ballanger, A.

    2001-07-01

    As a neutron tube manufacturer, SODERN is now in charge of manufacturing tritium targets for accelerators, in cooperation with CEA/DAM/DTMN in Valduc. Specific deuterium and tritium targets are manufactured on request, according to the requirements of the users, starting from titanium target on copper substrate, and going to more sophisticated devices. A wide range of possible uses is covered, including thin targets for neutron calibration, thick targets with controlled loading of deuterium and tritium, rotating targets for higher lifetimes, or large size rotating targets for accelerators used in boron neutron therapy. Activity of targets lies in the 1 to 1000 Curie, diameter of targets being up to 30 cm. Special targets are also considered, including surface layer targets for lowering tritium desorption under irradiation, or those made from different kinds of occluders such as titanium, zirconium, erbium, scandium, with different substrates. It is then possible to optimize either neutron output, or lifetime and stability, or thermal behavior.

  8. Predicting oligonucleotide affinity to nucleic acid targets.

    PubMed Central

    Mathews, D H; Burkard, M E; Freier, S M; Wyatt, J R; Turner, D H

    1999-01-01

    A computer program, OligoWalk, is reported that predicts the equilibrium affinity of complementary DNA or RNA oligonucleotides to an RNA target. This program considers the predicted stability of the oligonucleotide-target helix and the competition with predicted secondary structure of both the target and the oligonucleotide. Both unimolecular and bimolecular oligonucleotide self structure are considered with a user-defined concentration. The application of OligoWalk is illustrated with three comparisons to experimental results drawn from the literature. PMID:10580474

  9. 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.

  10. Bacteriophages and medical oncology: targeted gene therapy of cancer.

    PubMed

    Bakhshinejad, Babak; Karimi, Marzieh; Sadeghizadeh, Majid

    2014-08-01

    Targeted gene therapy of cancer is of paramount importance in medical oncology. Bacteriophages, viruses that specifically infect bacterial cells, offer a variety of potential applications in biomedicine. Their genetic flexibility to go under a variety of surface modifications serves as a basis for phage display methodology. These surface manipulations allow bacteriophages to be exploited for targeted delivery of therapeutic genes. Moreover, the excellent safety profile of these viruses paves the way for their potential use as cancer gene therapy platforms. The merge of phage display and combinatorial technology has led to the emergence of phage libraries turning phage display into a high throughput technology. Random peptide libraries, as one of the most frequently used phage libraries, provide a rich source of clinically useful peptide ligands. Peptides are known as a promising category of pharmaceutical agents in medical oncology that present advantages such as inexpensive synthesis, efficient tissue penetration and the lack of immunogenicity. Phage peptide libraries can be screened, through biopanning, against various targets including cancer cells and tissues that results in obtaining cancer-homing ligands. Cancer-specific peptides isolated from phage libraries show huge promise to be utilized for targeting of various gene therapy vectors towards malignant cells. Beyond doubt, bacteriophages will play a more impressive role in the future of medical oncology.

  11. Infrared dim-small target tracking via singular value decomposition and improved Kernelized correlation filter

    NASA Astrophysics Data System (ADS)

    Qian, Kun; Zhou, Huixin; Rong, Shenghui; Wang, Bingjian; Cheng, Kuanhong

    2017-05-01

    Infrared small target tracking plays an important role in applications including military reconnaissance, early warning and terminal guidance. In this paper, an effective algorithm based on the Singular Value Decomposition (SVD) and the improved Kernelized Correlation Filter (KCF) is presented for infrared small target tracking. Firstly, the super performance of the SVD-based algorithm is that it takes advantage of the target's global information and obtains a background estimation of an infrared image. A dim target is enhanced by subtracting the corresponding estimated background with update from the original image. Secondly, the KCF algorithm is combined with Gaussian Curvature Filter (GCF) to eliminate the excursion problem. The GCF technology is adopted to preserve the edge and eliminate the noise of the base sample in the KCF algorithm, helping to calculate the classifier parameter for a small target. At last, the target position is estimated with a response map, which is obtained via the kernelized classifier. Experimental results demonstrate that the presented algorithm performs favorably in terms of efficiency and accuracy, compared with several state-of-the-art algorithms.

  12. Multifunctional magnetic nanoparticles for targeted imaging and therapy

    PubMed Central

    McCarthy, Jason R.; Weissleder, Ralph

    2008-01-01

    Magnetic nanoparticles have become important tools for the imaging of prevalent diseases, such as cancer, atherosclerosis, diabetes, and others. While first generation nanoparticles were fairly nonspecific, newer generations have been targeted to specific cell types and molecular targets via affinity ligands. Commonly, these ligands emerge from phage or small molecule screens, or are based on antibodies or aptamers. Secondary reporters and combined therapeutic molecules have further opened potential clinical applications of these materials. This review summarizes some of the recent biomedical applications of these newer magnetic nanomaterials. PMID:18508157

  13. Multifunctional nanosheets based on folic acid modified manganese oxide for tumor-targeting theranostic application

    NASA Astrophysics Data System (ADS)

    Hao, Yongwei; Wang, Lei; Zhang, Bingxiang; Zhao, Hongjuan; Niu, Mengya; Hu, Yujie; Zheng, Cuixia; Zhang, Hongling; Chang, Junbiao; Zhang, Zhenzhong; Zhang, Yun

    2016-01-01

    It is highly desirable to develop smart nanocarriers with stimuli-responsive drug-releasing and diagnostic-imaging functions for cancer theranostics. Herein, we develop a reduction and pH dual-responsive tumor theranostic platform based on degradable manganese dioxide (MnO2) nanosheets. The MnO2 nanosheets with a size of 20-60 nm were first synthesized and modified with (3-Aminopropyl) trimethoxysilane (APTMS) to get amine-functionalized MnO2, and then functionalized by NH2-PEG2000-COOH (PEG). The tumor-targeting group, folic acid (FA), was finally conjugated with the PEGylated MnO2 nanosheets. Then, doxorubicin (DOX), a chemotherapeutic agent, was loaded onto the modified nanosheets through a physical adsorption, which was designated as MnO2-PEG-FA/DOX. The prepared MnO2-PEG-FA/DOX nanosheets with good biocompatibility can not only efficiently deliver DOX to tumor cells in vitro and in vivo, leading to enhanced anti-tumor efficiency, but can also respond to a slightly acidic environment and high concentration of reduced glutathione (GSH), which caused degradation of MnO2 into manganese ions enabling magnetic resonance imaging (MRI). The longitudinal relaxation rate r 1 was 2.26 mM-1 s-1 at pH 5.0 containing 2 mM GSH. These reduction and pH dual-responsive biodegradable nanosheets combining efficient MRI and chemotherapy provide a novel and promising platform for tumor-targeting theranostic application.

  14. Vector design for liver specific expression of multiple interfering RNAs that target hepatitis B virus transcripts

    PubMed Central

    Snyder, Lindsey L.; Esser, Jonathan M.; Pachuk, Catherine J.; Steel, Laura F.

    2008-01-01

    RNA interference (RNAi) is a process that can target intracellular RNAs for degradation in a highly sequence specific manner, making it a powerful tool that is being pursued in both research and therapeutic applications. Hepatitis B virus (HBV) is a serious public health problem in need of better treatment options, and aspects of its life cycle make it an excellent target for RNAi-based therapeutics. We have designed a vector that expresses interfering RNAs that target HBV transcripts, including both viral RNA replicative intermediates and mRNAs encoding viral proteins. Our vector design incorporates many features of endogenous microRNA (miRNA) gene organization that are proving useful for the development of reagents for RNAi. In particular, our vector contains an RNA pol II driven gene cassette that leads to tissue specific expression and efficient processing of multiple interfering RNAs from a single transcript, without the co-expression of any protein product. This vector shows potent silencing of HBV targets in cell culture models of HBV infection. The vector design will be applicable to silencing of additional cellular or disease-related genes. PMID:18499277

  15. Application of stem cells in targeted therapy of breast cancer: a systematic review.

    PubMed

    Madjd, Zahra; Gheytanchi, Elmira; Erfani, Elham; Asadi-Lari, Mohsen

    2013-01-01

    The aim of this systematic review was to investigate whether stem cells could be effectively applied in targeted therapy of breast cancer. A systematic literature search was performed for original articles published from January 2007 until May 2012. Nine studies met the inclusion criteria for phase I or II clinical trials, of which three used stem cells as vehicles, two trials used autologous hematopoetic stem cells and in four trials cancer stem cells were targeted. Mesenchymal stem cells (MSCs) were applied as cellular vehicles to transfer therapeutic agents. Cell therapy with MSC can successfully target resistant cancers. Cancer stem cells were selectively targeted via a proteasome-dependent suicide gene leading to tumor regression. Wnt/β-catenin signaling pathway has been also evidenced to be an attractive CSC-target. This systematic review focused on two different concepts of stem cells and breast cancer marking a turning point in the trials that applied stem cells as cellular vehicles for targeted delivery therapy as well as CSC-targeted therapies. Applying stem cells as targeted therapy could be an effective therapeutic approach for treatment of breast cancer in the clinic and in therapeutic marketing; however this needs to be confirmed with further clinical investigations.

  16. A small molecule nanodrug consisting of amphiphilic targeting ligand-chemotherapy drug conjugate for targeted cancer therapy.

    PubMed

    Mou, Quanbing; Ma, Yuan; Zhu, Xinyuan; Yan, Deyue

    2016-05-28

    Targeted drug delivery is a broadly applicable approach for cancer therapy. However, the nanocarrier-based targeted delivery system suffers from batch-to-batch variation, quality concerns and carrier-related toxicity issues. Thus, to develop a carrier-free targeted delivery system with nanoscale characteristics is very attractive. Here, a novel targeting small molecule nanodrug self-delivery system consisting of targeting ligand and chemotherapy drug was constructed, which combined the advantages of small molecules and nano-assemblies together and showed excellent targeting ability and long blood circulation time with well-defined structure, high drug loading ratio and on-demand drug release behavior. As a proof-of-concept, lactose (Lac) and doxorubicin (DOX) were chosen as the targeting ligand and chemotherapy drug, respectively. Lac and DOX were conjugated through a pH-responsive hydrazone group. For its intrinsic amphiphilic property, Lac-DOX conjugate could self-assemble into nanoparticles in water. Both in vitro and in vivo assays indicated that Lac-DOX nanoparticles exhibited enhanced anticancer activity and weak side effects. This novel active targeting nanodrug delivery system shows great potential in cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Antibacterial application of engineered bacteriophage nanomedicines: antibody-targeted, chloramphenicol prodrug loaded bacteriophages for inhibiting the growth of Staphylococcus aureus bacteria.

    PubMed

    Vaks, Lilach; Benhar, Itai

    2011-01-01

    The increasing development of bacterial resistance to traditional antibiotics has reached alarming levels, thus there is an urgent need to develop new antimicrobial agents. To be effective, these new antimicrobials should possess novel modes of action and/or different cellular targets compared with existing antibiotics. Bacteriophages (phages) have been used for over a century as tools for the treatment of bacterial infections, for nearly half a century as tools in genetic research, for about two decades as tools for the discovery of specific target-binding proteins and peptides, and for almost a decade as tools for vaccine development. We describe a new application in the area of antibacterial nanomedicines where filamentous phages can be formulated as targeted drug-delivery vehicles of nanometric dimensions (phage nanomedicines) and used for therapeutic purposes. This protocol involves both genetic and chemical engineering of these phages. The genetic engineering of the phage coat, which results in the display of a target-specificity-conferring peptide or protein on the phage coat, can be used to design the drug-release mechanism and is not described herein. However, the methods used to chemically conjugate cytotoxic drugs at high density on the phage coat are described. Further, assays to measure the drug load on the surface of the phage and the potency of the system in the inhibition of growth of target cells as well as assessment of the therapeutic potential of the phages in a mouse disease model are discussed.

  18. Nanobody-derived nanobiotechnology tool kits for diverse biomedical and biotechnology applications.

    PubMed

    Wang, Yongzhong; Fan, Zhen; Shao, Lei; Kong, Xiaowei; Hou, Xianjuan; Tian, Dongrui; Sun, Ying; Xiao, Yazhong; Yu, Li

    2016-01-01

    Owing to peculiar properties of nanobody, including nanoscale size, robust structure, stable and soluble behaviors in aqueous solution, reversible refolding, high affinity and specificity for only one cognate target, superior cryptic cleft accessibility, and deep tissue penetration, as well as a sustainable source, it has been an ideal research tool for the development of sophisticated nanobiotechnologies. Currently, the nanobody has been evolved into versatile research and application tool kits for diverse biomedical and biotechnology applications. Various nanobody-derived formats, including the nanobody itself, the radionuclide or fluorescent-labeled nanobodies, nanobody homo- or heteromultimers, nanobody-coated nanoparticles, and nanobody-displayed bacteriophages, have been successfully demonstrated as powerful nanobiotechnological tool kits for basic biomedical research, targeting drug delivery and therapy, disease diagnosis, bioimaging, and agricultural and plant protection. These applications indicate a special advantage of these nanobody-derived technologies, already surpassing the "me-too" products of other equivalent binders, such as the full-length antibodies, single-chain variable fragments, antigen-binding fragments, targeting peptides, and DNA-based aptamers. In this review, we summarize the current state of the art in nanobody research, focusing on the nanobody structural features, nanobody production approach, nanobody-derived nanobiotechnology tool kits, and the potentially diverse applications in biomedicine and biotechnology. The future trends, challenges, and limitations of the nanobody-derived nanobiotechnology tool kits are also discussed.

  19. Mixture model normalization for non-targeted gas chromatography/mass spectrometry metabolomics data.

    PubMed

    Reisetter, Anna C; Muehlbauer, Michael J; Bain, James R; Nodzenski, Michael; Stevens, Robert D; Ilkayeva, Olga; Metzger, Boyd E; Newgard, Christopher B; Lowe, William L; Scholtens, Denise M

    2017-02-02

    Metabolomics offers a unique integrative perspective for health research, reflecting genetic and environmental contributions to disease-related phenotypes. Identifying robust associations in population-based or large-scale clinical studies demands large numbers of subjects and therefore sample batching for gas-chromatography/mass spectrometry (GC/MS) non-targeted assays. When run over weeks or months, technical noise due to batch and run-order threatens data interpretability. Application of existing normalization methods to metabolomics is challenged by unsatisfied modeling assumptions and, notably, failure to address batch-specific truncation of low abundance compounds. To curtail technical noise and make GC/MS metabolomics data amenable to analyses describing biologically relevant variability, we propose mixture model normalization (mixnorm) that accommodates truncated data and estimates per-metabolite batch and run-order effects using quality control samples. Mixnorm outperforms other approaches across many metrics, including improved correlation of non-targeted and targeted measurements and superior performance when metabolite detectability varies according to batch. For some metrics, particularly when truncation is less frequent for a metabolite, mean centering and median scaling demonstrate comparable performance to mixnorm. When quality control samples are systematically included in batches, mixnorm is uniquely suited to normalizing non-targeted GC/MS metabolomics data due to explicit accommodation of batch effects, run order and varying thresholds of detectability. Especially in large-scale studies, normalization is crucial for drawing accurate conclusions from non-targeted GC/MS metabolomics data.

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

    PubMed Central

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

    2017-01-01

    ABSTRACT Traditional approaches to drug discovery are frustratingly inefficient and have several key limitations that severely constrain our capacity to rapidly identify and develop novel experimental therapeutics. To address this, we have devised a second-generation target-based whole-cell screening assay based on the principles of competitive fitness, which can rapidly identify target-specific and physiologically active compounds. Briefly, strains expressing high, intermediate, and low levels of a preselected target protein are constructed, tagged with spectrally distinct fluorescent proteins (FPs), and pooled. The pooled strains are then grown in the presence of various small molecules, and the relative growth of each strain within the mixed culture is compared by measuring the intensity of the corresponding FP tags. Chemical-induced population shifts indicate that the bioactivity of a small molecule is dependent upon the target protein’s abundance and thus establish a specific functional interaction. Here, we describe the molecular tools required to apply this technique in the prevalent human fungal pathogen Candida albicans and validate the approach using two well-characterized drug targets—lanosterol demethylase and dihydrofolate reductase. However, our approach, which we have termed target abundance-based fitness screening (TAFiS), should be applicable to a wide array of molecular targets and in essentially any genetically tractable microbe. IMPORTANCE Conventional drug screening typically employs either target-based or cell-based approaches. The first group relies on biochemical assays to detect modulators of a purified target. However, hits frequently lack drug-like characteristics such as membrane permeability and target specificity. Cell-based screens identify compounds that induce a desired phenotype, but the target is unknown, which severely restricts further development and optimization. To address these issues, we have developed a second

  1. Cancer active targeting by nanoparticles: a comprehensive review of literature

    PubMed Central

    Bazak, Remon; Houri, Mohamad; Achy, Samar El; Kamel, Serag

    2016-01-01

    Purpose Cancer is one of the leading causes of death, and thus, the scientific community has but great efforts to improve cancer management. Among the major challenges in cancer management is development of agents that can be used for early diagnosis and effective therapy. Conventional cancer management frequently lacks accurate tools for detection of early tumors and has an associated risk of serious side effects of chemotherapeutics. The need to optimize therapeutic ratio as the difference with which a treatment affects cancer cells versus healthy tissues lead to idea that it is needful to have a treatment that could act a the “magic bullet”—recognize cancer cells only. Nanoparticle platforms offer a variety of potentially efficient solutions for development of targeted agents that can be exploited for cancer diagnosis and treatment. There are two ways by which targeting of nanoparticles can be achieved, namely passive and active targeting. Passive targeting allows for the efficient localization of nanoparticles within the tumor microenvironment. Active targeting facilitates the active uptake of nanoparticles by the tumor cells themselves. Methods Relevant English electronic databases and scientifically published original articles and reviews were systematically searched for the purpose of this review. Results In this report, we present a comprehensive review of literatures focusing on the active targeting of nanoparticles to cancer cells, including antibody and antibody fragment-based targeting, antigen-based targeting, aptamer-based targeting, as well as ligand-based targeting. Conclusion To date, the optimum targeting strategy has not yet been announced, each has its own advantages and disadvantages even though a number of them have found their way for clinical application. Perhaps, a combination of strategies can be employed to improve the precision of drug delivery, paving the way for a more effective personalized therapy. PMID:25005786

  2. The Physics of Advanced High-Gain Targets for Inertial Fusion Energy

    NASA Astrophysics Data System (ADS)

    Perkins, L. John

    2010-11-01

    In ca. 2011-2012, the National Ignition Facility is poised to demonstrate fusion ignition and gain in the laboratory for the first time. This key milestone in the development of inertial confinement fusion (ICF) can be expected to engender interest in the development of inertial fusion energy (IFE) and expanded efforts on a number of advanced targets that may achieve high fusion energy gain at lower driver energies. In this tutorial talk, we will discuss the physics underlying ICF ignition and thermonuclear burn, examine the requirements for high gain, and outline candidate R&D programs that will be required to assess the performance of these target concepts under various driver systems including lasers, heavy-ions and pulsed power. Such target concepts include those operating by fast ignition, shock ignition, impact ignition, dual-density, magnetically-insulated, one- and two-sided drive, etc., some of which may have potential to burn advanced, non-DT fusion fuels. We will then delineate the role of such targets in their application to the production of high average fusion power. Here, systems studies of IFE economics suggest that we should strive for target fusion gains of around 100 at drive energies of 1MJ, together with corresponding rep-rates of up to 10Hz and driver electrical efficiencies around 15%. In future years, there may be exciting opportunities to study such ``innovative confinement concepts'' with prospects of fielding them on facilities such as NIF to obtain high fusion energy gains on a single shot basis.

  3. Biocompatible Quantum Dots for Biological Applications

    PubMed Central

    Rosenthal, Sandra J.; Chang, Jerry C.; Kovtun, Oleg; McBride, James R.; Tomlinson, Ian D.

    2011-01-01

    Semiconductor quantum dots are quickly becoming a critical diagnostic tool for discerning cellular function at the molecular level. Their high brightness, long-lasting, sizetunable, and narrow luminescence set them apart from conventional fluorescence dyes. Quantum dots are being developed for a variety of biologically oriented applications, including fluorescent assays for drug discovery, disease detection, single protein tracking, and intracellular reporting. This review introduces the science behind quantum dots and describes how they are made biologically compatible. Several applications are also included, illustrating strategies toward target specificity, and are followed by a discussion on the limitations of quantum dot approaches. The article is concluded with a look at the future direction of quantum dots. PMID:21276935

  4. 42 CFR 457.310 - Targeted low-income child.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false Targeted low-income child. 457.310 Section 457.310... (CONTINUED) STATE CHILDREN'S HEALTH INSURANCE PROGRAMS (SCHIPs) ALLOTMENTS AND GRANTS TO STATES State Plan Requirements: Eligibility, Screening, Applications, and Enrollment § 457.310 Targeted low-income child. (a...

  5. 42 CFR 457.310 - Targeted low-income child.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 4 2012-10-01 2012-10-01 false Targeted low-income child. 457.310 Section 457.310... (CONTINUED) STATE CHILDREN'S HEALTH INSURANCE PROGRAMS (SCHIPs) ALLOTMENTS AND GRANTS TO STATES State Plan Requirements: Eligibility, Screening, Applications, and Enrollment § 457.310 Targeted low-income child. (a...

  6. 42 CFR 457.310 - Targeted low-income child.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Targeted low-income child. 457.310 Section 457.310... (CONTINUED) STATE CHILDREN'S HEALTH INSURANCE PROGRAMS (SCHIPs) ALLOTMENTS AND GRANTS TO STATES State Plan Requirements: Eligibility, Screening, Applications, and Enrollment § 457.310 Targeted low-income child. (a...

  7. 42 CFR 457.310 - Targeted low-income child.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false Targeted low-income child. 457.310 Section 457.310... (CONTINUED) STATE CHILDREN'S HEALTH INSURANCE PROGRAMS (SCHIPs) ALLOTMENTS AND GRANTS TO STATES State Plan Requirements: Eligibility, Screening, Applications, and Enrollment § 457.310 Targeted low-income child. (a...

  8. 42 CFR 457.310 - Targeted low-income child.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Targeted low-income child. 457.310 Section 457.310... (CONTINUED) STATE CHILDREN'S HEALTH INSURANCE PROGRAMS (SCHIPs) ALLOTMENTS AND GRANTS TO STATES State Plan Requirements: Eligibility, Screening, Applications, and Enrollment § 457.310 Targeted low-income child. (a...

  9. Targets and methods for target preparation for radionuclide production

    DOEpatents

    Zhuikov, Boris L; Konyakhin, Nicolai A; Kokhanyuk, Vladimir M; Srivastava, Suresh C

    2012-10-16

    The invention relates to nuclear technology, and to irradiation targets and their preparation. One embodiment of the present invention includes a method for preparation of a target containing intermetallic composition of antimony Ti--Sb, Al--Sb, Cu--Sb, or Ni--Sb in order to produce radionuclides (e.g., tin-117 m) with a beam of accelerated particles. The intermetallic compounds of antimony can be welded by means of diffusion welding to a copper backing cooled during irradiation on the beam of accelerated particles. Another target can be encapsulated into a shell made of metallic niobium, stainless steel, nickel or titanium cooled outside by water during irradiation. Titanium shell can be plated outside by nickel to avoid interaction with the cooling water.

  10. Tumor-targeting peptides from combinatorial libraries.

    PubMed

    Liu, Ruiwu; Li, Xiaocen; Xiao, Wenwu; Lam, Kit S

    2017-02-01

    Cancer is one of the major and leading causes of death worldwide. Two of the greatest challenges in fighting cancer are early detection and effective treatments with no or minimum side effects. Widespread use of targeted therapies and molecular imaging in clinics requires high affinity, tumor-specific agents as effective targeting vehicles to deliver therapeutics and imaging probes to the primary or metastatic tumor sites. Combinatorial libraries such as phage-display and one-bead one-compound (OBOC) peptide libraries are powerful approaches in discovering tumor-targeting peptides. This review gives an overview of different combinatorial library technologies that have been used for the discovery of tumor-targeting peptides. Examples of tumor-targeting peptides identified from each combinatorial library method will be discussed. Published tumor-targeting peptide ligands and their applications will also be summarized by the combinatorial library methods and their corresponding binding receptors. Copyright © 2017. Published by Elsevier B.V.

  11. The future impacts of non-targeted effects.

    PubMed

    Bright, Scott; Kadhim, Munira

    2018-04-11

    Ionizing radiation was traditionally thought to exert its detrimental effects through interaction with sensitive cellular targets, nuclear DNA being of most importance. This theory has since merged with a more recently described radiation response called non-targeted effects (NTE). This review will briefly look at the various types of NTE and the potential implications they may have for radiobiology research and its applications. The most well-known NTE are genomic instability (GI) and bystander effects (BE). Other NTE include abscopal effects, which are similar to bystander effects but are generally based in a clinical environment with immune involvement as the defining feature. Currently, our understanding of NTE is limited to certain signaling pathways/molecules, and as yet there is no theory that describes or can accurately predict the occurrence or outcome of these NTE. There are numerous groups investigating these processes in vitro and in vivo, and thus steady progress is being made. Developing a deeper understanding of NTE has potential impacts for therapy and diagnosis, safer occupational exposures, space flight and our general understanding of radiation biology.

  12. The implications of recent advances in carboxymethyl chitosan based targeted drug delivery and tissue engineering applications.

    PubMed

    Upadhyaya, Laxmi; Singh, Jay; Agarwal, Vishnu; Tewari, Ravi Prakash

    2014-07-28

    Over the last decade carboxymethyl chitosan (CMCS) has emerged as a promising biopolymer for the development of new drug delivery systems and improved scaffolds along with other tissue engineering devices for regenerative medicine that is currently one of the most rapidly growing fields in the life sciences. CMCS is amphiprotic ether, derived from chitosan, exhibiting enhanced aqueous solubility, excellent biocompatibility, controllable biodegradability, osteogenesis ability and numerous other outstanding physicochemical and biological properties. More strikingly, it can load hydrophobic drugs and displays strong bioactivity which highlight its suitability and extensive usage for preparing different drug delivery and tissue engineering formulations respectively. This review provides a comprehensive introduction to various types of CMCS based formulations for delivery of therapeutic agents and tissue regeneration and further describes their preparation procedures and applications in different tissues/organs. Detailed information of CMCS based nano/micro systems for targeted delivery of drugs with emphasis on cancer specific and organ specific drug delivery have been described. Further, we have discussed various CMCS based tissue engineering biomaterials along with their preparation procedures and applications in different tissues/organs. The article then, gives a brief account of therapy combining drug delivery and tissue engineering. Finally, identification of major challenges and opportunities for current and ongoing application of CMCS based systems in the field are summarised. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2012-02-20

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

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

    PubMed Central

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

    2011-01-01

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

  15. Dual-targeting siRNAs

    PubMed Central

    Tiemann, Katrin; Höhn, Britta; Ehsani, Ali; Forman, Stephen J.; Rossi, John J.; Sætrom, Pål

    2010-01-01

    We have developed an algorithm for the prediction of dual-targeting short interfering RNAs (siRNAs) in which both strands are deliberately designed to separately target different mRNA transcripts with complete complementarity. An advantage of this approach versus the use of two separate duplexes is that only two strands, as opposed to four, are competing for entry into the RNA-induced silencing complex. We chose to design our dual-targeting siRNAs as Dicer substrate 25/27mer siRNAs, since design features resembling pre-microRNAs (miRNAs) can be introduced for Dicer processing. Seven different dual-targeting siRNAs targeting genes that are potential targets in cancer therapy have been developed including Bcl2, Stat3, CCND1, BIRC5, and MYC. The dual-targeting siRNAs have been characterized for dual target knockdown in three different cell lines (HEK293, HCT116, and PC3), where they were as effective as their corresponding single-targeting siRNAs in target knockdown. The algorithm developed in this study should prove to be useful for predicting dual-targeting siRNAs in a variety of different targets and is available from http://demo1.interagon.com/DualTargeting/. PMID:20410240

  16. Actinide targets for fundamental research in nuclear physics

    NASA Astrophysics Data System (ADS)

    Eberhardt, K.; Düllmann, Ch. E.; Haas, R.; Mokry, Ch.; Runke, J.; Thörle-Pospiech, P.; Trautmann, N.

    2018-05-01

    Thin actinide layers deposited on various substrates are widely used as calibration sources in nuclear spectroscopy. Other applications include fundamental research in nuclear chemistry and -physics, e.g., the chemical and physical properties of super-heavy elements (SHE, Z > 103) or nuclear reaction studies with heavy ions. For the design of future nuclear reactors like fast-fission reactors and accelerator-driven systems for transmutation of nuclear waste, precise data for neutron absorption as well as neutron-induced fission cross section data for 242Pu with neutrons of different energies are of particular importance, requiring suitable Pu-targets. Another application includes studies of nuclear transitions in 229Th harvested as α-decay recoil product from a thin layer of its 233U precursor. For this, a thin and very smooth layer of 233U is used. We report here on the production of actinide layers mostly obtained by Molecular Plating (MP). MP is currently the only fabrication method in cases where the desired actinide material is available only in very limited amounts or possesses a high specific activity. Here, deposition is performed from organic solution applying a current density of 1-2 mA/cm2. Under these conditions target thicknesses of 500-1000 μg/cm2 are possible applying a single deposition step with deposition yields approaching 100 %. For yield determination α-particle spectroscopy, γ-spectroscopy and Neutron Activation Analysis is routinely used. Layer homogeneity is checked with Radiographic Imaging. As an alternative technique to MP the production of thin lanthanide and actinide layers by the so-called "Drop on Demand"-technique applied e.g., in ink-jet printing is currently under investigation.

  17. New Molecular Targets of Anticancer Therapy - Current Status and Perspectives.

    PubMed

    Zajac, Marianna; Muszalska, Izabela; Jelinska, Anna

    2016-01-01

    Molecularly targeted anticancer therapy involves the use of drugs or other substances affecting specific molecular targets that play a part in the development, progression and spread of a given neoplasm. By contrast, the majority of classical chemotherapeutics act on all rapidly proliferating cells, both healthy and cancerous ones. Target anticancer drugs are designed to achieve a particular aim and they usually act cytostatically, not cytotoxically like classical chemotherapeutics. At present, more than 300 biological molecular targets have been identified. The proteins involved in cellular metabolism include (among others) receptor proteins, signal transduction proteins, mRNA thread matrix synthesis proteins participating in neoplastic transformation, cell cycle control proteins, functional and structural proteins. The receptor proteins that are targeted by currently used anticancer drugs comprise the epithelial growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR) and vascular endothelial growth factor receptor(VEGFR). Target anticancer drugs may affect extracellular receptor domains (antibodies) or intracellular receptor domains (tyrosine kinase inhibitors). The blocking of the mRNA thread containing information about the structure of oncogenes (signal transduction proteins) is another molecular target of anticancer drugs. That type of treatment, referred to as antisense therapy, is in clinical trials. When the synthesis of genetic material is disturbed, in most cases the passage to the next cycle phase is blocked. The key proteins responsible for the blockage are cyclines and cycline- dependent kinases (CDK). Clinical trials are focused on natural and synthetic substances capable of blocking various CDKs. The paper discusses the molecular targets and chemical structure of target anticancer drugs that have been approved for and currently applied in antineoplastic therapy together with indications and contraindications for their

  18. Effects of major parameters of nanoparticles on their physical and chemical properties and recent application of nanodrug delivery system in targeted chemotherapy

    PubMed Central

    Liu, Zefa; Chen, Baoan

    2017-01-01

    Chemotherapy is still one of the main cancer therapy treatments, but the curative effect of chemotherapy is relatively low, as such the development of a new cancer treatment is highly desirable. The gradual maturation of nanotechnology provides an innovative perspective not only for cancer therapy but also for many other applications. There are a diverse variety of nanoparticles available, and choosing the appropriate carriers according to the demand is the key issue. The performance of nanoparticles is affected by many parameters, mainly size, shape, surface charge, and toxicity. Using nanoparticles as the carriers to realize passive targeting and active targeting can improve the efficacy of chemotherapy drugs significantly, reduce the mortality rate of cancer patients, and improve the quality of life of patients. In recent years, there has been extensive research on nanocarriers. In this review, the effects of several major parameters of nanoparticles on their physical and chemical properties are reviewed, and then the recent progress in the application of several commonly used nanoparticles is presented. PMID:29238188

  19. Advances in HYDRA and its application to simulations of Inertial Confinement Fusion targets

    NASA Astrophysics Data System (ADS)

    Marinak, M. M.; Kerbel, G. D.; Koning, J. M.; Patel, M. V.; Sepke, S. M.; Brown, P. N.; Chang, B.; Procassini, R.; Veitzer, S. A.

    2008-11-01

    We will outline new capabilities added to the HYDRA 2D/3D multiphysics ICF simulation code. These include a new SN multigroup radiation transport package (1D), constitutive models for elastic-plastic (strength) effects, and a mix model. A Monte Carlo burn package is being incorporated to model diagnostic signatures of neutrons, gamma rays and charged particles. A 3D MHD package that treats resistive MHD is available. Improvements to HYDRA's implicit Monte Carlo photonics package, including the addition of angular biasing, now enable integrated hohlraum simulations to complete in substantially shorter time. The heavy ion beam deposition package now includes a new model for ion stopping power developed by the Tech-X Corporation, with improved accuracy below the Bragg peak. Examples will illustrate HYDRA's enhanced capabilities to simulate various aspects of inertial confinement fusion targets.This work was performed under the auspices of the Lawrence Livermore National Security, LLC, (LLNS) under Contract No. DE-AC52-07NA27344. The work of Tech-X personnel was funded by the Department of Energy under Small Business Innovation Research Contract No. DE-FG02-03ER83797.

  20. CRISPR guide RNA design for research applications.

    PubMed

    Mohr, Stephanie E; Hu, Yanhui; Ewen-Campen, Benjamin; Housden, Benjamin E; Viswanatha, Raghuvir; Perrimon, Norbert

    2016-09-01

    The rapid rise of CRISPR as a technology for genome engineering and related research applications has created a need for algorithms and associated online tools that facilitate design of on-target and effective guide RNAs (gRNAs). Here, we review the state of the art in CRISPR gRNA design for research applications of the CRISPR-Cas9 system, including knockout, activation, and inhibition. Notably, achieving good gRNA design is not solely dependent on innovations in CRISPR technology. Good design and design tools also rely on availability of high-quality genome sequence and gene annotations, as well as on availability of accumulated data regarding off-targets and effectiveness metrics. © 2016 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  1. 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.

  2. Targeted Therapeutics in Patients With High-Grade Gliomas: Past, Present, and Future.

    PubMed

    Chen, Ricky; Cohen, Adam L; Colman, Howard

    2016-08-01

    High-grade gliomas remain incurable despite current therapies, which are plagued by high morbidity and mortality. Molecular categorization of glioma subtypes using mutations in isocitrate dehydrogenase 1/2 (IDH1/2), TP53, and ATRX; codeletion of chromosomes 1p and 19q; DNA methylation; and amplification of genes such as epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor, alpha polypeptide provides a more accurate prognostication and biologic classification than classical histopathological diagnoses, and a number of molecular markers are being incorporated in the new World Health Organization classification of gliomas. However, despite the improved understanding of the molecular subtypes of gliomas and the underlying alterations in specific signaling pathways, these observations have so far failed to result in the successful application of targeted therapies, as has occurred in other solid tumors. To date, the only targeted therapy for gliomas approved by the US Food and Drug Administration is bevacizumab, which targets vascular endothelial growth factor. EGFR remains a dominant molecular alteration in specific glioma subtypes and represents a potentially promising target, with drugs of multiple types targeting EGFR in development including vaccines, antibody drug conjugates, and chimeric antigen receptor (CAR) T cells, despite the prior failures of EGFR tyrosine kinase inhibitors. Immune therapies under investigation include checkpoint inhibitors, vaccines against tumor-associated antigens and tumor-specific antigens, pulsed dendritic cells, heat shock protein-tumor conjugates, and CAR T cells. Mutations in the IDH1/2 genes are central to gliomagenesis in a high proportion of grade II and III gliomas, and ongoing trials are examining vaccines against IDH1, small molecular inhibitors of IDH1 and IDH2, and metabolic components including NAD+ depletion to target IDH-mutated gliomas. The central role of DNA methylation in a subset of

  3. 45 CFR 2517.410 - What must a qualified organization include in an application for a grant or a subgrant?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false What must a qualified organization include in an application for a grant or a subgrant? 2517.410 Section 2517.410 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE COMMUNITY-BASED SERVICE-LEARNING...

  4. 45 CFR 2517.410 - What must a qualified organization include in an application for a grant or a subgrant?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 4 2011-10-01 2011-10-01 false What must a qualified organization include in an application for a grant or a subgrant? 2517.410 Section 2517.410 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE COMMUNITY-BASED SERVICE-LEARNING...

  5. A model for combined targeting and tracking tasks in computer applications.

    PubMed

    Senanayake, Ransalu; Hoffmann, Errol R; Goonetilleke, Ravindra S

    2013-11-01

    Current models for targeted-tracking are discussed and shown to be inadequate as a means of understanding the combined task of tracking, as in the Drury's paradigm, and having a final target to be aimed at, as in the Fitts' paradigm. It is shown that the task has to be split into components that are, in general, performed sequentially and have a movement time component dependent on the difficulty of the individual component of the task. In some cases, the task time may be controlled by the Fitts' task difficulty, and in others, it may be dominated by the Drury's task difficulty. Based on an experiment carried out that captured movement time in combinations of visually controlled and ballistic movements, a model for movement time in targeted-tracking was developed.

  6. 45 CFR 2519.400 - What must an applicant include in an application for a grant?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... information and assurances specified by the Corporation in the grant application package. (c) Assurances that... to the program as may be required for fiscal audits and program evaluation; (2) Comply with the... and protect the rights of those employees; and (4) Comply with any other assurances that the...

  7. Molecular targets for small-molecule modulators of circadian clocks

    PubMed Central

    He, Baokun; Chen, Zheng

    2016-01-01

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

  8. Time reversal acoustics for small targets using decomposition of the time reversal operator

    NASA Astrophysics Data System (ADS)

    Simko, Peter C.

    The method of time reversal acoustics has been the focus of considerable interest over the last twenty years. Time reversal imaging methods have made consistent progress as effective methods for signal processing since the initial demonstration that physical time reversal methods can be used to form convergent wave fields on a localized target, even under conditions of severe multipathing. Computational time reversal methods rely on the properties of the so-called 'time reversal operator' in order to extract information about the target medium. Applications for which time reversal imaging have previously been explored include medical imaging, non-destructive evaluation, and mine detection. Emphasis in this paper will fall on two topics within the general field of computational time reversal imaging. First, we will examine previous work on developing a time reversal imaging algorithm based on the MUltiple SIgnal Classification (MUSIC) algorithm. MUSIC, though computationally very intensive, has demonstrated early promise in simulations using array-based methods applicable to true volumetric (three-dimensional) imaging. We will provide a simple algorithm through which the rank of the time reversal operator subspaces can be properly quantified so that the rank of the associated null subspace can be accurately estimated near the central pulse wavelength in broadband imaging. Second, we will focus on the scattering from small acoustically rigid two dimensional cylindrical targets of elliptical cross section. Analysis of the time reversal operator eigenmodes has been well-studied for symmetric response matrices associated with symmetric systems of scattering targets. We will expand these previous results to include more general scattering systems leading to asymmetric response matrices, for which the analytical complexity increases but the physical interpretation of the time reversal operator remains unchanged. For asymmetric responses, the qualitative properties of the

  9. Enantioselective Effects of Chiral Pesticides on their Primary Targets and Secondary Targets.

    PubMed

    Yang, Ye; Zhang, Jianyun; Yao, Yijun

    2017-01-01

    Enantioselectivity has been well recognized in the environmental fate and effects of chiral pesticides. Enantiospecific action of the optical enantiomers on the biological molecules establishes the mechanistic basis for the enantioselective toxicity of chiral pesticides to both target and non-target organisms. We undertook a structured search of bibliographic databases for research literature concerning the enantioselective effects of chiral pesticides, including insecticides, herbicides and fungicides, on biomolecules in various species by using some key words. The results of the relevant literatures were reviewed in the text and summarized in tables. Pesticides generally exert their activity on the target organisms via disrupting the primary target biomolecules. In non-target species, effects of pesticides on the secondary targets distinguished from the primary ones make great contribution to their toxicity. Recent investigations have provided convincing evidence of enantioselective toxicity of chiral pesticides to both target and non-target species which is recognized to result from their enantiospecific action on the primary or secondary targets in organisms. This review confirms that chiral pesticides have enantiospecific effects on both primary and secondary target biomolecules in organisms. Future studies regarding toxicological effects of chiral pesticides should focus on the relationship between the enantiomeric difference in the compound-biomolecules interaction and the enantioselectivity in their toxicity.

  10. Specific genetic modifications of domestic animals by gene targeting and animal cloning

    PubMed Central

    Wang, Bin; Zhou, Jiangfeng

    2003-01-01

    The technology of gene targeting through homologous recombination has been extremely useful for elucidating gene functions in mice. The application of this technology was thought impossible in the large livestock species until the successful creation of the first mammalian clone "Dolly" the sheep. The combination of the technologies for gene targeting of somatic cells with those of animal cloning made it possible to introduce specific genetic mutations into domestic animals. In this review, the principles of gene targeting in somatic cells and the challenges of nuclear transfer using gene-targeted cells are discussed. The relevance of gene targeting in domestic animals for applications in bio-medicine and agriculture are also examined. PMID:14614774

  11. Peroxisome proliferator-activated receptors (PPARs) as therapeutic target in neurodegenerative disorders

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

    Agarwal, Swati; Yadav, Anuradha; Academy of Scientific and Innovative Research

    Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors and they serve to be a promising therapeutic target for several neurodegenerative disorders, which includes Parkinson disease, Alzheimer's disease, Huntington disease and Amyotrophic Lateral Sclerosis. PPARs play an important role in the downregulation of mitochondrial dysfunction, proteasomal dysfunction, oxidative stress, and neuroinflammation, which are the major causes of the pathogenesis of neurodegenerative disorders. In this review, we discuss about the role of PPARs as therapeutic targets in neurodegenerative disorders. Several experimental approaches suggest potential application of PPAR agonist as well as antagonist in the treatment of neurodegenerative disorders. Several epidemiological studies found thatmore » the regular usage of PPAR activating non-steroidal anti-inflammatory drugs is effective in decreasing the progression of neurodegenerative diseases including PD and AD. We also reviewed the neuroprotective effects of PPAR agonists and associated mechanism of action in several neurodegenerative disorders both in vitro as well as in vivo animal models. - Highlights: • Peroxisome -activated receptors (PPARs) serve to be a promising therapeutic target for several neurodegenerative disorders. • PPAR agonist as well as provides neuroprotection in vitro as well as in vivo animal models of neurodegenerative disorders. • PPAR activating anti-inflammatory drugs use is effective in decreasing progression of neurodegenerative diseases.« less

  12. Optimized ion acceleration using high repetition rate, variable thickness liquid crystal targets

    NASA Astrophysics Data System (ADS)

    Poole, Patrick; Willis, Christopher; Cochran, Ginevra; Andereck, C. David; Schumacher, Douglass

    2015-11-01

    Laser-based ion acceleration is a widely studied plasma physics topic for its applications to secondary radiation sources, advanced imaging, and cancer therapy. Recent work has centered on investigating new acceleration mechanisms that promise improved ion energy and spectrum. While the physics of these mechanisms is not yet fully understood, it has been observed to dominate for certain ranges of target thickness, where the optimum thickness depends on laser conditions including energy, pulse width, and contrast. The study of these phenomena is uniquely facilitated by the use of variable-thickness liquid crystal films, first introduced in P. L. Poole et al. PoP21, 063109 (2014). Control of the formation parameters of these freely suspended films such as volume, temperature, and draw speed allows on-demand thickness variability between 10 nanometers and several 10s of microns, fully encompassing the currently studied thickness regimes with a single target material. The low vapor pressure of liquid crystal enables in-situ film formation and unlimited vacuum use of these targets. Details on the selection and optimization of ion acceleration mechanism with target thickness will be presented, including recent experiments on the Scarlet laser facility and others. This work was performed with support from the DARPA PULSE program through a grant from AMRDEC and by the NNSA under contract DE-NA0001976.

  13. 48 CFR 216.403-1 - Fixed-price incentive (firm target) contracts.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... (firm target) contracts. 216.403-1 Section 216.403-1 Federal Acquisition Regulations System DEFENSE... CONTRACTS Incentive Contracts 216.403-1 Fixed-price incentive (firm target) contracts. (b) Application. (1... target) contracts, especially for acquisitions moving from development to production. (2) The contracting...

  14. 28 CFR 20.32 - Includable offenses.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Exchange of Criminal History Record Information § 20.32 Includable offenses. (a) Criminal history record... by a § 20.32(a) offense. These exclusions may not be applicable to criminal history records maintained in state criminal history record repositories, including those states participating in the NFF. (c...

  15. 28 CFR 20.32 - Includable offenses.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Exchange of Criminal History Record Information § 20.32 Includable offenses. (a) Criminal history record... by a § 20.32(a) offense. These exclusions may not be applicable to criminal history records maintained in state criminal history record repositories, including those states participating in the NFF. (c...

  16. 28 CFR 20.32 - Includable offenses.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Exchange of Criminal History Record Information § 20.32 Includable offenses. (a) Criminal history record... by a § 20.32(a) offense. These exclusions may not be applicable to criminal history records maintained in state criminal history record repositories, including those states participating in the NFF. (c...

  17. 28 CFR 20.32 - Includable offenses.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Exchange of Criminal History Record Information § 20.32 Includable offenses. (a) Criminal history record... by a § 20.32(a) offense. These exclusions may not be applicable to criminal history records maintained in state criminal history record repositories, including those states participating in the NFF. (c...

  18. 28 CFR 20.32 - Includable offenses.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Exchange of Criminal History Record Information § 20.32 Includable offenses. (a) Criminal history record... by a § 20.32(a) offense. These exclusions may not be applicable to criminal history records maintained in state criminal history record repositories, including those states participating in the NFF. (c...

  19. [Functional targets of Chinese herbal medicine].

    PubMed

    Xiao, Bin; Wang, Yun

    2010-12-01

    In order to elucidate the mechanisms of Chinese herbal medicine, much work has been done based on chemical constituent-target in the molecular system. It cannot comply with the holistic efficacy of Chinese herbal medicine. Thus, the authors of this paper proposed to study the functional target adopted from Western medicine. The data of Chinese herbal function were collected from 2005 edition of The People's Republic of China Pharmacopoeia. A total of 135 functional targets were found, and a network about functional target and mode of action was built. The authors also explored the applications of functional target and the network combined with Sijunzi Decoction and Mahuang Decoction. The results, reflecting the feature of Chinese herbal medicine, will not only be helpful to elucidate the holistic mechanisms of Chinese herbal medicine, but also beneficial to studying the theory of Chinese formulas and developing new formulas.

  20. Hyperspectral target detection analysis of a cluttered scene from a virtual airborne sensor platform using MuSES

    NASA Astrophysics Data System (ADS)

    Packard, Corey D.; Viola, Timothy S.; Klein, Mark D.

    2017-10-01

    The ability to predict spectral electro-optical (EO) signatures for various targets against realistic, cluttered backgrounds is paramount for rigorous signature evaluation. Knowledge of background and target signatures, including plumes, is essential for a variety of scientific and defense-related applications including contrast analysis, camouflage development, automatic target recognition (ATR) algorithm development and scene material classification. The capability to simulate any desired mission scenario with forecast or historical weather is a tremendous asset for defense agencies, serving as a complement to (or substitute for) target and background signature measurement campaigns. In this paper, a systematic process for the physical temperature and visible-through-infrared radiance prediction of several diverse targets in a cluttered natural environment scene is presented. The ability of a virtual airborne sensor platform to detect and differentiate targets from a cluttered background, from a variety of sensor perspectives and across numerous wavelengths in differing atmospheric conditions, is considered. The process described utilizes the thermal and radiance simulation software MuSES and provides a repeatable, accurate approach for analyzing wavelength-dependent background and target (including plume) signatures in multiple band-integrated wavebands (multispectral) or hyperspectrally. The engineering workflow required to combine 3D geometric descriptions, thermal material properties, natural weather boundary conditions, all modes of heat transfer and spectral surface properties is summarized. This procedure includes geometric scene creation, material and optical property attribution, and transient physical temperature prediction. Radiance renderings, based on ray-tracing and the Sandford-Robertson BRDF model, are coupled with MODTRAN for the inclusion of atmospheric effects. This virtual hyperspectral/multispectral radiance prediction methodology has been

  1. Endothelial Targeting of Semi-permeable Polymer Nanocarriers for Enzyme Therapies

    PubMed Central

    Dziubla, Thomas D; Shuvaev, Vladimir V.; Hong, Nan Kang; Hawkins, Brian; Muniswamy, Madesh; Takano, Hajime; Simone, Eric; Nakada, Marian T.; Fisher, Aron; Albelda, Steven M.; Muzykantov, Vladimir R.

    2007-01-01

    The medical utility of proteins, e.g. therapeutic enzymes, is greatly restricted by their liable nature and inadequate delivery. Most therapeutic enzymes do not accumulate in their targets and are inactivated by proteases. Targeting of enzymes encapsulated into substrate-permeable Polymeric Nano-Carriers (PNC) impermeable for proteases might overcome these limitations. To test this hypothesis, we designed endothelial targeted PNC loaded with catalase, the H2O2-detoxifying enzyme, and tested if this approach protects against vascular oxidative stress, a pathological process implicated in ischemia-reperfusion and other disease conditions. Encapsulation of catalase (MW 240KD), peroxidase (MW 42kD) and xanthine oxidase (XO, MW 300 kD) into ~300nm diameter PNC composed of co-polymers of PEG-PLGA (polyethylene glycol and poly-lactic/poly-glycolic acid) was in the range ~10% for all enzymes. PNC/catalase and PNC/peroxidase were protected from external proteolysis and exerted the enzymatic activity on their PNC diffusible substrates, H2O2 and ortho-phenylendiamine, whereas activity of encapsulated XO was negligible due to polymer impermeability to the substrate. PNC targeted to platelet-endothelial cell adhesion molecule-1 delivered active encapsulated catalase to endothelial cells and protected the endothelium against oxidative stress in cell culture and animal studies. Vascular targeting of PNC-loaded detoxifying enzymes may find wide medical applications including management of oxidative stress and other toxicities. PMID:17950837

  2. Chiral PCB 91 and 149 Toxicity Testing in Embryo and Larvae (Danio rerio): Application of Targeted Metabolomics via UPLC-MS/MS

    NASA Astrophysics Data System (ADS)

    Chai, Tingting; Cui, Feng; Yin, Zhiqiang; Yang, Yang; Qiu, Jing; Wang, Chengju

    2016-09-01

    In this study, we aimed to investigate the dysfunction of zebrafish embryos and larvae induced by rac-/(+)-/(-)- PCB91 and rac-/(-)-/(+)- PCB149. UPLC-MS/MS (Ultra-performance liquid chromatography coupled with mass spectrometry) was employed to perform targeted metabolomics analysis, including the quantification of 22 amino acids and the semi-quantitation of 22 other metabolites. Stereoselective changes in target metabolites were observed in embryos and larvae after exposure to chiral PCB91 and PCB149, respectively. In addition, statistical analyses, including PCA and PLS-DA, combined with targeted metabolomics were conducted to identify the characteristic metabolites and the affected pathways. Most of the unique metabolites in embryos and larvae after PCB91/149 exposure were amino acids, and the affected pathways for zebrafish in the developmental stage were metabolic pathways. The stereoselective effects of PCB91/149 on the metabolic pathways of zebrafish embryos and larvae suggest that chiral PCB91/149 exposure has stereoselective toxicity on the developmental stages of zebrafish.

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

    NASA Technical Reports Server (NTRS)

    Liao, Min-Ju; Johnson, Walter W.

    2004-01-01

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

  4. Targeted therapies: a nursing perspective.

    PubMed

    Kay, Polly

    2006-02-01

    To review the development of targeted therapies and the biology of relevant therapeutic targets. To analyze the relevance of targeted agents as part of current clinical practice. Research articles. Several targeted agents are now available for clinical use. Their mechanisms of action are more specific against tumor cells than traditional cytotoxics. Monotherapy regimens based on targeted agents tend to be better tolerated than chemotherapy, and most combination regimens with targeted agents have proven feasible. Their availability has greatly expanded cancer treatment options, especially for chemorefractory patients. Nurses involved in the care of patients with cancer can benefit from an increased understanding of targeted therapies, including their mechanisms of action, their efficacy profile, as well as prophylaxis and management of adverse events and administration procedures.

  5. 41 CFR 301-74.16 - What must be included in any advertisement or application form relating to conference attendance?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 4 2010-07-01 2010-07-01 false What must be included in any advertisement or application form relating to conference attendance? 301-74.16 Section 301-74.16 Public Contracts and Property Management Federal Travel Regulation System TEMPORARY DUTY (TDY) TRAVEL ALLOWANCES AGENCY RESPONSIBILITIES 74...

  6. QMRAcatch: Microbial Quality Simulation of Water Resources including Infection Risk Assessment

    PubMed Central

    Schijven, Jack; Derx, Julia; de Roda Husman, Ana Maria; Blaschke, Alfred Paul; Farnleitner, Andreas H.

    2016-01-01

    Given the complex hydrologic dynamics of water catchments and conflicts between nature protection and public water supply, models may help to understand catchment dynamics and evaluate contamination scenarios and may support best environmental practices and water safety management. A catchment model can be an educative tool for investigating water quality and for communication between parties with different interests in the catchment. This article introduces an interactive computational tool, QMRAcatch, that was developed to simulate concentrations in water resources of Escherichia coli, a human-associated Bacteroidetes microbial source tracking (MST) marker, enterovirus, norovirus, Campylobacter, and Cryptosporidium as target microorganisms and viruses (TMVs). The model domain encompasses a main river with wastewater discharges and a floodplain with a floodplain river. Diffuse agricultural sources of TMVs that discharge into the main river are not included in this stage of development. The floodplain river is fed by the main river and may flood the plain. Discharged TMVs in the river are subject to dilution and temperature-dependent degradation. River travel times are calculated using the Manning–Gauckler–Strickler formula. Fecal deposits from wildlife, birds, and visitors in the floodplain are resuspended in flood water, runoff to the floodplain river, or infiltrate groundwater. Fecal indicator and MST marker data facilitate calibration. Infection risks from exposure to the pathogenic TMVs by swimming or drinking water consumption are calculated, and the required pathogen removal by treatment to meet a health-based quality target can be determined. Applicability of QMRAcatch is demonstrated by calibrating the tool for a study site at the River Danube near Vienna, Austria, using field TMV data, including a sensitivity analysis and evaluation of the model outcomes. PMID:26436266

  7. Processing negative valence of word pairs that include a positive word.

    PubMed

    Itkes, Oksana; Mashal, Nira

    2016-09-01

    Previous research has suggested that cognitive performance is interrupted by negative relative to neutral or positive stimuli. We examined whether negative valence affects performance at the word or phrase level. Participants performed a semantic decision task on word pairs that included either a negative or a positive target word. In Experiment 1, the valence of the target word was congruent with the overall valence conveyed by the word pair (e.g., fat kid). As expected, response times were slower in the negative condition relative to the positive condition. Experiment 2 included target words that were incongruent with the overall valence of the word pair (e.g., fat salary). Response times were longer for word pairs whose overall valence was negative relative to positive, even though these word pairs included a positive word. Our findings support the Cognitive Primacy Hypothesis, according to which emotional valence is extracted after conceptual processing is complete.

  8. Hyperspectral target detection using manifold learning and multiple target spectra

    DOE PAGES

    Ziemann, Amanda K.; Theiler, James; Messinger, David W.

    2016-03-31

    Imagery collected from satellites and airborne platforms provides an important tool for remotely analyzing the content of a scene. In particular, the ability to remotely detect a specific material within a scene is of critical importance in nonproliferation and other applications. The sensor systems that process hyperspectral images collect the high-dimensional spectral information necessary to perform these detection analyses. For a d-dimensional hyperspectral image, however, where d is the number of spectral bands, it is common for the data to inherently occupy an m-dimensional space with m << d. In the remote sensing community, this has led to recent interestmore » in the use of manifold learning, which seeks to characterize the embedded lower-dimensional, nonlinear manifold that the data discretely approximate. The research presented in this paper focuses on a graph theory and manifold learning approach to target detection, using an adaptive version of locally linear embedding that is biased to separate target pixels from background pixels. Finally, this approach incorporates multiple target signatures for a particular material, accounting for the spectral variability that is often present within a solid material of interest.« less

  9. Target Detection Using an AOTF Hyperspectral Imager

    NASA Technical Reports Server (NTRS)

    Cheng, L-J.; Mahoney, J.; Reyes, F.; Suiter, H.

    1994-01-01

    This paper reports results of a recent field experiment using a prototype system to evaluate the acousto-optic tunable filter polarimetric hyperspectral imaging technology for target detection applications.

  10. Development and application of a quantitative multiplexed small GTPase activity assay using targeted proteomics.

    PubMed

    Zhang, Cheng-Cheng; Li, Ru; Jiang, Honghui; Lin, Shujun; Rogalski, Jason C; Liu, Kate; Kast, Juergen

    2015-02-06

    Small GTPases are a family of key signaling molecules that are ubiquitously expressed in various types of cells. Their activity is often analyzed by western blot, which is limited by its multiplexing capability, the quality of isoform-specific antibodies, and the accuracy of quantification. To overcome these issues, a quantitative multiplexed small GTPase activity assay has been developed. Using four different binding domains, this assay allows the binding of up to 12 active small GTPase isoforms simultaneously in a single experiment. To accurately quantify the closely related small GTPase isoforms, a targeted proteomic approach, i.e., selected/multiple reaction monitoring, was developed, and its functionality and reproducibility were validated. This assay was successfully applied to human platelets and revealed time-resolved coactivation of multiple small GTPase isoforms in response to agonists and differential activation of these isoforms in response to inhibitor treatment. This widely applicable approach can be used for signaling pathway studies and inhibitor screening in many cellular systems.

  11. Just War Theory and its Applicability to Targeted Killing

    DTIC Science & Technology

    2011-06-10

    sported a laser turret in the nose for precision targeting and Hellfire AGM-114 laser guided missiles on its wings (Williams 2010, 872). The advent...use lethal force against suspected terrorists in ― anticipatory ‖ self-defense. By classifying terrorism as an act of war, rather than as a crime

  12. Studies of Ion Acceleration from Thin Solid-Density Targets on High-Intensity Lasers

    NASA Astrophysics Data System (ADS)

    Willis, Christopher R.

    Over the past two decades, a number of experiments have been performed demonstrating the acceleration of ions from the interaction of an intense laser pulse with a thin, solid density target. These ions are accelerated by quasi-static electric fields generated by energetic electrons produced at the front of the target, resulting in ion energies up to tens of MeV. These ions have been widely studied for a variety of potential applications ranging from treatment of cancer to the production of neutrons for advanced radiography techniques. However, realization of these applications will require further optimization of the maximum energy, spectrum, or species of the accelerated ions, which has been a primary focus of research to date. This thesis presents two experiments designed to optimize several characteristics of the accelerated ion beam. The first of these experiments took place on the GHOST laser system at the University of Texas at Austin, and was designed to demonstrate reliable acceleration of deuterium ions, as needed for the most efficient methods of neutron generation from accelerated ions. This experiment leveraged cryogenically cooled targets coated in D2 O ice to suppress the protons which typically dominate the accelerated ions, producing as many as 2 x 1010 deuterium ions per 1 J laser shot, exceeding the proton yield by an average ratio of 5:1. The second major experiment in this work was performed on the Scarlet laser system at The Ohio State University, and studied the accelerated ion energy, yield, and spatial distribution as a function of the target thickness. In principle, the peak energy increases with decreasing target thickness, with the thinnest targets accessing additional acceleration mechanisms which provide favorable scaling with the laser intensity. However, laser prepulse characteristics provide a lower bound for the target thickness, yielding an optimum target thickness for ion acceleration which is dependent on the laser system. This

  13. The effect of mood state on visual search times for detecting a target in noise: An application of smartphone technology

    PubMed Central

    Maekawa, Toru; de Brecht, Matthew; Yamagishi, Noriko

    2018-01-01

    The study of visual perception has largely been completed without regard to the influence that an individual’s emotional status may have on their performance in visual tasks. However, there is a growing body of evidence to suggest that mood may affect not only creative abilities and interpersonal skills but also the capacity to perform low-level cognitive tasks. Here, we sought to determine whether rudimentary visual search processes are similarly affected by emotion. Specifically, we examined whether an individual’s perceived happiness level affects their ability to detect a target in noise. To do so, we employed pop-out and serial visual search paradigms, implemented using a novel smartphone application that allowed search times and self-rated levels of happiness to be recorded throughout each twenty-four-hour period for two weeks. This experience sampling protocol circumvented the need to alter mood artificially with laboratory-based induction methods. Using our smartphone application, we were able to replicate the classic visual search findings, whereby pop-out search times remained largely unaffected by the number of distractors whereas serial search times increased with increasing number of distractors. While pop-out search times were unaffected by happiness level, serial search times with the maximum numbers of distractors (n = 30) were significantly faster for high happiness levels than low happiness levels (p = 0.02). Our results demonstrate the utility of smartphone applications in assessing ecologically valid measures of human visual performance. We discuss the significance of our findings for the assessment of basic visual functions using search time measures, and for our ability to search effectively for targets in real world settings. PMID:29664952

  14. The effect of mood state on visual search times for detecting a target in noise: An application of smartphone technology.

    PubMed

    Maekawa, Toru; Anderson, Stephen J; de Brecht, Matthew; Yamagishi, Noriko

    2018-01-01

    The study of visual perception has largely been completed without regard to the influence that an individual's emotional status may have on their performance in visual tasks. However, there is a growing body of evidence to suggest that mood may affect not only creative abilities and interpersonal skills but also the capacity to perform low-level cognitive tasks. Here, we sought to determine whether rudimentary visual search processes are similarly affected by emotion. Specifically, we examined whether an individual's perceived happiness level affects their ability to detect a target in noise. To do so, we employed pop-out and serial visual search paradigms, implemented using a novel smartphone application that allowed search times and self-rated levels of happiness to be recorded throughout each twenty-four-hour period for two weeks. This experience sampling protocol circumvented the need to alter mood artificially with laboratory-based induction methods. Using our smartphone application, we were able to replicate the classic visual search findings, whereby pop-out search times remained largely unaffected by the number of distractors whereas serial search times increased with increasing number of distractors. While pop-out search times were unaffected by happiness level, serial search times with the maximum numbers of distractors (n = 30) were significantly faster for high happiness levels than low happiness levels (p = 0.02). Our results demonstrate the utility of smartphone applications in assessing ecologically valid measures of human visual performance. We discuss the significance of our findings for the assessment of basic visual functions using search time measures, and for our ability to search effectively for targets in real world settings.

  15. Functionalized carbon nanotubes: biomedical applications

    PubMed Central

    Vardharajula, Sandhya; Ali, Sk Z; Tiwari, Pooja M; Eroğlu, Erdal; Vig, Komal; Dennis, Vida A; Singh, Shree R

    2012-01-01

    Carbon nanotubes (CNTs) are emerging as novel nanomaterials for various biomedical applications. CNTs can be used to deliver a variety of therapeutic agents, including biomolecules, to the target disease sites. In addition, their unparalleled optical and electrical properties make them excellent candidates for bioimaging and other biomedical applications. However, the high cytotoxicity of CNTs limits their use in humans and many biological systems. The biocompatibility and low cytotoxicity of CNTs are attributed to size, dose, duration, testing systems, and surface functionalization. The functionalization of CNTs improves their solubility and biocompatibility and alters their cellular interaction pathways, resulting in much-reduced cytotoxic effects. Functionalized CNTs are promising novel materials for a variety of biomedical applications. These potential applications are particularly enhanced by their ability to penetrate biological membranes with relatively low cytotoxicity. This review is directed towards the overview of CNTs and their functionalization for biomedical applications with minimal cytotoxicity. PMID:23091380

  16. Functionalized carbon nanotubes: biomedical applications.

    PubMed

    Vardharajula, Sandhya; Ali, Sk Z; Tiwari, Pooja M; Eroğlu, Erdal; Vig, Komal; Dennis, Vida A; Singh, Shree R

    2012-01-01

    Carbon nanotubes (CNTs) are emerging as novel nanomaterials for various biomedical applications. CNTs can be used to deliver a variety of therapeutic agents, including biomolecules, to the target disease sites. In addition, their unparalleled optical and electrical properties make them excellent candidates for bioimaging and other biomedical applications. However, the high cytotoxicity of CNTs limits their use in humans and many biological systems. The biocompatibility and low cytotoxicity of CNTs are attributed to size, dose, duration, testing systems, and surface functionalization. The functionalization of CNTs improves their solubility and biocompatibility and alters their cellular interaction pathways, resulting in much-reduced cytotoxic effects. Functionalized CNTs are promising novel materials for a variety of biomedical applications. These potential applications are particularly enhanced by their ability to penetrate biological membranes with relatively low cytotoxicity. This review is directed towards the overview of CNTs and their functionalization for biomedical applications with minimal cytotoxicity.

  17. Targeted Prostate Thermal Therapy with Catheter-Based Ultrasound Devices and MR Thermal Monitoring

    NASA Astrophysics Data System (ADS)

    Diederich, Chris; Ross, Anthony; Kinsey, Adam; Nau, Will H.; Rieke, Viola; Butts Pauly, Kim; Sommer, Graham

    2006-05-01

    Catheter-based ultrasound devices have significant advantages for thermal therapy procedures, including potential for precise spatial and dynamic control of heating patterns to conform to targeted volumes. Interstitial and transurethral ultrasound applicators, with associated treatment strategies, were developed for thermal ablation of prostate combined with MR thermal monitoring. Four types of multielement transurethral applicators were devised, each with different levels of selectivity and intended therapeutic goals: sectored tubular transducer devices with fixed directional heating patterns; planar and lightly focused curvilinear devices with narrow heating patterns; and multi-sectored tubular devices capable of dynamic angular control without applicator movement. These devices are integrated with a 4 mm delivery catheter, incorporate an inflatable cooling balloon (10 mm OD) for positioning within the prostate and capable of rotation via an MR-compatible motor. Similarly, interstitial devices (2.4 mm OD) have been developed for percutaneous implantation with fixed directional heating patterns (e.g., 180 deg.). In vivo experiments in canine prostate (n=15) under MR temperature imaging were used to evaluate the heating technology and develop treatment strategies. MR thermal imaging in a 0.5 T interventional MRI was used to monitor temperature contours and thermal dose in multiple slices through the target volume. Sectored transurethral devices produce directional coagulation zones, extending 15-20 mm radial distance to the outer prostate capsule. The curvilinear applicator produces distinct 2-3 mm wide lesions, and with sequential rotation and modulated dwell time can precisely conform thermal ablation to selected areas or the entire prostate gland. Multi-sectored transurethral applicators can dynamically control the angular heating profile and target large regions of the gland in short treatment times without applicator manipulation. Interstitial implants with

  18. Probing microbubble targeting with atomic force microscopy.

    PubMed

    Sboros, V; Glynos, E; Ross, J A; Moran, C M; Pye, S D; Butler, M; McDicken, W N; Brown, S B; Koutsos, V

    2010-10-01

    Microbubble science is expanding beyond ultrasound imaging applications to biological targeting and drug/gene delivery. The characteristics of molecular targeting should be tested by a measurement system that can assess targeting efficacy and strength. Atomic force microscopy (AFM) is capable of piconewton force resolution, and is reported to measure the strength of single hydrogen bonds. An in-house targeted microbubble modified using the biotin-avidin chemistry and the CD31 antibody was used to probe cultures of Sk-Hep1 hepatic endothelial cells. We report that the targeted microbubbles provide a single distribution of adhesion forces with a median of 93pN. This interaction is assigned to the CD31 antibody-antigen unbinding event. Information on the distances between the interaction forces was obtained and could be important for future microbubble fabrication. In conclusion, the capability of single microbubbles to target cell lines was shown to be feasible with AFM.

  19. Microfluidic droplet enrichment for targeted sequencing

    PubMed Central

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

    2015-01-01

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

  20. Compounds From Celastraceae Targeting Cancer Pathways and Their Potential Application in Head and Neck Squamous Cell Carcinoma: A Review

    PubMed Central

    Hernandes, Camila; Pereira, Ana Maria Soares; Severino, Patricia

    2017-01-01

    Squamous cell carcinoma of the head and neck is one of the most common cancer types worldwide. It initiates on the epithelial lining of the upper aerodigestive tract, at most instances as a consequence of tobacco and alcohol consumption. Treatment options based on conventional therapies or targeted therapies under development have limited efficacy due to multiple genetic alterations typically found in this cancer type. Natural products derived from plants often possess biological activities that may be valuable in the development of new therapeutic agents for cancer treatment. Several genera from the family Celastraceae have been studied in this context. This review reports studies on chemical constituents isolated from species from the Celastraceae family targeting cancer mechanisms studied to date. These results are then correlated with molecular characteristics of head and neck squamous cell carcinoma in an attempt to identify constituents with potential application in the treatment of this complex disease at the molecular level. PMID:28503090