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Sample records for versatile targeting system

  1. A Versatile Multiple Target Detection System Based on DNA Nano-assembled Linear FRET Arrays.

    Science.gov (United States)

    Li, Yansheng; Du, Hongwu; Wang, Wenqian; Zhang, Peixun; Xu, Liping; Wen, Yongqiang; Zhang, Xueji

    2016-05-27

    DNA molecules have been utilized both as powerful synthetic building blocks to create nanoscale architectures and as inconstant programmable templates for assembly of biosensors. In this paper, a versatile, scalable and multiplex detection system is reported based on an extending fluorescent resonance energy transfer (FRET) cascades on a linear DNA assemblies. Seven combinations of three kinds of targets are successfully detected through the changes of fluorescence spectra because of the three-steps FRET or non-FRET continuity mechanisms. This nano-assembled FRET-based nanowire is extremely significant for the development of rapid, simple and sensitive detection system. The method used here could be extended to a general platform for multiplex detection through more-step FRET process.

  2. Holographic versatile disc system

    Science.gov (United States)

    Horimai, Hideyoshi; Tan, Xiaodi

    2005-09-01

    A Holographic Versatile Disc (HVD) system, using Collinear Technologies for a high capacity and high data transfer rates storage system, is proposed. With its unique configuration the optical pickup can be designed as small as a DVD's, and can be placed on one side of the disc. With the HVD's special structure, the system can servo the focus/track and locate reading/writing address. A unique selectable capacity recording format of HVD and its standardization activity are also introduced. Experimental and theoretical studies suggest that the tilt, wavelength, defocus and de-track margins are wide enough to miniaturize the HVD system at a low cost. HVD systems using Collinear Technologies will be compatible with existing disc storage systems, like CD and DVD, and will enable us to expand its applications into other optical information storage systems.

  3. Predominance of a versatile-peroxidase-encoding gene, mnp4, as demonstrated by gene replacement via a gene targeting system for Pleurotus ostreatus.

    Science.gov (United States)

    Salame, Tomer M; Knop, Doriv; Tal, Dana; Levinson, Dana; Yarden, Oded; Hadar, Yitzhak

    2012-08-01

    Pleurotus ostreatus (the oyster mushroom) and other white rot filamentous basidiomycetes are key players in the global carbon cycle. P. ostreatus is also a commercially important edible fungus with medicinal properties and is important for biotechnological and environmental applications. Efficient gene targeting via homologous recombination (HR) is a fundamental tool for facilitating comprehensive gene function studies. Since the natural HR frequency in Pleurotus transformations is low (2.3%), transformed DNA is predominantly integrated ectopically. To overcome this limitation, a general gene targeting system was developed by producing a P. ostreatus PC9 homokaryon Δku80 strain, using carboxin resistance complemented by the development of a protocol for hygromycin B resistance protoplast-based DNA transformation and homokaryon isolation. The Δku80 strain exhibited exclusive (100%) HR in the integration of transforming DNA, providing a high efficiency of gene targeting. Furthermore, the Δku80 strains produced showed a phenotype similar to that of the wild-type PC9 strain, with similar growth fitness, ligninolytic functionality, and capability of mating with the incompatible strain PC15 to produce a dikaryon which retained its resistance to the corresponding selection and was capable of producing typical fruiting bodies. The applicability of this system is demonstrated by inactivation of the versatile peroxidase (VP) encoded by mnp4. This enzyme is part of the ligninolytic system of P. ostreatus, being one of the nine members of the manganese-peroxidase (MnP) gene family, and is the predominantly expressed VP in Mn(2+)-deficient media. mnp4 inactivation provided a direct proof that mnp4 encodes a key VP responsible for the Mn(2+)-dependent and Mn(2+)-independent peroxidase activity under Mn(2+)-deficient culture conditions.

  4. Predominance of a Versatile-Peroxidase-Encoding Gene, mnp4, as Demonstrated by Gene Replacement via a Gene Targeting System for Pleurotus ostreatus

    Science.gov (United States)

    Salame, Tomer M.; Knop, Doriv; Tal, Dana; Levinson, Dana; Yarden, Oded

    2012-01-01

    Pleurotus ostreatus (the oyster mushroom) and other white rot filamentous basidiomycetes are key players in the global carbon cycle. P. ostreatus is also a commercially important edible fungus with medicinal properties and is important for biotechnological and environmental applications. Efficient gene targeting via homologous recombination (HR) is a fundamental tool for facilitating comprehensive gene function studies. Since the natural HR frequency in Pleurotus transformations is low (2.3%), transformed DNA is predominantly integrated ectopically. To overcome this limitation, a general gene targeting system was developed by producing a P. ostreatus PC9 homokaryon Δku80 strain, using carboxin resistance complemented by the development of a protocol for hygromycin B resistance protoplast-based DNA transformation and homokaryon isolation. The Δku80 strain exhibited exclusive (100%) HR in the integration of transforming DNA, providing a high efficiency of gene targeting. Furthermore, the Δku80 strains produced showed a phenotype similar to that of the wild-type PC9 strain, with similar growth fitness, ligninolytic functionality, and capability of mating with the incompatible strain PC15 to produce a dikaryon which retained its resistance to the corresponding selection and was capable of producing typical fruiting bodies. The applicability of this system is demonstrated by inactivation of the versatile peroxidase (VP) encoded by mnp4. This enzyme is part of the ligninolytic system of P. ostreatus, being one of the nine members of the manganese-peroxidase (MnP) gene family, and is the predominantly expressed VP in Mn2+-deficient media. mnp4 inactivation provided a direct proof that mnp4 encodes a key VP responsible for the Mn2+-dependent and Mn2+-independent peroxidase activity under Mn2+-deficient culture conditions. PMID:22636004

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

    Science.gov (United States)

    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

  6. Versatile RNA interference nanoplatform for systemic delivery of RNAs.

    Science.gov (United States)

    Choi, Ki Young; Silvestre, Oscar F; Huang, Xinglu; Min, Kyung Hyun; Howard, Gregory P; Hida, Naoki; Jin, Albert J; Carvajal, Nicole; Lee, Sang Wook; Hong, Jong-In; Chen, Xiaoyuan

    2014-05-27

    Development of nontoxic, tumor-targetable, and potent in vivo RNA delivery systems remains an arduous challenge for clinical application of RNAi therapeutics. Herein, we report a versatile RNAi nanoplatform based on tumor-targeted and pH-responsive nanoformulas (NFs). The NF was engineered by combination of an artificial RNA receptor, Zn(II)-DPA, with a tumor-targetable and drug-loadable hyaluronic acid nanoparticle, which was further modified with a calcium phosphate (CaP) coating by in situ mineralization. The NF can encapsulate small-molecule drugs within its hydrophobic inner core and strongly secure various RNA molecules (siRNAs, miRNAs, and oligonucleotides) by utilizing Zn(II)-DPA and a robust CaP coating. We substantiated the versatility of the RNAi nanoplatform by demonstrating effective delivery of siRNA and miRNA for gene silencing or miRNA replacement into different human types of cancer cells in vitro and into tumor-bearing mice in vivo by intravenous administration. The therapeutic potential of NFs coloaded with an anticancer drug doxorubicin (Dox) and multidrug resistance 1 gene target siRNA (siMDR) was also demonstrated in this study. NFs loaded with Dox and siMDR could successfully sensitize drug-resistant OVCAR8/ADR cells to Dox and suppress OVCAR8/ADR tumor cell proliferation in vitro and tumor growth in vivo. This gene/drug delivery system appears to be a highly effective nonviral method to deliver chemo- and RNAi therapeutics into host cells.

  7. The Q-System: A Versatile Expression System for Drosophila.

    Science.gov (United States)

    Riabinina, Olena; Potter, Christopher J

    2016-01-01

    Binary expression systems are flexible and versatile genetic tools in Drosophila. The Q-system is a recently developed repressible binary expression system that offers new possibilities for transgene expression and genetic manipulations. In this review chapter, we focus on current state-of-the-art Q-system tools and reagents. We also discuss in vivo applications of the Q-system, together with GAL4/UAS and LexA/LexAop systems, for simultaneous expression of multiple effectors, intersectional labeling, and clonal analysis.

  8. Nucleolin-targeted Extracellular Vesicles as a Versatile Platform for Biologics Delivery to Breast Cancer.

    Science.gov (United States)

    Wang, Yayu; Chen, Xiaojia; Tian, Baoqing; Liu, Jiafan; Yang, Li; Zeng, Lilan; Chen, Tianfen; Hong, An; Wang, Xiaogang

    2017-01-01

    Small interfering RNAs (siRNA)/microRNAs (miRNA) have promising therapeutic potential, yet their clinical application has been hampered by the lack of appropriate delivery systems. Herein, we employed extracellular vesicles (EVs) as a targeted delivery system for small RNAs. EVs are cell-derived small vesicles that participate in cell-to-cell communication for protein and RNA delivery. We used the aptamer AS1411-modified EVs for targeted delivery of siRNA/microRNA to breast cancer tissues. Tumor targeting was facilitated via AS1411 binding to nucleolin, which is highly expressed on the surface membrane of breast cancer cells. This delivery vesicle targeted let-7 miRNA delivery to MDA-MB-231 cells in vitro as confirmed with fluorescent microscopic imaging and flow cytometry. Also, intravenously delivered AS1411-EVs loaded with miRNA let-7 labeled with the fluorescent marker, Cy5, selectively targeted tumor tissues in tumor-bearing mice and inhibited tumor growth. Importantly, the modified EVs were well tolerated and showed no evidence of nonspecific side effects or immune response. Thus, the RNAi nanoplatform is versatile and can deliver siRNA or miRNA to breast cancer cells both in vitro and in vivo. Our results suggest that the AS1411-EVs have a great potential as drug delivery vehicles to treat cancers.

  9. DIHYDROFOLATE REDUCTASE AS A VERSATILE DRUG TARGET IN HEALTHCARE

    Directory of Open Access Journals (Sweden)

    Naira Rashid

    2016-09-01

    Full Text Available Dihydrofolate reductase is one of the important enzymes for thymidylate and purine synthesis. It has been used as a drug target for treatment of various diseases. A large number of pharmaceutical drugs have been designed to inhibit the activity of dihydrofolate reductase. However, over the period of time some organisms have developed resistance against some of these drugs. There is also a chance of cross reactivity for these drugs, as they may target the dihydrofolate reductase enzyme of other organisms. Although using NMR spectroscopy, phylogenetic sequence analysis, comparative sequence analysis between dihydrofolate enzymes of various organisms and molecular modeling studies, a lot has been unraveled about the difference in the structure of this enzyme in various organisms, yet there is a need for deeper understanding of these differences so as to design drugs that are specific to their targets and reduce the chance for cross reactivity. The dihydrofolate enzyme can also be explored for treatment of various other diseases that are associated with the folate cycle.

  10. A Versatile Prototyping System for Capacitive Sensing

    Directory of Open Access Journals (Sweden)

    Daniel HRACH

    2008-04-01

    Full Text Available This paper presents a multi-purpose and easy to handle rapid prototyping platform that has been designed for capacitive measurement systems. The core of the prototype platform is a Digital Signal Processor board that allows for the entire data acquisition, data (pre- processing and storage, and communication with any host computer. The platform is running on uCLinux operating system and features the possibility of a fast design and evaluation of capacitive sensor developments. To show the practical benefit of the prototyping platform, three exemplary applications are presented. For all applications, the platform is just plugged to the electrode structure of the sensor front-end without the need for analogue signal pre-conditioning.

  11. Distance-dependent magnetic resonance tuning as a versatile MRI sensing platform for biological targets

    Science.gov (United States)

    Choi, Jin-Sil; Kim, Soojin; Yoo, Dongwon; Shin, Tae-Hyun; Kim, Hoyoung; Gomes, Muller D.; Kim, Sun Hee; Pines, Alexander; Cheon, Jinwoo

    2017-05-01

    Nanoscale distance-dependent phenomena, such as Förster resonance energy transfer, are important interactions for use in sensing and imaging, but their versatility for bioimaging can be limited by undesirable photon interactions with the surrounding biological matrix, especially in in vivo systems. Here, we report a new type of magnetism-based nanoscale distance-dependent phenomenon that can quantitatively and reversibly sense and image intra-/intermolecular interactions of biologically important targets. We introduce distance-dependent magnetic resonance tuning (MRET), which occurs between a paramagnetic `enhancer' and a superparamagnetic `quencher', where the T1 magnetic resonance imaging (MRI) signal is tuned ON or OFF depending on the separation distance between the quencher and the enhancer. With MRET, we demonstrate the principle of an MRI-based ruler for nanometre-scale distance measurement and the successful detection of both molecular interactions (for example, cleavage, binding, folding and unfolding) and biological targets in in vitro and in vivo systems. MRET can serve as a novel sensing principle to augment the exploration of a wide range of biological systems.

  12. CORRTEX: a compact and versatile system for time domain reflectometry

    Energy Technology Data Exchange (ETDEWEB)

    Deupree, R.G.; Eilers, D.D.; McKown, T.O.; Storey, W.H.

    1981-01-01

    The CORRTEX (COntinuous Reflectometry for Radius versus Time EXperiments) system was designed to be an adaptable and versatile unit for performing time domain reflectometry (TDR). The system consists of a coaxial cable, a digital TDR, which uses a Motorola 6800 microprocessor, a power source or battery pack, and an output terminal or recording driver. Desirable criteria for the system are discussed as well as the operation of the CORRTEX system. The types of present applications of the CORRTEX system are summarized and data presented.

  13. Read-only holographic versatile disc system using laser diode

    Science.gov (United States)

    Horimai, Hideyoshi; Tan, Xiaodi

    2006-05-01

    A Read-only Holographic Versatile Disc (HVD-ROM) system, using a laser diode for high capacity and high data transfer rates storage system, is proposed. With the collinear technologies' unique configuration the optical pickup can be designed as small as a DVD's, and can be placed on one side of the disc. With the HVD's special structure, the system can servo the focus/tracking and locate reading/writing address. The experiments and theoretical studies suggest that a laser diode is very suitable as a light source of our HVD-ROM system.

  14. Microscale Symmetrical Electroporator Array as a Versatile Molecular Delivery System

    Science.gov (United States)

    Ouyang, Mengxing; Hill, Winfield; Lee, Jung Hyun; Hur, Soojung Claire

    2017-03-01

    Successful developments of new therapeutic strategies often rely on the ability to deliver exogenous molecules into cytosol. We have developed a versatile on-chip vortex-assisted electroporation system, engineered to conduct sequential intracellular delivery of multiple molecules into various cell types at low voltage in a dosage-controlled manner. Micro-patterned planar electrodes permit substantial reduction in operational voltages and seamless integration with an existing microfluidic technology. Equipped with real-time process visualization functionality, the system enables on-chip optimization of electroporation parameters for cells with varying properties. Moreover, the system’s dosage control and multi-molecular delivery capabilities facilitate intracellular delivery of various molecules as a single agent or in combination and its utility in biological research has been demonstrated by conducting RNA interference assays. We envision the system to be a powerful tool, aiding a wide range of applications, requiring single-cell level co-administrations of multiple molecules with controlled dosages.

  15. A new versatile in-process monitoring system for milling

    CERN Document Server

    Ritou, Mathieu; Furet, Benoît; Hascoët, Jean-Yves

    2013-01-01

    Tool condition monitoring (TCM) systems can improve productivity and ensure workpiece quality, yet, there is a lack of reliable TCM solutions for small-batch or one-off manufacturing of industrial parts. TCM methods which include the characteristics of the cut seem to be particularly suitable for these demanding applications. In the first section of this paper, three process-based indicators have been retrieved from literature dealing with TCM. They are analysed using a cutting force model and experiments are carried out in industrial conditions. Specific transient cuttings encountered during the machining of the test part reveal the indicators to be unreliable. Consequently, in the second section, a versatile in-process monitoring method is suggested. Based on experiments carried out under a range of different cutting conditions, an adequate indicator is proposed: the relative radial eccentricity of the cutters is estimated at each instant and characterizes the tool state. It is then compared with the previo...

  16. A versatile computer-controlled high-resolution LBIC system

    Energy Technology Data Exchange (ETDEWEB)

    Martin, J.; Fernandez-Lorenzo, C.; Poce-Fatou, J.A.; Alcantara, R. [Facultad de Ciencias, Cadiz (Spain). Dpto. de Quimica Fisica

    2004-07-01

    This paper presents the design of versatile equipment for obtaining laser-beam-induced current (LBIC) images which allows the study of large surfaces as well as conversion areas of a few micrometers. The modular optomechanical design enables the user to modify the size of the irradiation spot by simply changing the microscope objective used as focal lens, albeit within the limits set by the wavelength. The use of an appropriate calculation algorithm makes it possible to rely on a computerized system to adjust the distance at which the focusing lens must be placed with respect to the sample plane. The possibility of working at micrometer resolution allows one to obtain very significant information for the study of irregularities, manufacturing defects, impurities, grain boundaries, dislocations, recombination centers, etc. in photovoltaic wafers. (author)

  17. Solid-Phase Bioconjugation of Heterobifunctional Adaptors for Versatile Assembly of Bispecific Targeting Ligands

    Science.gov (United States)

    2015-01-01

    High-throughput generation of bispecific molecules promises to expedite the discovery of new molecular therapeutics and guide engineering of novel multifunctional constructs. However, high synthesis complexity and cost have hampered the discovery of bispecific molecules in drug development and biomedical research. Herein we describe a simple solid-phase bioconjugation procedure for preparation of Protein A(G,L)-PEG-Streptavidin heterobifunctional adaptors (with 1:1:1 stoichiometry), which enable self-assembly of unmodified antibodies and biotinylated molecules into bispecific targeting ligands in a versatile mix-and-use manner. Utility of such adaptors is demonstrated by assembly of anti-CD3 and anti-Her2 antibodies into bispecific CD3xHer2 targeting ligands, which efficiently drive T-cell-mediated lysis of Her2-positive cancer cells. In comparison to bioconjugation in solution, the solid-phase procedure described here offers precise stoichiometry control, ease of purification, and high yield of functional conjugates. Simplicity and versatility should prove this methodology instrumental for preparation of bispecific ligands, as well as for high-throughput screening of bispecific combinations, before proceeding to synthesis of lead candidates via recombinant engineering or chemical cross-linking. PMID:25010411

  18. A versatile stereoscopic visual display system for vestibular and oculomotor research.

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    Kramer, P D; Roberts, D C; Shelhamer, M; Zee, D S

    1998-01-01

    Testing of the vestibular system requires a vestibular stimulus (motion) and/or a visual stimulus. We have developed a versatile, low cost, stereoscopic visual display system, using "virtual reality" (VR) technology. The display system can produce images for each eye that correspond to targets at any virtual distance relative to the subject, and so require the appropriate ocular vergence. We elicited smooth pursuit, "stare" optokinetic nystagmus (OKN) and after-nystagmus (OKAN), vergence for targets at various distances, and short-term adaptation of the vestibulo-ocular reflex (VOR), using both conventional methods and the stereoscopic display. Pursuit, OKN, and OKAN were comparable with both methods. When used with a vestibular stimulus, VR induced appropriate adaptive changes of the phase and gain of the angular VOR. In addition, using the VR display system and a human linear acceleration sled, we adapted the phase of the linear VOR. The VR-based stimulus system not only offers an alternative to more cumbersome means of stimulating the visual system in vestibular experiments, it also can produce visual stimuli that would otherwise be impractical or impossible. Our techniques provide images without the latencies encountered in most VR systems. Its inherent versatility allows it to be useful in several different types of experiments, and because it is software driven it can be quickly adapted to provide a new stimulus. These two factors allow VR to provide considerable savings in time and money, as well as flexibility in developing experimental paradigms.

  19. A versatile PCR-based tandem epitope tagging system for Streptomyces coelicolor genome.

    Science.gov (United States)

    Kim, Ji-Nu; Yi, Jeong Sang; Lee, Bo-Rahm; Kim, Eun-Jung; Kim, Min Woo; Song, Yoseb; Cho, Byung-Kwan; Kim, Byung-Gee

    2012-07-20

    Epitope tagging approaches have been widely used for the analysis of functions, interactions and subcellular distributions of proteins. However, incorporating epitope sequence into protein loci in Streptomyces is time-consuming procedure due to the absence of the versatile tagging methods. Here, we developed a versatile PCR-based tandem epitope tagging tool for the Streptomyces genome engineering. We constructed a series of template plasmids that carry repeated sequence of c-myc epitope, Flp recombinase target (FRT) sites, and apramycin resistance marker to insert epitope tags into any desired spot of the chromosomal loci. A DNA module which includes the tandem epitope-encoding sequence and a selectable marker was amplified by PCR with primers that carry homologous extensions to the last portion and downstream region of the targeted gene. We fused the epitope tags at the 3' region of global transcription factors of Streptomyces coelicolor to test the validity of this system. The proper insertion of the epitope tag was confirmed by PCR and western blot analysis. The recombinants showed the identical phenotype to the wild-type that proved the conservation of in vivo function of the tagged proteins. Finally, the direct binding targets were successfully detected by chromatin immunoprecipitation with the increase in the signal-to-noise ratio. The epitope tagging system describes here would provide wide applications to study the protein functions in S. coelicolor. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Collinear technology for holographic versatile disc (HVD) system

    Science.gov (United States)

    Tan, Xiaodi; Horimai, Hideyoshi; Shimura, Tsutomu; Ichimura, Shotaro; Fujimura, Ryushi; Kuroda, Kazuo

    2006-09-01

    Holographic Versatile Disc (HVD TM) using Collinear TM Technologies is proposed by OPTWARE Corporation, in which the information and reference beams are displayed co-axially by the same SLM. With this unique configuration the optical pickup can be designed as small as the DVD's, and can be placed on one side of the recording disc. In HVD TM structure, the pre-formatted meta-data reflective layer is used for the focus/tracking servo and reading address information, and the dichroic mirror layer is used for detecting holographic recording information without interfering with the preformatted information. A 2-dimensional digital page data format is used and the shift-multiplexing method is employed to increased recording density of HVD TM. Experimental and theoretical studies suggest that the holographic material is very effective to increased recording density of the system. As the servo technology is being introduced to control the objective lens to be maintained precisely to the disc in the recording and the reconstructing process, a vibration isolator is no longer necessary. HVD TM will be compatible with existing disc storage systems, like CD and DVD, and enable us to expand its applications into other optical information storage systems.

  1. Versatility of cyclodextrins in self-assembly systems of amphiphiles.

    Science.gov (United States)

    Jiang, Lingxiang; Yan, Yun; Huang, Jianbin

    2011-11-14

    Recently, cyclodextrins (CDs) were found to play important yet complicated (or even apparently opposite sometimes) roles in self-assembly systems of amphiphiles or surfactants. Herein, we try to review and clarify the versatility of CDs in surfactant assembly systems by 1) classifying the roles played by CDs into two groups (modulator and building unit) and four subgroups (destructive and constructive modulators, amphiphilic and unamphiphilic building units), 2) comparing these subgroups, and 3) analyzing mechanisms. As a modulator, although CDs by themselves do not participate into the final surfactant aggregates, they can greatly affect the aggregates in two ways. In most cases CDs will destroy the aggregates by depleting surfactant molecules from the aggregates (destructive), or in certain cases CDs can promote the aggregates to grow by selectively removing the less-aggregatable surfactant molecules from the aggregates (constructive). As an amphiphilic building unit, CDs can be chemically (by chemical bonds) or physically (by host-guest interaction) attached to a hydrophobic moiety, and the resultant compounds act as classic amphiphiles. As an unamphiphilic building unit, CD/surfactant complexes or even CDs on their own can assemble into aggregates in an unconventional, unamphiphilic manner driven by CD-CD H-bonds. Moreover, special emphasis is put on two recently appeared aspects: the constructive modulator and unamphiphilic building unit. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Versatile rogue waves in scalar, vector, and multidimensional nonlinear systems

    Science.gov (United States)

    Chen, Shihua; Baronio, Fabio; Soto-Crespo, Jose M.; Grelu, Philippe; Mihalache, Dumitru

    2017-11-01

    This review is dedicated to recent progress in the active field of rogue waves, with an emphasis on the analytical prediction of versatile rogue wave structures in scalar, vector, and multidimensional integrable nonlinear systems. We first give a brief outline of the historical background of the rogue wave research, including referring to relevant up-to-date experimental results. Then we present an in-depth discussion of the scalar rogue waves within two different integrable frameworks—the infinite nonlinear Schrödinger (NLS) hierarchy and the general cubic-quintic NLS equation, considering both the self-focusing and self-defocusing Kerr nonlinearities. We highlight the concept of chirped Peregrine solitons, the baseband modulation instability as an origin of rogue waves, and the relation between integrable turbulence and rogue waves, each with illuminating examples confirmed by numerical simulations. Later, we recur to the vector rogue waves in diverse coupled multicomponent systems such as the long-wave short-wave equations, the three-wave resonant interaction equations, and the vector NLS equations (alias Manakov system). In addition to their intriguing bright–dark dynamics, a series of other peculiar structures, such as coexisting rogue waves, watch-hand-like rogue waves, complementary rogue waves, and vector dark three sisters, are reviewed. Finally, for practical considerations, we also remark on higher-dimensional rogue waves occurring in three closely-related (2  +  1)D nonlinear systems, namely, the Davey–Stewartson equation, the composite (2  +  1)D NLS equation, and the Kadomtsev–Petviashvili I equation. As an interesting contrast to the peculiar X-shaped light bullets, a concept of rogue wave bullets intended for high-dimensional systems is particularly put forward by combining contexts in nonlinear optics.

  3. Antisense-mediated RNA targeting: versatile and expedient genetic manipulation in the brain

    Directory of Open Access Journals (Sweden)

    Ioannis eZalachoras

    2011-07-01

    Full Text Available A limiting factor in brain research still is the difficulty to evaluate in vivo the role of the increasing number of proteins implicated in neuronal processes. We discuss here the potential of antisense-mediated RNA targeting approaches. We mainly focus on those that manipulate splicing (exon skipping and exon inclusion, but will also briefly discuss mRNA targeting. Classic knockdown of expression by mRNA targeting is only one possible application of antisense oligonucleotides (AON in the control of gene function. Exon skipping and inclusion are based on the interference of AONs with splicing of pre-mRNAs. These are powerful, specific and particularly versatile techniques, which can be used to circumvent pathogenic mutations, shift splice variant expression, knock down proteins, or to create molecular models using in-frame deletions. Pre-mRNA targeting is currently used both as a research tool, e.g. in models for motor neuron disease, and in clinical trials for Duchenne muscular dystrophy and amyotrophic lateral sclerosis.AONs are particularly promising in relation to brain research, as the modified AONs are taken up extremely fast in neurons and glial cells with a long residence, and without the need for viral vectors or other delivery tools, once inside the blood brain barrier. In this review we cover 1. The principles of antisense-mediated techniques, chemistry and efficacy.2. The pros and cons of AON approaches in the brain compared to other techniques of interfering with gene function, such as transgenesis and short hairpin RNAs, in terms of specificity of the manipulation, spatial and temporal control over gene expression, toxicity and delivery issues.3. The potential applications for Neuroscience. We conclude that there is good evidence from animal studies that the CNS can be successfully targeted, but the potential of the diverse AON-based approaches appears to be under-recognized.

  4. Dextran-coated iron oxide nanoparticles: a versatile platform for targeted molecular imaging, molecular diagnostics, and therapy.

    Science.gov (United States)

    Tassa, Carlos; Shaw, Stanley Y; Weissleder, Ralph

    2011-10-18

    Advances in our understanding of the genetic basis of disease susceptibility coupled with prominent successes for molecular targeted therapies have resulted in an emerging strategy of personalized medicine. This approach envisions risk stratification and therapeutic selection based on an individual's genetic makeup and physiologic state (the latter assessed through cellular or molecular phenotypes). Molecularly targeted nanoparticles can play a key role in this vision through noninvasive assessments of molecular processes and specific cell populations in vivo, sensitive molecular diagnostics, and targeted delivery of therapeutics. A superparamagnetic iron oxide nanoparticle with a cross-linked dextran coating, or CLIO, is a powerful and illustrative nanoparticle platform for these applications. These structures and their derivatives support diagnostic imaging by magnetic resonance (MRI), optical, and positron emission tomography (PET) modalities and constitute a versatile platform for conjugation to targeting ligands. A variety of conjugation methods exist to couple the dextran surface to different functional groups; in addition, a robust bioorthogonal [4 + 2] cycloaddition reaction between 1,2,4,5-tetrazene (Tz) and trans-cyclooctene (TCO) can conjugate nanoparticles to targeting ligands or label pretargeted cells. The ready availability of conjugation methods has given rise to the synthesis of libraries of small molecule modified nanoparticles, which can then be screened for nanoparticles with specificity for a specific cell type. Since most nanoparticles display their targeting ligands in a multivalent manner, a detailed understanding of the kinetics and affinity of a nanoparticle's interaction with its target (as determined by surface plasmon resonance) can yield functionally important insights into nanoparticle design. In this Account, we review applications of the CLIO platform in several areas relevant to the mission of personalized medicine. We demonstrate

  5. Versatile surface engineering of porous nanomaterials with bioinspired polyphenol coatings for targeted and controlled drug delivery

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    Li, Juan; Wu, Shuxian; Wu, Cuichen; Qiu, Liping; Zhu, Guizhi; Cui, Cheng; Liu, Yuan; Hou, Weijia; Wang, Yanyue; Zhang, Liqin; Teng, I.-Ting; Yang, Huang-Hao; Tan, Weihong

    2016-04-01

    The development of biocompatible drug delivery systems with targeted recognition and controlled release has experienced a number of design challenges, including, for example, complicated preparation steps and premature drug release. Herein, we address these problems through an in situ self-polymerization method that synthesizes biodegradable polyphenol-coated porous nanomaterials for targeted and controlled drug delivery. As a proof of concept, we synthesized polyphenol-coated mesoporous silica nanoparticles, termed MSN@polyphenol. The polyphenol coatings not only improved colloidal stability and prevented premature drug leakage, but also provided a scaffold for immobilization of targeting moieties, such as aptamers. Both immobilization of targeting aptamers and synthesis of polyphenol coating are easily accomplished without the aid of any other organic reagents. Importantly, the polyphenol coating (EGCg) used in this study could be biodegraded by acidic pH and intracellular glutathione, resulting in the release of trapped anticancer drugs. Based on confocal fluorescence microscopy and cytotoxicity experiments, drug-loaded and polyphenol-coated MSNs were shown to possess highly efficient internalization and an apparent cytotoxic effect on target cancer, but not control, cells. Our results suggest that these highly biocompatible and biodegradable polyphenol-coated MSNs are promising vectors for controlled-release biomedical applications and cancer therapy.The development of biocompatible drug delivery systems with targeted recognition and controlled release has experienced a number of design challenges, including, for example, complicated preparation steps and premature drug release. Herein, we address these problems through an in situ self-polymerization method that synthesizes biodegradable polyphenol-coated porous nanomaterials for targeted and controlled drug delivery. As a proof of concept, we synthesized polyphenol-coated mesoporous silica nanoparticles

  6. Origami: A Versatile Modeling System for Visualising Chemical Structure and Exploring Molecular Function

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    Davis, James; Leslie, Ray; Billington, Susan; Slater, Peter R.

    2010-01-01

    The use of "Origami" is presented as an accessible and transferable modeling system through which to convey the intricacies of molecular shape and highlight structure-function relationships. The implementation of origami has been found to be a versatile alternative to conventional ball-and-stick models, possessing the key advantages of being both…

  7. CRISPR-Cas9 systems: versatile cancer modelling platforms and promising therapeutic strategies.

    Science.gov (United States)

    Wen, Wan-Shun; Yuan, Zhi-Min; Ma, Shi-Jie; Xu, Jiang; Yuan, Dong-Tang

    2016-03-15

    The RNA-guided nuclease CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR associated nuclease 9) and its variants such as nickase Cas9, dead Cas9, guide RNA scaffolds and RNA-targeting Cas9 are convenient and versatile platforms for site-specific genome editing and epigenome modulation. They are easy-to-use, simple-to-design and capable of targeting multiple loci simultaneously. Given that cancer develops from cumulative genetic and epigenetic alterations, CRISPR-Cas9 and its variants (hereafter referred to as CRISPR-Cas9 systems) hold extensive application potentials in cancer modeling and therapy. To date, they have already been applied to model oncogenic mutations in cell lines (e.g., Choi and Meyerson, Nat Commun 2014;5:3728) and in adult animals (e.g., Xue et al., Nature 2014;514:380-4), as well as to combat cancer by disabling oncogenic viruses (e.g., Hu et al., Biomed Res Int 2014;2014:612823) or by manipulating cancer genome (e.g., Liu et al., Nat Commun 2014;5:5393). Given the importance of epigenome and transcriptome in tumourigenesis, manipulation of cancer epigenome and transcriptome for cancer modeling and therapy is a promising area in the future. Whereas (epi)genetic modifications of cancer microenvironment with CRISPR-Cas9 systems for therapeutic purposes represent another promising area in cancer research. Herein, we introduce the functions and mechanisms of CRISPR-Cas9 systems in genome editing and epigenome modulation, retrospect their applications in cancer modelling and therapy, discuss limitations and possible solutions and propose future directions, in hope of providing concise and enlightening information for readers interested in this area. © 2015 UICC.

  8. Quantum Dot Systems : A versatile platform for quantum simulations

    NARCIS (Netherlands)

    Barthelemy, P.J.C.; Vandersypen, L.M.K.

    2013-01-01

    Quantum mechanics often results in extremely complex phenomena, especially when the quantum system under consideration is composed of many interacting particles. The states of these many-body systems live in a space so large that classical numerical calculations cannot compute them. Quantum

  9. Merlin: a fast versatile readout system for Medipix3

    Science.gov (United States)

    Plackett, R.; Horswell, I.; Gimenez, E. N.; Marchal, J.; Omar, D.; Tartoni, N.

    2013-01-01

    This contribution reports on the development of a new high rate readout system for the Medipix3 hybrid pixel ASIC developed by the Detector Group at Diamond Light Source. It details the current functionality of the system and initial results from tests on Diamond's B16 beamline. The Merlin system is based on a National Instruments PXI/FlexRIO system running a Xilinx Virtex5 FPGA. It is capable of recording Medipix3 256 by 256 by 12 bit data frames at over 1 kHz in bursts of 1200 frames and running at over 100 Hz continuously to disk or over a TCP/IP link. It is compatible with the standard Medipix3 single chipboards developed at CERN and is capable of driving them over cable lengths of up to 10 m depending on the data rate required. In addition to a standalone graphical interface, a system of remote TCP/IP control and data transfer has been developed to allow easy integration with third party control systems and scripting languages. Two Merlin systems are being deployed on the B16 and I16 beamlines at Diamond and the system has been integrated with the EPICS/GDA control systems used. Results from trigger synchronisation, fast burst and high rate tests made on B16 in March are reported and demonstrate an encouraging reliability and timing accuracy. In addition to normal high resolution imaging applications of Medipix3, the results indicate the system could profitably be used in `pump and probe' style experiments, where a very accurate, high frame rate is especially beneficial. In addition to these two systems, Merlin is being used by the Detector Group to test the Excalibur 16 chip hybrid modules, and by the LHCb VELO Pixel Upgrade group in their forthcoming testbeams. Additionally the contribution looks forward to further developments and improvements in the system, including full rate quad chip readout capability, multi-FPGA support, long distance optical communication and further functionality enhancements built on the capabilities of the Medipix3 chips.

  10. Saccharomyces cerevisiae: a versatile eukaryotic system in virology

    Directory of Open Access Journals (Sweden)

    Breinig Tanja

    2007-10-01

    Full Text Available Abstract The yeast Saccharomyces cerevisiae is a well-established model system for understanding fundamental cellular processes relevant to higher eukaryotic organisms. Less known is its value for virus research, an area in which Saccharomyces cerevisiae has proven to be very fruitful as well. The present review will discuss the main achievements of yeast-based studies in basic and applied virus research. These include the analysis of the function of individual proteins from important pathogenic viruses, the elucidation of key processes in viral replication through the development of systems that allow the replication of higher eukayotic viruses in yeast, and the use of yeast in antiviral drug development and vaccine production.

  11. Versatile Friction Stir Welding/Friction Plug Welding System

    Science.gov (United States)

    Carter, Robert

    2006-01-01

    A proposed system of tooling, machinery, and control equipment would be capable of performing any of several friction stir welding (FSW) and friction plug welding (FPW) operations. These operations would include the following: Basic FSW; FSW with automated manipulation of the length of the pin tool in real time [the so-called auto-adjustable pin-tool (APT) capability]; Self-reacting FSW (SRFSW); SR-FSW with APT capability and/or real-time adjustment of the distance between the front and back shoulders; and Friction plug welding (FPW) [more specifically, friction push plug welding] or friction pull plug welding (FPPW) to close out the keyhole of, or to repair, an FSW or SR-FSW weld. Prior FSW and FPW systems have been capable of performing one or two of these operations, but none has thus far been capable of performing all of them. The proposed system would include a common tool that would have APT capability for both basic FSW and SR-FSW. Such a tool was described in Tool for Two Types of Friction Stir Welding (MFS- 31647-1), NASA Tech Briefs, Vol. 30, No. 10 (October 2006), page 70. Going beyond what was reported in the cited previous article, the common tool could be used in conjunction with a plug welding head to perform FPW or FPPW. Alternatively, the plug welding head could be integrated, along with the common tool, into a FSW head that would be capable of all of the aforementioned FSW and FPW operations. Any FSW or FPW operation could be performed under any combination of position and/or force control.

  12. Acidic phospholipid bicelles: a versatile model membrane system.

    Science.gov (United States)

    Struppe, J; Whiles, J A; Vold, R R

    2000-01-01

    With the aim of establishing acidic bicellar solutions as a useful membrane model system, we have used deuterium NMR spectroscopy to investigate the properties of dimyristoyl/dihexanoylphosphatidylcholine (DMPC/DHPC) bicelles containing 25% (w/w in H(2)O) of either dimyristoylphosphatidylserine (DMPS) or dimyristoylphosphatidylglycerol (DMPG). The addition of the acidic lipid component to this lyotropic liquid crystalline system reduces its range of stability because of poor miscibility of the two dimyristoylated phospholipids. Compared to the neutral bicelles, which are stable at pH 4 to pH 7, acidic bicelles are stable only from pH 5.5 to pH 7. Solid-state deuterium NMR analysis of d(54)-DMPC showed similar ordering in neutral and acidic bicelles. Fully deuterated DMPS or DMPG is ordered in a way similar to that of DMPC. Study of the binding of the myristoylated N-terminal 14-residue peptide mu-GSSKSKPKDPSQRR from pp60(nu-src) to both neutral and acidic bicelles shows the utility of these novel membrane mimetics. PMID:10620292

  13. A versatile low-cost Czochralski crystal growth system for nonlinear optical organic materials

    Science.gov (United States)

    Aggarwal, M. D.; Wang, W. S.; Shields, Angela W.; Penn, Benjamin G.; Frazier, Donald O.

    1992-01-01

    A versatile low-cost Czochralski system for pulling crystals from melt has been described. It is designed for low melting, transparent, and nonlinear optical materials. One of the most important novel feature of this crystal growth system is that the entire growth process including the solid-liquid interface can be viewed from any direction. Another is the use of an after-heater to reduce excess heat loss from the surface of the melt.

  14. A Versatile Beam Loss Monitoring System for CLIC

    CERN Document Server

    Kastriotou, Maria; Farabolini, Wilfrid; Holzer, Eva Barbara; Nebot Del Busto, Eduardo; Tecker, Frank; Welsch, Carsten

    2016-01-01

    The design of a potential CLIC beam loss monitoring (BLM) system presents multiple challenges. To successfully cover the 48 km of beamline, ionisation chambers and optical fibre BLMs are under investigation. The former fulfils all CLIC requirements but would need more than 40000 monitors to protect the whole facility. For the latter, the capability of reconstructing the original loss position with a multi-bunch beam pulse and multiple loss locations still needs to be quantified. Two main sources of background for beam loss measurements are identified for CLIC. The two-beam accelerator scheme introduces so-called crosstalk, i.e. detection of losses originating in one beam line by the monitors protecting the other. Moreover, electrons emitted from the inner surface of RF cavities and boosted by the high RF gradients may produce signals in neighbouring BLMs, limiting their ability to detect real beam losses. This contribution presents the results of dedicated experiments performed in the CLIC Test Facility to qu...

  15. Versatile, low-cost, computer-controlled, sample positioning system for vacuum applications

    Science.gov (United States)

    Vargas-Aburto, Carlos; Liff, Dale R.

    1991-01-01

    A versatile, low-cost, easy to implement, microprocessor-based motorized positioning system (MPS) suitable for accurate sample manipulation in a Second Ion Mass Spectrometry (SIMS) system, and for other ultra-high vacuum (UHV) applications was designed and built at NASA LeRC. The system can be operated manually or under computer control. In the latter case, local, as well as remote operation is possible via the IEEE-488 bus. The position of the sample can be controlled in three linear orthogonal and one angular coordinates.

  16. Polymeric nano-micelles: versatile platform for targeted delivery in cancer.

    Science.gov (United States)

    Mohamed, Salma; Parayath, Neha N; Taurin, Sebastien; Greish, Khaled

    2014-10-01

    Polymeric micelles are among the most promising delivery systems in nanomedicine. The growing interest in polymeric micelles as drug delivery vehicle is promoted by the advantages they offer for hydrophobic anticancer agents. The size of most polymeric micelles lies within the range 10-100 nm ensuring that they can selectively leave the circulation at tumor site via the enhanced permeability and retention effect. Their unique structure allows them to solubilize hydrophobic drugs, prolongs their circulatory half-life and eventually leads to enhanced therapeutic efficacy. In addition, they can undergo several structural modifications to further augment tumor cell uptake. In this review, we will discuss various micellar systems that have been studied in preclinical and clinical settings.

  17. A Versatile System for USER Cloning-Based Assembly of Expression Vectors for Mammalian Cell Engineering

    DEFF Research Database (Denmark)

    Lund, Anne Mathilde; Kildegaard, Helene Faustrup; Petersen, Maja Borup Kjær

    2014-01-01

    A new versatile mammalian vector system for protein production, cell biology analyses, and cell factory engineering was developed. The vector system applies the ligation-free uracil-excision based technique – USER cloning – to rapidly construct mammalian expression vectors of multiple DNA fragments...... efficiency above 90%. The functionality of basic vectors for FAST assembly was tested and validated by transient expression of fluorescent model proteins in CHO, U-2-OS and HEK293 cell lines. In this test, we included many of the most common vector elements for heterologous gene expression in mammalian cells......, in addition the system is fully extendable by other users. The vector system is designed to facilitate high-throughput genome-scale studies of mammalian cells, such as the newly sequenced CHO cell lines, through the ability to rapidly generate high-fidelity assembly of customizable gene expression vectors....

  18. Implementation of a versatile research data acquisition system using a commercially available medical ultrasound scanner

    DEFF Research Database (Denmark)

    Hemmsen, Martin Christian; Nikolov, Svetoslav Ivanov; Pedersen, Mads Møller

    2012-01-01

    This paper describes the design and implementation of a versatile, open-architecture research data acquisition system using a commercially available medical ultrasound scanner. The open architecture will allow researchers and clinicians to rapidly develop applications and move them relatively easy...... to the clinic. The system consists of a standard PC equipped with a camera link and an ultrasound scanner equipped with a research interface. The ultrasound scanner is an easy-to-use imaging device that is capable of generating high-quality images. In addition to supporting the acquisition of multiple data...... to give researchers and clinicians the ability to utilize third-party software for data analysis and flexible manipulation of control parameters. Because of the advantages of speed of acquisition and clinical benefit, research projects have successfully used the system to test and implement...

  19. Versatile microwave-driven trapped ion spin system for quantum information processing.

    Science.gov (United States)

    Piltz, Christian; Sriarunothai, Theeraphot; Ivanov, Svetoslav S; Wölk, Sabine; Wunderlich, Christof

    2016-07-01

    Using trapped atomic ions, we demonstrate a tailored and versatile effective spin system suitable for quantum simulations and universal quantum computation. By simply applying microwave pulses, selected spins can be decoupled from the remaining system and, thus, can serve as a quantum memory, while simultaneously, other coupled spins perform conditional quantum dynamics. Also, microwave pulses can change the sign of spin-spin couplings, as well as their effective strength, even during the course of a quantum algorithm. Taking advantage of the simultaneous long-range coupling between three spins, a coherent quantum Fourier transform-an essential building block for many quantum algorithms-is efficiently realized. This approach, which is based on microwave-driven trapped ions and is complementary to laser-based methods, opens a new route to overcoming technical and physical challenges in the quest for a quantum simulator and a quantum computer.

  20. A versatile molecular tagging method for targeting proteins to avian reovirus muNS inclusions. Use in protein immobilization and purification.

    Directory of Open Access Journals (Sweden)

    Alberto Brandariz-Nuñez

    Full Text Available BACKGROUND: Avian reoviruses replicate in viral factories, which are dense cytoplasmic compartments established by protein-protein interactions. The non-structural protein muNS forms the factory scaffold that attracts other viral components in a controlled fashion. To create such a three-dimensional network, muNS uses several different self-interacting domains. METHODOLOGY/PRINCIPAL FINDINGS: In this study we have devised a strategy to identify muNS regions containing self-interacting domains, based on the capacity of muNS-derived inclusions to recruit muNS fragments. The results revealed that the muNS region consisting of residues 477-542 was recruited with the best efficiency, and this raised the idea of using this fragment as a molecular tag for delivering foreign proteins to muNS inclusions. By combining such tagging system with our previously established method for purifying muNS inclusions from baculovirus-infected insect cells, we have developed a novel protein purification protocol. CONCLUSIONS/SIGNIFICANCE: We show that our tagging and inclusion-targeting system can be a simple, versatile and efficient method for immobilizing and purifying active proteins expressed in baculovirus-infected cells. We also demonstrate that muNS inclusions can simultaneously recruit several tagged proteins, a finding which may be used to generate protein complexes and create multiepitope particulate material for immunization purposes.

  1. A versatile molecular tagging method for targeting proteins to avian reovirus muNS inclusions. Use in protein immobilization and purification.

    Science.gov (United States)

    Brandariz-Nuñez, Alberto; Menaya-Vargas, Rebeca; Benavente, Javier; Martinez-Costas, Jose

    2010-11-12

    Avian reoviruses replicate in viral factories, which are dense cytoplasmic compartments established by protein-protein interactions. The non-structural protein muNS forms the factory scaffold that attracts other viral components in a controlled fashion. To create such a three-dimensional network, muNS uses several different self-interacting domains. In this study we have devised a strategy to identify muNS regions containing self-interacting domains, based on the capacity of muNS-derived inclusions to recruit muNS fragments. The results revealed that the muNS region consisting of residues 477-542 was recruited with the best efficiency, and this raised the idea of using this fragment as a molecular tag for delivering foreign proteins to muNS inclusions. By combining such tagging system with our previously established method for purifying muNS inclusions from baculovirus-infected insect cells, we have developed a novel protein purification protocol. We show that our tagging and inclusion-targeting system can be a simple, versatile and efficient method for immobilizing and purifying active proteins expressed in baculovirus-infected cells. We also demonstrate that muNS inclusions can simultaneously recruit several tagged proteins, a finding which may be used to generate protein complexes and create multiepitope particulate material for immunization purposes.

  2. Versatile dual-technology system for markerless allele replacement in Burkholderia pseudomallei.

    Science.gov (United States)

    López, Carolina M; Rholl, Drew A; Trunck, Lily A; Schweizer, Herbert P

    2009-10-01

    Burkholderia pseudomallei is the etiologic agent of melioidosis, a rare but serious tropical disease. In the United States, genetic research with this select agent bacterium is strictly regulated. Although several select agent compliant methods have been developed for allelic replacement, all of them suffer from some drawbacks, such as a need for specific host backgrounds or use of minimal media. Here we describe a versatile select agent compliant allele replacement system for B. pseudomallei based on a mobilizable vector, pEXKm5, which contains (i) a multiple cloning site within a lacZalpha gene for facile cloning of recombinant DNA fragments, (ii) a constitutively expressed gusA indicator gene for visual detection of merodiploid formation and resolution, and (iii) elements required for resolution of merodiploids using either I-SceI homing endonuclease-stimulated recombination or sacB-based counterselection. The homing endonuclease-based allele replacement system is completed by pBADSce, which contains an araC-P(BAD)-I-sceI expression cassette for arabinose-inducible I-SceI expression and a temperature-sensitive pRO1600 replicon for facile plasmid curing. Complementing these systems is the improved Deltaasd Escherichia coli mobilizer strain RHO3. This strain is susceptible to commonly used antibiotics and allows nutritional counterselection on rich media because of its diaminopimelic acid auxotrophy. The versatility of the I-SceI- and sacB-based methods afforded by pEXKm5 in conjunction with E. coli RHO3 was demonstrated by isolation of diverse deletion mutants in several clinical, environmental, and laboratory B. pseudomallei strains. Finally, sacB-based counterselection was employed to isolate a defined chromosomal fabD(Ts) allele that causes synthesis of a temperature-sensitive FabD, an essential fatty acid biosynthesis enzyme.

  3. EEI`s wafer-cell bipolar battery: Versatile technology for a variety of military systems

    Energy Technology Data Exchange (ETDEWEB)

    Brown, J.T.; Klein, M.G.; Reisner, D.E. [Electro Energy, Inc., Danbury, CT (United States)

    1996-11-01

    A new versatile cell design based on stackable wafer cells is described which forms the unit building block of a new generation of bipolar battery systems for a wide variety of military applications. Current is transported across an outer envelope of conductive plastic film. This innovative bipolar design approach offers improved energy density based on more efficient packaging in prismatic containers as well as elimination of cell hardware. Higher power capability is achieved from the intrinsic low resistance operation in a bipolar mode. These performance improvements are achieved in a low-cost package by virtue of the design simplicity and use of non-graphitic plastic-bonded electrodes. EEI has demonstrated the viability of the wafer cell approach in Ni-MH with sealed cell cycle life in excess of 2,000 cycles. Results are also reported for Ag-MH.

  4. BarTeL, a Genetically Versatile, Bioluminescent and Granule Neuron Precursor-Targeted Mouse Model for Medulloblastoma.

    Directory of Open Access Journals (Sweden)

    Gregory M Shackleford

    Full Text Available Medulloblastomas are the most common malignant pediatric brain tumor and have been divided into four major molecular subgroups. Animal models that mimic the principal molecular aberrations of these subgroups will be important tools for preclinical studies and allow greater understanding of medulloblastoma biology. We report a new transgenic model of medulloblastoma that possesses a unique combination of desirable characteristics including, among others, the ability to incorporate multiple and variable genes of choice and to produce bioluminescent tumors from a limited number of somatic cells within a normal cellular environment. This model, termed BarTeL, utilizes a Barhl1 homeobox gene promoter to target expression of a bicistronic transgene encoding both the avian retroviral receptor TVA and an eGFP-Luciferase fusion protein to neonatal cerebellar granule neuron precursor (cGNP cells, which are cells of origin for the sonic hedgehog (SHH subgroup of human medulloblastomas. The Barhl1 promoter-driven transgene is expressed strongly in mammalian cGNPs and weakly or not at all in mature granule neurons. We efficiently induced bioluminescent medulloblastomas expressing eGFP-luciferase in BarTeL mice by infection of a limited number of somatic cGNPs with avian retroviral vectors encoding the active N-terminal fragment of SHH and a stabilized MYCN mutant. Detection and quantification of the increasing bioluminescence of growing tumors in young BarTeL mice was facilitated by the declining bioluminescence of their uninfected maturing cGNPs. Inclusion of eGFP in the transgene allowed enriched sorting of cGNPs from neonatal cerebella. Use of a single bicistronic avian vector simultaneously expressing both Shh and Mycn oncogenes increased the medulloblastoma incidence and aggressiveness compared to mixed virus infections. Bioluminescent tumors could also be produced by ex vivo transduction of neonatal BarTeL cerebellar cells by avian retroviruses and

  5. BarTeL, a Genetically Versatile, Bioluminescent and Granule Neuron Precursor-Targeted Mouse Model for Medulloblastoma.

    Science.gov (United States)

    Shackleford, Gregory M; Shi, Xiang-He; Swanson, Kimberly S; Mahdi, Min Y; Gonzalez-Gomez, Ignacio; Asgharzadeh, Shahab; D'Apuzzo, Massimo; Erdreich-Epstein, Anat; Moats, Rex A

    2016-01-01

    Medulloblastomas are the most common malignant pediatric brain tumor and have been divided into four major molecular subgroups. Animal models that mimic the principal molecular aberrations of these subgroups will be important tools for preclinical studies and allow greater understanding of medulloblastoma biology. We report a new transgenic model of medulloblastoma that possesses a unique combination of desirable characteristics including, among others, the ability to incorporate multiple and variable genes of choice and to produce bioluminescent tumors from a limited number of somatic cells within a normal cellular environment. This model, termed BarTeL, utilizes a Barhl1 homeobox gene promoter to target expression of a bicistronic transgene encoding both the avian retroviral receptor TVA and an eGFP-Luciferase fusion protein to neonatal cerebellar granule neuron precursor (cGNP) cells, which are cells of origin for the sonic hedgehog (SHH) subgroup of human medulloblastomas. The Barhl1 promoter-driven transgene is expressed strongly in mammalian cGNPs and weakly or not at all in mature granule neurons. We efficiently induced bioluminescent medulloblastomas expressing eGFP-luciferase in BarTeL mice by infection of a limited number of somatic cGNPs with avian retroviral vectors encoding the active N-terminal fragment of SHH and a stabilized MYCN mutant. Detection and quantification of the increasing bioluminescence of growing tumors in young BarTeL mice was facilitated by the declining bioluminescence of their uninfected maturing cGNPs. Inclusion of eGFP in the transgene allowed enriched sorting of cGNPs from neonatal cerebella. Use of a single bicistronic avian vector simultaneously expressing both Shh and Mycn oncogenes increased the medulloblastoma incidence and aggressiveness compared to mixed virus infections. Bioluminescent tumors could also be produced by ex vivo transduction of neonatal BarTeL cerebellar cells by avian retroviruses and subsequent

  6. A Versatile and Reproducible Multi-Frequency Electrical Impedance Tomography System

    Directory of Open Access Journals (Sweden)

    James Avery

    2017-01-01

    Full Text Available A highly versatile Electrical Impedance Tomography (EIT system, nicknamed the ScouseTom, has been developed. The system allows control over current amplitude, frequency, number of electrodes, injection protocol and data processing. Current is injected using a Keithley 6221 current source, and voltages are recorded with a 24-bit EEG system with minimum bandwidth of 3.2 kHz. Custom PCBs interface with a PC to control the measurement process, electrode addressing and triggering of external stimuli. The performance of the system was characterised using resistor phantoms to represent human scalp recordings, with an SNR of 77.5 dB, stable across a four hour recording and 20 Hz to 20 kHz. In studies of both haeomorrhage using scalp electrodes, and evoked activity using epicortical electrode mats in rats, it was possible to reconstruct images matching established literature at known areas of onset. Data collected using scalp electrode in humans matched known tissue impedance spectra and was stable over frequency. The experimental procedure is software controlled and is readily adaptable to new paradigms. Where possible, commercial or open-source components were used, to minimise the complexity in reproduction. The hardware designs and software for the system have been released under an open source licence, encouraging contributions and allowing for rapid replication.

  7. Versatile dual reporter gene systems for investigating stop codon readthrough in plants.

    Directory of Open Access Journals (Sweden)

    Nga T Lao

    2009-10-01

    Full Text Available Translation is most often terminated when a ribosome encounters the first in-frame stop codon (UAA, UAG or UGA in an mRNA. However, many viruses (and some cellular mRNAs contain "stop" codons that cause a proportion of ribosomes to terminate and others to incorporate an amino acid and continue to synthesize a "readthrough", or C-terminally extended, protein. This dynamic redefinition of codon meaning is dependent on specific sequence context.We describe two versatile dual reporter systems which facilitate investigation of stop codon readthrough in vivo in intact plants, and identification of the amino acid incorporated at the decoded stop codon. The first is based on the reporter enzymes NAN and GUS for which sensitive fluorogenic and histochemical substrates are available; the second on GST and GFP.We show that the NAN-GUS system can be used for direct in planta measurements of readthrough efficiency following transient expression of reporter constructs in leaves, and moreover, that the system is sufficiently sensitive to permit measurement of readthrough in stably transformed plants. We further show that the GST-GFP system can be used to affinity purify readthrough products for mass spectrometric analysis and provide the first definitive evidence that tyrosine alone is specified in vivo by a 'leaky' UAG codon, and tyrosine and tryptophan, respectively, at decoded UAA, and UGA codons in the Tobacco mosaic virus (TMV readthrough context.

  8. Fast, versatile, and non-destructive biscuit inspection system using spectral imaging

    DEFF Research Database (Denmark)

    Carstensen, Jens Michael

    2017-01-01

    A fast, versatile, and non-destructive method for assessing biscuit quality is presented. The method integrates color (or browning) measurement, moisture assessment, compositional and dimensional measurements on a spectral imaging platform using the silicon range 400–1000 nm.......A fast, versatile, and non-destructive method for assessing biscuit quality is presented. The method integrates color (or browning) measurement, moisture assessment, compositional and dimensional measurements on a spectral imaging platform using the silicon range 400–1000 nm....

  9. An aerogel obtained from chemo-enzymatically oxidized fenugreek galactomannans as a versatile delivery system.

    Science.gov (United States)

    Rossi, Bianca; Campia, Paola; Merlini, Luca; Brasca, Milena; Pastori, Nadia; Farris, Stefano; Melone, Lucio; Punta, Carlo; Galante, Yves M

    2016-06-25

    We describe a new aerogel obtained from laccase-oxidized galactomannans of the leguminous plant fenugreek (Trigonella foenum-graecum) and suggest its potential practical use. Laccase/TEMPO oxidation of fenugreek in aqueous solution caused a viscosity increase of over 15-fold. A structured, elastic, stable hydrogel was generated, due to formation of carbonyl groups from primary OH of galactose side units and subsequent establishment of hemiacetalic bonds with available free hydroxyl groups. Upon lyophilization of this hydrogel, a water-insoluble aerogel was obtained (EOLFG), capable of uptaking aqueous or organic solvents over 20 times its own weight. The material was characterized by scanning electron microscopy, FT-IR, elemental analysis and (13)C CP-MAS NMR spectroscopy and its mechanical properties were investigated. To test the EOLFG as a delivery system, the anti-microbial enzyme lysozyme was used as model active principle. Lysozyme was added before or after formation of the aerogel, entrapped or absorbed in the gel, retained and released in active form, as proven by its hydrolytic glycosidase activity on lyophilized Micrococcus lysodeikticus cells wall peptidoglycans. This new biomaterial, composed of a chemo-enzymatically modified plant polysaccharide, might represent a versatile, biocompatible "delivery system" of active principles in food and non-food products. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Guidance system for laser targets

    Science.gov (United States)

    Porter, Gary D.; Bogdanoff, Anatoly

    1978-01-01

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

  11. BioMEA: a versatile high-density 3D microelectrode array system using integrated electronics.

    Science.gov (United States)

    Charvet, Guillaume; Rousseau, Lionel; Billoint, Olivier; Gharbi, Sadok; Rostaing, Jean-Pierre; Joucla, Sébastien; Trevisiol, Michel; Bourgerette, Alain; Chauvet, Philippe; Moulin, Céline; Goy, François; Mercier, Bruno; Colin, Mikael; Spirkovitch, Serge; Fanet, Hervé; Meyrand, Pierre; Guillemaud, Régis; Yvert, Blaise

    2010-04-15

    Microelectrode arrays (MEAs) offer a powerful tool to both record activity and deliver electrical microstimulations to neural networks either in vitro or in vivo. Microelectronics microfabrication technologies now allow building high-density MEAs containing several hundreds of microelectrodes. However, dense arrays of 3D micro-needle electrodes, providing closer contact with the neural tissue than planar electrodes, are not achievable using conventional isotropic etching processes. Moreover, increasing the number of electrodes using conventional electronics is difficult to achieve into compact devices addressing all channels independently for simultaneous recording and stimulation. Here, we present a full modular and versatile 256-channel MEA system based on integrated electronics. First, transparent high-density arrays of 3D-shaped microelectrodes were realized by deep reactive ion etching techniques of a silicon substrate reported on glass. This approach allowed achieving high electrode aspect ratios, and different shapes of tip electrodes. Next, we developed a dedicated analog 64-channel Application Specific Integrated Circuit (ASIC) including one amplification stage and one current generator per channel, and analog output multiplexing. A full modular system, called BIOMEA, has been designed, allowing connecting different types of MEAs (64, 128, or 256 electrodes) to different numbers of ASICs for simultaneous recording and/or stimulation on all channels. Finally, this system has been validated experimentally by recording and electrically eliciting low-amplitude spontaneous rhythmic activity (both LFPs and spikes) in the developing mouse CNS. The availability of high-density MEA systems with integrated electronics will offer new possibilities for both in vitro and in vivo studies of large neural networks. 2010 Elsevier B.V. All rights reserved.

  12. Implementation of a versatile research data acquisition system using a commercially available medical ultrasound scanner.

    Science.gov (United States)

    Hemmsen, Martin Christian; Nikolov, Svetoslav Ivanov; Pedersen, Mads Møller; Pihl, Michael Johannes; Enevoldsen, Marie Sand; Hansen, Jens Munk; Jensen, Jørgen Arendt

    2012-07-01

    This paper describes the design and implementation of a versatile, open-architecture research data acquisition system using a commercially available medical ultrasound scanner. The open architecture will allow researchers and clinicians to rapidly develop applications and move them relatively easy to the clinic. The system consists of a standard PC equipped with a camera link and an ultrasound scanner equipped with a research interface. The ultrasound scanner is an easy-to-use imaging device that is capable of generating high-quality images. In addition to supporting the acquisition of multiple data types, such as B-mode, M-mode, pulsed Doppler, and color flow imaging, the machine provides users with full control over imaging parameters such as transmit level, excitation waveform, beam angle, and focal depth. Beamformed RF data can be acquired from regions of interest throughout the image plane and stored to a file with a simple button press. For clinical trials and investigational purposes, when an identical image plane is desired for both an experimental and a reference data set, interleaved data can be captured. This form of data acquisition allows switching between multiple setups while maintaining identical transducer, scanner, region of interest, and recording time. Data acquisition is controlled through a graphical user interface running on the PC. This program implements an interface for third-party software to interact with the application. A software development toolkit is developed to give researchers and clinicians the ability to utilize third-party software for data analysis and flexible manipulation of control parameters. Because of the advantages of speed of acquisition and clinical benefit, research projects have successfully used the system to test and implement their customized solutions for different applications. Three examples of system use are presented in this paper: evaluation of synthetic aperture sequential beamformation, transverse

  13. Versatile optical manipulation system for inspection, laser processing, and isolation of individual living cells

    Science.gov (United States)

    Stuhrmann, B.; Jahnke, H.-G.; Schmidt, M.; Jähn, K.; Betz, T.; Müller, K.; Rothermel, A.; Käs, J.; Robitzki, A. A.

    2006-06-01

    Isolation of individual cells from a heterogeneous cell population is an invaluable step in the analysis of single cell properties. The demands in molecular and cellular biology as well as molecular medicine are the selection, isolation, and monitoring of single cells and cell clusters of biopsy material. Of particular interest are methods which complement a passive optical or spectroscopic selection with a variety of active single cell processing techniques such as mechanical, biochemical, or genetic manipulation prior to isolation. Sophisticated laser-based cell processing systems are available which can perform single cell processing in a contact-free and sterile manner. Until now, however, these multipurpose turnkey systems offer only basic micromanipulation and are not easily modified or upgraded, whereas laboratory situations often demand simple but versatile and adaptable solutions. We built a flexible laser micromanipulation platform combining contact-free microdissection and catapulting capabilities using a pulsed ultraviolet (337nm) laser with simultaneous generation of optical tweezing forces using a continuous wave infrared (1064nm) laser. The potential of our platform is exemplified with techniques such as local laser-induced injection of biomolecules into individual living cells, laser surgery, isolation of single cells by laser catapulting, and control of neuronal growth using optical gradient forces. Arbitrary dynamic optical force patterns can be created by fast laser scanning with acousto-optical deflectors and galvanometer mirrors, allowing multibeam contact-free micromanipulation, a prerequisite for reliable handling of material in laboratory-on-a-chip applications. All common microscopy techniques can be used simultaneously with the offered palette of micromanipulation methods. Taken together, we show that advanced optical micromanipulation systems can be designed which combine quality, cost efficiency, and adaptability.

  14. Versatile recombinant SUMOylation system for the production of SUMO-modified protein.

    Directory of Open Access Journals (Sweden)

    Alain R Weber

    Full Text Available Posttranslational modification by small ubiquitin-like modifiers (SUMO is being associated with a growing number of regulatory functions in diverse cellular processes. The biochemical investigation into the underlying molecular mechanisms, however, has been lagging behind due to the difficulty to generate sufficient amounts of recombinant SUMOylated proteins. Here, we present two newly designed two-component vector systems for the expression and purification of SUMO-modified target proteins in Escherichia coli. One system consists of a vector for SUMO conjugation, expressing human SUMO-activating (SAE1/SAE2 and conjugating (Ubc9 enzymes together with His6-tagged SUMO1, 2 or 3, that can be combined with commonly used expression constructs for any gene of interest. To facilitate SUMOylation of targets normally requiring a SUMO-E3 ligase for efficient modification, a second system is designed to express the target protein as a fusion with the human SUMO-conjugating enzyme Ubc9, thus compensating the absence of a potential SUMO ligase. We demonstrate the proficiency of these systems by SUMOylation of two DNA repair proteins, the thymine DNA glycosylase (TDG and XRCC1, and describe purification schemes for SUMOylated proteins in native and active form. This SUMO toolbox facilitates "in-cell" and "in-extract" production and purification of recombinant SUMO-modified target proteins for functional and structural analysis.

  15. Spin-Projected Matrix Product States: Versatile Tool for Strongly Correlated Systems.

    Science.gov (United States)

    Li, Zhendong; Chan, Garnet Kin-Lic

    2017-06-13

    We present a new wave function ansatz that combines the strengths of spin projection with the language of matrix product states (MPS) and matrix product operators (MPO) as used in the density matrix renormalization group (DMRG). Specifically, spin-projected matrix product states (SP-MPS) are constructed as [Formula: see text], where [Formula: see text] is the spin projector for total spin S and |ΨMPS(N,M)⟩ is an MPS wave function with a given particle number N and spin projection M. This new ansatz possesses several attractive features: (1) It provides a much simpler route to achieve spin adaptation (i.e., to create eigenfunctions of Ŝ2) compared to explicitly incorporating the non-Abelian SU(2) symmetry into the MPS. In particular, since the underlying state |ΨMPS(N,M)⟩ in the SP-MPS uses only Abelian symmetries, one does not need the singlet embedding scheme for nonsinglet states, as normally employed in spin-adapted DMRG, to achieve a single consistent variationally optimized state. (2) Due to the use of |ΨMPS(N,M)⟩ as its underlying state, the SP-MPS can be closely connected to broken-symmetry mean-field states. This allows one to straightforwardly generate the large number of broken-symmetry guesses needed to explore complex electronic landscapes in magnetic systems. Further, this connection can be exploited in the future development of quantum embedding theories for open-shell systems. (3) The sum of MPOs representation for the Hamiltonian and spin projector [Formula: see text] naturally leads to an embarrassingly parallel algorithm for computing expectation values and optimizing SP-MPS. (4) Optimizing SP-MPS belongs to the variation-after-projection (VAP) class of spin-projected theories. Unlike usual spin-projected theories based on determinants, the SP-MPS ansatz can be made essentially exact simply by increasing the bond dimensions in |ΨMPS(N,M)⟩. Computing excited states is also simple by imposing orthogonality constraints, which are simple

  16. CRISPR-Cas9 System as a Versatile Tool for Genome Engineering in Human Cells

    Directory of Open Access Journals (Sweden)

    Xuelian Wang

    2016-01-01

    Full Text Available Targeted nucleases are influential instruments for intervening in genome revision with great accuracy. RNA-guided Cas9 nucleases produced from clustered regularly interspaced short palindromic repeats (CRISPR-Cas systems have noticeably altered the means to modify the genomes of distinct organisms. They can be notably used to facilitate effective genome manipulation in eukaryotic cells by clearly detailing a 20-nt targeting sequence inside its directed RNA. We discuss the most recent advancements in the molecular basis of the type II CRISPR/Cas system and encapsulate applications and elements affecting its use in human cells. We also propose possible applications covering its uses ranging from basic science to implementation in the clinic.

  17. CRISPR-Cas9 System as a Versatile Tool for Genome Engineering in Human Cells.

    Science.gov (United States)

    Wang, Xuelian; Huang, Xiumin; Fang, Xiuli; Zhang, Youzhong; Wang, Wanpeng

    2016-11-15

    Targeted nucleases are influential instruments for intervening in genome revision with great accuracy. RNA-guided Cas9 nucleases produced from clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems have noticeably altered the means to modify the genomes of distinct organisms. They can be notably used to facilitate effective genome manipulation in eukaryotic cells by clearly detailing a 20-nt targeting sequence inside its directed RNA. We discuss the most recent advancements in the molecular basis of the type II CRISPR/Cas system and encapsulate applications and elements affecting its use in human cells. We also propose possible applications covering its uses ranging from basic science to implementation in the clinic.

  18. A Versatile Laser-Induced Incandescence System for Non-Intrusive Measurements of Particle Size and Mass in Aircraft Emissions Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose to develop a versatile and affordable system to measure the average diameter of primary soot particles along with their mass concentration in aircraft...

  19. A new versatile primer set targeting a short fragment of the mitochondrial COI region for metabarcoding metazoan diversity: application for characterizing coral reef fish gut contents.

    Science.gov (United States)

    Leray, Matthieu; Yang, Joy Y; Meyer, Christopher P; Mills, Suzanne C; Agudelo, Natalia; Ranwez, Vincent; Boehm, Joel T; Machida, Ryuji J

    2013-01-01

    The PCR-based analysis of homologous genes has become one of the most powerful approaches for species detection and identification, particularly with the recent availability of Next Generation Sequencing platforms (NGS) making it possible to identify species composition from a broad range of environmental samples. Identifying species from these samples relies on the ability to match sequences with reference barcodes for taxonomic identification. Unfortunately, most studies of environmental samples have targeted ribosomal markers, despite the fact that the mitochondrial Cytochrome c Oxidase subunit I gene (COI) is by far the most widely available sequence region in public reference libraries. This is largely because the available versatile ("universal") COI primers target the 658 barcoding region, whose size is considered too large for many NGS applications. Moreover, traditional barcoding primers are known to be poorly conserved across some taxonomic groups. We first design a new PCR primer within the highly variable mitochondrial COI region, the "mlCOIintF" primer. We then show that this newly designed forward primer combined with the "jgHCO2198" reverse primer to target a 313 bp fragment performs well across metazoan diversity, with higher success rates than versatile primer sets traditionally used for DNA barcoding (i.e. LCO1490/HCO2198). Finally, we demonstrate how the shorter COI fragment coupled with an efficient bioinformatics pipeline can be used to characterize species diversity from environmental samples by pyrosequencing. We examine the gut contents of three species of planktivorous and benthivorous coral reef fish (family: Apogonidae and Holocentridae). After the removal of dubious COI sequences, we obtained a total of 334 prey Operational Taxonomic Units (OTUs) belonging to 14 phyla from 16 fish guts. Of these, 52.5% matched a reference barcode (>98% sequence similarity) and an additional 32% could be assigned to a higher taxonomic level using

  20. RGD peptide functionalized and reconstituted high-density lipoprotein nanoparticles as a versatile and multimodal tumor targeting molecular imaging probe

    NARCIS (Netherlands)

    Chen, Wei; Jarzyna, Peter A.; van Tilborg, Geralda A. F.; Nguyen, Van Anh; Cormode, David P.; Klink, Ahmed; Griffioen, Arjan W.; Randolph, Gwendalyn J.; Fisher, Edward A.; Mulder, Willem J. M.; Fayad, Zahi A.

    2010-01-01

    High density lipoprotein (HDL), an endogenous nanoparticle, transports fat throughout the body and is capable of transferring cholesterol from atheroma in the vessel wall to the liver. In the present study, we utilized HDL as a multimodal nanoparticle platform for tumor targeting and imaging via

  1. Versatility of the Novalis system to deliver image-guided stereotactic body radiation therapy (SBRT) for various anatomical sites.

    Science.gov (United States)

    Teh, Bin S; Paulino, Arnold C; Lu, Hsin H; Chiu, J Kam; Richardson, Susan; Chiang, Stephen; Amato, Robert; Butler, E Brian; Bloch, Charles

    2007-08-01

    data obtained using 4D-CT while the patient is immobilized in the body cast aids in planning treatment margin and determining the need for respiratory motion control, e.g., abdominal compressor, gating, or active breathing control. The inclusion of PET/CT to the Brainlab treatment planning system further refines the target delineation and possibly guides differential fraction size prescription and delivery. The majority of the patients tolerated the SBRT treatment well despite the longer daily treatment time when compared to that of conventional treatment. All patients achieved good pain relief after SBRT. Compared to conventional standard radiotherapy of lower daily fraction size, we observed that the patients achieved faster pain relief and possibly more durable symptom control. Very high local control with stable disease on imaging was observed post SBRT. Our initial experience shows that the Brainlab Novalis system is very versatile in delivering image-guided SBRT to various anatomical sites. This SBRT approach can be applied to either primary or metastatic lesions in the primary, "boost," or re-irradiation settings. The understanding of fraction size, total dose, BED, and DVH of normal tissues is very important in the treatment planning. Appropriate use of immobilization devices, radio-opaque markers for image-guidance, 4D-CT for tumor/organ motion estimates, and fusion of planning CT scans with biological/functional imaging will further improve the planning and delivery of SBRT, hopefully leading to better treatment outcome.

  2. Targeted Therapy in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Murray Baron

    2016-10-01

    Full Text Available Targeted therapies use an understanding of the pathophysiology of a disease in an individual patient. Although targeted therapy for systemic sclerosis (SSc, scleroderma has not yet reached the level of patient-specific treatments, recent developments in the understanding of the global pathophysiology of the disease have led to new treatments based on the cells and pathways that have been shown to be involved in the disease pathogenesis. The presence of a B cell signature in skin biopsies has led to the trial of rituximab, an anti-CD20 antibody, in SSc. The well-known properties of transforming growth factor (TGF-β in promoting collagen synthesis and secretion has led to a small trial of fresolimumab, a human IgG4 monoclonal antibody capable of neutralizing TGF-β. Evidence supporting important roles for interleukin-6 in the pathogenesis of SSc have led to a large trial of tocilizumab in SSc. Soluble guanylate cyclase (sGC is an enzyme that catalyzes the production of cyclic guanosine monophosphate (cGMP upon binding of nitric oxide (NO to the sGC molecule. Processes such as cell growth and proliferation are regulated by cGMP. Evidence that sGC may play a role in SSc has led to a trial of riociguat, a molecule that sensitizes sGC to endogenous NO. Tyrosine kinases (TKs are involved in a wide variety of physiologic and pathological processes including vascular remodeling and fibrogenesis such as occurs in SSc. This has led to a trial of nintedanib, a next-generation tyrosine-kinase (TK inhibitor which targets multiple TKs, in SSc.

  3. A new versatile electrochemical etching chamber (VECEC) system for multi-size and multi-shape detector processing

    CERN Document Server

    Sohrabi, M

    1999-01-01

    A new versatile electrochemical etching ECE chamber (VECE) system is introduced in which the effective electrochemically etched area can have variable sizes and/or shapes required using templet etching. The flat rubber washers act as templets and holders of the etchant, and control the size and shape of the effective etched area of the detector which can be of various shapes and sizes desired. The system was operated in two operation modes A and B in which the both sides and one side of the detector were etched respectively. Detectors with etched areas having diameters from 1 to 18 cm have also been successfully etched by this system. Multi-chambers have been also designed using this principle for larger-scale multi-detector processing. The effects of etching area and time on the current through the detector have also been studied.

  4. Molecular Characterization of Adenylyl Cyclase Complex Proteins Using Versatile Protein-Tagging Plasmid Systems in Cryptococcus neoformans.

    Science.gov (United States)

    So, Yee-Seul; Yang, Dong-Hoon; Jung, Kwang-Woo; Huh, Won-Ki; Bahn, Yong-Sun

    2017-02-28

    In this study, we aimed to generate a series of versatile tagging plasmids that can be used in diverse molecular biological studies of the fungal pathogen Cryptococcus neoformans. We constructed 12 plasmids that can be used to tag a protein of interest with a GFP, mCherry, 4×FLAG, or 6×HA, along with nourseothricin-, neomycin-, or hygromycin-resistant selection markers. Using this tagging plasmid set, we explored the adenylyl cyclase complex (ACC), consisting of adenylyl cyclase (Cac1) and its associated protein Aca1, in the cAMP-signaling pathway, which is critical for the pathogenicity of C. neoformans. We found that Cac1-mCherry and Aca1-GFP were mainly colocalized as punctate forms in the cell membrane and nonnuclear cellular organelles. We also demonstrated that Cac1 and Aca1 interacted in vivo by coimmunoprecipitation, using Cac1-6×HA and Aca1-4×FLAG tagging strains. Bimolecular fluorescence complementation further confirmed the in vivo interaction of Cac1 and Aca1 in live cells. Finally, protein pull-down experiments using aca1Δ::ACA1-GFP and aca1Δ::ACA1- GFP cac1Δ strains and comparative mass spectrometry analysis identified Cac1 and a number of other novel ACC-interacting proteins. Thus, this versatile tagging plasmid system will facilitate diverse mechanistic studies in C. neoformans and further our understanding of its biology.

  5. Guidance and targeting for the Strategic Target System

    Science.gov (United States)

    White, John E.

    Guidance algorithms and targeting procedures for the Strategic Target System (STARS) launch vehicle are described. The STARS vehicle is a three stage booster, based partly upon retired Polaris A3 missile assets, which is intended to support development and testing of the Strategic Defense Initiative by delivering target payloads to the vicinity of the Kwajalein Atoll. STARS will be launched from the Kauai Test Facility located on Kauai, Hawaii. The STARS guidance objective is to deliver payloads to a prescribed target location with maximum accuracy at intercontinental ballistic missile velocities. Mission objectives are achieved with a combination of guidance algorithms.

  6. Unmanned Aircraft Systems (UAS) Sensor and Targeting

    Science.gov (United States)

    2010-07-27

    mission, a pre-determined number of different targets should be shuffled between the target locations in the array. Example targets for this subtest are...UNFOV Ultra Narrow Field of View UTM Universal Transverse Mercator VBLSS Video-Based Laser Scoring System VRT Vertical Reference Target WFOV

  7. A unique nickel system having versatile catalytic activity of biological significance.

    Science.gov (United States)

    Chattopadhyay, Tanmay; Mukherjee, Madhuparna; Mondal, Arindam; Maiti, Pali; Banerjee, Arpita; Banu, Kazi Sabnam; Bhattacharya, Santanu; Roy, Bappaditya; Chattopadhyay, D J; Mondal, Tapan Kumar; Nethaji, Munirathinam; Zangrando, Ennio; Das, Debasis

    2010-04-05

    A new dinuclear nickel(II) complex, [Ni(2)(LH(2))(H(2)O)(2)(OH)(NO(3))](NO(3))(3) (1), of an "end-off" compartmental ligand 2,6-bis(N-ethylpiperazine-iminomethyl)-4-methyl-phenolato, has been synthesized and structurally characterized. The X-ray single crystal structure analysis shows that the piperazine moieties assume the expected chair conformation and are protonated. The complex 1 exhibits versatile catalytic activities of biological significance, viz. catecholase, phosphatase, and DNA cleavage activities, etc. The catecholase activity of the complex observed is very dependent on the nature of the solvent. In acetonitrile medium, the complex is inactive to exhibit catecholase activity. On the other hand, in methanol, it catalyzes not only the oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC) but also tetrachlorocatechol (TCC), a catechol which is very difficult to oxidize, under aerobic conditions. UV-vis spectroscopic investigation shows that TCC oxidation proceeds through the formation of an intermediate. The intermediate has been characterized by an electron spray ionizaton-mass spectrometry study, which suggests a bidentate rather than a monodentate mode of TCC coordination in that intermediate, and this proposition have been verified by density functional theory calculation. The complex also exhibits phosphatase (with substrate p-nitrophenylphosphate) and DNA cleavage activities. The DNA cleavage activity exhibited by complex 1 most probably proceeds through a hydroxyl radical pathway. The bioactivity study suggests the possible applications of complex 1 as a site specific recognition of DNA and/or as an anticancer agent.

  8. Poly(3-hydroxybutyrate-co-R-3-hydroxyhexanoate) nanoparticles with polyethylenimine coat as simple, safe, and versatile vehicles for cell targeting

    DEFF Research Database (Denmark)

    Wu, Linping; Wang, Danyang; Parhamifar, Ladan

    2014-01-01

    A simple and highly safe poly(3-hydroxybutyrate-co-R-3-hydroxyhexanoate) nanoparticulate delivery system that targets different cell types is developed. A sub-cytotoxic level of polyethylenimine coat mediates universal cell targeting. Internalized nanoparticles traffic along endolysosomal...... compartments, endoplasmic reticulum and the Golgi complex. Nanoparticles have no detrimental effects on cell morphology and respiration....

  9. Development of a versatile readout and test system and characterization of a capacitively coupled active pixel sensor

    Energy Technology Data Exchange (ETDEWEB)

    Janssen, Jens; Gonella, Laura; Hemperek, Tomasz; Hirono, Toko; Huegging, Fabian; Krueger, Hans; Wermes, Norbert [Institute of Physics, University of Bonn, Bonn (Germany); Peric, Ivan [Karlsruher Institut fuer Technologie, Karlsruhe (Germany); Collaboration: ATLAS-Collaboration

    2015-07-01

    With the availability of high voltage and high resistivity CMOS processes, active pixel sensors are becoming increasingly interesting for radiation detection in high energy physics experiments. Although the pixel signal-to-noise ratio and the sensor radiation tolerance were improved, active pixel sensors cannot yet compete with state-of-the-art hybrid pixel detector in a high radiation environment. Hence, active pixel sensors are possible candidates for the outer tracking detector in HEP experiments where production cost plays a role. The investigation of numerous prototyping steps and different technologies is still ongoing and requires a versatile test and readout system, which will be presented in this talk. A capacitively coupled active pixel sensor fabricated in AMS 180 nm high voltage CMOS process is investigated. The sensor is designed to be glued to existing front-end pixel readout chips. Results from the characterization are presented in this talk.

  10. Bring your own camera to the trap: An inexpensive, versatile, and portable triggering system tested on wild hummingbirds.

    Science.gov (United States)

    Rico-Guevara, Alejandro; Mickley, James

    2017-07-01

    The study of animals in the wild offers opportunities to collect relevant information on their natural behavior and abilities to perform ecologically relevant tasks. However, it also poses challenges such as accounting for observer effects, human sensory limitations, and the time intensiveness of this type of research. To meet these challenges, field biologists have deployed camera traps to remotely record animal behavior in the wild. Despite their ubiquity in research, many commercial camera traps have limitations, and the species and behavior of interest may present unique challenges. For example, no camera traps support high-speed video recording. We present a new and inexpensive camera trap system that increases versatility by separating the camera from the triggering mechanism. Our system design can pair with virtually any camera and allows for independent positioning of a variety of sensors, all while being low-cost, lightweight, weatherproof, and energy efficient. By using our specialized trigger and customized sensor configurations, many limitations of commercial camera traps can be overcome. We use this system to study hummingbird feeding behavior using high-speed video cameras to capture fast movements and multiple sensors placed away from the camera to detect small body sizes. While designed for hummingbirds, our application can be extended to any system where specialized camera or sensor features are required, or commercial camera traps are cost-prohibitive, allowing camera trap use in more research avenues and by more researchers.

  11. Versatile Padding

    Science.gov (United States)

    1976-01-01

    Dynamic Systems, Inc. started after NASA-Ames scientists began work on a padding concept in 1968. They were looking for a better airplane seat. They found a new foam material that today has all kinds of additional applications including wheelchairs, x-ray table pads, off road vehicle seats, ski boots, and football helmet liners. Temper foam exhibits about 340% less shock from impact. Material is an open-cell polyurethane silicone plastic foam that takes shape of impressed objects but returns to its original shape even after 90% compression.

  12. A versatile low-cost Automation System for an Electroionization Experiment.

    OpenAIRE

    Servais, Christian; Locht, Robert; Momigny, J.

    1986-01-01

    A cheap complete automation system designed for an electoionization experiment is described. This system is based on a Sinclair ZX Spectrum computer and a modular architecture. The control program and general building blocks diagrams are discussed and give a general idea of how to build modules or procedures adapted to different applications. Peer reviewed

  13. A versatile selection system for folding competent proteins using genetic complementation in a eukaryotic host

    DEFF Research Database (Denmark)

    Lyngsø, C.; Kjaerulff, S.; Muller, S.

    2010-01-01

    -control systems to retain misfolded proteins in the ER and redirect them for cytosolic degradation, thereby only allowing folded proteins to reach the cell surface. Accordingly, the folding potential of the tested protein determines the ability of autotrophic colony growth. This system was successfully......Recombinant expression of native or modified eukaryotic proteins is pivotal for structural and functional studies and for industrial and pharmaceutical production of proteins. However, it is often impeded by the lack of proper folding. Here, we present a stringent and broadly applicable eukaryotic...... in vivo selection system for folded proteins. It is based on genetic complementation of the Schizosaccharomyces pombe growth marker gene invertase fused C-terminally to a protein library. The fusion proteins are directed to the secretion system, utilizing the ability of the eukaryotic protein quality...

  14. Directly Transforming PCR-Amplified DNA Fragments into Plant Cells Is a Versatile System That Facilitates the Transient Expression Assay

    Science.gov (United States)

    Lu, Yuming; Chen, Xi; Wu, Yuxuan; Wang, Yanping; He, Yuqing; Wu, Yan

    2013-01-01

    A circular plasmid containing a gene coding sequence has been broadly used for studying gene regulation in cells. However, to accommodate a quick screen plasmid construction and preparation can be time consuming. Here we report a PCR amplified dsDNA fragments (PCR-fragments) based transient expression system (PCR-TES) for suiting in the study of gene regulation in plant cells. Instead of transforming plasmids into plant cells, transient expression of PCR-fragments can be applicable. The transformation efficiency and expression property of PCR-fragments are comparable to transformation using plasmids. We analyzed the transformation efficiency in PCR-TES at transcription and protein levels. Our results indicate that the PCR-TES is as versatile as the conventional transformation system using plasmid DNA. Through reconstituting PYR1-mediated ABA signaling pathway in Arabidopsis mesophyll protoplasts, we were not only validating the practicality of PCR-TES but also screening potential candidates of CDPK family members which might be involved in the ABA signaling. Moreover, we determined that phosphorylation of ABF2 by CPK4 could be mediated by ABA-induced PYR1 and ABI1, demonstrating a crucial role of CDPKs in the ABA signaling. In summary, PCR-TES can be applicable to facilitate analyzing gene regulation and for the screen of putative regulatory molecules at the high throughput level in plant cells. PMID:23468926

  15. Evaluation of environmental filtration control of engineered nanoparticles using the Harvard Versatile Engineered Nanomaterial Generation System (VENGES)

    Science.gov (United States)

    Tsai, Candace S.-J.; Echevarría-Vega, Manuel E.; Sotiriou, Georgios A.; Santeufemio, Christopher; Schmidt, Daniel; Demokritou, Philip; Ellenbecker, Michael

    2012-05-01

    Applying engineering controls to airborne engineered nanoparticles (ENPs) is critical to prevent environmental releases and worker exposure. This study evaluated the effectiveness of two air sampling and six air cleaning fabric filters at collecting ENPs using industrially relevant flame-made engineered nanoparticles generated using a versatile engineered nanomaterial generation system (VENGES), recently designed and constructed at Harvard University. VENGES has the ability to generate metal and metal oxide exposure atmospheres while controlling important particle properties such as primary particle size, aerosol size distribution, and agglomeration state. For this study, amorphous SiO2 ENPs with a 15.4 nm primary particle size were generated and diluted with HEPA-filtered air. The aerosol was passed through the filter samples at two different filtration face velocities (2.3 and 3.5 m/min). Particle concentrations as a function of particle size were measured upstream and downstream of the filters using a specially designed filter test system to evaluate filtration efficiency. Real time instruments (FMPS and APS) were used to measure particle concentration for diameters from 5 to 20,000 nm. Membrane-coated fabric filters were found to have enhanced nanoparticle collection efficiency by 20-46 % points compared to non-coated fabric and could provide collection efficiency above 95 %.

  16. Evaluation of environmental filtration control of engineered nanoparticles using the Harvard Versatile Engineered Nanomaterial Generation System (VENGES)

    Science.gov (United States)

    Echevarría-Vega, Manuel E.; Sotiriou, Georgios A.; Santeufemio, Christopher; Schmidt, Daniel; Demokritou, Philip; Ellenbecker, Michael

    2013-01-01

    Applying engineering controls to airborne engineered nanoparticles (ENPs) is critical to prevent environmental releases and worker exposure. This study evaluated the effectiveness of two air sampling and six air cleaning fabric filters at collecting ENPs using industrially relevant flame-made engineered nanoparticles generated using a versatile engineered nanomaterial generation system (VENGES), recently designed and constructed at Harvard University. VENGES has the ability to generate metal and metal oxide exposure atmospheres while controlling important particle properties such as primary particle size, aerosol size distribution, and agglomeration state. For this study, amorphous SiO2 ENPs with a 15.4 nm primary particle size were generated and diluted with HEPA-filtered air. The aerosol was passed through the filter samples at two different filtration face velocities (2.3 and 3.5 m/min). Particle concentrations as a function of particle size were measured upstream and downstream of the filters using a specially designed filter test system to evaluate filtration efficiency. Real time instruments (FMPS and APS) were used to measure particle concentration for diameters from 5 to 20,000 nm. Membrane-coated fabric filters were found to have enhanced nanoparticle collection efficiency by 20–46 % points compared to non-coated fabric and could provide collection efficiency above 95 %. PMID:23412707

  17. Directly transforming PCR-amplified DNA fragments into plant cells is a versatile system that facilitates the transient expression assay.

    Directory of Open Access Journals (Sweden)

    Yuming Lu

    Full Text Available A circular plasmid containing a gene coding sequence has been broadly used for studying gene regulation in cells. However, to accommodate a quick screen plasmid construction and preparation can be time consuming. Here we report a PCR amplified dsDNA fragments (PCR-fragments based transient expression system (PCR-TES for suiting in the study of gene regulation in plant cells. Instead of transforming plasmids into plant cells, transient expression of PCR-fragments can be applicable. The transformation efficiency and expression property of PCR-fragments are comparable to transformation using plasmids. We analyzed the transformation efficiency in PCR-TES at transcription and protein levels. Our results indicate that the PCR-TES is as versatile as the conventional transformation system using plasmid DNA. Through reconstituting PYR1-mediated ABA signaling pathway in Arabidopsis mesophyll protoplasts, we were not only validating the practicality of PCR-TES but also screening potential candidates of CDPK family members which might be involved in the ABA signaling. Moreover, we determined that phosphorylation of ABF2 by CPK4 could be mediated by ABA-induced PYR1 and ABI1, demonstrating a crucial role of CDPKs in the ABA signaling. In summary, PCR-TES can be applicable to facilitate analyzing gene regulation and for the screen of putative regulatory molecules at the high throughput level in plant cells.

  18. Kansas Water Quality Action Targeting System (KATS)

    Data.gov (United States)

    Kansas Data Access and Support Center — This system is a revision of the original KATS system developed in 1990 as a tool to aid resource managers target Kansas valuable and vulnerable water resources for...

  19. Structural Versatility of Bicellar Systems and Their Possibilities as Colloidal Carriers

    Directory of Open Access Journals (Sweden)

    López Olga

    2011-09-01

    Full Text Available Bicellar systems are lipid nanostructures formed by long- and short-chained phospholipids dispersed in aqueous solution. The morphological transitions of bicellar aggregates due to temperature, composition and time variations have been revised in this work. To this end, two bicellar systems have been considered; one formed by dimyristoyl-phosphatidylcholine (DMPC and dihexanoyl- phosphatidylcholine (DHPC and another formed by dipalmitoyl-phosphatidylcholine (DPPC and DHPC. The relationship between the magnetic alignment, the morphology of the aggregates and the phase transition temperature (Tm of lipids is discussed. In general terms, the non-alignable samples present rounded objects at temperature below the Tm. Above this temperature, an increase of viscosity is followed by the formation of large elongated aggregates. Alignable samples presented discoidal objects below the Tm. The best alignment was achieved above this temperature with large areas of lamellar stacked bilayers and some multilamellar vesicles. The effect of the inclusion of ceramides with different chain lengths in the structure of bicelles is also revised in the present article. A number of physical techniques show that the bicellar structures are affected by both the concentration and the type of ceramide. Systems are able to incorporate 10% mol of ceramides that probably are organized forming domains. The addition of 20% mol of ceramides promotes destabilization of bicelles, promoting the formation of mixed systems that include large structures. Bicellar systems have demonstrated to be morphologically stable with time, able to encapsulate different actives and to induce specific effects on the skin. These facts make bicellar systems good candidates as colloidal carriers for dermal delivery. However, water dilution induces structural changes and formation of vesicular structures in the systems; stabilization strategies have been been explored in recent works and are also

  20. A Versatile Readout System for Small to Medium Scale Gaseous and Silicon Detectors

    Science.gov (United States)

    Calvet, Denis

    2014-02-01

    This paper presents the design and performance of a readout system for gaseous and silicon detectors built for the Minos nuclear physics experiment. A major constraint was to provide a multi-thousand channel, high performance readout system with low manpower effort and tight cost. This was achieved by the re-use of some earlier ASIC and front-end card (FEC) developments, the design of a new digital readout card, called the Feminos, and the use of commercial off-the-shelf components. The proposed system fully exploits the capability of the existing 72-channel AFTER chip designed for the T2K experiment and allows seamless migration to the 64-channel AGET chip, a pin-compatible evolution under production by the GET collaboration. The Feminos is a low complexity card designed to read out a FEC equipped with four AFTER chips (T2K model) or a newly assembled FEC populated with four AGET chips. The trigger clock module (TCM) is a synchronization board that allows system scaling up to 6912 channels with 24 Feminos and FECs, a commercial Gigabit Ethernet switch, and a data acquisition PC. The design of the Feminos hardware, firmware and embedded software are detailed and it is explained how high performance, rapid development and low cost were reached. System operation and data acquisition throughput scaling with multiple Feminos are investigated.

  1. HVJ envelope vector, a versatile delivery system: its development, application, and perspectives.

    Science.gov (United States)

    Zhang, Qingxian; Li, Ying; Shi, Yonghong; Zhang, Yanling

    2008-08-29

    An efficient and minimally invasive vector system is the "bottle neck" of both gene transfer and drug delivery. Numerous viral and non-viral (synthetic) delivery systems have been developed and improved. Hemagglutinating virus of Japan (HVJ, Sendai virus) envelope vector is a novel and unique system which combined the advantages of viral and non-viral vectors with the following features and advantages: (1) safe and easy as a "non-viral" transfection reagent; (2) delivery of various molecules including plasmid DNA, siRNA, protein, antisense oligonucleotide; (3) wide usability from in vitro to in vivo. In this review, the development, application, and perspectives of the HVJ envelope vector will be discussed.

  2. RehaMovePro: A versatile mobile stimulation system for transcutaneous FES applications

    Directory of Open Access Journals (Sweden)

    Markus Valtin

    2016-06-01

    Full Text Available Functional Electrical Stimulation is a commonly used method in clinical rehabilitation and research to trigger useful muscle contractions by electrical stimuli. In this work, we present a stimulation system for transcutaneous electrical stimulation that gives extensive control over the stimulation waveform and the stimulation timing. The system supports electrode arrays, which have been suggested to achieve better selectivity and to simplify electrode placement. Electromyography (EMG measurements are obtained from the active stimulation electrodes (between the stimulation pulses or from separate surface EMG electrodes. The modular design enables the implementation of sophisticated stimulation control systems including external triggers or wireless sensors. This is demonstrated by the standalone implementation of a feedback-controlled drop foot neuroprosthesis, which uses a wireless inertial sensor for real-time gait phase detection and foot orientation measurement.

  3. HYBRID2: A versatile model of the performance of hybrid power systems

    Science.gov (United States)

    Green, H. James; Manwell, James

    1995-04-01

    In 1993, the National Renewable Laboratory (NREL) made an assessment of the available tools from the United States and Europe for predicting the long-term performance of hybrid power systems. By hybrid power the authors mean combinations of two or more power sources wind turbines, photovoltaics (PV), diesel gensets, or other generators into integrated systems for electric power generation in remote locations. Their conclusion was that there was no single, user-friendly tool capable of modeling the full range of hybrid power technologies being considered for the 1990s and beyond. The existing tools were, in particular, lacking flexibility in system configuration and in dispatch of components. As a result, NREL developed a specification for a model, called HYBRID2, for making comparisons of competing technology options on a level playing field. This specification was prepared with a range of potential users in mind including not only the US Department of Energy (DOE) renewable energy programs, but also the US wind industry, technical consultants, international development institutions/banks, and rural electrification programs in developing countries. During 1994, NREL and subcontractor, the University of Massachusetts (UMass), began development of HYBRID2 with funding from the DOE Wind Energy Program. It builds on the wind/diesel model, HYBRID1, developed previously by UMass, and expands that model to accommodate the wider array of technologies used in hybrid power systems. This paper will provide an overview of the model's features, functions, and status.

  4. A versatile class of prototype dynamical systems for complex bifurcation cascades of limit cycles

    Science.gov (United States)

    Sándor, Bulcsú; Gros, Claudius

    2015-07-01

    A general class of prototype dynamical systems is introduced, which allows to study the generation of complex bifurcation cascades of limit cycles, including bifurcations breaking spontaneously a symmetry of the system, period doubling and homoclinic bifurcations, and transitions to chaos induced by sequences of limit cycle bifurcations. The prototype systems are adaptive, with friction forces f(V(x)) being functionally dependent exclusively on the mechanical potential V(x), characterized in turn by a finite number of local minima. We discuss several low-dimensional systems, with friction forces f(V) which are linear, quadratic or cubic polynomials in the potential V. We point out that the zeros of f(V) regulate both the relative importance of energy uptake and dissipation respectively, serving at the same time as bifurcation parameters, hence allowing for an intuitive interpretation of the overall dynamical behavior. Starting from simple Hopf- and homoclinic bifurcations, complex sequences of limit cycle bifurcations are observed when the energy uptake gains progressively in importance.

  5. An Efficient and Versatile System for Visualization and Genetic Modification of Dopaminergic Neurons in Transgenic Mice.

    Directory of Open Access Journals (Sweden)

    Karsten Tillack

    Full Text Available The brain dopaminergic (DA system is involved in fine tuning many behaviors and several human diseases are associated with pathological alterations of the DA system such as Parkinson's disease (PD and drug addiction. Because of its complex network integration, detailed analyses of physiological and pathophysiological conditions are only possible in a whole organism with a sophisticated tool box for visualization and functional modification.Here, we have generated transgenic mice expressing the tetracycline-regulated transactivator (tTA or the reverse tetracycline-regulated transactivator (rtTA under control of the tyrosine hydroxylase (TH promoter, TH-tTA (tet-OFF and TH-rtTA (tet-ON mice, to visualize and genetically modify DA neurons. We show their tight regulation and efficient use to overexpress proteins under the control of tet-responsive elements or to delete genes of interest with tet-responsive Cre. In combination with mice encoding tet-responsive luciferase, we visualized the DA system in living mice progressively over time.These experiments establish TH-tTA and TH-rtTA mice as a powerful tool to generate and monitor mouse models for DA system diseases.

  6. A versatile and light-weight slow control system for small-scale applications

    Science.gov (United States)

    Zappa, P.; Bütikofer, L.; Coderre, D.; Kaminsky, B.; Schumann, M.; von Sivers, M.

    2016-09-01

    We present an open source slow control system for small and medium scale projects. Thanks to its modular and flexible design, where the various instruments are read and controlled by independent plugins, Doberman (Detector OBsERving and Monitoring ApplicatioN) can be quickly adapted for many applications, also making use of existing code or proprietary components. The system uses a SQL database to store the data from the instruments and provides an online application to display and browse through the data. It allows the modification of device settings while the program is running and features a protocol to handle exceptions, including the automated distribution of alarm messages. We present two case studies from astroparticle physics, on which Doberman is successfully deployed: a low-background screening facility installed in a remote underground laboratory and a detector R&D platform using cryogenic liquid xenon.

  7. A Versatile Molecular Beam Epitaxy System for Low-Temperature STM: Instrument Design and Initial Results

    Science.gov (United States)

    Bowman, Adam; Ding, Hao; Jeon, Sangjun; Yazdani, Ali

    Efficient combination of molecular beam epitaxy (MBE) with scanning tunneling microscopy (STM) is essential for engineering and studying new materials with topological and superconducting properties. Particularly valuable are the capabilities to grow clean material interfaces, single monolayer films, and 2D systems with proximitized superconductivity. A new MBE system designed for STM was constructed to allow reliable ultra-high vacuum sample transfer, growth between 77 K and 1500 K, direct current sample flashing, and RHEED surface monitoring. Six Knudsen cells and electron beam evaporators allow growth of a variety of superconducting, topological, and metallic films. UHV transfer from the MBE via a vacuum suitcase can be accomplished within an hour to preserve clean surfaces. Initial low-temperature STM results on bismuth and monolayer iron selenide (FeSe) films will be presented. This work is supported by the Moore Foundation, ONR, and NSF.

  8. GreenGate---a novel, versatile, and efficient cloning system for plant transgenesis.

    Directory of Open Access Journals (Sweden)

    Athanasios Lampropoulos

    Full Text Available Building expression constructs for transgenesis is one of the fundamental day-to-day tasks in modern biology. Traditionally it is based on a multitude of type II restriction endonucleases and T4 DNA ligase. Especially in case of long inserts and applications requiring high-throughput, this approach is limited by the number of available unique restriction sites and the need for designing individual cloning strategies for each project. Several alternative cloning systems have been developed in recent years to overcome these issues, including the type IIS enzyme based Golden Gate technique. Here we introduce our GreenGate system for rapidly assembling plant transformation constructs, which is based on the Golden Gate method. GreenGate cloning is simple and efficient since it uses only one type IIS restriction endonuclease, depends on only six types of insert modules (plant promoter, N-terminal tag, coding sequence, C-terminal tag, plant terminator and plant resistance cassette, but at the same time allows assembling several expression cassettes in one binary destination vector from a collection of pre-cloned building blocks. The system is cheap and reliable and when combined with a library of modules considerably speeds up cloning and transgene stacking for plant transformation.

  9. GreenGate---a novel, versatile, and efficient cloning system for plant transgenesis.

    Science.gov (United States)

    Lampropoulos, Athanasios; Sutikovic, Zoran; Wenzl, Christian; Maegele, Ira; Lohmann, Jan U; Forner, Joachim

    2013-01-01

    Building expression constructs for transgenesis is one of the fundamental day-to-day tasks in modern biology. Traditionally it is based on a multitude of type II restriction endonucleases and T4 DNA ligase. Especially in case of long inserts and applications requiring high-throughput, this approach is limited by the number of available unique restriction sites and the need for designing individual cloning strategies for each project. Several alternative cloning systems have been developed in recent years to overcome these issues, including the type IIS enzyme based Golden Gate technique. Here we introduce our GreenGate system for rapidly assembling plant transformation constructs, which is based on the Golden Gate method. GreenGate cloning is simple and efficient since it uses only one type IIS restriction endonuclease, depends on only six types of insert modules (plant promoter, N-terminal tag, coding sequence, C-terminal tag, plant terminator and plant resistance cassette), but at the same time allows assembling several expression cassettes in one binary destination vector from a collection of pre-cloned building blocks. The system is cheap and reliable and when combined with a library of modules considerably speeds up cloning and transgene stacking for plant transformation.

  10. JobCenter: an open source, cross-platform, and distributed job queue management system optimized for scalability and versatility.

    Science.gov (United States)

    Jaschob, Daniel; Riffle, Michael

    2012-07-30

    Laboratories engaged in computational biology or bioinformatics frequently need to run lengthy, multistep, and user-driven computational jobs. Each job can tie up a computer for a few minutes to several days, and many laboratories lack the expertise or resources to build and maintain a dedicated computer cluster. JobCenter is a client-server application and framework for job management and distributed job execution. The client and server components are both written in Java and are cross-platform and relatively easy to install. All communication with the server is client-driven, which allows worker nodes to run anywhere (even behind external firewalls or "in the cloud") and provides inherent load balancing. Adding a worker node to the worker pool is as simple as dropping the JobCenter client files onto any computer and performing basic configuration, which provides tremendous ease-of-use, flexibility, and limitless horizontal scalability. Each worker installation may be independently configured, including the types of jobs it is able to run. Executed jobs may be written in any language and may include multistep workflows. JobCenter is a versatile and scalable distributed job management system that allows laboratories to very efficiently distribute all computational work among available resources. JobCenter is freely available at http://code.google.com/p/jobcenter/.

  11. A highly controllable protein self-assembly system with morphological versatility induced by reengineered host-guest interactions.

    Science.gov (United States)

    Li, Xiumei; Bai, Yushi; Huang, Zupeng; Si, Chengye; Dong, Zeyuan; Luo, Quan; Liu, Junqiu

    2017-06-14

    Manipulating proteins to self-assemble into highly ordered nanostructures not only provides insights into the natural protein assembly process but also allows access to advanced biomaterials. Host-guest interactions have been widely used in the construction of artificial protein assemblies in recent years. CB[8] can selectively associate with two tripeptide Phe-Gly-Gly (FGG) tags with an extraordinarily high binding affinity (Kter = 1.5 × 10(11) M(-2)). However, the FGG tags utilized before are all fixed to the N-termini via genetic fusion; this spatial limitation greatly confined the availability of the CB[8]/FGG pair in the construction of more sophisticated protein nanostructures. Here we first designed and synthesized a maleimide-functionalized Phe-Gly-Gly tag as a versatile site-specific protein modification tool; this designed tag can site-selectively introduce desired guest moieties onto protein surfaces for host-guest driven protein assembly. When regulating the self-assembly process of proteins and CB[8], the constructed protein nanosystem can exhibit distinctive morphological diversities ranging from nanorings, nanospirals, nanowires to superwires. This work developed a new strategy for site-specific protein modification of the CB[8] binding tag and provides a possible direction for the construction of 'smart', dynamic self-assembly systems.

  12. JobCenter: an open source, cross-platform, and distributed job queue management system optimized for scalability and versatility

    Directory of Open Access Journals (Sweden)

    Jaschob Daniel

    2012-07-01

    Full Text Available Abstract Background Laboratories engaged in computational biology or bioinformatics frequently need to run lengthy, multistep, and user-driven computational jobs. Each job can tie up a computer for a few minutes to several days, and many laboratories lack the expertise or resources to build and maintain a dedicated computer cluster. Results JobCenter is a client–server application and framework for job management and distributed job execution. The client and server components are both written in Java and are cross-platform and relatively easy to install. All communication with the server is client-driven, which allows worker nodes to run anywhere (even behind external firewalls or “in the cloud” and provides inherent load balancing. Adding a worker node to the worker pool is as simple as dropping the JobCenter client files onto any computer and performing basic configuration, which provides tremendous ease-of-use, flexibility, and limitless horizontal scalability. Each worker installation may be independently configured, including the types of jobs it is able to run. Executed jobs may be written in any language and may include multistep workflows. Conclusions JobCenter is a versatile and scalable distributed job management system that allows laboratories to very efficiently distribute all computational work among available resources. JobCenter is freely available at http://code.google.com/p/jobcenter/.

  13. A Versatile High-Vacuum Cryo-transfer System for Cryo-microscopy and Analytics

    Science.gov (United States)

    Tacke, Sebastian; Krzyzanek, Vladislav; Nüsse, Harald; Wepf, Roger Albert; Klingauf, Jürgen; Reichelt, Rudolf

    2016-01-01

    Cryogenic microscopy methods have gained increasing popularity, as they offer an unaltered view on the architecture of biological specimens. As a prerequisite, samples must be handled under cryogenic conditions below their recrystallization temperature, and contamination during sample transfer and handling must be prevented. We present a high-vacuum cryo-transfer system that streamlines the entire handling of frozen-hydrated samples from the vitrification process to low temperature imaging for scanning transmission electron microscopy and transmission electron microscopy. A template for cryo-electron microscopy and multimodal cryo-imaging approaches with numerous sample transfer steps is presented. PMID:26910419

  14. LED Systems Target Plant Growth

    Science.gov (United States)

    2010-01-01

    To help develop technologies for growing edible biomass (food crops) in space, Kennedy Space Center partnered with Orbital Technologies Corporation (ORBITEC), of Madison, Wisconsin, through the Small Business Innovation Research (SBIR) program. One result of this research was the High Efficiency Lighting with Integrated Adaptive Control (HELIAC) system, components of which have been incorporated into a variety of agricultural greenhouse and consumer aquarium lighting features. The new lighting systems can be adapted to a specific plant species during a specific growth stage, allowing maximum efficiency in light absorption by all available photosynthetic tissues.

  15. Essential Oils Against Pathogen and Spoilage Microorganisms of Fruit Juices: Use of Versatile Antimicrobial Delivery Systems.

    Science.gov (United States)

    Trinetta, Valentina; Morgan, Mark T; Coupland, John N; Yucel, Umut

    2017-02-01

    Essential oils (EO) are increasingly used as natural antimicrobial compounds, however the effect of delivery system to enhance their antimicrobial activity has not been widely studied. Limonene (0 to 10 μL/mL) was added to microbial suspensions (∼10 5 CFU/mL) of selected foodborne pathogens (Listeria monocytogenes Scott A, Salmonella enterica Typhimurium, Escherichia coli and Staphylococcus aureus), and spoilage microorganisms (Lactobacillus plantarum, Saccharomyces cerevisiae, and Candida albicans). S. aureus was found to be the most sensitive foodborne pathogen while Salmonella enterica showed continued growth under all concentrations. Stable nanoemulsions and solid lipid nanoparticles (SLN) (d ∼ 170 nm) were prepared using an alkane carrier oil (n-tetradecane and n-eicosane, respectively). Interfacial effects and homogenous distribution of limonene in nanoemulsions improved its (8 and 12 μL/mL) antimicrobial effect against S. aureus. Higher aqueous concentrations as a result of expulsion from SLN further enhanced the antimicrobial activity pronounced at higher limonene concentrations. Therefore, our findings confirm that the emulsion-based delivery systems are able to effectively distribute limonene inside a microbial suspension to improve its antimicrobial activity. © 2017 Institute of Food Technologists®.

  16. HaloTag: a new versatile reporter gene system in plant cells.

    Science.gov (United States)

    Lang, Christina; Schulze, Jutta; Mendel, Ralf-R; Hänsch, Robert

    2006-01-01

    HaloTag Interchangeable Labeling Technology (HaloTag) was originally developed for mammalian cell analysis. In this report, the use of HaloTag is demonstrated in plant cells for the first time. This system allows different fluorescent colours to be used to visualize the localization of the non-fluorescent HaloTag protein within living cells. A vector was constructed which expresses the HaloTag protein under the control of the 35S promoter of cauliflower mosaic virus. The functionality of the HaloTag construct was tested in transient assays by (i) transforming tobacco protoplasts and (ii) using biolistic transformation of intact leaf cells of tobacco and poplar plants. Two to fourteen days after transformation, the plant material was incubated with ligands specific for labelling the HaloTag protein, and fluorescence was visualized by confocal laser scanning microscopy. The results demonstrate that HaloTag technology is a flexible system which generates efficient fluorescence in different types of plant cells. The ligand-specific labelling of HaloTag protein was not hampered by the plant cell wall.

  17. A versatile viral system for expression and depletion of proteins in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Eric Campeau

    2009-08-01

    Full Text Available The ability to express or deplete proteins in living cells is crucial for the study of biological processes. Viral vectors are often useful to deliver DNA constructs to cells that are difficult to transfect by other methods. Lentiviruses have the additional advantage of being able to integrate into the genomes of non-dividing mammalian cells. However, existing viral expression systems generally require different vector backbones for expression of cDNA, small hairpin RNA (shRNA or microRNA (miRNA and provide limited drug selection markers. Furthermore, viral backbones are often recombinogenic in bacteria, complicating the generation and maintenance of desired clones. Here, we describe a collection of 59 vectors that comprise an integrated system for constitutive or inducible expression of cDNAs, shRNAs or miRNAs, and use a wide variety of drug selection markers. These vectors are based on the Gateway technology (Invitrogen whereby the cDNA, shRNA or miRNA of interest is cloned into an Entry vector and then recombined into a Destination vector that carries the chosen viral backbone and drug selection marker. This recombination reaction generates the desired product with >95% efficiency and greatly reduces the frequency of unwanted recombination in bacteria. We generated Destination vectors for the production of both retroviruses and lentiviruses. Further, we characterized each vector for its viral titer production as well as its efficiency in expressing or depleting proteins of interest. We also generated multiple types of vectors for the production of fusion proteins and confirmed expression of each. We demonstrated the utility of these vectors in a variety of functional studies. First, we show that the FKBP12 Destabilization Domain system can be used to either express or deplete the protein of interest in mitotically-arrested cells. Also, we generate primary fibroblasts that can be induced to senesce in the presence or absence of DNA damage

  18. Antigen 43-mediated autotransporter display, a versatile bacterial cell surface presentation system

    DEFF Research Database (Denmark)

    Kjærgaard, Kristian; Hasman, Henrik; Schembri, Mark

    2002-01-01

    to the outer membrane and secretion through the cell envelope is contained within the protein itself. Ag43 consists of two subunits (alpha and beta), where the beta-subunit forms an integral outer membrane translocator to which the alpha-subunit is noncovalently attached. The simplicity of the Ag43 system...... makes it ideally suited as a surface display scaffold. Here we demonstrate that the Ag43 alpha-module can accommodate and display correctly folded inserts and has the ability to display entire functional protein domains, exemplified by the FimH lectin domain. The presence of heterologous cysteine...... bridges does not interfere with surface display, and Ag43 chimeras are correctly processed into alpha- and beta-modules, offering optional and easy release of the chimeric alpha-subunits. Furthermore, Ag43 can be displayed in many gram-negative bacteria. This feature is exploited for display of our...

  19. 1997 to Present: Quality and Versatile Access to the Deep Biosphere with Coupled Advanced CORKs and Fluid Pumping Systems

    Science.gov (United States)

    Cowen, J. P.; Lin, H.; Jungbluth, S.; Hsieh, C.; Rappe, M.; Glazer, B. T.; Matzinger, M.; Becker, K.; Fisher, A. T.; Amend, J. P.; Johnson, H. P.

    2011-12-01

    In 1997, a simple 'BioColumn' sampler was coupled to the CORK observatory at borehole 1026B to sample fluid chemistry, biomass and microbial community diversity (16S rRNA). The results demonstrated that the 65oC fluids from the 3.5 My old sediment-buried ocean basement support a diverse Bacteria and Archaea community (Cowen et al. 2003, Science 299, 120-123). The large bore of the overpressured CORK body provided high unassisted flow rates through the BioColumn, but possessed the disadvantage of the unknown extent to which the basement fluids were altered by the chemically and biologically (e.g., biofilm community) reactive surface of CORK's steel pipe. Subsequently, new generations of CORKs have incorporated less reactive materials in the CORK body, the use of stainless steel or inert PVDF (Teflon-like) 0.5" ID fluid delivery lines (FDL) running continuously from basement depths to accessible ports at the seafloor, and multiple FDLs from distinct depth horizons within basement. Simultaneously, we have developed increasingly capable fluid sensor and sampling systems for both real-time (Mobile Pumping and Sampling System-MPSS) and long-term autonomous applications (GeoMICROBE sleds). Both incorporate strong efficient pumps to overcome the drag inherent in the 0.5" or smaller bore FDL, multiple sensors (e.g., flow rate, temperature, O2, pH and redox-voltametry chemistry), versatile multi-port large volume fluid collection and/or in situ filtration systems, integrating computer controller/software and non-contaminating (inert) plumbing. These combined developments now provide unparalleled opportunities for access to large volumes of pristine basement samples for geochemical and microbial ecology studies. The MPSS and GeoMICROBE will be described. The multi-year results of organic geochemical and microbial community studies from recent studies at CORK observatories (boreholes 1301A, 1362A 1362B) on the Juan de Fuca Ridge flank will be summarized.

  20. RandaDB: a versatile management system for landslide movement monitoring data

    Science.gov (United States)

    Ornstein, P.; Rouiller, J.-D.; Jaboyedoff, M.

    2003-04-01

    Areas affected by landslides cover about 6 to 8% of the Swiss territory. In 1989, a preliminary inventory compiled in the canton of Valais has enumerated more than 200 slope instabilities. For more than 10 years in Valais, slope movements over sites likely to induce potential damage over inhabited areas and/or facilities, have been continuously or regularly monitored. This monitoring generates large volumes of data, especially following the use of automatic measurement devices (e.g. extensometer, GPS, weather station, etc.). The management of monitoring data, as well as dynamic information relative to monitoring network configurations, leads to the need for an efficient, structured and flexible data storage system. RandaDB is an original software application that has been designed and implemented to meet this need. It integrates a relational database with a suitable data model for the storage of 1-D and 3-D geodetic measurements, as well as descriptive data on monitoring network and other related information that are useful for data analysis (measurement campaigns, network maintenance, field observations, data corrections, pictures, maps, etc.). In addition to these functions, RandaDB offers a set of functionalities for the handling of data, including the tabulation of measurements, displacements plotting as graphs (1-D data) or stereographic representation (3-D data), and basic statistical and regression tools for checking the consistency of data. Furthermore, the integration of GIS and mapping components to the system allows dynamic and interactive map representations of 1-D and 3-D movements. The RandaDB application has been developed using the WinDev 5.5 development environment and MapObjects software. This tool is used since 2000 to insure the management of geodetics data related to the monitoring of the Randa site in the Mattertal valley (Valais, CH), where there occurred in April-May of 1991 one of the largest rockfalls recorded in Europe during the 20th

  1. A versatile, quantitative analytical method for pharmaceutical relevant lipids in drug delivery systems.

    Science.gov (United States)

    Jeschek, Dominik; Lhota, Gabriele; Wallner, Jakob; Vorauer-Uhl, Karola

    2016-02-05

    Over the past few years, liposomal formulations as drug carrier systems have markedly advanced in pharmaceutical research and development. Therefore, analytical methods to characterize liposome-based formulations are required. One particular issue in liposome analysis is the imbalance of lipid ratios within the vesicle formulations and the detectability of degradation products such as lysophospholipids and fatty acids caused by hydrolysis, especially in low molar ranges. Here, a highly sensitive and selective reversed-phase high-performance liquid chromatography (rp-HPLC) method is described by the combination of an organic solvent/trifluoroacetic acid (TFA) triggered gradient and the application of an evaporative light scattering detector (ELSD). Gain setting adjustments of the ELSD were applied to obtain an optimal detection profile of the analyzed substances. This optimization provides simultaneous separation and quantification of 16 components, including different phosphatidylcholines, phosphatidylglycerols and their degradation products, as well as cholesterol. Parameters such as limit of detection (LOD) and limit of quantification (LOQ) were determined for each of the components and had ranges from 0.25-1.00mg/mL (LOD) and 0.50-2.50μg/mL (LOQ), respectively. The intra-day precision for all analytes is less than 3% (RSD) and inter-day precision is about 8%. The applicability of the method was verified by analyzing two different liposome formulations consisting of DSPC:DPPC:DSPG:Chol (35:35:20:10) and DSPC:DPPC:DSPG (38:38:24). For degradation studies, both formulations were stored at 4°C and at ambient temperature. Additionally, forced degradation experiments were performed to determine hydrolysis mass balances. A total recovery of 96-102% for phospholipid compounds was found. Analytical data revealed that the sensitivity, selectivity, accuracy, and resolution are appropriate for the detection and quantification of phospholipids and their hydrolysis products

  2. Magnetic confinement system using charged ammonia targets

    Science.gov (United States)

    Porter, Gary D.; Bogdanoff, Anatoly

    1979-01-01

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

  3. V-stand--a versatile surgical platform for oromandibular reconstruction using a 3-dimensional virtual modeling system.

    Science.gov (United States)

    Reiser, Vadim; Alterman, Michael; Shuster, Amir; Kleinman, Shlomi; Shlomi, Benjamin; Yanko-Arzi, Ravit; Zaretski, Arik; Amir, Aharon; Fliss, Dan M

    2015-06-01

    The challenge of oromandibular reconstruction (OMR) after oncologic resections has been repeatedly addressed in the literature. Although final oncologic margins can be decided only during surgery, various attempts have been made to create an ideal and accurate platform for OMR. The purpose of this article is to present the V-stand, a versatile surgical platform for OMR using a 3-dimensional (3D) virtual modeling system. Seventeen patients requiring an OMR were included in the study. A presurgical computed tomogram was obtained and virtual resection and reconstruction with a free fibular flap were planned using 3D virtual surgery software. The mandible was reconstructed intraoperatively using the V-stand, which served as a template for the lower border of the mandible and the lateral aspects of the stand were fixed to the proximal mandibular segments using 2-mm titanium screws. Patients' average age was 53 years (5 to 72 yr). Median follow-up was 19 months (2 to 35 months). All reconstructed mandibles resulted in good function and esthetics. The V-stand offers a safe and time-efficient method for OMR. It provides an excellent means for accurate spatial positioning of a fibular free flap. The V-stand preserves the original dimensions of the reconstructed mandible and can overcome surgical ablation modifications because it is not dependent on the precision of the resection, but rather provides a mold for the entire mandible. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  4. An easy and versatile 2-step protocol for targeted modification and subcloning of DNA from bacterial artificial chromosomes using non-commercial plasmids

    Directory of Open Access Journals (Sweden)

    Hartwich Heiner

    2012-03-01

    Full Text Available Abstract Background Promoter-specific expression of foreign DNA in transgenic organisms often relies on bacterial artificial chromosomes (BACs. This approach requires modification and subcloning of BAC-DNA by recombineering technologies in Escherichia coli. Most current protocols rely on commercial kits or isolation of BACs, their transfer between different host strains, and their restriction. Findings In this report we present a 2-step protocol for efficient modification and subcloning of DNA from bacterial artificial chromosomes using the non-commercial plasmids pKM208 and pTP223, distributed from addgene.com. A targeting cassette was successfully integrated into a BAC and 42 kb of this construct were subcloned. Both a plasmid-derived substrate with longer homology arms and a PCR-generated substrate with short homology arms (50 bp were used for recombination. pKM208 and pTP223 contain all required genes for recombineering, but differ in their antibiotic resistance genes. This makes the system independent of the selection markers on the DNA molecules targeted for recombination. Conclusions The time and cost saving protocol presented here compares favorably to currently used systems. Using non-commercial plasmids, it allows targeted modification and cloning of large DNA (> 40 kb fragments in vivo without restriction and ligation. Furthermore, both steps are performed in the same host eliminating the need to isolate BAC DNA and to use different bacterial strains.

  5. An easy and versatile 2-step protocol for targeted modification and subcloning of DNA from bacterial artificial chromosomes using non-commercial plasmids.

    Science.gov (United States)

    Hartwich, Heiner; Nothwang, Hans Gerd

    2012-03-20

    Promoter-specific expression of foreign DNA in transgenic organisms often relies on bacterial artificial chromosomes (BACs). This approach requires modification and subcloning of BAC-DNA by recombineering technologies in Escherichia coli. Most current protocols rely on commercial kits or isolation of BACs, their transfer between different host strains, and their restriction. In this report we present a 2-step protocol for efficient modification and subcloning of DNA from bacterial artificial chromosomes using the non-commercial plasmids pKM208 and pTP223, distributed from addgene.com. A targeting cassette was successfully integrated into a BAC and 42 kb of this construct were subcloned. Both a plasmid-derived substrate with longer homology arms and a PCR-generated substrate with short homology arms (50 bp) were used for recombination. pKM208 and pTP223 contain all required genes for recombineering, but differ in their antibiotic resistance genes. This makes the system independent of the selection markers on the DNA molecules targeted for recombination. The time and cost saving protocol presented here compares favorably to currently used systems. Using non-commercial plasmids, it allows targeted modification and cloning of large DNA (> 40 kb) fragments in vivo without restriction and ligation. Furthermore, both steps are performed in the same host eliminating the need to isolate BAC DNA and to use different bacterial strains. © 2011 Hartwich et al; licensee BioMed Central Ltd.

  6. Versatile quantitative phase imaging system applied to high-speed, low noise and multimodal imaging (Conference Presentation)

    Science.gov (United States)

    Federici, Antoine; Aknoun, Sherazade; Savatier, Julien; Wattellier, Benoit F.

    2017-02-01

    Quadriwave lateral shearing interferometry (QWLSI) is a well-established quantitative phase imaging (QPI) technique based on the analysis of interference patterns of four diffraction orders by an optical grating set in front of an array detector [1]. As a QPI modality, this is a non-invasive imaging technique which allow to measure the optical path difference (OPD) of semi-transparent samples. We present a system enabling QWLSI with high-performance sCMOS cameras [2] and apply it to perform high-speed imaging, low noise as well as multimodal imaging. This modified QWLSI system contains a versatile optomechanical device which images the optical grating near the detector plane. Such a device is coupled with any kind of camera by varying its magnification. In this paper, we study the use of a sCMOS Zyla5.5 camera from Andor along with our modified QWLSI system. We will present high-speed live cell imaging, up to 200Hz frame rate, in order to follow intracellular fast motions while measuring the quantitative phase information. The structural and density information extracted from the OPD signal is complementary to the specific and localized fluorescence signal [2]. In addition, QPI detects cells even when the fluorophore is not expressed. This is very useful to follow a protein expression with time. The 10 µm spatial pixel resolution of our modified QWLSI associated to the high sensitivity of the Zyla5.5 enabling to perform high quality fluorescence imaging, we have carried out multimodal imaging revealing fine structures cells, like actin filaments, merged with the morphological information of the phase. References [1]. P. Bon, G. Maucort, B. Wattellier, and S. Monneret, "Quadriwave lateral shearing interferometry for quantitative phase microscopy of living cells," Opt. Express, vol. 17, pp. 13080-13094, 2009. [2] P. Bon, S. Lécart, E. Fort and S. Lévêque-Fort, "Fast label-free cytoskeletal network imaging in living mammalian cells," Biophysical journal, 106

  7. Emotional System for Military Target Identification

    Science.gov (United States)

    2009-10-01

    J. & Ioerger, T.R. (2000). FLAME– fuzzy logic adaptive model of emotions. Autonomous Agents and Multi-Agent Systems , 3(3), 219–257. Emotional...Proceedings of the Sixteenth European Meeting on Cybernetics and System Research, Vienna, 751–756. [16] Doya K. (2002). Meta-learning and neuro ...RTO-MP-IST-087 18 - 1 UNCLASSIFIED/UNLIMITED UNCLASSIFIED/UNLIMITED Emotional System for Military Target Identification Prof. Dr. Adnan

  8. A simplified and versatile system for the simultaneous expression of multiple siRNAs in mammalian cells using Gibson DNA Assembly.

    Science.gov (United States)

    Deng, Fang; Chen, Xiang; Liao, Zhan; Yan, Zhengjian; Wang, Zhongliang; Deng, Youlin; Zhang, Qian; Zhang, Zhonglin; Ye, Jixing; Qiao, Min; Li, Ruifang; Denduluri, Sahitya; Wang, Jing; Wei, Qiang; Li, Melissa; Geng, Nisha; Zhao, Lianggong; Zhou, Guolin; Zhang, Penghui; Luu, Hue H; Haydon, Rex C; Reid, Russell R; Yang, Tian; He, Tong-Chuan

    2014-01-01

    RNA interference (RNAi) denotes sequence-specific mRNA degradation induced by short interfering double-stranded RNA (siRNA) and has become a revolutionary tool for functional annotation of mammalian genes, as well as for development of novel therapeutics. The practical applications of RNAi are usually achieved by expressing short hairpin RNAs (shRNAs) or siRNAs in cells. However, a major technical challenge is to simultaneously express multiple siRNAs to silence one or more genes. We previously developed pSOS system, in which siRNA duplexes are made from oligo templates driven by opposing U6 and H1 promoters. While effective, it is not equipped to express multiple siRNAs in a single vector. Gibson DNA Assembly (GDA) is an in vitro recombination system that has the capacity to assemble multiple overlapping DNA molecules in a single isothermal step. Here, we developed a GDA-based pSOK assembly system for constructing single vectors that express multiple siRNA sites. The assembly fragments were generated by PCR amplifications from the U6-H1 template vector pB2B. GDA assembly specificity was conferred by the overlapping unique siRNA sequences of insert fragments. To prove the technical feasibility, we constructed pSOK vectors that contain four siRNA sites and three siRNA sites targeting human and mouse β-catenin, respectively. The assembly reactions were efficient, and candidate clones were readily identified by PCR screening. Multiple β-catenin siRNAs effectively silenced endogenous β-catenin expression, inhibited Wnt3A-induced β-catenin/Tcf4 reporter activity and expression of Wnt/β-catenin downstream genes. Silencing β-catenin in mesenchymal stem cells inhibited Wnt3A-induced early osteogenic differentiation and significantly diminished synergistic osteogenic activity between BMP9 and Wnt3A in vitro and in vivo. These findings demonstrate that the GDA-based pSOK system has been proven simplistic, effective and versatile for simultaneous expression of multiple

  9. An automatic versatile system integrating solid-phase extraction with ultra-high performance liquid chromatography-tandem mass spectrometry using a dual-dilution strategy for direct analysis of auxins in plant extracts.

    Science.gov (United States)

    Zhong, Qisheng; Qiu, Xiongxiong; Lin, Caiyong; Shen, Lingling; Huo, Yin; Zhan, Song; Yao, Jinting; Huang, Taohong; Kawano, Shin-ichi; Hashi, Yuki; Xiao, Langtao; Zhou, Ting

    2014-09-12

    An automatic versatile system which integrated solid phase extraction (SPE) with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed. Diverse commercial SPE columns can be used under an ambient pressure in this online system realized by a dual-dilution strategy. The first dilution enabled the direct injection of complex samples with minimal pretreatment, and the second dilution realized direct introduction of large volume of strong eluent into the UHPLC column without causing peak broadening or distortion. In addition, a post-column compensation mode was also designed for the matrix-effects evaluation. The features of the online system were systematically investigated, including the dilution effect, the capture of desorption solution, the column-head stacking effect and the system recovery. Compared with the offline UHPLC system, this online system showed significant advantages such as larger injection volume, higher sensitivity, shorter analysis time and better repeatability. The feasibility of the system was demonstrated by the direct analysis of three auxins from different plant tissues, including leaves of Dracaena sanderiana, buds and petals of Bauhinia. Under the optimized conditions, the whole analysis procedure took only 7min. All the correlation coefficients were greater than 0.9987, the limits of detection and the limits of quantitation were in the range of 0.560-0.800ng/g and 1.80-2.60ng/g, respectively. The recoveries of the real samples ranged from 61.0 to 117%. Finally, the post-column compensation mode was applied and no matrix-effects were observed under the analysis conditions. The automatic versatile system was rapid, sensitive and reliable. We expect this system could be extended to other target analytes in complex samples utilizing diverse SPE columns. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Systemic Targeted Alpha Radiotherapy for Cancer

    Directory of Open Access Journals (Sweden)

    Allan B. J.

    2013-09-01

    Full Text Available Background: The fundamental principles of internal targeted alpha therapy for cancer were established many decades ago.The high linear energy transfer (LET of alpha radiation to the targeted cancer cellscauses double strand breaks in DNA. At the same time, the short range radiation spares adjacent normal tissues. This targeted approach complements conventional external beam radiotherapy and chemotherapy. Such therapies fail on several fronts, such as lack of control of some primary cancers (e.g.glioblastoma multiformeand to inhibit the development of lethal metastatic cancer after successful treatment of the primary cancer. Objective: This review charts the developing role of systemic high LET, internal radiation therapy. Method: Targeted alpha therapy is a rapidly advancing experimental therapy that holds promise to deliver high cytotoxicity to targeted cancer cells. Initially thought to be indicated for leukemia and micrometastases, there is now evidence that solid tumors can also be regressed. Results: Alpha therapy may be molecular or physiological in its targeting. Alpha emitting radioisotopes such as Bi-212, Bi-213, At-211 and Ac-225 are used to label monoclonal antibodies or proteins that target specifc cancer cells. Alternatively, Radium-233 is used for palliative therapy of breast and prostate cancers because of its bone seeking properties. Conclusion: Preclinical studies and clinical trials of alpha therapy are discussed for leukemia, lymphoma, melanoma, glioblastoma multiforme, bone metastases, ovarian cancer, pancreatic cancer and other cancers.

  11. mCAL: A New Approach for Versatile Multiplex Action of Cas9 Using One sgRNA and Loci Flanked by a Programmed Target Sequence

    Science.gov (United States)

    Finnigan, Gregory C.; Thorner, Jeremy

    2016-01-01

    Genome editing exploiting CRISPR/Cas9 has been adopted widely in academia and in the biotechnology industry to manipulate DNA sequences in diverse organisms. Molecular engineering of Cas9 itself and its guide RNA, and the strategies for using them, have increased efficiency, optimized specificity, reduced inappropriate off-target effects, and introduced modifications for performing other functions (transcriptional regulation, high-resolution imaging, protein recruitment, and high-throughput screening). Moreover, Cas9 has the ability to multiplex, i.e., to act at different genomic targets within the same nucleus. Currently, however, introducing concurrent changes at multiple loci involves: (i) identification of appropriate genomic sites, especially the availability of suitable PAM sequences; (ii) the design, construction, and expression of multiple sgRNA directed against those sites; (iii) potential difficulties in altering essential genes; and (iv) lingering concerns about “off-target” effects. We have devised a new approach that circumvents these drawbacks, as we demonstrate here using the yeast Saccharomyces cerevisiae. First, any gene(s) of interest are flanked upstream and downstream with a single unique target sequence that does not normally exist in the genome. Thereafter, expression of one sgRNA and cotransformation with appropriate PCR fragments permits concomitant Cas9-mediated alteration of multiple genes (both essential and nonessential). The system we developed also allows for maintenance of the integrated, inducible Cas9-expression cassette or its simultaneous scarless excision. Our scheme—dubbed mCAL for “Multiplexing of Cas9 at Artificial Loci”—can be applied to any organism in which the CRISPR/Cas9 methodology is currently being utilized. In principle, it can be applied to install synthetic sequences into the genome, to generate genomic libraries, and to program strains or cell lines so that they can be conveniently (and repeatedly

  12. Development of an autonomous target tracking system

    Science.gov (United States)

    Gidda, Venkata Ramaiah

    In recent years, surveillance and border patrol have become one of the key research areas in UAV research. Increase in the computational capability of the computers and embedded electronics, coupled with compatibility of various commercial vision algorithms and commercial off the shelf (COTS) embedded electronics, and has further fuelled the research. The basic task in these applications is perception of environment through the available visual sensors like camera. Visual tracking, as the name implies, is tracking of objects using a camera. The process of autonomous target tracking starts with the selection of the target in a sequence of video frames transmitted from the on-board camera. We use an improved fast dynamic template matching algorithm coupled with Kalman Filter to track the selected target in consecutive video frames. The selected target is saved as a reference template. On the ground station computer, the reference template is overlaid on the live streaming video from the on-board system, starting from the upper left corner of the video frame. The template is slid pixel by pixel over the entire source image. A comparison of the pixels is performed between the template and source image. A confidence value R of the match is calculated at each pixel. Based on the method used to perform the template matching, the best match pixel location is found according to the highest or lowest confidence value R. The best match pixel location is communicated to the on-board gimbal controller over the wireless Xbee network. The software on the controller actuates the pan-tilt servos to continuously to hold the selected target at the center of the video frame. The complete system is a portable control system assembled from commercial off the shelf parts. The tracking system is tested on a target having several motion patterns.

  13. Two-dimensional flow-through microcosms - Versatile test systems to study biodegradation processes in porous aquifers

    Science.gov (United States)

    Bauer, Robert D.; Rolle, Massimo; Kürzinger, Petra; Grathwohl, Peter; Meckenstock, Rainer U.; Griebler, Christian

    2009-05-01

    SummaryA fundamental prerequisite of any remedial activity is a sound knowledge of both the biotic and abiotic processes involved in transport and degradation of contaminants. Investigations of these aspects in situ often seem infeasible due to the complexity of interacting processes. A simplified portrayal of nature can be facilitated in laboratory-based two-dimensional (2D) sediment flow-through microcosms. This paper describes the versatility of such simple aquifer model systems with respect to biodegradation of aromatic hydrocarbons, i.e. toluene and ethylbenzene, under various environmental conditions. Initially constructed to study non-reactive and bioreactive transport of organic contaminants in homogeneous porous media under steady state hydraulic conditions, experimental setups developed towards more realistic heterogeneous sediment packing and transient hydraulic conditions. High-resolution spatial and temporal sampling allowed to obtain new insights on the distribution of bioactivities in contaminant plumes and associated controlling and limiting factors. Major biodegradation activities in saturated porous sediments are located at the fringes of contaminant plumes and are driven by dispersive mixing. These hot-spots of contaminant biotransformation are characterized by steep physical-chemical gradients in the millimeter to centimeter range. Sediment heterogeneity, i.e. high-conductivity zones, was shown to significantly enhance transverse mixing and subsequently biodegradation. On the contrary, transient hydraulic conditions may generate intermediate disturbances to biodegrader populations and thus may interfere with optimized contaminant conversion. However, a bacterial strain aerobically degrading toluene, i.e. Pseudomonas putida F1, was shown to adapt to vertically moving contaminant plumes, in the way that it regained full biodegradation potential two-times faster in areas with a mid-term (days to weeks) contamination history than in areas not

  14. Characterization and calibration of gas sensor systems at ppb level—a versatile test gas generation system

    Science.gov (United States)

    Leidinger, Martin; Schultealbert, Caroline; Neu, Julian; Schütze, Andreas; Sauerwald, Tilman

    2018-01-01

    This article presents a test gas generation system designed to generate ppb level gas concentrations from gas cylinders. The focus is on permanent gases and volatile organic compounds (VOCs) for applications like indoor and outdoor air quality monitoring or breath analysis. In the design and the setup of the system, several issues regarding handling of trace gas concentrations have been considered, addressed and tested. This concerns not only the active fluidic components (flow controllers, valves), which have been chosen specifically for the task, but also the design of the fluidic tubing regarding dead volumes and delay times, which have been simulated for the chosen setup. Different tubing materials have been tested for their adsorption/desorption characteristics regarding naphthalene, a highly relevant gas for indoor air quality monitoring, which has generated high gas exchange times in a previous gas mixing system due to long time adsorption/desorption effects. Residual gas contaminations of the system and the selected carrier air supply have been detected and quantified using both an analytical method (GC-MS analysis according to ISO 16000-6) and a metal oxide semiconductor gas sensor, which detected a maximum contamination equivalent to 28 ppb of carbon monoxide. A measurement strategy for suppressing even this contamination has been devised, which allows the system to be used for gas sensor and gas sensor system characterization and calibration in the low ppb concentration range.

  15. RI and Target recovery system of Lanthanides

    Energy Technology Data Exchange (ETDEWEB)

    Choi, K. H.; Park, U. J.; Jung, S. H.; Kim, J. B.; Moon, J. H.; Nam, S. S.; Jang, K. D. [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-10-15

    Separation of adjacent lanthanides is complicated process to obtain pure target nuclide. Several papers have reported that the ionic character change of lanthanides with appropriate chelating agents can isolate the target lanthanides. These specific agents to the metal ion are called as complexing agents including-HIBA, tartaric acid, mandelic acid, lactic acid etc. Radioisotope research division of KAERI has developed separating technique for target lanthanides, total 20mg scale, by using complexing agents and ion-pairing agents in cold state. The reactor-produced radiolanthanides have been pivotal for development of therapeutic radiopharmaceuticals. Some radiolanthanides show excellent theranostic effects in that they have proper Let (Linear Energy Transfer) to induce apoptosis for cancer treatment and gamma ray to use as a tracer for cancer diagnosis. This system was designed for automated separation of the (n,γ) reaction product. Especially, we are focused on getting the carrier free Ho-166 which is the first attempt at KAERI. Even though we have already developed to produce c.a Ho-166(carrier added form), we did not try to develop to produce carrier free Ho-166 since the separating process is difficult as well as production process follows double (n,γ) reaction. After HANARO is re-operated, we are schedule to produce n.c.a Ho by using this recovery system.

  16. The apelinergic system: a promising therapeutic target.

    Science.gov (United States)

    Falcão-Pires, Inês; Ladeiras-Lopes, Ricardo; Leite-Moreira, Adelino F

    2010-06-01

    Apelin is a bioactive peptide known as the ligand of the G-protein-coupled receptor APJ. In recent years, there has been a growing body of evidence regarding the importance of apelin and APJ in the pathophysiology of cardiovascular, metabolic and gastrointestinal diseases, brain signalling, HIV infection and tumor angiogenesis. Therefore, the apelinergic system is involved in the pathogenesis of several diseases that represent a major burden to our society. The goal of this paper is to give an up-to-date review of existing information on apelin/APJ since the discovery of apelin in 1998, with particular focus on their involvement in the regulation of human body systems and potential therapeutic applications. An overview of the most important physiological functions of the apelinergic system and the diseases that may benefit in the future from its modulation as a therapeutic target. Today, the established biological effects of apelin involve major cardiovascular actions, neoangiogenesis, immunologic modulation and insulinemia control as well as body fluid and glucose homeostasis. However, the physiological and pathophysiological role of endogenous apelin is still unsettled and a better and profound knowledge of this system in humans is necessary for the development of novel apelinergic-based therapeutic targets.

  17. Chitosan-based gene delivery vectors targeted to the peripheral nervous system.

    Science.gov (United States)

    Oliveira, Hugo; Pires, Liliana R; Fernandez, Ramon; Martins, M Cristina L; Simões, Sérgio; Pêgo, Ana P

    2010-12-01

    A non-toxic, targeted, simple and efficient system that can specifically transfect peripheral sensorial neurons can pave the way towards the development of new therapeutics for the treatment of peripheral neuropathies. In this study chitosan (CH), a biodegradable polymer, was used as the starting material in the design of a multicomponent vector targeted to the peripheral nervous system (PNS). Polycation-DNA complexes were optimized using imidazole- and thiol-grafted CH (CHimiSH), in order to increase transfection efficiency and allow the formation of ligand conjugated nanocomplexes, respectively. The 50 kDa non-toxic fragment from the tetanus toxin (HC), shown to interact specifically with peripheral neurons and undergo retrograde transport, was grafted to the binary complex via a bi-functional poly(ethylene glycol) (HC-PEG) reactive for the thiol moieties present in the complex surface. The targeting of the developed nanocomplexes was assessed by means of internalization and transfection studies in the ND7/23 (neuronal) vs. NIH 3T3 (fibroblast) cell lines. Targeted transfection was further confirmed in dorsal root ganglion dissociated primary cultures. A versatile, multi-component nanoparticle system that successfully targets and transfects neuronal cell lines, as well as dorsal root ganglia (DRG) primary neuron cultures was obtained for the 1.0 (w/w) HC-PEG/DNA formulation. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.

  18. Biodegradable glycopolymer-b-poly(ε-caprolactone) block copolymer micelles: Versatile construction, tailored lactose functionality, and hepatoma-targeted drug delivery

    NARCIS (Netherlands)

    Chen, Wei; Meng, Fenghua; Cheng, Ru; Deng, Chao; Feijen, Jan; Zhong, Zhiyuan

    2015-01-01

    Glycopolymer-b-poly(ε-caprolactone) (GP-PCL) block copolymer micelles (‘glycomicelles’) with tailored lactose functionalities were developed and investigated for hepatoma-targeted doxorubicin (DOX) delivery. Amphiphilic GP-PCL copolymers were readily prepared with controlled lactobionic acid (LBA)

  19. LIBS: a new versatile field-deployable real-time detector system with potential for landmine detection

    Science.gov (United States)

    Harmon, Russell S.; De Lucia, Frank C.; Winkel, Raymond J., Jr.; LaPointe, Aaron; Grossman, Scott L.; McNesby, Kevin L.; Miziolek, Andrzej W.

    2003-09-01

    Laser Induced Breakdown Spectroscopy (LIBS) is an atomic emission spectroscopic technique that utilizes a pulsed laser to create a microplasma on the target together with an array spectrometer to capture the transient light for elemental identification and quantification. LIBS has certain important characteristics that make it a very attractive sensor technology for military uses. Such attributes include that facts that LIBS (1) is relatively simple and straightforward, (2) requires no sample preparation, (3) generates a real-time response, and (4) only engages a very small sample (pg-ng) of matter in each laser shot and microplasma event, (5) has inherent high sensitivity, and (6) responds to all forms of unknowns, and, therefore, is particularly suited for the sensing of dangerous materials. Additionally, a LIBS sensor system can be inexpensive, configured to be man-portable, and designed for both in-situ point sensing and remote stand-off detection with distances of up to 20-25 meters. Broadband LIBS results covering the spectral region from 200-970 nm acquired at the Army Research Laboratory (ARL) under laboratory conditions for a variety of landmine casings and explosive materials. This data will illustrate the potential that LIBS has to be developed into a hand-deployable device that could be utilized as a confirmatory sensor in landmine detection. The concept envisioned is a backpack-size system in which an eyesafe micro-laser is contained in the handle of a deminer's probe and light is delivered and collected through an optical fiber in the tapered tip of the probe. In such a configuration, analyses can be made readily by touching the buried object that one is interested in identifying.

  20. Mitoxantrone Loaded Superparamagnetic Nanoparticles for Drug Targeting: A Versatile and Sensitive Method for Quantification of Drug Enrichment in Rabbit Tissues Using HPLC-UV

    Directory of Open Access Journals (Sweden)

    Rainer Tietze

    2010-01-01

    Full Text Available In medicine, superparamagnetic nanoparticles bound to chemotherapeutics are currently investigated for their feasibility in local tumor therapy. After intraarterial application, these particles can be accumulated in the targeted area by an external magnetic field to increase the drug concentration in the region of interest (Magnetic-Drug-Targeting. We here present an analytical method (HPLC-UV, to detect pure or ferrofluid-bound mitoxantrone in a complex matrix even in trace amounts in order to perform biodistribution studies. Mitoxantrone could be extracted in high yields from different tissues. Recovery of mitoxantrone in liver tissue (5000 ng/g was 76±2%. The limit of quantification of mitoxantrone standard was 10 ng/mL ±12%. Validation criteria such as linearity, precision, and stability were evaluated in ranges achieving the FDA requirements. As shown for pilot samples, biodistribution studies can easily be performed after application of pure or ferrofluid-bound mitoxantrone.

  1. Tumour targeting with systemically administered bacteria.

    LENUS (Irish Health Repository)

    Morrissey, David

    2012-01-31

    Challenges for oncology practitioners and researchers include specific treatment and detection of tumours. The ideal anti-cancer therapy would selectively eradicate tumour cells, whilst minimising side effects to normal tissue. Bacteria have emerged as biological gene vectors with natural tumour specificity, capable of homing to tumours and replicating locally to high levels when systemically administered. This property enables targeting of both the primary tumour and secondary metastases. In the case of invasive pathogenic species, this targeting strategy can be used to deliver genes intracellularly for tumour cell expression, while non-invasive species transformed with plasmids suitable for bacterial expression of heterologous genes can secrete therapeutic proteins locally within the tumour environment (cell therapy approach). Many bacterial genera have been demonstrated to localise to and replicate to high levels within tumour tissue when intravenously (IV) administered in rodent models and reporter gene tagging of bacteria has permitted real-time visualisation of this phenomenon. Live imaging of tumour colonising bacteria also presents diagnostic potential for this approach. The nature of tumour selective bacterial colonisation appears to be tumour origin- and bacterial species- independent. While originally a correlation was drawn between anaerobic bacterial colonisation and the hypoxic nature of solid tumours, it is recently becoming apparent that other elements of the unique microenvironment within solid tumours, including aberrant neovasculature and local immune suppression, may be responsible. Here, we consider the pre-clinical data supporting the use of bacteria as a tumour-targeting tool, recent advances in the area, and future work required to develop it into a beneficial clinical tool.

  2. How to use a very simple microcomputing system for a dynamical conformational analysis of versatile molecules. The case of some anticancer inorganic ring systems

    Science.gov (United States)

    Lahana, Roger; Labarre, Jean-Francois

    A very simple use of a suitable microcomputing system allows discrimination of a set of X-ray structures of anticancer drugs which (i) are the "natural" preferred conformations and (ii) are the direct relationships logically linking these conformations together. Such an approach appears the main interest for a deep understanding of the relative antitumour activities of drugs, whatever the target may be.

  3. Octadecylamine-Mediated Versatile Coating of CoFe2O4 NPs for the Sustained Release of Anti-Inflammatory Drug Naproxen and in Vivo Target Selectivity.

    Science.gov (United States)

    Georgiadou, Violetta; Makris, George; Papagiannopoulou, Dionysia; Vourlias, Georgios; Dendrinou-Samara, Catherine

    2016-04-13

    Magnetic nanoparticles (MNPs) can play a distinct role in magnetic drug delivery via their distribution to the targeted area. The preparation of such MNPs is a challenging multiplex task that requires the optimization of size, magnetic, and surface properties for the achievement of desirable target selectivity, along with the sustained drug release as a prerequisite. In that context, CoFe2O4 MNPs with a small size of ∼7 nm and moderate saturation magnetization of ∼60 emu g(-1) were solvothermally synthesized in the presence of octadecylamine (ODA) with a view to investigate the functionalization route effect on the drug release. Synthetic regulations allowed us to prepare MNPs with aminated (AmMNPs) and amine-free (FAmMNPs) surface. The addition of the nonsteroidal anti-inflammatory drug with a carboxylate donor, Naproxen (NAP), was achieved by direct coupling with the NH2 groups, rendered by ODA, through the formation of an amide bond in the case of AmMNPs. In the case of FAmMNPs, indirect coupling of NAP was performed through an intermediate linker (polyethylenimine) and on PEG-ylated MNPs. FT-IR, (1)H NMR, (13)C NMR, and UV-vis data confirmed the addition of NAP, whereas diverse drug-release behavior was observed for the different functionalization approaches. The biological behavior of the MNPs@NAP was evaluated in vitro in rat serum and in vivo in mice, after radiolabeling with a γ-emitting radionuclide, (99m)Tc. The in vivo fate of MNPs@NAP carriers was in straightforward relation with the direct or indirect coupling of NAP. Furthermore, an inflammation was induced intramuscularly, where the directly coupled (99m)Tc-MNPs@NAP carriers showed increased accumulation at the inflammation site.

  4. Chemoinformatics in multi-target drug discovery for anti-cancer therapy: in silico design of potent and versatile anti-brain tumor agents.

    Science.gov (United States)

    Speck-Planche, Alejandro; Kleandrova, Valeria V; Luan, Feng; Cordeiro, M Natália D S

    2012-07-01

    A brain tumor (BT) constitutes a neoplasm located in the brain or the central spinal canal. The number of new diagnosed cases with BT increases with the pass of the time. Understanding the biology of BT is essential for the development of novel therapeutic strategies, in order to prevent or deal with this disease. An active area for the search of new anti-BT therapies is the use of Chemoinformatics and/or Bioinformatics toward the design of new and potent anti-BT agents. The principal limitation of all these approaches is that they consider small series of structurally related compounds and/or the studies are realized for only one target like protein. The present work is an effort to overcome this problem. We introduce here the first Chemoinformatics multi-target approach for the in silico design and prediction of anti-BT agents against several cell lines. Here, a fragment-based QSAR model was developed. The model correctly classified 89.63% and 90.93% of active and inactive compounds respectively, in training series. The validation of the model was carried out by using prediction series which showed 88.00% of correct classification for active and 88.59% for inactive compounds. Some fragments were extracted from the molecules and their contributions to anti-BT activity were calculated. Several fragments were identified as potential substructural features responsible of anti-BT activity and new molecular entities designed from fragments with positive contributions were suggested as possible anti-BT agents.

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

    Science.gov (United States)

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

    2017-07-01

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

  6. DVD - digital versatile disks

    Energy Technology Data Exchange (ETDEWEB)

    Gaunt, R.

    1997-05-01

    An international standard has emerged for the first true multimedia format. Digital Versatile Disk (by its official name), you may know it as Digital Video Disks. DVD has applications in movies, music, games, information CD-ROMS, and many other areas where massive amounts of digital information is needed. Did I say massive amounts of data? Would you believe over 17 gigabytes on a single piece of plastic the size of an audio-CD? That`s the promise, at least, by the group of nine electronics manufacturers who have agreed to the format specification, and who hope to make this goal a reality by 1998. In this major agreement, which didn`t come easily, the manufacturers will combine Sony and Phillip`s one side double-layer NMCD format with Toshiba and Matsushita`s double sided Super-Density disk. By Spring of this year, they plan to market the first 4.7 gigabyte units. The question is: Will DVD take off? Some believe that read-only disks recorded with movies will be about as popular as video laser disks. They say that until the eraseable/writable DVD arrives, the consumer will most likely not buy it. Also, DVD has a good market for replacement of CD- Roms. Back in the early 80`s, the international committee deciding the format of the audio compact disk decided its length would be 73 minutes. This, they declared, would allow Beethoven`s 9th Symphony to be contained entirely on a single CD. Similarly, today it was agreed that playback length of a single sided, single layer DVD would be 133 minutes, long enough to hold 94% of all feature-length movies. Further, audio can be in Dolby`s AC-3 stereo or 5.1 tracks of surround sound, better than CD-quality audio (16-bits at 48kHz). In addition, there are three to five language tracks, copy protection and parental ``locks`` for R rated movies. DVD will be backwards compatible with current CD-ROM and audio CD formats. Added versatility comes by way of multiple aspect rations: 4:3 pan-scan, 4:3 letterbox, and 16:9 widescreen. MPEG

  7. Acquisition of the Joint Surveillance Target Attack Radar System

    National Research Council Canada - National Science Library

    Meling, John

    1994-01-01

    .... Joint STARS is a surveillance, battle-management, and target attack support system being developed to detect, locate, and track moving and stationary targets located beyond the forward line of our troops...

  8. Versatility of microbial transglutaminase.

    Science.gov (United States)

    Strop, Pavel

    2014-05-21

    Although microbial transglutaminases (mTGs) were initially discovered to offset the cost of producing mammalian transglutaminases for food applications, they have quickly become important tools in research and biotechnology. Today, mTGs are utilized for a large number of applications to conjugate proteins and peptides to small molecules, polymers, surfaces, and DNA, as well as to other proteins. It is important to know how to maximize the advantages of the enzymatic approach and avoid undesired cross-linking. This review focuses on the versatility of transglutaminases in the field of bioconjugation and covers recent developments in utilizing mTG for generating antibody drug conjugates (ADCs) for therapeutic applications.

  9. A novel nanoparticle delivery system for in vivo targeting of the sciatic nerve: impact on regeneration.

    Science.gov (United States)

    Gonçalves, Nádia Pereira; Oliveira, Hugo; Pêgo, Ana Paula; Saraiva, Maria João

    2012-08-01

    Innovative solutions in the development of drug delivery systems targeting the nerve tissue are awaited. In this regard, a novel system for the delivery of drugs to the sciatic nerve was created using nanomedical principles. Chitosan was the vehicle material used in the experiment. Heparin bound to growth factors has been administered to enhance peripheral nerve regeneration, and since heparin possesses the appropriate charge to be able to form nanoparticles with chitosan, it appears to be a good candidate to base this new delivery system on. Maximal absorption took place throughout the extracellular matrix at day 15. No major inflammatory response was observed, indicating that this is a safe and biocompatible system for drug delivery to nerves. Sensorimotor performance and nerve regeneration of mice receiving these nanoparticles were superior as compared with controls. Our work demonstrates a versatile nanoparticle delivery system that successfully targets drugs 'in vivo' to the sciatic nerve, opening novel avenues in the field of nanomedicine to the design of therapeutic strategies that enhance axonal regeneration.

  10. Magnetic biosensor system to detect biological targets

    KAUST Repository

    Li, Fuquan

    2012-09-01

    Magneto-resistive sensors in combination with magnetic beads provide sensing platforms, which are small in size and highly sensitive. These platforms can be fully integrated with microchannels and electronics to enable devices capable of performing complex tasks. Commonly, a sandwich method is used that requires a specific coating of the sensor\\'s surface to immobilize magnetic beads and biological targets on top of the sensor. This paper concerns a micro device to detect biological targets using magnetic concentration, magnetic as well as mechanical trapping and magnetic sensing. Target detection is based on the size difference between bare magnetic beads and magnetic beads with targets attached. This method remedies the need for a coating layer and reduces the number of steps required to run an experiment. © 2012 IEEE.

  11. LoMA-B: a simple and versatile lab-on-a-chip system based on single-channel bisulfite conversion for DNA methylation analysis.

    Science.gov (United States)

    Yoon, Jaeyun; Park, Mi Kyoung; Lee, Tae Yoon; Yoon, Yong-Jin; Shin, Yong

    2015-09-07

    Miniaturized lab-on-a-chip (LOC) systems have been developed for genetic and epigenetic analyses in clinical applications because of advantages such as reduced sample size and reagent consumption, rapid processing speed, simplicity, and enhanced sensitivity. Despite tremendous efforts made towards developing LOC systems for use in the clinical setting, the development of LOC systems to analyze DNA methylation, which is an emerging epigenetic marker causing the abnormal silencing of genes including tumor suppressor genes, is still challenging because of the gold standard methods involving a bisulfite conversion step. Existing bisulfite conversion-based techniques are not suitable for clinical use due to their long processing time, labor intensiveness, and the purification steps involved. Here, we present a lab-on-a-chip system for DNA methylation analysis based on bisulfite conversion (LoMA-B), which couples a sample pre-processing module for on-chip bisulfite conversion and a label-free, real-time detection module for rapid analysis of DNA methylation status using an isothermal DNA amplification/detection technique. The methylation status of the RARβ gene in human genomic DNA extracted from MCF-7 cells was analyzed by the LoMA-B system within 80 min (except 16 h for sensor preparation) compared to conventional MS-PCR within 24 h. Furthermore, the LoMA-B system is highly sensitive and can detect as little as 1% methylated DNA in a methylated/unmethylated cell mixture. Therefore, the LoMA-B system is an efficient diagnostic tool for the simple, versatile, and quantitative evaluation of DNA methylation patterns for clinical applications.

  12. A versatile fibre optic sensor interrogation system for the Ariane Launcher based on an electro-optically tuneable laser diode

    Science.gov (United States)

    Plattner, M. P.; Hirth, F.; Müller, M. S.; Hoffmann, L.; Buck, T. C.; Koch, A. W.

    2017-11-01

    Availability of reliable flight sensor data and knowledge of the structural behaviour are essential for safe operation of the Ariane launcher. The Ariane launcher is currently monitored by hundreds of electric sensors during test and qualification. Fibre optic sensors are regarded as a potential technique to overcome limitations of recent monitoring systems for the Ariane launcher [1]. These limitations include cumbersome application of sensors and harness as well as a very limited degree of distributed sensing capability. But, in order to exploit the various advantages of fibre optic sensors (high degree of multiplexing, distributed sensing capability, lower mass impact, etc.) dedicated measurement systems have to be developed and investigated. State-of-the-art fibre optic measurement systems often use free beam setups making them bulky and sensitive to vibration impact. Therefore a new measurement system is developed as part of the ESAstudy [2].

  13. Hydroponics: A Versatile System to Study Nutrient Allocation and Plant Responses to Nutrient Availability and Exposure to Toxic Elements.

    Science.gov (United States)

    Nguyen, Nga T; McInturf, Samuel A; Mendoza-Cózatl, David G

    2016-07-13

    Hydroponic systems have been utilized as one of the standard methods for plant biology research and are also used in commercial production for several crops, including lettuce and tomato. Within the plant research community, numerous hydroponic systems have been designed to study plant responses to biotic and abiotic stresses. Here we present a hydroponic protocol that can be easily implemented in laboratories interested in pursuing studies on plant mineral nutrition. This protocol describes the hydroponic system set up in detail and the preparation of plant material for successful experiments. Most of the materials described in this protocol can be found outside scientific supply companies, making the set up for hydroponic experiments less expensive and convenient. The use of a hydroponic growth system is most advantageous in situations where the nutrient media need to be well controlled and when intact roots need to be harvested for downstream applications. We also demonstrate how nutrient concentrations can be modified to induce plant responses to both essential nutrients and toxic non-essential elements.

  14. Hydroponics: A Versatile System to Study Nutrient Allocation and Plant Responses to Nutrient Availability and Exposure to Toxic Elements

    Science.gov (United States)

    Nguyen, Nga T.; McInturf, Samuel A.; Mendoza-Cózatl, David G.

    2016-01-01

    Hydroponic systems have been utilized as one of the standard methods for plant biology research and are also used in commercial production for several crops, including lettuce and tomato. Within the plant research community, numerous hydroponic systems have been designed to study plant responses to biotic and abiotic stresses. Here we present a hydroponic protocol that can be easily implemented in laboratories interested in pursuing studies on plant mineral nutrition. This protocol describes the hydroponic system set up in detail and the preparation of plant material for successful experiments. Most of the materials described in this protocol can be found outside scientific supply companies, making the set up for hydroponic experiments less expensive and convenient. The use of a hydroponic growth system is most advantageous in situations where the nutrient media need to be well controlled and when intact roots need to be harvested for downstream applications. We also demonstrate how nutrient concentrations can be modified to induce plant responses to both essential nutrients and toxic non-essential elements. PMID:27500800

  15. LCR/MEL: A versatile system for high-level expression of heterologous proteins in erythroid cells.

    NARCIS (Netherlands)

    M. Needham; C. Gooding; K. Hudson; M. Antoniou (Michael); F.G. Grosveld (Frank); M. Hollis

    1992-01-01

    textabstractWe have used the human globin locus control region (LCR) to assemble an expression system capable of high-level, integration position-independent expression of heterologous genes and cDNAs in murine erythroleukaemia (MEL) cells. The cDNAs are inserted between the human beta-globin

  16. Detection technique of targets for missile defense system

    Science.gov (United States)

    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.

  17. Feasibility of target communities in a Dutch brook valley system

    NARCIS (Netherlands)

    Prins, AH; Bekker, RM

    As a reaction to the ongoing deterioration of nature conservation interest in The Netherlands, an offensive nature strategy was formulated in the 1990 Nature Policy Plan. In this Plan, target communities and target plant species are mentioned. For the 'Drentse A brook valley system', target

  18. Anti-drift and auto-alignment mechanism for an astigmatic atomic force microscope system based on a digital versatile disk optical head.

    Science.gov (United States)

    Hwu, E-T; Illers, H; Wang, W-M; Hwang, I-S; Jusko, L; Danzebrink, H-U

    2012-01-01

    In this work, an anti-drift and auto-alignment mechanism is applied to an astigmatic detection system (ADS)-based atomic force microscope (AFM) for drift compensation and cantilever alignment. The optical path of the ADS adopts a commercial digital versatile disc (DVD) optical head using the astigmatic focus error signal. The ADS-based astigmatic AFM is lightweight, compact size, low priced, and easy to use. Furthermore, the optical head is capable of measuring sub-atomic displacements of high-frequency AFM probes with a sub-micron laser spot (~570 nm, FWHM) and a high-working bandwidth (80 MHz). Nevertheless, conventional DVD optical heads suffer from signal drift problems. In a previous setup, signal drifts of even thousands of nanometers had been measured. With the anti-drift and auto-alignment mechanism, the signal drift is compensated by actuating a voice coil motor of the DVD optical head. A nearly zero signal drift was achieved. Additional benefits of this mechanism are automatic cantilever alignment and simplified design.

  19. Applying technical versatility

    Energy Technology Data Exchange (ETDEWEB)

    None

    1970-01-01

    The breadth and depth of the diversified technical programs at Mound Laboratory since its inception are characterized by a record of competence and versatility during the past generation. A spectrum of mission assignments has been completed successfully in such diverse technical areas as process development and manufacturing of explosive components, research on fuels for the Civilian Power Reactor Program, separation of radioactive materials, fabrication of radioisotopic heat sources, stable gaseous isotope separation and purification, and many other areas. Mound Laboratory is one of the key U.S. Atomic Energy Commission sites that has demonstrated its technical competence in both weapons and non-weapons activities. This report has been prepared to complement the AEC’s vigorous program of scientific information dissemination. Three broad areas of technical competence are highlighted here: explosive technology, radionuclide technology, and stable gaseous isotope separation, which encompass a broad variety of techniques and supporting disciplines.

  20. Versatile by design

    CERN Multimedia

    Katarina Anthony

    2014-01-01

    CHARM (CERN High energy AcceleRator Mixed field) is a new and unique testing facility that will complete CERN's radiation testing installations. Located in the East Area, CHARM will provide teams with a venue to test their equipment in radiation environments similar to those found in the accelerator chain.   Team at work in the irradiation zone of the CHARM facility. First envisaged in 2007, the CHARM facility fulfils a growing demand for a large-scale tailor-made radiation testing facility. Unlike commercial facilities, CHARM features a wide spectrum of radiation types and energies (called mixed-field radiation environments), the space to test large equipment and even the possibility to adjust the environment using mobile shielding. "CHARM is versatile by design, allowing us to recreate any of the radiation environments found in the accelerator chain," says Markus Brugger, head of the R2E (Radiation to Electronics) project team that developed the CHARM facility. &a...

  1. SWUIS-A: A Versatile, Low-Cost UV/VIS/IR Imaging System for Airborne Astronomy and Aeronomy Research

    Science.gov (United States)

    Durda, Daniel D.; Stern, S. Alan; Tomlinson, William; Slater, David C.; Vilas, Faith

    2001-01-01

    We have developed and successfully flight-tested on 14 different airborne missions the hardware and techniques for routinely conducting valuable astronomical and aeronomical observations from high-performance, two-seater military-type aircraft. The SWUIS-A (Southwest Universal Imaging System - Airborne) system consists of an image-intensified CCD camera with broad band response from the near-UV to the near IR, high-quality foreoptics, a miniaturized video recorder, an aircraft-to-camera power and telemetry interface with associated camera controls, and associated cables, filters, and other minor equipment. SWUIS-A's suite of high-quality foreoptics gives it selectable, variable focal length/variable field-of-view capabilities. The SWUIS-A camera frames at 60 Hz video rates, which is a key requirement for both jitter compensation and high time resolution (useful for occultation, lightning, and auroral studies). Broadband SWUIS-A image coadds can exceed a limiting magnitude of V = 10.5 in research done on each research mission. Key advantages of the small, high-performance aircraft on which we can fly SWUIS-A include significant cost savings over larger, more conventional airborne platforms, worldwide basing obviating the need for expensive, campaign-style movement of specialized large aircraft and their logistics support teams, and ultimately faster reaction times to transient events. Compared to ground-based instruments, airborne research platforms offer superior atmospheric transmission, the mobility to reach remote and often-times otherwise unreachable locations over the Earth, and virtually-guaranteed good weather for observing the sky. Compared to space-based instruments, airborne platforms typically offer substantial cost advantages and the freedom to fly along nearly any groundtrack route for transient event tracking such as occultations and eclipses.

  2. Improving Performance and Versatility of Systems Based on Single-Frequency DFT Detectors Such as AD5933

    Directory of Open Access Journals (Sweden)

    Leonid Matsiev

    2014-12-01

    Full Text Available Turning grand concepts such as the Internet of Things (IoT and Smart Cities into reality requires the development and deployment of a wide variety of computing devices incorporated into the Internet infrastructure. Unsupervised sensing is the cornerstone capability that these devices must have to perform useful functions, while also having low cost of acquisition and ownership, little energy consumption and a small footprint. Impedimetric sensing systems based on the so-called single-frequency DFT detectors possess many of these desirable attributes and are often introduced in remote monitoring and wearable devices. This study presents new methods of improving performance of such detectors. It demonstrates that the main source of systematic errors is the discontinuous test phasor causing the crosstalk between the in-phase and quadrature outputs and the leakage of the input signal. The study derives expressions for these errors as a function of the number of samples and operating frequency, and provides methods for correction. The proposed methods are applied to the operation of a practical device—a network analyzer integrated circuit AD5933—and discussed in detail. These methods achieve complete elimination of leakage errors and expansion of the low limit of the operation frequency range by nearly two decades without additional hardware.

  3. Sustainable and Continuous Synthesis of Enantiopure l-Amino Acids by Using a Versatile Immobilised Multienzyme System.

    Science.gov (United States)

    Velasco-Lozano, Susana; da Silva, Eunice S; Llop, Jordi; López-Gallego, Fernando

    2017-10-09

    The enzymatic synthesis of α-amino acids is a sustainable and efficient alternative to chemical processes, through which achieving enantiopure products is difficult. To more address this synthesis efficiently, a hierarchical architecture that irreversibly co-immobilises an amino acid dehydrogenase with polyethyleneimine on porous agarose beads has been designed and fabricated. The cationic polymer acts as an irreversible anchoring layer for the formate dehydrogenase. In this architecture, the two enzymes and polymer colocalise across the whole microstructure of the porous carrier. This multifunctional heterogeneous biocatalyst was kinetically characterised and applied to the enantioselective synthesis of a variety of canonical and noncanonical α-amino acids in both discontinuous (batch) and continuous modes. The co-immobilised bienzymatic system conserves more than 50 % of its initial effectiveness after five batch cycles and 8 days of continuous operation. Additionally, the environmental impact of this process has been semiquantitatively calculated and compared with the state of the art. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. A model system for targeted drug release triggered by biomolecular signals logically processed through enzyme logic networks.

    Science.gov (United States)

    Mailloux, Shay; Halámek, Jan; Katz, Evgeny

    2014-03-07

    A new Sense-and-Act system was realized by the integration of a biocomputing system, performing analytical processes, with a signal-responsive electrode. A drug-mimicking release process was triggered by biomolecular signals processed by different logic networks, including three concatenated AND logic gates or a 3-input OR logic gate. Biocatalytically produced NADH, controlled by various combinations of input signals, was used to activate the electrochemical system. A biocatalytic electrode associated with signal-processing "biocomputing" systems was electrically connected to another electrode coated with a polymer film, which was dissolved upon the formation of negative potential releasing entrapped drug-mimicking species, an enzyme-antibody conjugate, operating as a model for targeted immune-delivery and consequent "prodrug" activation. The system offers great versatility for future applications in controlled drug release and personalized medicine.

  5. Monetary targeting and financial system characteristics : An empirical analysis

    NARCIS (Netherlands)

    Samarina, A..

    2012-01-01

    This paper investigates how reforms and characteristics of the financial system affect the likelihood of countries to abandon their strategy of monetary targeting. Apart from financial system characteristics, we include macroeconomic, fiscal, and institutional factors potentially associated with

  6. Compactness of cores of targets for nonlinear delay systems ...

    African Journals Online (AJOL)

    A relationship is established between the boundedness of cores of targets and the Euclidean controllability of the nonlinear system. This relationship gives vent to the establishment of the compactness of cores of target for the system. We complement Ukwu [9] and Chukwu [1] by answering in the affirmative that under ...

  7. Targeting the endocannabinoid system for therapeutic purposes

    OpenAIRE

    Busquets Garcia, Arnau

    2013-01-01

    The endocannabinoid system is an endogenous neuromodulatory system that regulates a plethora of physiological functions, including the modulation of memory, anxiety, pain, synaptic plasticity and neuronal excitability, among others. The activation of this system through exogenous or endogenous cannabinoid agonists has been proposed as a therapeutic strategy in different pathological states, although an important caveat to their use is the possible central adverse effects, such as memory impai...

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

    Directory of Open Access Journals (Sweden)

    Ajmal Hinas

    2017-12-01

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

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

    Science.gov (United States)

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

    2017-12-17

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

  10. Trypanosomes - versatile microswimmers

    Science.gov (United States)

    Krüger, Timothy; Engstler, Markus

    2016-11-01

    Evolution has generated a plethora of flagellate microswimmers. They populate all natural waters, from the deep sea to the ponds in our neighbourhood. But flagellates also thrive in the bodies of higher organisms, where they mostly remain undetected, but can also become pathogenic. Trypanosomes comprise a large group of mostly parasitic flagellates that cause many diseases, such as human sleeping sickness or the cattle plague nagana. We consider African trypanosomes as extremely versatile microswimmers, as they have to adapt to very diverse microenvironments. They swim efficiently in the blood of their mammalian hosts, but also in various tissue spaces and even in the human brain. Furthermore, in the transmitting tsetse fly, trypanosomes undergo characteristic morphological changes that are accompanied by amazing transitions between solitary and collective types of motion. In this review, we provide a basic introduction to trypanosome biology and then focus on the complex type of rotational movement that trypanosomes display. We relate their swimming performance to morphological parameters and the respective microenvironment, developing a contemporary view on the physics of trypanosome motility. The genetically programmed successions of life style-dependent motion patterns provide challenges and opportunities for interdisciplinary studies of microswimmers.

  11. A two-cassette reporter system for assessing target gene translation and target gene product inclusion body formation

    DEFF Research Database (Denmark)

    2016-01-01

    The present invention relates to a dual cassette reporter system capable of assessing target gene translation and target gene product folding. The present invention further relates to vectors and host cells comprising the dual cassette reporter system. In addition the invention relates to the use...... of the dual cassette reporter system for assessing target gene translation and target gene product folding....

  12. Low-flying target position finding with a seismic system

    Science.gov (United States)

    Cechak, Jaroslav; Hubacek, Petr; Vesely, Jiri

    2009-06-01

    The development of new sensor systems able to detect, identify and find position of the targets equipped with STEALTH technology began early in 1990s. Some of the sensor systems utilise acoustic, magnetic, seismic and/or other physical effects of target activity. A reason motivating the development of new sensor systems based on other than radar or optical principal of operation in detecting targets is that the systems usually emit no electromagnetic energy during operation. Thanks to their passive principle they provide the users with the advantages of hidden positioning and difficult discovery with reconnaissance tools. Therefore, some of the new UGS systems also allow detecting low-flying targets, such as helicopters, propeller or jet aircraft, etc., in the detection range of up to several kilometres. The information of flight direction is usually estimated and deduced from spatiotemporal sequence detections by multiple interlinked UGS systems. The submitted paper analyses low-flying target position finding principle on Time Direction Of Arrival (TDOA) basis. It presents the qualities of found UGS arrangement topologies and the characteristics of the unambiguous position determination of low-flying targets. It also contains mathematical description of signal digital processing intended to find low-flying target's position. The processed results are presented in table and diagram forms created in Matlab mathematical environment. All the presented detection and identification results were obtained from real recorded signals.

  13. The evaluation study of high performance gas target system

    Energy Technology Data Exchange (ETDEWEB)

    Hur, Min Goo; Yang, Seung Dae; Kim, Sang Wook

    2008-06-15

    The object of this study is a improvement of a gas target and targetry for increasing the radioisotope production yields. The main results are as follows 1. Improvement of beam entrance of the gas target : In this work, deep hole grid was designed for improvement of beam entrance. Using FEM(Finite Elements Method) analysis, it was verified that this design is more effective than the old one. 2. Improvement of target gas loading and withdrawing system : For the targetry, Helium gas and vacuum lines was installed for evaluating the production yields. Using these lines, it was proved that the recovery yields was improved and the residual impurity was reduced. 3. Improvement of target cooling efficiency : In case of the cylindrical target, it is more effective to use short length of target cavity for the high production yields. For improving the cooling efficiency, cooling fin was suggested to the target design. It is more effective to put the cooling fins inside the target cavity for the suppressed target pressure and density reduction effect during the proton beam irradiation. In conclusion, the target with fins inside the target cavity was better for high current irradiation and mass RI production.

  14. Treat-to-target in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    van Vollenhoven, Ronald F; Mosca, Marta; Bertsias, George

    2014-01-01

    guidance for healthcare providers and administrators. Thus, an initiative to evaluate possible therapeutic targets and develop treat-to-target guidance was believed to be highly appropriate in the management of systemic lupus erythematosus (SLE) patients as well. Specialists in rheumatology, nephrology...

  15. Multiple operating system rotation environment moving target defense

    Science.gov (United States)

    Evans, Nathaniel; Thompson, Michael

    2016-03-22

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

  16. Versatile Wireless Data Net Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed R&D is to develop a wireless data networking capability. A prototype capability will result from the Phase 1 and 2 contracts. The Versatile Wireless...

  17. Development of a Versatile Laser-Ultrasonic System and Application to the Online Measurement for Process Control of Wall Thickness and Eccentricity of Seamless Tubes

    Energy Technology Data Exchange (ETDEWEB)

    Robert V. Kolarik II

    2002-10-23

    A system for the online, non-contact measurement of wall thickness in steel seamless mechanical tubing has been developed and demonstrated at a tubing production line at the Timken Company in Canton, Ohio. The system utilizes laser-generation of ultrasound and laser-detection of time of flight with interferometry, laser-doppler velocimetry and pyrometry, all with fiber coupling. Accuracy (<1% error) and precision (1.5%) are at targeted levels. Cost and energy savings have exceeded estimates. The system has shown good reliability in measuring over 200,000 tubes in its first six months of deployment.

  18. Cryogenic control system of the large COMPASS polarized target

    CERN Document Server

    Gautheron, F; Baum, G; Berglund, P; Doshita, N; Görtz, S; Gustafsson, K K; Horikawa, N; Kisselev, Yu V; Koivuniemi, J H; Kondo, K; Meyer, Werner T; Reicherz, G

    2004-01-01

    The dilution refrigerator used to cool the large COMPASS polarized target is monitored through a PC running LabVIEW trademark 6.1 under Windows 2000 trademark . About 60 parameters of the target (temperatures, pressures, flow rates) are continuously plotted and checked. They are periodically recorded in an Oracle trademark database and in a data file. An alarm for every parameter can be individually activated and optionally connected to a GSM (Global System for Mobile Communication) delivery message system. A web server receives and publishes the online status of the target with online tables and graphics on a dedicated COMPASS polarized target information web site. A Siemens programmable logic controller (PLC) powered by an uninterruptable source keeps the cryogenic system safe and stable during the long beam periods by controlling valves and interlocks. This safety feature protects the dilution refrigerator against potential damages in case of power failure.

  19. The Research Progress of Targeted Drug Delivery Systems

    Science.gov (United States)

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

    2017-06-01

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

  20. The Versatile Link Demo Board (VLDB)

    Science.gov (United States)

    Martín Lesma, R.; Alessio, F.; Barbosa, J.; Baron, S.; Caplan, C.; Leitao, P.; Pecoraro, C.; Porret, D.; Wyllie, K.

    2017-02-01

    The Versatile Link Demonstrator Board (VLDB) is the evaluation kit for the radiation-hard Optical Link ecosystem, which provides a 4.8 Gbps data transfer link for communication between front-end (FE) and back-end (BE) of the High Energy Physics experiments. It gathers the Versatile link main radiation-hard custom Application-Specific Integrated Circuits (ASICs) and modules: GBTx, GBT-SCA and VTRx/VTTx plus the FeastMP, a radiation-hard in-house designed DC-DC converter. This board is the first design allowing system-level tests of the Link with a complete interconnection of the constitutive components, allowing data acquisition, control and monitoring of FE devices with the GBT-SCA pair.

  1. Targeted Drug Delivery System for Platinum-based Anticancer Drugs.

    Science.gov (United States)

    Gao, Chuanzhu; Zhang, Yan; Chen, Ji; Wang, Tianshuai; Qian, Yunxu; Yang, Bo; Dong, Peng; Zhang, Yingjie

    2016-01-01

    Platinum-based (Pt-based) anticancer drugs have been recognised as one of the most effective drugs for clinical treatment of malignant tumors due to its unique mechanism of action and broad range of anticancer spectrum. But, there are still some limitations such as side effects, drug resistance/cross resistance, no-specific targeting, becoming obstacles to restrict its expanding of clinical application. Targeted drug delivery system (TDDS) is a promising strategy for the research of novel Pt-based anticancer drugs. A variety of TDDS have been explored to improve the antitumor activity of Pt-based drugs such as nanoparticle drug systems, polymer-drug systems, drugs-macrocyclic compounds systems, etc. The review concentrates on recent development of various targeted drug delivery techniques, which could provide more opportunities for the development of Pt-based drugs with better efficiency, lower toxicity and less resistance.

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

    Science.gov (United States)

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

    2005-08-01

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

  3. System for manipulating and optically targeting micro objects

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to a system 100 for independently holding and manipulating one or more microscopic objects 158 and for targeting at least a part of the one or more microscopic objects within a trapping volume 102 with electromagnetic radiation 138. The system comprises trapping means...... for holding and manipulating the one or more microscopic objects and electromagnetic radiation targeting means (116). The light means comprising a light source and a spatial light modulator which serve to modify the light from the light source so as to enable specific illumination of at least a part...... of the one or more microscopic objects. The trapping means and the electromagnetic radiation targeting means (116) are enabled to function independently of each other, so that the trapped objects may be moved around without taking being dependent on which parts are being targeted and vice versa....

  4. Developing conservation targets in social-ecological systems

    Directory of Open Access Journals (Sweden)

    Phillip S. Levin

    2015-12-01

    Full Text Available The development of targets is foundational in conservation. Although progress has been made in setting targets, the diverse linkages among ecological and social components make target setting for coupled social-ecological systems extremely challenging. Developing integrated social-ecological targets is difficult because it forces policy makers to consider how management actions propagate throughout social-ecological systems, and because ultimately it is society, not scientists, that defines targets. We developed an interdisciplinary approach for identifying management targets and illustrate this approach using an example motivated by Puget Sound, USA. Our approach blends ecological modeling with empirical social science to articulate trade-offs and reveal societal preferences for different social-ecological states. The framework aims to place information in the hands of decision makers and promote discussion in the appropriate forums. Our ultimate objective is to encourage the informed participation of citizens in the development of social-ecological targets that reflect their values while also protecting key ecosystem attributes.

  5. Particulate Systems for Targeting of Macrophages: Basic and Therapeutic Concepts

    DEFF Research Database (Denmark)

    Moghimi, Seyed Moien; Parhamifar, Ladan; Ahmadvand, Davoud

    2012-01-01

    Particulate systems in the form of liposomes, polymeric micelles, polymeric nano- and microparticles, and many others offer a rational approach for selective delivery of therapeutic agents to the macrophage from different physiological portals of entry. Particulate targeting of macrophages and in...... at a particular subset of macrophages. Advances in basic and therapeutic concepts of particulate targeting of macrophages and related nanotechnology approaches for immune cell modifications are discussed.Copyright © 2012 S. Karger AG, Basel...

  6. Generation of gene-modified goats targeting MSTN and FGF5 via zygote injection of CRISPR/Cas9 system

    Science.gov (United States)

    Wang, Xiaolong; Yu, Honghao; Lei, Anmin; Zhou, Jiankui; Zeng, Wenxian; Zhu, Haijing; Dong, Zhiming; Niu, Yiyuan; Shi, Bingbo; Cai, Bei; Liu, Jinwang; Huang, Shuai; Yan, Hailong; Zhao, Xiaoe; Zhou, Guangxian; He, Xiaoling; Chen, Xiaoxu; Yang, Yuxin; Jiang, Yu; Shi, Lei; Tian, Xiue; Wang, Yongjun; Ma, Baohua; Huang, Xingxu; Qu, Lei; Chen, Yulin

    2015-01-01

    Recent advances in the study of the CRISPR/Cas9 system have provided a precise and versatile approach for genome editing in various species. However, the applicability and efficiency of this method in large animal models, such as the goat, have not been extensively studied. Here, by co-injection of one-cell stage embryos with Cas9 mRNA and sgRNAs targeting two functional genes (MSTN and FGF5), we successfully produced gene-modified goats with either one or both genes disrupted. The targeting efficiency of MSTN and FGF5 in cultured primary fibroblasts was as high as 60%, while the efficiency of disrupting MSTN and FGF5 in 98 tested animals was 15% and 21% respectively, and 10% for double gene modifications. The on- and off-target mutations of the target genes in fibroblasts, as well as in somatic tissues and testis of founder and dead animals, were carefully analyzed. The results showed that simultaneous editing of several sites was achieved in large animals, demonstrating that the CRISPR/Cas9 system has the potential to become a robust and efficient gene engineering tool in farm animals, and therefore will be critically important and applicable for breeding. PMID:26354037

  7. TARGET - NEW PAYMENT SYSTEM FOR THE EURO AREA

    Directory of Open Access Journals (Sweden)

    ELENA VIOLETA DRĂGOI

    2015-04-01

    Full Text Available At EU level, the funds transfer systems have undergone significant changes starting with the introduction of euro. The launch of the euro, the emergence of new technologies, introduction of financial innovations and the globalization have led to reorganization of funds transfer systems` infrastructure. The paper aims to offer an analysis of actual payment system for Euro area, a trans-European funds transfer system with gross settlement in real-time for payments in euro TARGET- to increase economical and operational efficiency of payments and also to reduce the risks in the electronic funds transfer system by creating efficient and secure payment systems.

  8. Temperature characterization of versatile transceivers

    CERN Document Server

    Olanterä, L.; Storey, S; Sigaud, C; Soos, C; Troska, J; Vasey, F

    2013-01-01

    The Versatile Transceiver is a part of the Versatile Link project, which is developing optical link architectures and components for future HL-LHC experiments. While having considerable size and weight constraints, Versatile Transceivers must work under severe environmental conditions. One such environmental parameter is the temperature: the operating temperature range is specified to be from -30 to +60°C. In this contribution we present the results of the temperature characterization of the VTRx transmitter and receiver. Several transmitter candidates from three different manufacturers have been characterized: multi-mode Vertical Cavity Surface-Emitting Lasers and a single-mode Edge-Emitter Laser. Also both single- and multi-mode receivers have been tested.

  9. Oral Nano-Delivery Systems for Colon Targeting Therapy.

    Science.gov (United States)

    Zhang, Tianxu; Zhu, Guanyin; Lu, Boyao; Peng, Qiang

    2017-01-01

    Targeting drug delivery is an attractive research area, as it enables localized treatment, improves the efficacy of therapeutics and reduces systemic toxicity. Colon targeting delivery is particularly beneficial to the treatment of colon diseases, such as inflammatory bowel disease and colon cancer, due to the improved local drug concentrations. The traditional strategies for colon targeting delivery include time-dependent and pH-dependent technologies, etc. In recent years, nanotechnology has emerged as a novel and efficient tool for targeting drug delivery. After oral administration, nano-based formulations are able to protect drug from the harsh gastrointestinal environment and selectively increase the drug concentration at the disease site. Various orally administered drug-loaded nano-systems for colon targeting delivery have been well documented and shown great potentials in colon disease therapy. In this work, we aim to provide a comprehensive understanding of the recent progress in the area of colon targeting delivery in combination with introduction of the pathophysiological changes of diseased colon sites and the obstacles for drug delivery. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Target plane imaging system for the Nova laser

    Energy Technology Data Exchange (ETDEWEB)

    Swift, C.D.; Bliss, E.S.; Jones, W.A.; Reeves, R.J.; Seppala, L.G.; Shelton, R.T.; VanArsdall, P.J.

    1985-12-12

    The Nova laser, in operation since December 1984, is capable of irradiating targets with light at 1.05 ..mu..m, 0.53 ..mu..m, and 0.35 ..mu..m. Correct alignment of these harmonic beams uses a system called a target plane imager (TPI). It is a large microscope (four meters long, weighing one thousand kilograms) that relays images from the target chamber center to a video optics module located on the outside of the chamber. Several modes of operation are possible including: near-field viewing and far-field viewing at three magnifications and three wavelengths. In addition, the entire instrument can be scanned in X,Y,Z to examine various planes near chamber center. Performance of this system and its computer controls will be described.

  11. Xanthan-A Versatile Gum

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 9; Issue 10. Xanthan – A Versatile Gum. Anil Lachke. General Article Volume 9 Issue 10 October 2004 pp 25-33. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/009/10/0025-0033. Keywords. Xanthan ...

  12. Thermo-hydraulic analysis of the windowless target system

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, Fosco [ENEA, Via Martiri di Monte Sole 4, 40129 Bologna (Italy)], E-mail: fosco.bianchi@bologna.enea.it; Ferri, Roberta [SIET, Via Nino Bixio 27, 29100 Piacenza (Italy); Moreau, Vincent [CRS4, Polaris Edificio 1 CP25, 09010 Pula (Canada) (Italy)

    2008-08-15

    The target system, whose function is to supply an external neutron source to a subcritical core in order to sustain the neutron chain reaction, is the most critical part of an ADS being subject to severe thermo-mechanical loading and material damage due to accelerator protons and fission neutrons. In order to reduce the material damage and to increase the life of the target system a windowless option was chosen in the framework of the European PDS-XADS project as reference configuration for the experimental ADS cooled by lead-bismuth eutectic alloy. This document deals with the results of the thermo-hydraulic analysis performed with STAR-CD and RELAP5 codes to assess the behaviour of the windowless target system during off-normal operating conditions. It also reports a description of modifications properly implemented in the codes for studying this kind of plant. The windowless target system shows a satisfactory thermo-hydraulic behaviour for the analysed accidents, except for the loss of both pumps without proton beam shut-off and for the beam trips lasting more than 1 s.

  13. Targeting the orexinergic system: Mainly but not only for sleep ...

    African Journals Online (AJOL)

    Orexin receptors belong to the big family of G protein coupled receptors (GPCRs) that constitute the main targets in the modern pharmacological approaches. Although the orexinergic system is involved in a variety of processes, treating sleep-wakefulness disorders such as narcolepsy and insomnia, remains the main ...

  14. Treat-to-target in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Mosca, Marta; Boumpas, Dimitrios T; Bruce, Ian N

    2013-01-01

    on May 8, 2012 to discuss whether a treat-to-target approach could be applied in the treatment of systemic lupus erythematosus (SLE) (T2T/SLE), define a research agenda, and establish a plan for moving forward. In the present paper, observations raised at the meeting and literature data on potential...

  15. Targeted mutagenesis in chicken using CRISPR/Cas9 system

    OpenAIRE

    Isao Oishi; Kyoko Yoshii; Daichi Miyahara; Hiroshi Kagami; Takahiro Tagami

    2016-01-01

    The CRISPR/Cas9 system is a simple and powerful tool for genome editing in various organisms including livestock animals. However, the system has not been applied to poultry because of the difficulty in accessing their zygotes. Here we report the implementation of CRISPR/Cas9-mediated gene targeting in chickens. Two egg white genes, ovalbumin and ovomucoid, were efficiently (>90%) mutagenized in cultured chicken primordial germ cells (PGCs) by transfection of circular plasmids encoding Cas9, ...

  16. Colon targeted drug delivery system: A review on current approaches

    OpenAIRE

    Altamash M. Qureshi*; Munira Momin; Sudha Rathod; Asish Dev; Chaitrali Kute

    2013-01-01

    The colon is the terminal part of the GIT which has gained as a potential site for delivery of various novel therapeutic drugs i.e. peptides. Colon targeted drug delivery system (CDDS) is an Promising tool for treatment of inflammatory bowel diseases such as ulcerative colitis, crohn’s disease, colon cancer, amobebiasis by both systemic and topical delivery of dug. This article review a detailed study about disease of colon, diagnosis of diseases of colon, anatomy of colon, factors affecting ...

  17. Multi-Stage System for Automatic Target Recognition

    Science.gov (United States)

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

    2010-01-01

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

  18. Thermal hydraulics of accelerator driven system windowless targets

    Directory of Open Access Journals (Sweden)

    Bruno ePanella

    2015-07-01

    Full Text Available The study of the fluid dynamics of the windowless spallation target of an Accelerator Driven System (ADS is presented. Several target mockup configurations have been investigated: the first one was a symmetrical target, that was made by two concentric cylinders, the other configurations are not symmetrical. In the experiments water has been used as hydraulic equivalent to lead-bismuth eutectic fluid. The experiments have been carried out at room temperature and flow rate up to 24 kg/s. The fluid velocity components have been measured by an ultrasound technique. The velocity field of the liquid within the target region either for the approximately axial-symmetrical configuration or for the not symmetrical ones as a function of the flow rate and the initial liquid level is presented. A comparison of experimental data with the prediction of the finite volume FLUENT code is also presented. Moreover the results of a 2D-3D numerical analysis that investigates the effect on the steady state thermal and flow fields due to the insertion of guide vanes in the windowless target unit of the EFIT project ADS nuclear reactor are presented, by analysing both the cold flow case (absence of power generation and the hot flow case (nominal power generation inside the target unit.

  19. CRISPR/Cas9 systems targeting β-globin and CCR5 genes have substantial off-target activity

    National Research Council Canada - National Science Library

    Cradick, Thomas J; Fine, Eli J; Antico, Christopher J; Bao, Gang

    2013-01-01

    .... Here we demonstrate that CRISPR/Cas9 systems targeting the human hemoglobin β and C-C chemokine receptor type 5 genes have substantial off-target cleavage, especially within the hemoglobin δ...

  20. Progress in brain targeting drug delivery system by nasal route.

    Science.gov (United States)

    Khan, Abdur Rauf; Liu, Mengrui; Khan, Muhammad Wasim; Zhai, Guangxi

    2017-09-06

    The blood-brain barrier (BBB) restricts the transport of potential therapeutic moieties to the brain. Direct targeting the brain via olfactory and trigeminal neural pathways by passing the BBB has gained an important consideration for delivery of wide range of therapeutics to brain. Intranasal route of transportation directly delivers the drugs to brain without systemic absorption, thus avoiding the side effects and enhancing the efficacy of neurotherapeutics. Over the last several decades, different drug delivery systems (DDSs) have been studied for targeting the brain by the nasal route. Novel DDSs such as nanoparticles (NPs), liposomes and polymeric micelles have gained potential as useful tools for targeting the brain without toxicity in nasal mucosa and central nervous system (CNS). Complex geometry of the nasal cavity presented a big challenge to effective delivery of drugs beyond the nasal valve. Recently, pharmaceutical firms utilized latest and emerging nasal drug delivery technologies to overcome these barriers. This review aims to describe the latest development of brain targeted DDSs via nasal administration. Carbopol 934p (PubChem CID: 6581) Carboxy methylcellulose (PubChem CID: 24748) Penetratin (PubChem CID: 101111470) Poly lactic-co-glycolic acid (PubChem CID: 23111554) Tween 80 (PubChem CID: 5284448). Copyright © 2017. Published by Elsevier B.V.

  1. Neural Network Target Identification System for False Alarm Reduction

    Science.gov (United States)

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

    2009-01-01

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

  2. Analysis of an XADS Target with the System Code TRACE

    Energy Technology Data Exchange (ETDEWEB)

    Jaeger, Wadim; Sanchez Espinoza, Victor H. [Forschungszentrum Karlsruhe GmbH, Institute for Reactor Safety, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen (Germany); Feng, Bo [Massachusetts Institute of Technology, 77 Massachusetts Avenue, NW12-219, Cambridge, MA 02139 (United States)

    2008-07-01

    Accelerator-driven systems (ADS) present an option to reduce the radioactive waste of the nuclear industry. The experimental Accelerator-Driven System (XADS) has been designed to investigate the feasibility of using ADS on an industrial scale to burn minor actinides. The target section lies in the middle of the subcritical core and is bombarded by a proton beam to produce spallation neutrons. The thermal energy produced from this reaction requires a heat removal system for the target section. The target is cooled by liquid lead-bismuth-eutectics (LBE) in the primary system which in turn transfers the heat via a heat exchanger (HX) to the secondary coolant, Diphyl THT (DTHT), a synthetic diathermic fluid. Since this design is still in development, a detailed investigation of the system is necessary to evaluate the behavior during normal and transient operations. Due to the lack of experimental facilities and data for ADS, the analyses are mostly done using thermal hydraulic codes. In addition to evaluating the thermal hydraulics of the XADS, this paper also benchmarks a new code developed by the NRC, TRACE, against other established codes. The events used in this study are beam power switch-on/off transients and a loss of heat sink accident. The obtained results from TRACE were in good agreement with the results of various other codes. (authors)

  3. Cooperative nanomaterial system to sensitize, target, and treat tumors

    Science.gov (United States)

    Park, Ji-Ho; von Maltzahn, Geoffrey; Xu, Mary Jue; Fogal, Valentina; Kotamraju, Venkata Ramana; Ruoslahti, Erkki; Bhatia, Sangeeta N.; Sailor, Michael J.

    2010-01-01

    A significant barrier to the clinical translation of systemically administered therapeutic nanoparticles is their tendency to be removed from circulation by the mononuclear phagocyte system. The addition of a targeting ligand that selectively interacts with cancer cells can improve the therapeutic efficacy of nanomaterials, although these systems have met with only limited success. Here, we present a cooperative nanosystem consisting of two discrete nanomaterials. The first component is gold nanorod (NR) “activators” that populate the porous tumor vessels and act as photothermal antennas to specify tumor heating via remote near-infrared laser irradiation. We find that local tumor heating accelerates the recruitment of the second component: a targeted nanoparticle consisting of either magnetic nanoworms (NW) or doxorubicin-loaded liposomes (LP). The targeting species employed in this work is a cyclic nine-amino acid peptide LyP-1 (Cys-Gly-Asn-Lys-Arg-Thr-Arg-Gly-Cys) that binds to the stress-related protein, p32, which we find to be upregulated on the surface of tumor-associated cells upon thermal treatment. Mice containing xenografted MDA-MB-435 tumors that are treated with the combined NR/LyP-1LP therapeutic system display significant reductions in tumor volume compared with individual nanoparticles or untargeted cooperative system. PMID:20080556

  4. Treat-to-target in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Mosca, Marta; Boumpas, Dimitrios T; Bruce, Ian N

    2013-01-01

    Multiple clinical trials performed over twenty years in the treatment of rheumatoid arthritis (RA) have clearly demonstrated that patients have better outcomes if their disease activity at each time-point for follow-up includes a pre-specified target. A European SLE expert panel met in Zurich...... on May 8, 2012 to discuss whether a treat-to-target approach could be applied in the treatment of systemic lupus erythematosus (SLE) (T2T/SLE), define a research agenda, and establish a plan for moving forward. In the present paper, observations raised at the meeting and literature data on potential...... therapeutic targets are reported. The working group on T2T/SLE will continue work over the coming year....

  5. Anaesthesia synchronization software: target controlled infusion system evaluation.

    Science.gov (United States)

    Bressan, Nadja; Paulo Moreira, A; Amorim, Pedro; Nunes, Catarina S

    2010-01-01

    Target Controlled Infusion (TCI) systems are based in drug Pharmacokinetic (Pk) and Pharmacodynamic (Pd) models implemented in an algorithm to drive an infusion device. Several studies had compare manual titration of anesthesia and TCI system use; some studies evaluate the performance of the control algorithms for TCI systems, and a considerable number of studies assess the performance of Pk/Pd models implemented into TCI systems. This study presents a set of tests to validate the performance of a TCI system as a computer-aided. The goal of the current study was to assess the performance of the TCI system, Anaesthesia Synchronization Software (ASYS), on clinical set up to evaluate communication consistence (computer - infusion device) and controller performance in real time. These measures provided quantitative and qualitative evidences of software robustness and accuracy to be used at clinical environment.

  6. Design and Validation of the APT Target/Blanket System

    Science.gov (United States)

    Waters, L. S.

    1998-04-01

    The Accelerator Production of Tritium (APT) project is now under development as part of DOE's dual track strategy for the replenishment of the nation's tritium supply. APT produces tritium through the He^3(n,p)t reaction, with neutrons generated in a tungsten spallation target and moderated in a surrounding lead blanket filled with He^3 gas tubes. A 100 mA, 1.7 GeV linac provides source protons for the target, and a separate tritium extraction facility continually processes the helium gas stream. Within APT, the Target/Blanket and Materials Engineering Development and Demonstration Project has primary responsibility for validating the neutronics performance of the Target/Blanket system, and for addressing materials issues for all of APT. The APT target design and T/B & Materials ED&D activities will be briefly reviewed, with special emphasis placed on activities leading to the development and validation of radiation transport codes and nuclear data used in the APT design. These include the evolution of the MCNPX simulation code, as well as theoretical work and cross section measurements now underway to support high energy nuclear data library evaluations. Large scale benchmarking measurements completed or planned at LANSCE, the Brookhaven AGS, and Saturne will also be discussed.

  7. High Resolution Software Defined Radar System for Target Detection

    Directory of Open Access Journals (Sweden)

    S. Costanzo

    2013-01-01

    Full Text Available The Universal Software Radio Peripheral USRP NI2920, a software defined transceiver so far mainly used in Software Defined Radio applications, is adopted in this work to design a high resolution L-Band Software Defined Radar system. The enhanced available bandwidth, due to the Gigabit Ethernet interface, is exploited to obtain a higher slant-range resolution with respect to the existing Software Defined Radar implementations. A specific LabVIEW application, performing radar operations, is discussed, and successful validations are presented to demonstrate the accurate target detection capability of the proposed software radar architecture. In particular, outdoor and indoor test are performed by adopting a metal plate as reference structure located at different distances from the designed radar system, and results obtained from the measured echo are successfully processed to accurately reveal the correct target position, with the predicted slant-range resolution equal to 6 m.

  8. Design, Operations, and Safety Report for the MERIT Target System

    Energy Technology Data Exchange (ETDEWEB)

    Graves, Van B [ORNL; Spampinato, Philip Thomas [ORNL

    2007-09-01

    The Mercury Intense Target Project (MERIT) is a proof-of-principal experiment to determine the feasibility of using a free-jet of Hg as a spallation target in a Neutrino Factory or a Muon Collider facility. The 1-cm-diameter, 20-m/sec jet will be generated inside a 15-Tesla magnetic field, and high-speed optical diagnostics will be used to photograph the interaction between the Hg jet and a 24-GeV proton beam.The experiment is scheduled to be conducted at CERN in 2007. ORNL is responsible for the design, fabrication, and testing of a system to deliver the Hg jet within the confines of the 15-cm magnet bore. This report documents the functional and safety requirements of the Hg system along with descriptions of its interfaces to the other experimental equipment.

  9. The Endocannabinoid System as a Therapeutic Target in Glaucoma

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Cairns

    2016-01-01

    Full Text Available Glaucoma is an irreversible blinding eye disease which produces progressive retinal ganglion cell (RGC loss. Intraocular pressure (IOP is currently the only modifiable risk factor, and lowering IOP results in reduced risk of progression of the disorder. The endocannabinoid system (ECS has attracted considerable attention as a potential target for the treatment of glaucoma, largely due to the observed IOP lowering effects seen after administration of exogenous cannabinoids. However, recent evidence has suggested that modulation of the ECS may also be neuroprotective. This paper will review the use of cannabinoids in glaucoma, presenting pertinent information regarding the pathophysiology of glaucoma and how alterations in cannabinoid signalling may contribute to glaucoma pathology. Additionally, the mechanisms and potential for the use of cannabinoids and other novel agents that target the endocannabinoid system in the treatment of glaucoma will be discussed.

  10. Circular Orbit Target Capture Using Space Tether-Net System

    Directory of Open Access Journals (Sweden)

    Guang Zhai

    2013-01-01

    Full Text Available The space tether-net system for on-orbit capture is proposed in this paper. In order to research the dynamic behaviors during system deployment, both free and nonfree deployment dynamics in circular orbit are developed; the system motion with respect to Local Vertical and Local Horizontal frame is also researched with analysis and simulation. The results show that in the case of free deployment, the capture net follows curve trajectories due to the relative orbit dynamic perturbation, and the initial deployment velocities are planned by state transformation equations for static and floating target captures; in the case of non-free deployment, the system undergoes an altitude libration along the Local Vertical, and the analytical solutions that describe the attitude libration are obtained by using variable separation and integration. Finally, the dynamics of postdeployment system is also proved marginally stable if the critical initial conditions are satisfied.

  11. Overview of target systems for the Spallation Neutron Source

    Energy Technology Data Exchange (ETDEWEB)

    Gabriel, Tony A.; Barnes, John M.; Charlton, Lowell A. [and others; DiStefano, James; Farrell, Ken; Haines, John; Johnson, Jeffrey O.; Mansur, Louis K.; Pawel, Steve J.; Siman-Tov, Moshe; Taleyarkhan, Rusi; Wendel, Mark W.; McManamy, Thomas J.; Rennich, Mark J.

    1997-01-01

    The purpose and requirements of target systems as well as the technologies that are being utilized to design and build a state-of-the-art neutron spallation source, the Spallation Neutron Source (SNS), are discussed. Emphasis is given to the technology issues that present the greatest scientific challenges. The present facility configuration, ongoing analysis, and the planned hardware research and development program are also described.

  12. Pogostick: a new versatile piggyBac vector for inducible gene over-expression and down-regulation in emerging model systems.

    Directory of Open Access Journals (Sweden)

    Bin Chen

    2011-04-01

    Full Text Available Non-traditional model systems need new tools that will enable them to enter the field of functional genetics. These tools should enable the exploration of gene function, via knock-downs of endogenous genes, as well as over-expression and ectopic expression of transgenes.We constructed a new vector called Pogostick that can be used to over-express or down-regulate genes in organisms amenable to germ line transformation by the piggyBac transposable element. Pogostick can be found at www.addgene.org, a non-profit plasmid repository. The vector currently uses the heat-shock promoter Hsp70 from Drosophila to drive transgene expression and, as such, will have immediate applicability to organisms that can correctly interpret this promotor sequence. We detail how to clone candidate genes into this vector and test its functionality in Drosophila by targeting a gene coding for the fluorescent protein DsRed. By cloning a single DsRed copy into the vector, and generating transgenic lines, we show that DsRed mRNA and protein levels are elevated following heat-shock. When cloning a second copy of DsRed in reverse orientation into a flanking site, and transforming flies constitutively expressing DsRed in the eyes, we show that endogenous mRNA and protein levels drop following heat-shock. We then test the over-expression vector, containing the complete cDNA of Ultrabithorax (Ubx gene, in an emerging model system, Bicyclus anynana. We produce a transgenic line and show that levels of Ubx mRNA expression rise significantly following a heat-shock. Finally, we show how to obtain genomic sequence adjacent to the Pogostick insertion site and to estimate transgene copy number in genomes of transformed individuals.This new vector will allow emerging model systems to enter the field of functional genetics with few hurdles.

  13. Targeting the immune system to treat hypertension: where are we?

    Science.gov (United States)

    Gooch, Jennifer L; Sharma, Avadhesh C

    2014-09-01

    Research over the past decade has significantly deepened our understanding of mechanisms that drive the development of hypertension. In particular, a novel paradigm of inflammation as a common mediator of cardiovascular and kidney disease has emerged. This review will summarize the role of the immune system in cardiovascular disease, explore some of the most promising new therapeutic directions and consider their potential as new treatments for hypertension. Recent data continue to demonstrate that targeting the immune system can prevent hypertension in a variety of experimental models. Tempering the enthusiasm for a long-awaited new approach to treating hypertension is decades of clinical data, showing that classic immunosuppression regimens are associated with significant side-effects - including cardiovascular disease - that effectively preclude their use in the setting of chronic hypertension. New, more specific therapies are being developed that target cytokines including IL-17, IL-6 and TNFα. Preclinical data convincingly demonstrate a key role for the immune system and specific cytokine mediators. Several biotherapeutics targeting these pathways are on the market and more are in development. Side-effects, however, continue to resemble those of classic immunosuppressants, highlighting the challenge of translating these research advances into new therapies for hypertension. http://links.lww.com/CONH/A9.

  14. New perspective for phage display as an efficient and versatile technology of functional proteomics.

    Science.gov (United States)

    Li, Wei; Caberoy, Nora B

    2010-01-01

    Phage display with antibody libraries has been widely used with versatile applications. However, phage display with cDNA libraries is rare and inefficient. Because of uncontrollable reading frames and stop codons in cDNA repertoires, high percentage of phage clones identified from conventional cDNA libraries are non-open reading frames (non-ORFs) encoding unnatural short peptides with minimal implications in protein networks. Consequently, phage display has not been used as a technology of functional proteomics to elucidate protein-protein interactions like yeast two-hybrid system and mass spectrometry-based technologies. Several strategies, including C-terminal display and ORF cDNA libraries, have been explored to circumvent the technical problem. The accumulative endeavors eventually led to the efficient elucidation of a large number of tubby- and phosphatidylserine-binding proteins in recent studies by ORF phage display with minimal reading frame issue. ORF phage display inherits all the versatile applications of antibody phage display, but enables efficient identification of real endogenous proteins with efficiency, sensitivity, and accuracy comparable to other technologies of functional proteomics. Its ELISA-like procedure can be conveniently adapted by individual laboratories or fully automated for high-throughput screening. Thus, ORF phage display is an efficient, sensitive, versatile, and convenient technology of functional proteomics for elucidation of global and pathway-specific protein-protein interactions, disease mechanisms, or therapeutic targets.

  15. Detection of Perfectly-Conducting Targets with Airborne Electromagnetic Systems

    Science.gov (United States)

    Smiarowski, Adam

    A significant problem with exploring for electrically conductive mineral deposits with airborne electromagnetic (AEM) methods is that many of the most valuable sulphide deposits are too conductive to be detected with conventional systems. High-grade sulphide deposits with bulk electrical conductivities on the order of 100,000 S/m can appear as "perfect conductors" to most EM systems because the decay of secondary fields (the "time constant" of the deposit) generated in the target by the system transmitter takes much longer than the short measuring time of EM systems. Their EM response is essentially undetectable with off-time measurements. One solution is to make measurements during the transmitter on-time when the secondary field of the target produced by magnetic flux exclusion is large. The difficulty is that the secondary field must be measured in the presence of a primary field which is orders of magnitude larger. The goal of this thesis is to advance the methodology of making AEM measurements during transmitter on-time by analysing experimental data from three different AEM systems. The first system analysed is a very large separation, two helicopter system where geometry is measured using GPS sensors. In order to calculate the primary field at the receiver with sufficient accuracy, the very large (nominally 400 m) separation requires geometry to be known to better than 1 m. Using the measured geometry to estimate and remove the primary field, I show that a very conductive target can be detected at depths of 200m using the total secondary field. I then used fluxgate magnetometers to correct for receiver rotation which allowed the component of the secondary field to be determined. The second system I examined was a large separation fixed-wing AEM system. Using a towed receiver bird with a smaller (≈ 135m) separation, the geometry must be known much more accurately. In the absence of direct measurement of this geometry, I used a least-squares prediction

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

    Science.gov (United States)

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

    2017-05-01

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

  17. Collinear technology for a holographic versatile disk

    Science.gov (United States)

    Horimai, Hideyoshi; Tan, Xiaodi

    2006-02-01

    A novel reading and writing technology for a holographic versatile disk (HVD) system called collinear technology is developed. With this method a two-dimensional data page can be recorded as volumetric holograms generated by a reference beam and a signal beam that are bundled on the same axis and that are irradiated on the recording medium through a single objective lens. The multiplex recording and reconstruction process is demonstrated, and it is shown that the optical configuration and the dichroic medium disk structure are suitable for a compact system. With the HVD's special structure, the system can use a servo to focus, track, and locate the reading and writing addresses. A unique selectable-capacity recording format of a HVD and its standardization activity are also introduced. This method will enable us to construct a small HVD system with CD and DVD upper compatibilities.

  18. A Versatile System for High-Throughput In Situ X-ray Screening and Data Collection of Soluble and Membrane-Protein Crystals

    Energy Technology Data Exchange (ETDEWEB)

    Broecker, Jana; Klingel, Viviane; Ou, Wei-Lin; Balo, Aidin R.; Kissick, David J.; Ogata, Craig M.; Kuo, Anling; Ernst, Oliver P.

    2016-10-12

    In recent years, in situ data collection has been a major focus of progress in protein crystallography. Here, we introduce the Mylar in situ method using Mylar-based sandwich plates that are inexpensive, easy to make and handle, and show significantly less background scattering than other setups. A variety of cognate holders for patches of Mylar in situ sandwich films corresponding to one or more wells makes the method robust and versatile, allows for storage and shipping of entire wells, and enables automated crystal imaging, screening, and goniometerbased X-ray diffraction data-collection at room temperature and under cryogenic conditions for soluble and membrane-protein crystals grown in or transferred to these plates. We validated the Mylar in situ method using crystals of the water-soluble proteins hen egg-white lysozyme and sperm whale myoglobin as well as the 7-transmembrane protein bacteriorhodopsin from Haloquadratum walsbyi. In conjunction with current developments at synchrotrons, this approach promises high-resolution structural studies of membrane proteins to become faster and more routine.

  19. TMAP - A Versatile Mobile Robot

    Science.gov (United States)

    Weiss, Joel A.; Simmons, Richard K.

    1989-03-01

    TMAP, the Teleoperated Mobile All-purpose Platform, provides the Army with a low cost, light weight, flexibly designed, modularly expandable platform for support of maneuver forces and light infantry units. The highly mobile, four wheel drive, diesel-hydraulic platform is controllable at distances of up to 4km from a portable operator control unit using either fiber optic or RF control links. The Martin Marietta TMAP system is based on a hierarchical task decomposition Real-time Control System architecture that readily supports interchange of mission packages and provides the capability for simple incorporation of supervisory control concepts leading to increased system autonomy and resulting force multiplication. TMAP has been designed to support a variety of missions including target designation, anti-armor, anti-air, countermine, and reconnaissance/surveillance. As a target designation system TMAP will provide the soldier with increased survivability and effectiveness by providing substantial combat standoff, and the firepower effectiveness of several manual designator operators. Force-on-force analysis of simulated TMAP engagements indicate that TMAP should provide significant force multiplication for the Army in Air-Land Battle 2000.

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

    Science.gov (United States)

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

    2018-01-01

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

  1. Versatile Supramolecular Gene Vector Based on Host-Guest Interaction

    NARCIS (Netherlands)

    Liu, Jia; Hennink, Wim E.; Van Steenbergen, Mies J.; Zhuo, Renxi; Jiang, Xulin

    2016-01-01

    It is a great challenge to arrange multiple functional components into one gene vector system to overcome the extra- and intracellular obstacles for gene therapy. In this study, we developed a supramolecular approach for constructing a versatile gene delivery system composed of adamantyl-terminated

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

    Energy Technology Data Exchange (ETDEWEB)

    Vetter, Douglas W

    2016-02-01

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

  3. Role of the immune system in hypertensive target organ damage.

    Science.gov (United States)

    Kvakan, Heda; Luft, Friedrich C; Muller, Dominik N

    2009-10-01

    Recent advances in our understanding of cardiovascular diseases clearly show that inflammation and activation of immunity are central features in the pathogenesis of atherosclerosis, ischemic myocardial injury, and also in hypertension-induced target organ damage. However, the idea that special immune cells could regulate immune responses in these conditions in favor of minimizing disease is a novel concept. Regulatory T cells have unique immune modulatory properties that offer an attractive alternative to common immunosuppressant drugs. Their application in animal models of autoimmunity and neoplastic conditions offers exciting therapeutic avenues. Thus, with the use of regulatory T cells in hypertension-induced target organ damage enables new insights into the pathophysiologic mechanisms and widen our knowledge of the role of the immune system in cardiovascular disease. The aim of this review was to summarize and discuss some of the most recent insights and put them into a perspective based on well-known interactions between immunity and hypertensive damage.

  4. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    Energy Technology Data Exchange (ETDEWEB)

    Fillat, Cristina, E-mail: cristina.fillat@crg.es; Jose, Anabel; Ros, Xavier Bofill-De; Mato-Berciano, Ana; Maliandi, Maria Victoria; Sobrevals, Luciano [Programa Gens i Malaltia, Centre de Regulació Genòmica-CRG, UPF, Parc de Recerca Biomedica de Barcelona-PRBB and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona (Spain)

    2011-01-18

    The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.

  5. Environmental Management System (EMS) objectives & targets annual results summary :

    Energy Technology Data Exchange (ETDEWEB)

    Vetter, Douglas Walter

    2013-02-01

    Sandia National Laboratories/New Mexicos (SNL/NM) Environmental Management System is the integrated approach for members of the workforce to identify and manage environmental risks. Each Fiscal Year (FY) SNL/NM performs an analysis to identify environmental aspects, and the environmental programs associated with them are charged with the task of routinely monitoring and measuring the objectives and targets that are established to mitigate potential impacts of SNL/NMs operations on the environment. An annual summary of the results achieved towards meeting established objectives and targets provides a connection to, and rational for, annually revised environmental aspects. The purpose of this document is to summarize the results achieved and documented in FY2012.

  6. Environmental management system objectives & targets results summary FY 2013

    Energy Technology Data Exchange (ETDEWEB)

    Vetter, Douglas Walter [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-04-01

    Sandia National Laboratories/New Mexicos (SNL/NM) Environmental Management System is the integrated approach for members of the workforce to identify and manage environmental risks. Each Fiscal Year (FY) SNL/NM performs an analysis to identify environmental aspects, and the environmental programs associated with them are charged with the task of routinely monitoring and measuring the objectives and targets that are established to mitigate potential impacts of SNL/NMs operations on the environment. An annual summary of the results achieved towards meeting established Sandia Corporation and SNL/NM Site-specific objectives and targets provides a connection to, and rational for, annually revised environmental aspects. The purpose of this document is to summarize the results achieved and documented in FY2013.

  7. Why Targeted Therapies are Necessary for Systemic Lupus Erythematosus

    Science.gov (United States)

    Durcan, Laura; Petri, Michelle

    2016-01-01

    Systemic lupus erythematosus (SLE) continues to have important morbidity and accelerated mortality despite therapeutic advances. Targeted therapies offer the possibility of improved efficacy with fewer side-effects. Current management strategies rely heavily on non-specific immunosuppressive agents. Prednisone, in particular, is responsible for a considerable burden of later organ damage. There are a multitude of diverse mechanisms of disease activity, immunogenic abnormalities and clinical manifestations to take into consideration in SLE. Many targeted agents with robust mechanistic pre-clinical data and promising early phase studies have ultimately been disappointing in phase III randomized controlled studies. Recent efforts have focused on B cell therapies, in particular given the success of belimumab in clinical trials, with limited success. We remain optimistic regarding other specific therapies being evaluated including interferon alpha blockade. It is likely that in SLE, given the heterogeneity of the population involved, precision medicine is needed, rather than expecting that any single biologic will be universally effective. PMID:27497251

  8. Pathogenic Inflammation and Its Therapeutic Targeting in Systemic Lupus Erythematosus

    Science.gov (United States)

    Gottschalk, Timothy A.; Tsantikos, Evelyn; Hibbs, Margaret L.

    2015-01-01

    Systemic lupus erythematosus (SLE, lupus) is a highly complex and heterogeneous autoimmune disease that most often afflicts women in their child-bearing years. It is characterized by circulating self-reactive antibodies that deposit in tissues, including skin, kidneys, and brain, and the ensuing inflammatory response can lead to irreparable tissue damage. Over many years, clinical trials in SLE have focused on agents that control B- and T-lymphocyte activation, and, with the single exception of an agent known as belimumab which targets the B-cell survival factor BAFF, they have been disappointing. At present, standard therapy for SLE with mild disease is the agent hydroxychloroquine. During disease flares, steroids are often used, while the more severe manifestations with major organ involvement warrant potent, broad-spectrum immunosuppression with cyclophosphamide or mycophenolate. Current treatments have severe and dose-limiting toxicities and thus a more specific therapy targeting a causative factor or signaling pathway would be greatly beneficial in SLE treatment. Moreover, the ability to control inflammation alongside B-cell activation may be a superior approach for disease control. There has been a recent focus on the innate immune system and associated inflammation, which has uncovered key players in driving the pathogenesis of SLE. Delineating some of these intricate inflammatory mechanisms has been possible with studies using spontaneous mouse mutants and genetically engineered mice. These strains, to varying degrees, exhibit hallmarks of the human disease and therefore have been utilized to model human SLE and to test new drugs. Developing a better understanding of the initiation and perpetuation of disease in SLE may uncover suitable novel targets for therapeutic intervention. Here, we discuss the involvement of inflammation in SLE disease pathogenesis, with a focus on several key proinflammatory cytokines and myeloid growth factors, and review the known

  9. Observing Solar System Targets with the James Webb Space Telescope

    Science.gov (United States)

    Norwood, James; Hammel, Heidi; Milam, Stefanie; Stansberry, John; Lunine, Jonathan; Chanover, Nancy; Hines, Dean; Sonneborn, George; Tiscareno, Matthew; Brown, Michael; Ferruit, Pierre

    2014-11-01

    With its anticipated launch date in October 2018, the James Webb Space Telescope will tremendously advance astronomy in the near- and mid-infrared, offering sensitivity and spatial/spectral resolution greatly surpassing its predecessors. We have developed a white paper that explores observations of Solar System targets with JWST, with the goals of highlighting anticipated Solar System capabilities, motivation of potential observers, and encouragement of further interest and discussion. This paper presents the most current information available concerning JWST instrument properties and observing techniques relevant to planetary science. It also illustrates example observing scenarios for a wide variety of Solar System objects, including the giant planets, Kuiper Belt objects, Europa, Titan, and more. We are also collaborating with a set of focus groups that have expanded upon this work, producing a series of further white papers dealing with individual subdisciplines. This work has been supported by NASA Grant NAG5-12457.

  10. The new control system of the SPS target sector

    CERN Document Server

    Carlier, E; Mecredy, N; O'Leary, J

    1999-01-01

    The SPS, the Super Proton Synchrotron at CERN, is an accelerator originally designed and commissioned in 1976 for protons. The control system of the SPS target stations, beam absorbers and other aperture limiting devices was developed in the seventies. It was mainly based on home made electronics and equipment dependent software. With time, this electronics has become obsolete, difficult to maintain in operation and not suitable for integration into a modern control system. In 1997, a project was set up to modernise the electronics and the related software. The new control system is largely based on standard industrial hardware and software components. SIEMENS Simatic S7-300 programmable logic controllers have been used as equipment controllers and connected through PROFIBUS to a Windows-NT front-end PC running the SIEMENS WinCC SCADA package which acts as local controller and remote access gateway. This fully industrial solution has been successfully integrated into the actual SPS accelerator control infrast...

  11. Flow cytometry as the spearhead for delivering sustainable and versatile laboratory services to HIV-burdened health care systems of the developing world: a Caribbean model.

    Science.gov (United States)

    Abayomi, E Akinola; Landis, R Clive

    2008-01-01

    HIV is targeting the developing nations of the world, threatening their economic development, overwhelming public health systems, and depleting human capital. The Caribbean is no exception, with the second highest incidence of HIV/AIDS outside Sub-Saharan Africa, sharing similar mixed fortunes from a postcolonial heritage, limited resources, and an HIV population dispersed in small population centers. Here we share the experience of Barbados, an island state of 280,000 people, in mounting a holistic and sustainable program against HIV/AIDS. At the forefront of this response has been the growth in clinical flow cytometry used for CD4 monitoring, which has prompted a welcome expansion in diagnostic capacity even beyond HIV/AIDS. A pan-Caribbean extension to Barbados' program has been the founding of the Caribbean Cytometry & Analytical Society (CCAS), which acts as a regional forum to accelerate technology transfer and develop the human resources needed to mount an effective response against HIV/AIDS. The 4th CCAS workshop in 2007 produced a consensus statement on the desirable characteristics for a "diagnostic dream machine": a simple-to-use, rugged flow cytometer capable of carrying out multiple diagnostic functions at the point of patient care in rural or island settings of the developing world, including CD4 count, blood count, and opportunistic infections, without the need for a supply cold-chain or dependable power source. It is our ambitious vision that the spread of flow cytometry, primarily to monitor CD4 in HIV/AIDS, can act as a Trojan horse to deliver better general and specialized diagnostic services to the developing world. Copyright 2008 Clinical Cytometry Society.

  12. Sine systemate chaos? A versatile tool for earthworm taxonomy: non-destructive imaging of freshly fixed and museum specimens using micro-computed tomography.

    Science.gov (United States)

    Fernández, Rosa; Kvist, Sebastian; Lenihan, Jennifer; Giribet, Gonzalo; Ziegler, Alexander

    2014-01-01

    In spite of the high relevance of lumbricid earthworms ('Oligochaeta': Lumbricidae) for soil structure and functioning, the taxonomy of this group of terrestrial invertebrates remains in a quasi-chaotic state. Earthworm taxonomy traditionally relies on the interpretation of external and internal morphological characters, but the acquisition of these data is often hampered by tedious dissections or restricted access to valuable and rare museum specimens. The present state of affairs, in conjunction with the difficulty of establishing primary homologies for multiple morphological features, has led to an almost unrivaled instability in the taxonomy and systematics of certain earthworm groups, including Lumbricidae. As a potential remedy, we apply for the first time a non-destructive imaging technique to lumbricids and explore the future application of this approach to earthworm taxonomy. High-resolution micro-computed tomography (μCT) scanning of freshly fixed and museum specimens was carried out using two cosmopolitan species, Aporrectodea caliginosa and A. trapezoides. By combining two-dimensional and three-dimensional dataset visualization techniques, we demonstrate that the morphological features commonly used in earthworm taxonomy can now be analyzed without the need for dissection, whether freshly fixed or museum specimens collected more than 60 years ago are studied. Our analyses show that μCT in combination with soft tissue staining can be successfully applied to lumbricid earthworms. An extension of the approach to other families is poised to strengthen earthworm taxonomy by providing a versatile tool to resolve the taxonomic chaos currently present in this ecologically important, but taxonomically neglected group of terrestrial invertebrates.

  13. Efficiency evaluation of proposed EAGLE target acquisition systems

    Science.gov (United States)

    Taylor, William D.; Evans, Chris J.; Schnetler, Hermine

    2008-07-01

    Efficient assignment of science targets to the individual channels of a multi-object astronomical instrument, such as EAGLE for the European Extremely Large Telescope (E-ELT), is crucial for maximising the utility of the instrument. This paper presents the results obtained by modelling the efficiencies of various pick-off system concepts: free standing Pick-Off Mirrors (POMs), POMs at the tip of moving arms, or a tiled focal plane. Consideration is also taken of the way in which the freestanding POMs are placed: by a pick and place robot, or a swarm of micro autonomous robots. Allocation algorithms were developed for each concept and applied to target fields which are representative of EAGLE's likely science cases. It is shown how the results of the modelling were used to generate a new system comparison criterion called Allocation Flexibility and how this influences the choice of the baseline solution. The allocation flexibility suggests that the best system will use free standing POMs with as small a footprint as possible, which reflect light to a raised beam steering mirror.

  14. Target-Tracking Camera for a Metrology System

    Science.gov (United States)

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

    2009-01-01

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

  15. Solute carrier transporters: potential targets for digestive system neoplasms.

    Science.gov (United States)

    Xie, Jing; Zhu, Xiao Yan; Liu, Lu Ming; Meng, Zhi Qiang

    2018-01-01

    Digestive system neoplasms are the leading causes of cancer-related death all over the world. Solute carrier (SLC) superfamily is composed of a series of transporters that are ubiquitously expressed in organs and tissues of digestive systems and mediate specific uptake of small molecule substrates in facilitative manner. Given the important role of SLC proteins in maintaining normal functions of digestive system, dysregulation of these protein in digestive system neoplasms may deliver biological and clinical significance that deserves systemic studies. In this review, we critically summarized the recent advances in understanding the role of SLC proteins in digestive system neoplasms. We highlighted that several SLC subfamilies, including metal ion transporters, transporters of glucose and other sugars, transporters of urea, neurotransmitters and biogenic amines, ammonium and choline, inorganic cation/anion transporters, transporters of nucleotide, amino acid and oligopeptide organic anion transporters, transporters of vitamins and cofactors and mitochondrial carrier, may play important roles in mediating the initiation, progression, metastasis, and chemoresistance of digestive system neoplasms. Proteins in these SLC subfamilies may also have diagnostic and prognostic values to particular cancer types. Differential expression of SLC proteins in tumors of digestive system was analyzed by extracting data from human cancer database, which revealed that the roles of SLC proteins may either be dependent on the substrates they transport or be tissue specific. In addition, small molecule modulators that pharmacologically regulate the functions of SLC proteins were discussed for their possible application in the treatment of digestive system neoplasms. This review highlighted the potential of SLC family proteins as drug target for the treatment of digestive system neoplasms.

  16. Targeting the Eph System with Peptides and Peptide Conjugates.

    Science.gov (United States)

    Riedl, Stefan J; Pasquale, Elena B

    2015-01-01

    Eph receptor tyrosine kinases and ephrin ligands constitute an important cell communication system that controls development, tissue homeostasis and many pathological processes. Various Eph receptors/ephrins are present in essentially all cell types and their expression is often dysregulated by injury and disease. Thus, the 14 Eph receptors are attracting increasing attention as a major class of potential drug targets. In particular, agents that bind to the extracellular ephrin-binding pocket of these receptors show promise for medical applications. This pocket comprises a broad and shallow groove surrounded by several flexible loops, which makes peptides particularly suitable to target it with high affinity and selectivity. Accordingly, a number of peptides that bind to Eph receptors with micromolar affinity have been identified using phage display and other approaches. These peptides are generally antagonists that inhibit ephrin binding and Eph receptor/ ephrin signaling, but some are agonists mimicking ephrin-induced Eph receptor activation. Importantly, some of the peptides are exquisitely selective for single Eph receptors. Most identified peptides are linear, but recently the considerable advantages of cyclic scaffolds have been recognized, particularly in light of potential optimization towards drug leads. To date, peptide improvements have yielded derivatives with low nanomolar Eph receptor binding affinity, high resistance to plasma proteases and/or long in vivo half-life, exemplifying the merits of peptides for Eph receptor targeting. Besides their modulation of Eph receptor/ephrin function, peptides can also serve to deliver conjugated imaging and therapeutic agents or various types of nanoparticles to tumors and other diseased tissues presenting target Eph receptors.

  17. Cooling System for the Merit High-Power Target Experiment

    CERN Document Server

    Haug, F; Silva, P; Pezzeti, M; Pavlov, O; Pirotte, O; Metselaar, J; Efthymiopoulos, I; Fabich, A; Lettry, J; Kirk, H G; McDonald, K T; Titus, P; Bennett, J R J

    2010-01-01

    MERIT is a proof-of-principle experiment of a target station suitable as source for future muon colliders or neutrino factories. When installed at the CERN (European Organization for Nuclear Research) PS (Proton Synchrotron)complex fast-extracted high-intensity proton beams intercepted a free mercury jet inside a normal-conducting, pulsed 15-T capture solenoid magnet cooled with liquid nitrogen. Up to 25 MJ of Joule heat was dissipated in the magnet during a pulse. The fully automated, remotely controlled cryogenic system of novel design permitted the transfer of nitrogen by the sole means of differential pressures inside the vessels. This fast cycling system permitted several hundred tests in less than three weeks during the 2007 data taking campaign.

  18. IRAG and novel PKG targeting in the cardiovascular system.

    Science.gov (United States)

    Schlossmann, Jens; Desch, Matthias

    2011-09-01

    Signaling by nitric oxide (NO) determines several cardiovascular functions including blood pressure regulation, cardiac and smooth muscle hypertrophy, and platelet function. NO stimulates the synthesis of cGMP by soluble guanylyl cyclases and thereby activates cGMP-dependent protein kinases (PKGs), mediating most of the cGMP functions. Hence, an elucidation of the PKG signaling cascade is essential for the understanding of the (patho)physiological aspects of NO. Several PKG signaling pathways were identified, meanwhile regulating the intracellular calcium concentration, mediating calcium desensitization or cytoskeletal rearrangement. During the last decade it emerged that the inositol trisphosphate receptor-associated cGMP-kinase substrate (IRAG), an endoplasmic reticulum-anchored 125-kDa membrane protein, is a main signal transducer of PKG activity in the cardiovascular system. IRAG interacts specifically in a trimeric complex with the PKG1β isoform and the inositol 1,4,5-trisphosphate receptor I and, upon phosphorylation, reduces the intracellular calcium release from the intracellular stores. IRAG motifs for phosphorylation and for targeting to PKG1β and 1,4,5-trisphosphate receptor I were identified by several approaches. The (patho)physiological functions for the regulation of smooth muscle contractility and the inhibition of platelet activation were perceived. In this review, the IRAG recognition, targeting, and function are summarized compared with PKG and several PKG substrates in the cardiovascular system.

  19. Target Diagnostic Control System Implementation for the National Ignition Facility

    Energy Technology Data Exchange (ETDEWEB)

    Shelton, R T; Kamperschroer, J H; Lagin, L J; Nelson, J R; O' Brien, D W

    2010-05-12

    The extreme physics of targets shocked by NIF's 192-beam laser are observed by a diverse suite of diagnostics. Many diagnostics are being developed by collaborators at other sites, but ad hoc controls could lead to unreliable and costly operations. A Diagnostic Control System (DCS) framework for both hardware and software facilitates development and eases integration. Each complex diagnostic typically uses an ensemble of electronic instruments attached to sensors, digitizers, cameras, and other devices. In the DCS architecture each instrument is interfaced to a low-cost Windows XP processor and Java application. Each instrument is aggregated with others as needed in the supervisory system to form an integrated diagnostic. The Java framework provides data management, control services and operator GUI generation. DCS instruments are reusable by replication with reconfiguration for specific diagnostics in XML. Advantages include minimal application code, easy testing, and high reliability. Collaborators save costs by assembling diagnostics with existing DCS instruments. This talk discusses target diagnostic instrumentation used on NIF and presents the DCS architecture and framework.

  20. CHAOS: An SDN-Based Moving Target Defense System

    Directory of Open Access Journals (Sweden)

    Yuan Shi

    2017-01-01

    Full Text Available Moving target defense (MTD has provided a dynamic and proactive network defense to reduce or move the attack surface that is available for exploitation. However, traditional network is difficult to realize dynamic and active security defense effectively and comprehensively. Software-defined networking (SDN points out a brand-new path for building dynamic and proactive defense system. In this paper, we propose CHAOS, an SDN-based MTD system. Utilizing the programmability and flexibility of SDN, CHAOS obfuscates the attack surface including host mutation obfuscation, ports obfuscation, and obfuscation based on decoy servers, thereby enhancing the unpredictability of the networking environment. We propose the Chaos Tower Obfuscation (CTO method, which uses the Chaos Tower Structure (CTS to depict the hierarchy of all the hosts in an intranet and define expected connection and unexpected connection. Moreover, we develop fast CTO algorithms to achieve a different degree of obfuscation for the hosts in each layer. We design and implement CHAOS as an application of SDN controller. Our approach makes it very easy to realize moving target defense in networks. Our experimental results show that a network protected by CHAOS is capable of decreasing the percentage of information disclosure effectively to guarantee the normal flow of traffic.

  1. Automated Navigation System based on Weapon-Target Assignment

    Directory of Open Access Journals (Sweden)

    Mohammad Khairudin

    2011-12-01

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

  2. [Research on Anti-Camouflaged Target System Based on Spectral Detection and Image Recognition].

    Science.gov (United States)

    Wang, Bo; Gao, Yu-bin; Lu, Xu-tao

    2015-05-01

    To be able to quickly and efficiently identify Enemy camouflaged maneuvering targets in the wild environment, target recognition system was designed based on spectral detection technology and video target recognition method. System was composed of the visible light image acquisition module and static interferometer module. The system used image recognition technology to obtain two dimensional video images of measurement region, and through spectrum detection technology to identify targets. Ultimately, measured target was rebuilt on the corresponding position in the image, so the visual target recognition was realized. After the theoretical derivation, identifiable target function formula of the system was obtained, and based on the functional relationship to complete the quantitative experiments for target recognition. In the experiments, maneuvering target in the battlefield environment was simulated by a car. At different distances, the background was respectively selected to detect a flat wasteland, bushes and abandoned buildings. Obvious target, coated camouflage target and covered disguises target was respectively spectrum detection. Experimental results show that spectrum detection technology can overcome the shortcomings of unrecognized the camouflaged target by traditional image target recognition method. Testing background had some influence on spectrum detection results, and the continuity of the background was conducive to target recognition. Covered disguises target was the hardest to identify in various camouflage mode. As the distance between the target and the system increases, signal to noise ratio of the system was reduced. In summary, the system can achieve effective recognition of camouflaged targets to meet the design requirements.

  3. Versatile Desktop Experiment Module (DEMo) on Heat Transfer

    Science.gov (United States)

    Minerick, Adrienne R.

    2010-01-01

    This paper outlines a new Desktop Experiment Module (DEMo) engineered for a chemical engineering junior-level Heat Transfer course. This new DEMo learning tool is versatile, fairly inexpensive, and portable such that it can be positioned on student desks throughout a classroom. The DEMo system can illustrate conduction of various materials,…

  4. Aging of the Immune System. Mechanisms and Therapeutic Targets.

    Science.gov (United States)

    Weyand, Cornelia M; Goronzy, Jörg J

    2016-12-01

    Beginning with the sixth decade of life, the human immune system undergoes dramatic aging-related changes, which continuously progress to a state of immunosenescence. The aging immune system loses the ability to protect against infections and cancer and fails to support appropriate wound healing. Vaccine responses are typically impaired in older individuals. Conversely, inflammatory responses mediated by the innate immune system gain in intensity and duration, rendering older individuals susceptible to tissue-damaging immunity and inflammatory disease. Immune system aging functions as an accelerator for other age-related pathologies. It occurs prematurely in some clinical conditions, most prominently in patients with the autoimmune syndrome rheumatoid arthritis (RA); and such patients serve as an informative model system to study molecular mechanisms of immune aging. T cells from patients with RA are prone to differentiate into proinflammatory effector cells, sustaining chronic-persistent inflammatory lesions in the joints and many other organ systems. RA T cells have several hallmarks of cellular aging; most importantly, they accumulate damaged DNA. Because of deficiency of the DNA repair kinase ataxia telangiectasia mutated, RA T cells carry a higher burden of DNA double-strand breaks, triggering cell-indigenous stress signals that shift the cell's survival potential and differentiation pattern. Immune aging in RA T cells is also associated with metabolic reprogramming; specifically, with reduced glycolytic flux and diminished ATP production. Chronic energy stress affects the longevity and the functional differentiation of older T cells. Altered metabolic patterns provide opportunities to therapeutically target the immune aging process through metabolic interference.

  5. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    Directory of Open Access Journals (Sweden)

    Maria Victoria Maliandi

    2011-01-01

    Full Text Available The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.

  6. Sleeping Beauty transposon-based system for cellular reprogramming and targeted gene insertion in induced pluripotent stem cells

    Science.gov (United States)

    Grabundzija, Ivana; Wang, Jichang; Sebe, Attila; Erdei, Zsuzsanna; Kajdi, Robert; Devaraj, Anantharam; Steinemann, Doris; Szuhai, Károly; Stein, Ulrike; Cantz, Tobias; Schambach, Axel; Baum, Christopher; Izsvák, Zsuzsanna; Sarkadi, Balázs; Ivics, Zoltán

    2013-01-01

    The discovery of direct cell reprogramming and induced pluripotent stem (iPS) cell technology opened up new avenues for the application of non-viral, transposon-based gene delivery systems. The Sleeping Beauty (SB) transposon is highly advanced for versatile genetic manipulations in mammalian cells. We established iPS cell reprogramming of mouse embryonic fibroblasts and human foreskin fibroblasts by transposition of OSKM (Oct4, Sox2, Klf4 and c-Myc) and OSKML (OSKM + Lin28) expression cassettes mobilized by the SB100X hyperactive transposase. The efficiency of iPS cell derivation with SB transposon system was in the range of that obtained with retroviral vectors. Co-expression of the miRNA302/367 cluster together with OSKM significantly improved reprogramming efficiency and accelerated the temporal kinetics of reprogramming. The iPS cells displayed a stable karyotype, and hallmarks of pluripotency including expression of stem cell markers and the ability to differentiate into embryoid bodies in vitro. We demonstrate Cre recombinase-mediated exchange allowing simultaneous removal of the reprogramming cassette and targeted knock-in of an expression cassette of interest into the transposon-tagged locus in mouse iPS cells. This strategy would allow correction of a genetic defect by site-specific insertion of a therapeutic gene construct into ‘safe harbor’ sites in the genomes of autologous, patient-derived iPS cells. PMID:23275558

  7. ACTIVE TARGETING WITH PARTICULATE CARRIER SYSTEMS IN THE BLOOD COMPARTMENT

    NARCIS (Netherlands)

    CROMMELIN, DJA; SCHERPHOF, G; STORM, G

    1995-01-01

    This review deals with active targeting of particulate drug carriers through (1) physico-chemical (e.g., complex formation between a homing device and a surface exposed molecule at the target site) and (2) physical means, Target sites discussed are restricted to those in the blood circulation.

  8. Green targeting predictor and ambiguous targeting predictor 2: the pitfalls of plant protein targeting prediction and of transient protein expression in heterologous systems.

    Science.gov (United States)

    Fuss, Janina; Liegmann, Oliver; Krause, Kirsten; Rensing, Stefan A

    2013-12-01

    The challenges of plant protein targeting prediction are the existence of dual subcellular targets and the bias of experimentally confirmed data towards few and mostly nonplant model species. To assess whether training with proteins from evolutionarily distant species has a negative impact on prediction accuracy, we developed the Green Targeting Predictor tool, which was trained with a species-specific data set for Physcomitrella patens. Its performance was compared with that of the same tool trained with a mixed data set. In addition, we updated the Ambiguous Targeting Predictor. We found that predictions deviated from in vivo observations predominantly for proteins diverging within the green lineage, as well as for dual targeted proteins. To evaluate the usefulness of heterologous expression systems, selected proteins were subjected to localization studies in P. patens, Arabidopsis thaliana and Nicotiana tabacum. Four out of six proteins that show dual targeting in the original plant system were located only in a single compartment in one or both heterologous systems. We conclude that targeting signals of divergent plant species exhibit differences, calling for custom in silico and in vivo approaches when aiming to unravel the actual distribution patterns of proteins within a plant cell. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  9. Aliskiren targets multiple systems to alleviate cancer cachexia.

    Science.gov (United States)

    Wang, Chaoyi; Guo, Dunwei; Wang, Qiang; You, Song; Qiao, Zhongpeng; Liu, Yong; Dai, Hang; Tang, Hua

    2016-11-01

    To examine the effects of aliskiren, a small-molecule renin inhibitor, on cancer cachexia and to explore the underlying mechanisms. A cancer cachexia model was established by subcutaneously injecting C26 mouse colon carcinoma cells into isogenic BALB/c mice. Aliskiren was administered intragastrically [10 mg/kg body weight (BW)] on day 5 (as a preventive strategy, AP group) or on day 12 (as a therapeutic strategy, AT group) after C26 injection. Mice that received no C26 injection (healthy controls, HC group) or only C26 injection but not aliskiren (cancer, CA group) were used as controls. BW, tumor growth, whole body functions, and survival were monitored daily in half of the mice in each group, whereas serum, tumors, and gastrocnemius muscles were harvested from the other mice after sacrifice on day 20 for further analysis. Aliskiren significantly alleviated multiple cachexia‑associated symptoms, including BW loss, tumor burden, muscle wasting, muscular dysfunction, and shortened survival. On the molecular level, aliskiren antagonized cachexia‑induced activation of the renin‑angiotensin system (RAS), systematic and muscular inflammation, oxidative stress, and autophagy‑lysosome as well as ubiquitin‑proteasome stimulation. In addition, early administration of aliskiren before cachexia development (AP group) resulted in more robust effects in alleviating cachexia or targeting underlying mechanisms than administration after cachexia development (AT group). Aliskiren exhibited potent anti‑cachexia activities. These activities were achieved through the targeting of at least four mechanisms underlying cachexia development: RAS activation, increase in systematic inflammation, upregulation of oxidative stress, and stimulation of autophagy-lysosome pathway (ALP) and ubiquitin-proteasome pathway (UPP).

  10. Glycodendrimers: versatile tools for nanotechnology

    Directory of Open Access Journals (Sweden)

    René Roy

    2013-01-01

    Full Text Available Combining nanotechnology with glycobiology has triggered an exponential growth of research activities in the design of novel functional bionanomaterials (glyconanotechnology. More specifically, recent synthetic advances towards the tailored and versatile design of glycosylated nanoparticles namely glyconanoparticles, considered as synthetic mimetics of natural glycoconjugates, paved the way toward diverse biomedical applications. The accessibility of a wide variety of these structured nanosystems, in terms of shapes, sizes, and organized around stable nanoparticles have readily contributed to their development and applications in nanomedicine. In this context, glycosylated gold-nanoparticles (GNPs, glycosylated quantum dots (QDs, fullerenes, single-wall natotubes (SWNTs, and self-assembled glycononanoparticles using amphiphilic glycopolymers or glycodendrimers have received considerable attention to afford powerful imaging, therapeutic, and biodiagnostic devices. This review will provide an overview of the most recent syntheses and applications of glycodendrimers in glycoscience that have permitted to deepen our understanding of multivalent carbohydrate-protein interactions. Together with synthetic breast cancer vaccines, inhibitors of bacterial adhesions to host tissues including sensitive detection devices, these novel bionanomaterials are finding extensive relevance.

  11. Imidazole: Having Versatile Biological Activities

    Directory of Open Access Journals (Sweden)

    Amita Verma

    2013-01-01

    Full Text Available Imidazoles have occupied a unique position in heterocyclic chemistry, and its derivatives have attracted considerable interests in recent years for their versatile properties in chemistry and pharmacology. Imidazole is nitrogen-containing heterocyclic ring which possesses biological and pharmaceutical importance. Thus, imidazole compounds have been an interesting source for researchers for more than a century. The imidazole ring is a constituent of several important natural products, including purine, histamine, histidine, and nucleic acid. Being a polar and ionisable aromatic compound, it improves pharmacokinetic characteristics of lead molecules and thus is used as a remedy to optimize solubility and bioavailability parameters of proposed poorly soluble lead molecules. There are several methods used for the synthesis of imidazole-containing compounds, and also their various structure reactions offer enormous scope in the field of medicinal chemistry. The imidazole derivatives possess extensive spectrum of biological activities such as antibacterial, anticancer, antitubercular, antifungal, analgesic, and anti-HIV activities. This paper aims to review the biological activities of imidazole during the past years.

  12. MAGNETIC MICROSPHERES AS A TARGETED DRUG DELIVERY SYSTEM : A REVIEW

    OpenAIRE

    TARUN PATEL; SHAILESH SONI; BHAUMIK THAKAR; VIKRAM PANDYA; PRAFUL BHARADIA

    2012-01-01

    The in-vivo targeting of tumors with magnetic microspheres is currently realized through the applicationof external non-uniform magnetic fields generated by rare-earth permanent magnets or electromagnets.This technique can be applied to magnetically targeted cancer therapy, magnetic embolization therapywith magnetic particles that contain anticancer agent, such as chemotherapeutic drugs or therapeuticradioisotopes. Drug targeting is one way of local or regional antitumor treatment. Magnetical...

  13. Muon-catalyzed fusion experiment target and detector system. Preliminary design report

    Energy Technology Data Exchange (ETDEWEB)

    Jones, S.E.; Watts, K.D.; Caffrey, A.J.; Walter, J.B.

    1982-03-01

    We present detailed plans for the target and particle detector systems for the muon-catalyzed fusion experiment. Requirements imposed on the target vessel by experimental conditions and safety considerations are delineated. Preliminary designs for the target vessel capsule and secondary containment vessel have been developed which meet these requirements. In addition, the particle detection system is outlined, including associated fast electronics and on-line data acquisition. Computer programs developed to study the target and detector system designs are described.

  14. A versatile-deployable bacterial detection system for food and environmental safety based on LabTube-automated DNA purification, LabReader-integrated amplification, readout and analysis.

    Science.gov (United States)

    Hoehl, Melanie M; Bocholt, Eva Schulte; Kloke, Arne; Paust, Nils; von Stetten, Felix; Zengerle, Roland; Steigert, Juergen; Slocum, Alexander H

    2014-06-07

    Contamination of foods is a public health hazard that episodically causes thousands of deaths and sickens millions worldwide. To ensure food safety and quality, rapid, low-cost and easy-to-use detection methods are desirable. Here, the LabSystem is introduced for integrated, automated DNA purification, amplification and detection. It consists of a disposable, centrifugally driven DNA purification platform (LabTube) and a low-cost UV/vis-reader (LabReader). For demonstration of the LabSystem in the context of food safety, purification of Escherichia coli (non-pathogenic E. coli and pathogenic verotoxin-producing E. coli (VTEC)) in water and milk and the product-spoiler Alicyclobacillus acidoterrestris (A. acidoterrestris) in apple juice was integrated and optimized in the LabTube. Inside the LabReader, the purified DNA was amplified, readout and analyzed using both qualitative isothermal loop-mediated DNA amplification (LAMP) and quantitative real-time PCR. For the LAMP-LabSystem, the combined detection limits for purification and amplification of externally lysed VTEC and A. acidoterrestris are 10(2)-10(3) cell-equivalents. In the PCR-LabSystem for E. coli cells, the quantification limit is 10(2) cell-equivalents including LabTube-integrated lysis. The demonstrated LabSystem only requires a laboratory centrifuge (to operate the disposable, fully closed LabTube) and a low-cost LabReader for DNA amplification, readout and analysis. Compared with commercial DNA amplification devices, the LabReader improves sensitivity and specificity by the simultaneous readout of four wavelengths and the continuous readout during temperature cycling. The use of a detachable eluate tube as an interface affords semi-automation of the LabSystem, which does not require specialized training. It reduces the hands-on time from about 50 to 3 min with only two handling steps: sample input and transfer of the detachable detection tube.

  15. Review of ISOL target-ion-source systems

    Energy Technology Data Exchange (ETDEWEB)

    Kirchner, R. E-mail: r.kirchner@gsi.de

    2003-05-01

    Any review of target-ion-source systems (TISS) is necessarily a variation of the ISOL-theme 'efficient, fast, selective'. In the first part, more than 30 years of TISS development are examined in view of these key characteristics. By looking at the lines of development that were successful, at the lines that were abandoned (partly for good, partly for less good reasons), the lines with the most promising perspectives emerge. The second part deals with on-line chemistry in the TISS and its possibly double benefits: enhanced selectivity or increased separation speed, or both in favourable cases, as the relatively new sulfide chemistry. For the group-IVa-elements germanium and tin, the separation as sulfide-ions does not only suppress strongly the contamination by the neighbouring elements. It also reduces the effusion part of the release by orders of magnitude to the level of the intrinsic delay caused by molecular flow. The homologue chemistry is likely to work for silicon, but not for lead. While selectivity requires that both the formed molecules and molecular ions are thermally stable, a gain in speed requires only sufficient stability of the molecule: e.g. antimony, which hardly forms sulfide ions, also migrates orders of magnitude faster in the presence of sulphur vapour.

  16. Review of ISOL target-ion-source systems

    CERN Document Server

    Kirchner, R

    2003-01-01

    Any review of target-ion-source systems (TISS) is necessarily a variation of the ISOL-theme 'efficient, fast, selective'. In the first part, more than 30 years of TISS development are examined in view of these key characteristics. By looking at the lines of development that were successful, at the lines that were abandoned (partly for good, partly for less good reasons), the lines with the most promising perspectives emerge. The second part deals with on-line chemistry in the TISS and its possibly double benefits: enhanced selectivity or increased separation speed, or both in favourable cases, as the relatively new sulfide chemistry. For the group-IVa-elements germanium and tin, the separation as sulfide-ions does not only suppress strongly the contamination by the neighbouring elements. It also reduces the effusion part of the release by orders of magnitude to the level of the intrinsic delay caused by molecular flow. The homologue chemistry is likely to work for silicon, but not for lead. While selectivity ...

  17. Programmable Ultrasonic Sensing System for Targeted Spraying in Orchards

    Directory of Open Access Journals (Sweden)

    Marko Hočevar

    2012-11-01

    Full Text Available This research demonstrates the basic elements of a prototype automated orchard sprayer which delivers pesticide spray selectively with respect to the characteristics of the targets. The density of an apple tree canopy was detected by PROWAVE 400EP250 ultrasound sensors controlled by a Cypress PSOC CY8C29466 microcontroller. The ultrasound signal was processed with an embedded computer built around a LPC1343 microcontroller and fed in real time to electro-magnetic valves which open/close spraying nozzles in relation to the canopy structure. The analysis focuses on the detection of appropriate thresholds on 15 cm ultrasound bands, which correspond to maximal response to tree density, and this was selected for accurate spraying guidance. Evaluation of the system was performed in an apple orchard by detecting deposits of tartrazine dye (TD on apple leaves. The employment of programmable microcontrollers and electro-magnetic valves decreased the amount of spray delivered by up to 48.15%. In contrast, the reduction of TD was only up to 37.7% at some positions within the tree crown and 65.1% in the gaps between trees. For all these reasons, this concept of precise orchard spraying can contribute to a reduction of costs and environmental pollution, while obtaining similar or even better leaf deposits.

  18. Programmable Ultrasonic Sensing System for Targeted Spraying in Orchards

    Science.gov (United States)

    Stajnko, Denis; Berk, Peter; Lešnik, Mario; Jejčič, Viktor; Lakota, Miran; Štrancar, Andrej; Hočevar, Marko; Rakun, Jurij

    2012-01-01

    This research demonstrates the basic elements of a prototype automated orchard sprayer which delivers pesticide spray selectively with respect to the characteristics of the targets. The density of an apple tree canopy was detected by PROWAVE 400EP250 ultrasound sensors controlled by a Cypress PSOC CY8C29466 microcontroller. The ultrasound signal was processed with an embedded computer built around a LPC1343 microcontroller and fed in real time to electro-magnetic valves which open/close spraying nozzles in relation to the canopy structure. The analysis focuses on the detection of appropriate thresholds on 15 cm ultrasound bands, which correspond to maximal response to tree density, and this was selected for accurate spraying guidance. Evaluation of the system was performed in an apple orchard by detecting deposits of tartrazine dye (TD) on apple leaves. The employment of programmable microcontrollers and electro-magnetic valves decreased the amount of spray delivered by up to 48.15%. In contrast, the reduction of TD was only up to 37.7% at some positions within the tree crown and 65.1% in the gaps between trees. For all these reasons, this concept of precise orchard spraying can contribute to a reduction of costs and environmental pollution, while obtaining similar or even better leaf deposits. PMID:23202220

  19. Magneto-mechanical trapping systems for biological target detection

    KAUST Repository

    Li, Fuquan

    2014-03-29

    We demonstrate a magnetic microsystem capable of detecting nucleic acids via the size difference between bare magnetic beads and bead compounds. The bead compounds are formed through linking nonmagnetic beads and magnetic beads by the target nucleic acids. The system comprises a tunnel magneto-resistive (TMR) sensor, a trapping well, and a bead-concentrator. The TMR sensor detects the stray field of magnetic beads inside the trapping well, while the sensor output depends on the number of beads. The size of the bead compounds is larger than that of bare magnetic beads, and fewer magnetic beads are required to fill the trapping well. The bead-concentrator, in turn, is capable of filling the trap in a controlled fashion and so to shorten the assay time. The bead-concentrator includes conducting loops surrounding the trapping well and a conducting line underneath. The central conducting line serves to attract magnetic beads in the trapping well and provides a magnetic field to magnetize them so to make them detectable by the TMR sensor. This system excels by its simplicity in that the DNA is incubated with magnetic and nonmagnetic beads, and the solution is then applied to the chip and analyzed in a single step. In current experiments, a signal-to-noise ratio of 40.3 dB was obtained for a solution containing 20.8 nM of DNA. The sensitivity and applicability of this method can be controlled by the size or concentration of the nonmagnetic bead, or by the dimension of the trapping well.

  20. Recent Developments of Versatile Photoinitiating Systems for Cationic Ring Opening Polymerization Operating at Any Wavelengths and under Low Light Intensity Sources

    OpenAIRE

    Jacques Lalevée; Haifaa Mokbel; Jean-Pierre Fouassier

    2015-01-01

    Photoinitiators (PI) or photoinitiating systems (PIS) usable in light induced cationic polymerization (CP) and free radical promoted cationic polymerization (FRPCP) reactions (more specifically for cationic ring opening polymerization (ROP)) together with the involved mechanisms are briefly reviewed. The recent developments of novel two- and three-component PISs for CP and FRPCP upon exposure to low intensity blue to red lights is emphasized in details. Examples of such reactions under vario...

  1. Recent Developments of Versatile Photoinitiating Systems for Cationic Ring Opening Polymerization Operating at Any Wavelengths and under Low Light Intensity Sources.

    Science.gov (United States)

    Lalevée, Jacques; Mokbel, Haifaa; Fouassier, Jean-Pierre

    2015-04-20

    Photoinitiators (PI) or photoinitiating systems (PIS) usable in light induced cationic polymerization (CP) and free radical promoted cationic polymerization (FRPCP) reactions (more specifically for cationic ring opening polymerization (ROP)) together with the involved mechanisms are briefly reviewed. The recent developments of novel two- and three-component PISs for CP and FRPCP upon exposure to low intensity blue to red lights is emphasized in details. Examples of such reactions under various experimental conditions are provided.

  2. Recent Developments of Versatile Photoinitiating Systems for Cationic Ring Opening Polymerization Operating at Any Wavelengths and under Low Light Intensity Sources

    Directory of Open Access Journals (Sweden)

    Jacques Lalevée

    2015-04-01

    Full Text Available Photoinitiators (PI or photoinitiating systems (PIS usable in light induced cationic polymerization (CP and free radical promoted cationic polymerization (FRPCP reactions (more specifically for cationic ring opening polymerization (ROP together with the involved mechanisms are briefly reviewed. The recent developments of novel two- and three-component PISs for CP and FRPCP upon exposure to low intensity blue to red lights is emphasized in details. Examples of such reactions under various experimental conditions are provided.

  3. SCIMPI: A versatile seafloor observatory for changing environments

    Science.gov (United States)

    Moran, K.; Lado Insua, T.; Kulin, I.; Farrington, S.; Newman, J.

    2011-12-01

    The Simple Cabled Instrument for Measuring Parameters In-situ (SCIMPI) is a new seafloor observatory instrument. SCIMPI is designed to take subsurface time series measurements of temperature, pressure and resistivity in the sub-seafloor. This instrument has a battery operational life of approximately two years, which can be replaced with a battery pack using a remotely-operated vehicle, and provides high resolution measurements of physical properties in the sediment. With either periodic battery replacement or connection to a fiber-optic cable, SCIMPI is a long-term observatory for understanding sub-seafloor dynamics. The main advantage of this system is the reduced equipment and installation requirements making this tool an affordable and versatile system for scientific research. The pressure and temperature sensors, integrated into the system, have been successfully used in other marine industrial and scientific applications. Its electrical resistivity sensor, casing, and array assembly are uniquely designed and can be adapted for each mission. SCIMPI is currently in its last phase of testing prior to deployment in an Integrated Ocean Drilling Program borehole. This first SCIMPI is designed for a water depth of 1000 m and a sediment depth up to ~300 m below seafloor. But future assemblies can be tailored for deeper conditions and environments. Here we present the SCIMPI design, deployment options, and its scientific potential in a long-term ocean observatory. Science applications include studies of fluid flow, hydrate formation, and seismically induced pore pressure changes. The cost of this instrument will enable these measurements to become more commonplace, thereby improving our temporal and spatial knowledge of sub-seafloor gas, fluid and pore pressure activity. Most notable of the target deployments for SCIMPI are sub-seafloor gas hydrate sites and sites with biogenic methane. Understanding the dynamics of methane's role in the oceans as climate change

  4. Versatile hyaluronic acid modified AQ4N-Cu(II)-gossypol infinite coordination polymer nanoparticles: Multiple tumor targeting, highly efficient synergistic chemotherapy, and real-time self-monitoring.

    Science.gov (United States)

    Shen, Shihong; Wu, Youshen; Li, Ke; Wang, Ya; Wu, Jimin; Zeng, Yun; Wu, Daocheng

    2018-02-01

    A novel strategy for the preparation of infinite coordination polymer nanoparticles (ICPs) based nanomedicines was developed, with which hyaluronic acid modified AQ4N-Cu(II)-gossypol nanoparticles (HA@AQ4N-Cu(II)-gossypol NPs) were obtained. This is a highly efficient nanomedicine, in which gossypol serves as a chemotherapeutic agent and a self-carrier material; Cu(II) serves as the connecting point and anti-tumor enhancer; AQ4N not only serves as a chemotherapeutic agent and self-carrier material, but also as the self-monitor based on its inherent fluorescence. HA@AQ4N-Cu(II)-gossypol NPs possessed a spherical shape with a dynamic size of 88.7 ± 7.4 nm, and the total drug-loading content and drug encapsulation efficiency are 77.41% and 100%, respectively. This nanomedicine has a multiple tumor-targeting ability caused by HA-receptor mediation and pH-responsive drug release. A significantly low combination index (0.097) of AQ4N and gossypol is ascertained. In vivo experiments indicate that it accumulates and significantly releases drugs at the tumor region. With the use of only one-fiftieth of AQ4N and half of gossypol of the generally administered dose, they can achieve significantly high anti-tumor efficiency with negligible side effects. Importantly, the switching-type changed fluorescence of AQ4N can be used for in vivo real-time self-monitoring of the drug release and distribution, which allows us to adjust the administration dose and time for different tumor types and stages for individual therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Versatile high-repetition-rate phase-locked chopper system for fast timing experiments in the vacuum ultraviolet and x-ray spectral region.

    Science.gov (United States)

    Plogmaker, Stefan; Linusson, Per; Eland, John H D; Baker, Neville; Johansson, Erik M J; Rensmo, Håkan; Feifel, Raimund; Siegbahn, Hans

    2012-01-01

    A novel light chopper system for fast timing experiments in the vacuum-ultraviolet (VUV) and x-ray spectral region has been developed. It can be phase-locked and synchronized with a synchrotron radiation storage ring, accommodating repetition rates in the range of ~8 to ~120 kHz by choosing different sets of apertures and subharmonics of the ring frequency (MHz range). Also the opening time of the system can be varied from some nanoseconds to several microseconds to meet the needs of a broad range of applications. Adjusting these parameters, the device can be used either for the generation of single light pulses or pulse packages from a microwave driven, continuous He gas discharge lamp or from storage rings which are otherwise often considered as quasi-continuous light sources. This chopper can be utilized for many different kinds of experiments enabling, for example, unambiguous time-of-flight (TOF) multi-electron coincidence studies of atoms and molecules excited by a single light pulse as well as time-resolved visible laser pump x-ray probe electron spectroscopy of condensed matter in the valence and core level region.

  6. Versatile high-repetition-rate phase-locked chopper system for fast timing experiments in the vacuum ultraviolet and x-ray spectral region

    Energy Technology Data Exchange (ETDEWEB)

    Plogmaker, Stefan; Johansson, Erik M. J.; Rensmo, Haakan; Feifel, Raimund; Siegbahn, Hans [Department of Physics and Astronomy, Uppsala University, Box 516, SE-751 20 Uppsala (Sweden); Linusson, Per [Department of Physics, Stockholm University, AlbaNova University Center, SE-106 91 Stockholm (Sweden); Eland, John H. D. [Department of Physics and Astronomy, Uppsala University, Box 516, SE-751 20 Uppsala (Sweden); Department of Chemistry, Physical and Theoretical Chemistry Laboratory, Oxford University, South Parks Road, Oxford OX1 3QZ (United Kingdom); Baker, Neville [Department of Chemistry, Physical and Theoretical Chemistry Laboratory, Oxford University, South Parks Road, Oxford OX1 3QZ (United Kingdom)

    2012-01-15

    A novel light chopper system for fast timing experiments in the vacuum-ultraviolet (VUV) and x-ray spectral region has been developed. It can be phase-locked and synchronized with a synchrotron radiation storage ring, accommodating repetition rates in the range of {approx}8 to {approx}120 kHz by choosing different sets of apertures and subharmonics of the ring frequency (MHz range). Also the opening time of the system can be varied from some nanoseconds to several microseconds to meet the needs of a broad range of applications. Adjusting these parameters, the device can be used either for the generation of single light pulses or pulse packages from a microwave driven, continuous He gas discharge lamp or from storage rings which are otherwise often considered as quasi-continuous light sources. This chopper can be utilized for many different kinds of experiments enabling, for example, unambiguous time-of-flight (TOF) multi-electron coincidence studies of atoms and molecules excited by a single light pulse as well as time-resolved visible laser pump x-ray probe electron spectroscopy of condensed matter in the valence and core level region.

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

    Energy Technology Data Exchange (ETDEWEB)

    Farmer, III, Orville T.; Liezers, Martin

    2016-09-13

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

  8. Methanol: A Versatile Fuel for Immediate Use

    Science.gov (United States)

    Reed, T. B.; Lerner, R. M.

    1973-01-01

    Advocates the large-scale production and use of methanol as a substitute for the diminishing reserves of low-cost petroleum resources. Describes the manufacturing process and advantages of the versatile fuel. (JR)

  9. Design of a Versatile and Low Cost μVolt Level A to D Conversion System for Use in Medical Instrumentation Applications

    Directory of Open Access Journals (Sweden)

    Neil Robinson

    2008-10-01

    Full Text Available Modern medical facilities place considerable reliance on electronic instrumentation for purposes of calibration and monitoring of therapeutic processes, many of which employ electrical and electronic apparatus that itself generates considerable levels of interference in the form of background electromagnetic radiation (EMR. Additionally diverse ambient conditions in the clinical environment such as uncontrolled temperature, humidity, noise, and vibration place added stress on sensitive instrumentation. In order to obtain accurate, repeatable, and reliable data in such environments, instrumentation used must be largely immune to these factors. Analogue instrumentation is particularly susceptible to unstable environmental conditions. Sensors typically output an analogue current or voltage and it can be demonstrated that considerable overall benefit to the measuring process would result if sensor outputs could be converted to a robust digital format at the earliest possible stage. A practical and low cost system for A to D conversion at μVolt signal levels is described in this work. It has been successfully employed in portable radiation dosimetry instrumentation and used under diverse clinical conditions and it affords an improvement in signal resolution in excess of an order of magnitude over commonly used analogue techniques.

  10. Low-cost, in-liquid measuring system using a novel compact oscillation circuit and quartz-crystal microbalances (QCMs as a versatile biosensor platform

    Directory of Open Access Journals (Sweden)

    S. Beißner

    2017-10-01

    Full Text Available Quartz-crystal microbalances (QCMs are commercially available mass sensors which mainly consist of a quartz resonator that oscillates at a characteristic frequency, which shifts when mass changes due to surface binding of molecules. In addition to mass changes, the viscosity of gases or liquids in contact with the sensor also shifts the resonance but also influences the quality factor (Q-factor. Typical biosensor applications demand operation in liquid environments leading to viscous damping strongly lowering Q-factors. For obtaining reliable measurements in liquid environments, excellent resonator control and signal processing are essential but standard resonator circuits like the Pierce and Colpitts oscillator fail to establish stable resonances. Here we present a low-cost, compact and robust oscillator circuit comprising of state-of-the-art commercially available surface-mount technology components which stimulates the QCMs oscillation, while it also establishes a control loop regulating the applied voltage. Thereby an increased energy dissipation by strong viscous damping in liquid solutions can be compensated and oscillations are stabilized. The presented circuit is suitable to be used in compact biosensor systems using custom-made miniaturized QCMs in microfluidic environments. As a proof of concept we used this circuit in combination with a customized microfabricated QCM in a microfluidic environment to measure the concentration of C-reactive protein (CRP in buffer (PBS down to concentrations as low as 5 µg mL−1.

  11. On the Versatility of Rheoreversible, Stimuli-responsive Hydraulic-Fracturing Fluids for Enhanced Geothermal Systems: Effect of Reservoir pH

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, Carlos A.; Shao, Hongbo; Bonneville, Alain; Varga, Tamas; Zhong, Lirong

    2016-04-25

    Abstract The primary challenge for the feasibility of enhanced geothermal systems (EGS) is to cost-effectively create high-permeability reservoirs inside deep crystalline bedrock. Although fracturing fluids are commonly used for oil/gas, standard fracturing methods are not developed or proven for EGS temperatures and pressures. Furthermore, the environmental impacts of currently used fracturing methods are only recently being determined. These authors recently reported an environmentally benign, CO2-activated, rheoreversible fracturing fluid that enhances permeability through fracturing due to in situ volume expansion and gel formation. The potential of this novel fracturing fluid is evaluated in this work towards its application at geothermal sites under different pH conditions. Laboratory-scale fracturing experiments using Coso Geothermal rock cores under different pH environments were performed followed by X-ray microtomography characterization. The results demonstrate that CO2-reactive aqueous solutions of environmentally amenable polyallylamine (PAA) consistently and reproducibly creates/propagates fracture networks through highly impermeable crystalline rock from Coso EGS sites at considerably lower effective stress as compared to conventional fracturing fluids. In addition, permeability was significantly enhanced in a wide range of formation-water pH values. This effective, and environmentally-friendly fracturing fluid technology represents a potential alternative to conventional fracturing fluids.

  12. Development of versatile multiaperture negative ion sources

    Science.gov (United States)

    Cavenago, M.; Serianni, G.; Antoni, V.; Bigi, M.; De Muri, M.; Pasqualotto, R.; Recchia, M.; Veltri, P.; Agostinetti, P.; Barbisan, M.; Baseggio, L.; Cervaro, V.; Cazzador, M.; Degli Agostini, F.; Franchin, L.; Kulevoy, T.; Laterza, B.; Mimo, A.; Minarello, A.; Petrenko, S.; Ravarotto, D.; Rossetto, F.; Sattin, M.; Zaniol, B.; Zucchetti, S.

    2015-04-01

    Enhancement of negative ion sources for production of large ion beams is a very active research field nowadays, driven from demand of plasma heating in nuclear fusion devices and accelerator applications. As a versatile test bench, the ion source NIO1 (Negative Ion Optimization 1) is being commissioned by Consorzio RFX and INFN. The nominal beam current of 135 mA at -60 kV is divided into 9 beamlets, with multiaperture extraction electrodes. The plasma is sustained by a 2 MHz radiofrequency power supply, with a standard matching box. A High Voltage Deck (HVD) placed inside the lead shielding surrounding NIO1 contains the radiofrequency generator, the gas control, electronics and power supplies for the ion source. An autonomous closed circuit water cooling system was installed for the whole system, with a branch towards the HVD, using carefully optimized helical tubing. Insulation transformer is installed in a nearby box. Tests of several magnetic configurations can be performed. Status of experiments, measured spectra and plasma luminosity are described. Upgrades of magnetic filter, beam calorimeter and extraction grid and related theoretical issues are reviewed.

  13. Development of a Versatile Laser Ultrasonic System and Application to On-Line Measurement for Process Control of Wall Thickness and Eccentrictiy of Steel Seamless Mechanical Tubing

    Energy Technology Data Exchange (ETDEWEB)

    Kisner, R.A.; Kercel, S.W.; Damiano, B.; Bingham, P.R.; Gee, T.F.; Tucker, R.W.; Moore, M.R.; Hileman, M.; Emery, M.; Lenarduzzi, R.; Hardy, J.E.; Weaver, K.; Crutcher, R.; Kolarik, R.V., II; Vandervaart, R.H.

    2002-04-24

    Researchers at the Timken Company conceived a project to develop an on-line instrument for wall thickness measurement of steel seamless mechanical tubing based on laser ultrasonic technology. The instrument, which has been installed and tested at a piercing mill, provides data on tube eccentricity and concentricity. Such measurements permit fine-tuning of manufacturing processes to eliminate excess material in the tube wall and therefore provide a more precisely dimensioned product for their customers. The resulting process energy savings are substantial, as is lowered environmental burden. The expected savings are $85.8 million per year in seamless mechanical tube piercing alone. Applied across the industry, this measurement has a potential of reducing energy consumption by 6 x 10{sup 12} BTU per year, greenhouse gas emissions by 0.3 million metric tons carbon equivalent per year, and toxic waste by 0.255 million pounds per year. The principal technical contributors to the project were the Timken Company, Industrial Materials Institute (IMI, a contractor to Timken), and Oak Ridge National Laboratory (ORNL). Timken provided mill access as well as process and metallurgical understanding. Timken researchers had previously developed fundamental ultrasonic analysis methods on which this project is based. IMI developed and fabricated the laser ultrasonic generation and receiver systems. ORNL developed Bayesian and wavelet based real-time signal processing, spread-spectrum wireless communication, and explored feature extraction and pattern recognition methods. The resulting instrument has successfully measured production tubes at one of Timken's piercing mills. This report concentrates on ORNL's contribution through the CRADA mechanism. The three components of ORNL's contribution were met with mixed success. The real-time signal-processing task accomplished its goal of improvement in detecting time of flight information with a minimum of false data. The

  14. Versatile composite resins simplifying the practice of restorative dentistry.

    Science.gov (United States)

    Margeas, Robert

    2014-01-01

    After decades of technical development and refinement, composite resins continue to simplify the practice of restorative dentistry, offering clinicians versatility, predictability, and enhanced physical properties. With a wide range of products available today, composite resins are a reliable, conservative, multi-functional restorative material option. As manufacturers strive to improve such properties as compression strength, flexural strength, elastic modulus, coefficient of thermal expansion, water sorption, and wear resistance, several classification systems of composite resins have been developed.

  15. Moving Target Indication for Multi-channel Airborne Radar Systems

    NARCIS (Netherlands)

    Lidicky, L.

    2010-01-01

    Moving target indication (MTI) using radar is of great interest in civil and military applications. Its uses include airborne or space-borne surveillance of ground moving vehicles (cars, trains) or ships at sea, for instance. Airborne (space-borne) radar offers several advantages when compared to

  16. Mock-up Test for Isotope Target Transport and Cooling System

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Sang-pil; Kwon, Hyeok-jung; Kim, Han-sung; Cho, Yong-sub; Chung, Bo-hyun; Seol, Kyung-tae; Song, Young-gi; Kim, Dae-il; Min, Yi-sub [KOMAC, Gyeongju (Korea, Republic of)

    2015-10-15

    In this paper, we described the design and fabrication of the test mock-up of target transport and cooling system for the isotope production by using the 100-MeV proton irradiation. For Sr-82 production, RbCl target and aluminum dummy target was prepared. These targets are contained in the target carrier, which could transported by drive chain and guide rail system. Korea multi-purpose Accelerator Complex (KOMAC) has a plan to construct the new proton beam irradiation facility for the production of radioisotopes. Sr-82 and Cu-67 were selected as the target isotope in this facility, they are promising isotope for the PET imaging and cancer therapy. To produce Sr-82 by 100- MeV proton irradiation, RbCl were chosen as a target material due to their high melting point and easy separation. For the facility construction, we have designed targetry system which consists of target, target transport system and target cooling system. This paper describes the details of targetry system.

  17. Targeted delivery of Dicer-substrate siRNAs using a dual targeting peptide decorated dendrimer delivery system.

    Science.gov (United States)

    Liu, Xiaoxuan; Liu, Cheng; Chen, Chao; Bentobji, Mélanie; Cheillan, Francine Azario; Piana, Jeanne Thomassin; Qu, Fanqi; Rocchi, Palma; Peng, Ling

    2014-11-01

    Small interfering RNAs (siRNA) are emerging as novel therapeutic agents, providing competent delivery systems that are available. Dendrimers, a special family of synthetic macromolecules, represent an exciting delivery platform by virtue of their well-defined dendritic structure and unique multivalency and cooperativity confined within a nanoscale volume. Here, we report a Dicer-substrate siRNA (dsiRNA) which, when delivered using a structurally flexible triethanolamine-core poly(amidoamine) dendrimer of generation 5 as the nanocarrier, gives rise to a much greater RNAi response than that produced with conventional siRNA. Further decoration of the dsiRNA/dendrimer complexes with a dual targeting peptide simultaneously promoted cancer cell targeting through interacting with integrins and cell penetration via the interaction with neuropilin-1 receptors, which led to improved gene silencing and anticancer activity. Altogether, our results disclosed here open a new avenue for therapeutic implementation of RNAi using dendrimer nanovector based targeted delivery. This study demonstrates superior therapeutic properties of siRNA when combined with a dendrimer-based targeted nano-delivery system. Similar approaches may eventually gain clinical utility following additional studies determining safety and efficacy. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Frequency of target crashes for IntelliDrive safety systems

    Science.gov (United States)

    2010-10-01

    This report estimates the frequency of different crash types that would potentially be addressed by various categories of Intelligent Transportation Systems as part of the IntelliDriveSM safety systems program. Crash types include light-vehicle crash...

  19. Measurement of the target current by inductive probe during laser interaction on terawatt laser system PALS

    Energy Technology Data Exchange (ETDEWEB)

    Cikhardt, J.; Klír, D.; Řezáč, K. [Czech Technical University in Prague, Faculty of Electrical Engineering, 166 27 Prague (Czech Republic); Institute of Plasma Physics AS CR, 182 00 Prague (Czech Republic); Krása, J.; De Marco, M.; Pfeifer, M.; Velyhan, A.; Krouský, E. [Institute of Physics AS CR, 182 21 Prague (Czech Republic); Cikhardtová, B.; Kubeš, P.; Kravárik, J. [Czech Technical University in Prague, Faculty of Electrical Engineering, 166 27 Prague (Czech Republic); Ullschmied, J.; Skála, J. [Institute of Plasma Physics AS CR, 182 00 Prague (Czech Republic)

    2014-10-15

    Measurements of the return-current flowing through a solid target irradiated with the sub-nanosecond kJ-class Prague Asterix Laser System is reported. A new inductive target probe was developed which allows us measuring the target current derivative in a kA/ns range. The dependences of the target current on the laser pulse energy for cooper, graphite, and polyethylene targets are reported. The experiment shows that the target current is proportional to the deposited laser energy and is strongly affected by the shot-to-shot fluctuations. The corresponding maximum target charge exceeded a value of 10 μC. A return-current dependence of the electromagnetic pulse produced by the laser-target interaction is presented.

  20. Information Systems curriculum: the moving target phenomenon of ...

    African Journals Online (AJOL)

    This article determines the scope and nature of Information Systems training at Technikons in South Africa. Due to rapid changes in technology, knowledge regarding technology becomes obsolete rapidly. Therefore Information Systems learners should have the means and skills to keep abreast of advances in the ...

  1. The peripheral GABAergic system as a target in endocrine disorders

    NARCIS (Netherlands)

    Gladkevich, A; Korf, J; Hakobyan, VP; Melkonyan, KV

    2006-01-01

    In addition to its well-recognized function as a cerebral inhibitory transmitter, less well established is the role of GABA in peripheral nervous and endocrine systems. We Summarize current evidence that GABA serves as a neurotransmitter or neuromodulator in the autonomic nervous system and as a

  2. Targeting oxidative stress in central nervous system disorders

    Science.gov (United States)

    Patel, Manisha

    2016-01-01

    There is widespread recognition that reactive oxygen species (ROS) play key roles in normal brain function and pathology in the context of neurological disease. Oxidative stress continues to remain a key therapeutic target for neurological diseases. In developing antioxidant therapies for neurological disease, special attention should be given to the brain’s unique vulnerability to oxidative insults and its architecture. Consideration of antioxidant therapy should be guided by a strong rationale for oxidative stress in the neurological disease. This review provides an overview of processes that can guide the development of antioxidant therapies in neurological diseases such as knowledge of basic redox mechanisms, unique features of brain pathophysiology, mechanisms and classes of antioxidants and desirable properties of drug candidates. PMID:27491897

  3. Nanoparticles laden in situ gelling system for ocular drug targeting

    Directory of Open Access Journals (Sweden)

    Divya Kumar

    2013-01-01

    Full Text Available Designing an ophthalmic drug delivery system is one of the most difficult challenges for the researchers. The anatomy and physiology of eye create barriers like blinking which leads to the poor retention time and penetration of drug moiety. Some conventional ocular drug delivery systems show shortcomings such as enhanced pre-corneal elimination, high variability in efficiency, and blurred vision. To overcome these problems, several novel drug delivery systems such as liposomes, nanoparticles, hydrogels, and in situ gels have been developed. In situ-forming hydrogels are liquid upon instillation and undergo phase transition in the ocular cul-de-sac to form viscoelastic gel and this provides a response to environmental changes. In the past few years, an impressive number of novel temperature, pH, and ion-induced in situ-forming systems have been reported for sustain ophthalmic drug delivery. Each system has its own advantages and drawbacks. Thus, a combination of two drug delivery systems, i.e., nanoparticles and in situ gel, has been developed which is known as nanoparticle laden in situ gel. This review describes every aspects of this novel formulation, which present the readers an exhaustive detail and might contribute to research and development.

  4. Numerical simulations of flow field in the target region of accelerator-driven subcritical reactor system

    CERN Document Server

    Chen Hai Yan

    2002-01-01

    Numerical simulations of flow field were performed by using the PHOENICS 3.2 code for the proposed spallation target of accelerator-driven subcritical reactor system (ADS). The fluid motion in the target is axisymmetric and is treated as a 2-D steady-state problem. A body-fitted coordinate system (BFC) is then chosen and a two-dimensional mesh of the flow channel is generated. Results are presented for the ADS target under both upward and downward flow, and for the target with diffuser plate installed below the window under downward flow

  5. Using a blackboard architecture or expert system to identify obfuscated targets from symptoms

    Science.gov (United States)

    Straub, Jeremy

    2015-05-01

    A variety of techniques exist for enhancing or inferring the existence and characteristics of an obscured or partially concealed target. Targets, however, may be completely blocked from view, presenting nothing to enhance and no image area to extend inferentially. Despite the difficulty, concealed (particularly intentionally) targets may be the most important to detect. This paper proposes a technique for using a Blackboard Architecture or Expert system to infer a target's existence from symptoms (maneuvers of other units, water and soil deformation, etc.) and discusses the differences between the two approaches (Blackboard Architecture and expert system) for doing so.

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

    Science.gov (United States)

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

    2017-08-01

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

  7. Guinea Pigs: Versatile Animals for the Classroom

    Science.gov (United States)

    Barman, Charles R.

    1977-01-01

    Guinea pigs are presented as versatile classroom animals. Suggestions for animal behavior and genetics studies are given. Also included is information concerning sex determination and the breeding of guinea pigs, and hints on keeping these animals in the classroom. References and illustrations complete the article. (MA)

  8. A Versatile Technique for Solving Quintic Equations

    Science.gov (United States)

    Kulkarni, Raghavendra G.

    2006-01-01

    In this paper we present a versatile technique to solve several types of solvable quintic equations. In the technique described here, the given quintic is first converted to a sextic equation by adding a root, and the resulting sextic equation is decomposed into two cubic polynomials as factors in a novel fashion. The resultant cubic equations are…

  9. Versatility of nodal affiliation to communities.

    Science.gov (United States)

    Shinn, Maxwell; Romero-Garcia, Rafael; Seidlitz, Jakob; Váša, František; Vértes, Petra E; Bullmore, Edward

    2017-06-27

    Graph theoretical analysis of the community structure of networks attempts to identify the communities (or modules) to which each node affiliates. However, this is in most cases an ill-posed problem, as the affiliation of a node to a single community is often ambiguous. Previous solutions have attempted to identify all of the communities to which each node affiliates. Instead of taking this approach, we introduce versatility, V, as a novel metric of nodal affiliation: V ≈ 0 means that a node is consistently assigned to a specific community; V > 0 means it is inconsistently assigned to different communities. Versatility works in conjunction with existing community detection algorithms, and it satisfies many theoretically desirable properties in idealised networks designed to maximise ambiguity of modular decomposition. The local minima of global mean versatility identified the resolution parameters of a hierarchical community detection algorithm that least ambiguously decomposed the community structure of a social (karate club) network and the mouse brain connectome. Our results suggest that nodal versatility is useful in quantifying the inherent ambiguity of modular decomposition.

  10. Random Noise Monopulse Radar System for Covert Tracking of Targets

    Science.gov (United States)

    Narayanan, Ram M.

    2002-07-01

    The University of Nebraska is currently developing a unique monopulse radar concept based on the use of random noise signal for covert tracking applications. This project is funded by the Missile Defense Agency (MDA). The advantage of this system over conventional frequency-modulated continuous wave (FMCW) or short pulse systems is its covertness resulting from the random waveform's immunity from interception and jamming. The system integrates a novel heterodyne correlation receiver with conventional monopulse architecture. Based on the previous work such as random noise interferometry, a series of theoretical analysis and simulations were conducted to examine the potential performance of this monopulse system. Furthermore, a prototype system is under development to exploit practical design aspects of phase comparison angle measurement. It is revealed that random noise monopulse radar can provide the same function as traditional monopulse radar, i.e., implement range and angular estimation and tracking in real time. The bandwidth of random noise signal can be optimized to achieve the best range resolution as well as the angular accuracy.

  11. Plasma properties of RF magnetron sputtering system using Zn target

    Energy Technology Data Exchange (ETDEWEB)

    Nafarizal, N.; Andreas Albert, A. R.; Sharifah Amirah, A. S.; Salwa, O.; Riyaz Ahmad, M. A. [Microelectronic and Nanotechnology - Shamsuddin Research Centre (MiNT-SRC), Faculty of Electrical and Electronic Engineering, Universiti Tun Hussein Onn Malaysia 86400 Parit Raja, Batu Pahat, Johor (Malaysia)

    2012-06-29

    In the present work, we investigate the fundamental properties of magnetron sputtering plasma using Zn target and its deposited Zn thin film. The magnetron sputtering plasma was produced using radio frequency (RF) power supply and Argon (Ar) as ambient gas. A Langmuir probe was used to collect the current from the plasma and from the current intensity, we calculate the electron density and electron temperature. The properties of Zn sputtering plasma at various discharge conditions were studied. At the RF power ranging from 20 to 100 W and gas pressure 5 mTorr, we found that the electron temperature was almost unchanged between 2-2.5 eV. On the other hand, the electron temperature increased drastically from 6 Multiplication-Sign 10{sup 9} to 1 Multiplication-Sign 10{sup 10}cm{sup -3} when the discharge gas pressure increased from 5 to 10 mTorr. The electron microscope images show that the grain size of Zn thin film increase when the discharge power is increased. This may be due to the enhancement of plasma density and sputtered Zn density.

  12. Targeting the humoral immune system of patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Teng, Yoe Kie Onno

    2008-01-01

    The aim of this thesis was to unravel the role of the humoral immune system in rheumatoid arthritis patients by employing new immunosuppressive strategies, i.e. specific B-cell depletion with Rituximab and non-specific lymfoablative treatment with high dose chemotherapy and hematopoeietic stem cell

  13. Target detect system in 3D using vision apply on plant reproduction by tissue culture

    Science.gov (United States)

    Vazquez Rueda, Martin G.; Hahn, Federico

    2001-03-01

    This paper presents the preliminary results for a system in tree dimension that use a system vision to manipulate plants in a tissue culture process. The system is able to estimate the position of the plant in the work area, first calculate the position and send information to the mechanical system, and recalculate the position again, and if it is necessary, repositioning the mechanical system, using an neural system to improve the location of the plant. The system use only the system vision to sense the position and control loop using a neural system to detect the target and positioning the mechanical system, the results are compared with an open loop system.

  14. Efficient Gene Targeting in Golden Syrian Hamsters by the CRISPR/Cas9 System

    OpenAIRE

    Zhiqiang Fan; Wei Li; Sang R Lee; Qinggang Meng; Bi Shi; Bunch, Thomas D.; Kenneth L White; Il-Keun Kong; Zhongde Wang

    2014-01-01

    The golden Syrian hamster is the model of choice or the only rodent model for studying many human diseases. However, the lack of gene targeting tools in hamsters severely limits their use in biomedical research. Here, we report the first successful application of the CRISPR/Cas9 system to efficiently conduct gene targeting in hamsters. We designed five synthetic single-guide RNAs (sgRNAs)--three for targeting the coding sequences for different functional domains of the hamster STAT2 protein, ...

  15. Development of a targeted flip-in system in avian DT40 cells.

    Directory of Open Access Journals (Sweden)

    Kaori Kobayashi

    Full Text Available Gene-targeting to create null mutants or designed-point mutants is a powerful tool for the molecular dissection of complex phenotypes involving DNA repair, signal transduction, and metabolism. Because gene-targeting is critically impaired in mutants exhibiting attenuated homologous recombination (HR, it is believed that gene-targeting is mediated via homologous recombination, though the precise mechanism remains unknown. We explored gene-targeting in yeast and avian DT40 cells. In animal cells, gene-targeting is activated by DNA double strand breaks introduced into the genomic region where gene-targeting occurs. This is evidenced by the fact that introducing double strand breaks at targeted genome sequences via artificial endonucleases such as TALEN and CRISPR facilitates gene-targeting. We found that in fission yeast, Schizosaccharomyces pombe, gene-targeting was initiated from double strand breaks on both edges of the homologous arms in the targeting construct. Strikingly, we also found efficient gene-targeting initiated on the edges of homologous arms in avian DT40 cells, a unique animal cell line in which efficient gene-targeting has been demonstrated. It may be that yeast and DT40 cells share some mechanism in which unknown factors detect and recombine broken DNA ends at homologous arms accompanied by crossover. We found efficient targeted integration of gapped plasmids accompanied by crossover in the DT40 cells. To take advantage of this finding, we developed a targeted flip-in system for avian DT40 cells. This flip-in system enables the rapid generation of cells expressing tag-fused proteins and the stable expression of transgenes from OVA loci.

  16. Targeting the humoral immune system of patients with rheumatoid arthritis

    OpenAIRE

    Teng, Yoe Kie Onno

    2008-01-01

    The aim of this thesis was to unravel the role of the humoral immune system in rheumatoid arthritis patients by employing new immunosuppressive strategies, i.e. specific B-cell depletion with Rituximab and non-specific lymfoablative treatment with high dose chemotherapy and hematopoeietic stem cell transplantation. This thesis evaluates the clinical benefit of these strategies as well as the immunological changes that coincide with clinical improvement. By combining clinical outcome with immu...

  17. Pattern-Recognition System for Approaching a Known Target

    Science.gov (United States)

    Huntsberger, Terrance; Cheng, Yang

    2008-01-01

    A closed-loop pattern-recognition system is designed to provide guidance for maneuvering a small exploratory robotic vehicle (rover) on Mars to return to a landed spacecraft to deliver soil and rock samples that the spacecraft would subsequently bring back to Earth. The system could be adapted to terrestrial use in guiding mobile robots to approach known structures that humans could not approach safely, for such purposes as reconnaissance in military or law-enforcement applications, terrestrial scientific exploration, and removal of explosive or other hazardous items. The system has been demonstrated in experiments in which the Field Integrated Design and Operations (FIDO) rover (a prototype Mars rover equipped with a video camera for guidance) is made to return to a mockup of Mars-lander spacecraft. The FIDO rover camera autonomously acquires an image of the lander from a distance of 125 m in an outdoor environment. Then under guidance by an algorithm that performs fusion of multiple line and texture features in digitized images acquired by the camera, the rover traverses the intervening terrain, using features derived from images of the lander truss structure. Then by use of precise pattern matching for determining the position and orientation of the rover relative to the lander, the rover aligns itself with the bottom of ramps extending from the lander, in preparation for climbing the ramps to deliver samples to the lander. The most innovative aspect of the system is a set of pattern-recognition algorithms that govern a three-phase visual-guidance sequence for approaching the lander. During the first phase, a multifeature fusion algorithm integrates the outputs of a horizontal-line-detection algorithm and a wavelet-transform-based visual-area-of-interest algorithm for detecting the lander from a significant distance. The horizontal-line-detection algorithm is used to determine candidate lander locations based on detection of a horizontal deck that is part of the

  18. Systems engineering meets quantitative systems pharmacology: from low-level targets to engaging the host defenses.

    Science.gov (United States)

    Androulakis, Ioannis P

    2015-01-01

    Quantitative systems pharmacology aims at systematizing, in a model-based manner, the integration of systems biology and pharmacology in an effort to rationalize the process of assessing the ability of a drug to enhance well-being by off-setting the effects of a disease. Systems engineering, on the other hand, has enabled us to develop principles and methodologies for designing and operating engineered networks of structures exploring the integration of the underlying governing (design) laws. Although the computational tools which have resulted in major advances in the design, analysis, and operation of complex engineered structures have had tremendous success in the analysis of systems pharmacology models, it is argued in this opinion paper, that exploring the underlying conceptual foundation of complex systems engineering will enable us to move toward integrated models at the host level to explore, and possibly, induce synergies between low-level drug targets and higher level, systemic, defense mechanisms. This is an approach which would require refocusing of the key activities; however, it is likely the more promising approach as we enter the new era of personalized and precision medicine. We finally argue for the development of an allostatic approach to quantitative systems pharmacology and the development of an integrated framework for considering drugs in their broader context, beyond their local site of action. WIREs Syst Biol Med 2015, 7:101-112. doi: 10.1002/wsbm.1294 For further resources related to this article, please visit the WIREs website. The author has declared no conflicts of interest for this article. © 2015 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Yu Yao

    2015-01-01

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

  20. Chemical tools selectively target components of the PKA system

    Directory of Open Access Journals (Sweden)

    Drewianka Stephan

    2009-02-01

    Full Text Available Abstract Background In the eukaryotic cell the cAMP-dependent protein kinase (PKA is a key enzyme in signal transduction and represents the main target of the second messenger cAMP. Here we describe the design, synthesis and characterisation of specifically tailored cAMP analogs which can be utilised as a tool for affinity enrichment and purification as well as for proteomics based analyses of cAMP binding proteins. Results Two sets of chemical binders were developed based on the phosphorothioate derivatives of cAMP, Sp-cAMPS and Rp-cAMPS acting as cAMP-agonists and -antagonists, respectively. These compounds were tested via direct surface plasmon resonance (SPR analyses for their binding properties to PKA R-subunits and holoenzyme. Furthermore, these analogs were used in an affinity purification approach to analyse their binding and elution properties for the enrichment and improvement of cAMP binding proteins exemplified by the PKA R-subunits. As determined by SPR, all tested Sp-analogs provide valuable tools for affinity chromatography. However, Sp-8-AEA-cAMPS displayed (i superior enrichment properties while maintaining low unspecific binding to other proteins in crude cell lysates, (ii allowing mild elution conditions and (iii providing the capability to efficiently purify all four isoforms of active PKA R-subunit in milligram quantities within 8 h. In a chemical proteomics approach both sets of binders, Rp- and Sp-cAMPS derivatives, can be employed. Whereas Sp-8-AEA-cAMPS preferentially binds free R-subunit, Rp-AHDAA-cAMPS, displaying antagonist properties, not only binds to the free PKA R-subunits but also to the intact PKA holoenzyme both from recombinant and endogenous sources. Conclusion In summary, all tested cAMP analogs were useful for their respective application as an affinity reagent which can enhance purification of cAMP binding proteins. Sp-8-AEA-cAMPS was considered the most efficient analog since Sp-8-AHA-cAMPS and Sp-2-AHA

  1. Pendrin, a Novel Transcriptional Target of the Uroguanylin System

    Directory of Open Access Journals (Sweden)

    Julia Rozenfeld

    2013-12-01

    Full Text Available Guanylin (GN and uroguanylin (UGN are low-molecular-weight peptide hormones produced mainly in the intestinal mucosa in response to oral salt load. GN and UGN (guanylin peptides induce secretion of electrolytes and water in both intestine and kidney. Thought to act as “intestinal natriuretic factors”, GN and UGN modulate renal salt secretion by both endocrine mechanisms (linking the digestive system and kidney and paracrine/autocrine (intrarenal mechanisms. The cellular function of GN and UGN in intestine and proximal tubule is mediated by guanylyl cyclase C (GC-C-, cGMP-, and G protein-dependent pathways, whereas, in principal cells of the cortical collecting duct (CCD, these peptide hormones act via GC-C-independent signaling through phospholipase A2 (PLA2. The Cl-/HCO-3 exchanger pendrin (SLC26A4, encoded by the PDS gene, is expressed in non-α intercalated cells of the CCD. Pendrin is essential for CCD bicarbonate secretion and is also involved in NaCl balance and blood pressure regulation. Our recent studies have provided evidence that pendrin-mediated anion exchange in the CCD is regulated at the transcriptional level by UGN. UGN exerts an inhibitory effect on the pendrin gene promoter likely via heat shock factor 1 (HSF1 action at a defined heat shock element (HSE site. Recent studies have unraveled novel roles for guanylin peptides in several organ systems including involvement in appetite regulation, olfactory function, cell proliferation and differentiation, inflammation, and reproductive function. Both the guanylin system and pendrin have also been implicated in airway function. Future molecular research into the receptors and signal transduction pathways involved in the action of guanylin peptides and the pendrin anion exchanger in the kidney and other organs, and into the links between them, may facilitate discovery of new therapies for hypertension, heart failure, hepatic failure and other fluid retention syndromes, as well as

  2. Sirtuins in the Cardiovascular System: Potential Targets in Pediatric Cardiology.

    Science.gov (United States)

    Ianni, Alessandro; Yuan, Xuejun; Bober, Eva; Braun, Thomas

    2018-03-02

    Cardiovascular diseases represent a major cause of death and morbidity. Cardiac and vascular pathologies develop predominantly in the aged population in part due to lifelong exposure to numerous risk factors but are also found in children and during adolescence. In comparison to adults, much has to be learned about the molecular pathways driving cardiovascular diseases in the pediatric population. Sirtuins are highly conserved enzymes that play pivotal roles in ensuring cardiac homeostasis under physiological and stress conditions. In this review, we discuss novel findings about the biological functions of these molecules in the cardiovascular system and their possible involvement in pediatric cardiovascular diseases.

  3. Video Automatic Target Tracking System (VATTS) Operating Procedure,

    Science.gov (United States)

    1980-08-15

    AO-AIO𔃾 790 BOM CORP MCLEAN VA F/A 17/8 VIDEO AUTOMATIC TARGE T TRACKING SYSTEM (VATTS) OPERATING PROCEO -ETC(U) AUG Go C STAMM J P ORRESTER, J...Tape Transport Number Two TKI Tektronics I/0 Terminal DS1 Removable Disk Storage Unit DSO Fixed Disk Storage Unit CRT Cathode Ray Tube 1-3 THE BDM...file (mark on Mag Tape) AZEL Quick look at Trial Information Program DUPTAPE Allows for duplication of magnetic tapes CA Cancel ( terminates program on

  4. Professional soldier assessment of a rifle-mounted target hand-off system

    NARCIS (Netherlands)

    Levesque, J.; Banko, K.; Binsch, O.

    2015-01-01

    The miniaturization of digital image acquisition and processing hardware, positional sensors, and batteries has enabled the creation of assisted targeting systems light enough to be integrated onto small firearms to increase the probability of soldiers detecting and hitting targets. As well, the

  5. A Versatile Link for High-Speed, Radiation Resistant Optical Transmission in LHC Upgrades

    Science.gov (United States)

    Xiang, A.; Gong, D.; Hou, S.; Huffman, T.; Kwan, S.; Liu, K.; Liu, T.; Prosser, A.; Soos, C.; Su, D.; Teng, P.; Troska, J.; Vasey, F.; Weidberg, T.; Ye, J.

    The Versatile Link project is developing a general purpose physical layer optical link with high bandwidth, radiation resistance and magnetic-field tolerance that meets the requirements of LHC upgrade experiments. This paper presents recent work on system specifications, front-end transceiver prototypes, passive components studies and commercial back-end transceiver evaluations. System optical power budgets are specified for single mode (1310nm) and multi-mode (850nm) links, with a target data rate of 4.8 Gbps and a transmission length of 150 meters. Noise and interference penalties are simulated using the 10GbE link model and verified by bit error ratio measurement on reference links. The power margin is particularly constrained by radiation degradation of the front-end receivers. We report the power budgets for all link variants where at least 1.8 dB safety margins are maintained. The Versatile Transceiver (VTRx) - the front-end module to be installed on-detector - is based on a commercial small form pluggable (SFP+) package, modified to optimize size and mass, assembled to host a qualified laser, PIN photodiode, custom-designed radiation tolerant laser driver and receiving amplifier. A set of VTRxs with validated components have been prototyped and compliance tested. We also present the radiation test results on front-end components and passive components. The total fluence tests for lasers and PINs have been carried out with pions and neutrons up to 4 x 1015/cm2. SEU tests have been performed on PIN photodiodes and the full receiver optical subassembly. Radiation induced absorption in a number of single mode and multi-mode fibers, at -25¡C and up to 500 kGy, have been measured and high performance candidates identified. Commercial off-of-the-shelf parts have been examined for use as back-end transceivers. Compliance tests on SFP+, 4+4 parallel optical engines and SNAP 12 transmitter/receivers have been completed.

  6. AuNP-CTG based probing system targeting CAG repeat DNA and RNA sequences.

    Science.gov (United States)

    Le, Binh Huy; Joo, Han Na; Hwang, Do Won; Kim, Kyu Wan; Seo, Young Jun

    2017-08-15

    We have developed a AuNP-CTG based probing system that is applicable to the detection of many units of CAG repeat sequences which was synthesized by a rolling circle amplification (RCA) system with changes in fluorescence. We also demonstrate that our AuNP-CTG based probing system could transfect without using transfection reagent and detect target CAG repeat sequences in HeLa cells with dramatic changes in fluorescence. This AuNP-CTG based probing system could also be used, in conjunction with the CAG repeat RCA system, to detect target DNA. This system was so sensitive to the target DNA that it could detect even picomolar amounts with amplification of the fluorescence signal. Furthermore, we have used our gold-based CAG probing system for the detection of RNA CAG repeat sequences. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Versatile equipment for mechanical testing of active materials

    Energy Technology Data Exchange (ETDEWEB)

    Bertsch, Johannes; Heimgartner, Peter

    2005-01-01

    At the Paul Scherrer Institute (PSI) 3 different project groups presently perform aging research on active materials. The research fields are fusion, high neutron flux targets and LWR relevant components. Up to now mechanical testing has been performed with small, low dose rate samples behind local shielding, not appropriate for highly activated material. To overcome this situation, a cell concept for active mechanical testing was elaborated and has been erected in PSI's Hotlab. It consists of 4 shielded cells. 3 connected cells are versatile and independently operable for highly beta/gamma active samples. One cell is an alpha/beta/gamma-box which will be realized in a second phase. This paper presents the versatility especially of the beta/gamma-cells: The different user groups perform experiments in these cells, whereas different machines can be placed into the cells. As consequence of the need of heavily shielded cell doors, a special strengthening and levelling of the floor has been required. In all cells the relevant media are installed. Besides the performance of the cells, the project progress as the difficulties and their solutions are described. (Author)

  8. A versatile patterning process based on easily soluble sacrificial bilayers

    Science.gov (United States)

    Harada, Takayuki; Tsukazaki, Atsushi

    2017-08-01

    Development of a microfabrication process is essential to embed fascinating physical properties of functional materials into mesoscopic devices. Different from well-investigated materials with established microfabrication process, newly-discovered materials often meet difficulty when scaling down into a mesoscopic size, because process damages cause serious deterioration of their functionalities. Here, we demonstrate a versatile lift-off method using a carefully designed sacrificial bilayer, composed of an easily soluble layer and a thermally stable rigid layer. In this method, the target films can be grown in optimum conditions, such as high temperature and high oxygen partial pressure, on the stable pre-patterned substrate with the inorganic sacrificial bilayer. After film deposition, measurable patterned devices can be obtained just by a short-time lift-off in a mild chemical solution. We carried out micron-scale patterning and electrical measurements by applying this technique to one of perovskite oxides, SrRuO3, and Fe-based chalcogenide superconductors, FeSe, both of which are incompatible with conventional photolithography and dry-etching processes. The demonstrated narrowest line width of 5 μm is successfully patterned with maintaining the almost identical properties of the pristine films, exemplifying that process damage is minimized. The demonstrated versatile patterning process expands the range of application of emerging functional materials in thin film devices.

  9. Versatile supramolecular organogel with outstanding stability toward aqueous interfaces.

    Science.gov (United States)

    Bonifazi, Evelyn L; Edelsztein, Valeria C; Menéndez, Guillermo O; Samaniego López, Cecilia; Spagnuolo, Carla C; Di Chenna, Pablo H

    2014-06-25

    In this communication, we report on a novel and versatile low-molecular-weight organogelator. The methanolic gel exhibits an exceptional water-enhanced stability as evidenced by a 30 °C increase in Tg with up to 10%v/v of water. This atypical property not observed with other solvents makes of this supramolecular gel a highly stable matrix compatible with aqueous interfaces. As a proof of principle we present the sensing performance of a symmetric tricarbocyanine fluorophore bearing a Zn(II)chelator unit. The system retained its remarkable physical integrity for a long period of time opening new possibilities for other organic-aqueous interface applications.

  10. Research and Analysis Laser Target Optics Characteristics and Signal Recognition Processing in Detection Screen System

    National Research Council Canada - National Science Library

    Hanshan Li; Yanran Li

    2014-01-01

      In order to improve the measurement accuracy of the laser measurement distance system, this paper studies the laser target optics characteristics based on the laser detection principle in the laser...

  11. Coping with Atmospheric Turbulence in the Selection of Laser Hardening Technology for FCS Targeting Systems

    National Research Council Canada - National Science Library

    Pritchett, Timothy M

    2004-01-01

    ... by frequency-agile battlefield lasers at both long and short range. Evidently, the selection of sensor protection technologies for incorporation into the final targeting system will be based on their optical limiting performance under field conditions...

  12. Cannabinoid CB1 receptor-interacting proteins: novel targets for central nervous system drug discovery?

    National Research Council Canada - National Science Library

    Smith, Tricia H; Sim-Selley, Laura J; Selley, Dana E

    2010-01-01

    ...), including CB1 and CB2 receptors. The CB1 receptor is the major cannabinoid receptor in the central nervous system and has gained increasing interest as a target for drug discovery for treatment of nausea, cachexia, obesity, pain...

  13. An Underwater Target Detection System for Electro-Optical Imagery Data

    Science.gov (United States)

    2010-06-01

    The detection method involves identifying frames of interest (FOI) containing the potential targets. Once the FOI have been identified, regions of...complicated one. Previous work on EO data has been focused on Streak Tube Imaging Lidar ( STIL ) system [1]–[4], and laser line scan (LLS) [5]–[7...based systems. STIL sensor produces high- resolution 3-D images of underwater objects by scanning (line by line), on the target field [1]. The collected

  14. [Research progress in developing reporter systems for the enrichment of positive cells with targeted genome modification].

    Science.gov (United States)

    Bai, Yi-chun; Xu, Kun; Wei, Ze-hui; Ma, Zheng; Zhang, Zhi-ying

    2016-01-01

    Targeted genome editing technology plays an important role in studies of gene function, gene therapy and transgenic breeding. Moreover, the efficiency of targeted genome editing is increased dramatically with the application of recently developed artificial nucleases such as ZFNs, TALENs and CRISPR/Cas9. However, obtaining positive cells with targeted genome modification is restricted to some extent by nucleases expression plasmid transfection efficiency, nucleases expression and activity, and repair efficiency after genome editing. Thus, the enrichment and screening of positive cells with targeted genome modification remains a problem that need to be solved. Surrogate reporter systems could be used to reflect the efficiency of nucleases indirectly and enrich genetically modified positive cells effectively, which may increase the efficiency of the enrichment and screening of positive cells with targeted genome modification. In this review, we mainly summarized principles and applications of reporter systems based on NHEJ and SSA repair mechanisms, which may provide references for related studies in future.

  15. Systems biology approaches in identifying the targets of natural compounds for cancer therapy.

    Science.gov (United States)

    Tan, Yi; Wu, Qiong; Xia, Jun; Miele, Lucio; Sarkar, Fazlul H; Wang, Zhiwei

    2013-06-01

    Natural compounds have been known to exert inhibitory effects on the development and progression of human cancers. However, the targets of these naturally occurring agents are largely elusive. Recently, systems biology approaches based on high-throughput technologies such as DNA microarrays have begun to be utilized for investigating the targets of drugs including natural compounds. Therefore, in this review article, we will briefly introduce the several systems biology approaches, and will discuss the application of these new technologies for identifying the therapeutic targets of natural compounds for supporting their roles in the prevention and/or treatment of human cancers. Furthermore, identification of the novel targets will be useful for designing more effective and targeted therapeutic strategies for achieving better treatment outcome in patients diagnosed with cancers.

  16. An analytical approach of thermodynamic behavior in a gas target system on a medical cyclotron.

    Science.gov (United States)

    Jahangiri, Pouyan; Zacchia, Nicholas A; Buckley, Ken; Bénard, François; Schaffer, Paul; Martinez, D Mark; Hoehr, Cornelia

    2016-01-01

    An analytical model has been developed to study the thermo-mechanical behavior of gas targets used to produce medical isotopes, assuming that the system reaches steady-state. It is based on an integral analysis of the mass and energy balance of the gas-target system, the ideal gas law, and the deformation of the foil. The heat transfer coefficients for different target bodies and gases have been calculated. Excellent agreement is observed between experiments performed at TRIUMF's 13 MeV cyclotron and the model. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. How versatile are inositol phosphate kinases?

    OpenAIRE

    Shears, Stephen B.

    2004-01-01

    This review assesses the extent and the significance of catalytic versatility shown by several inositol phosphate kinases: the inositol phosphate multikinase, the reversible Ins(1,3,4) P (3)/Ins(3,4,5,6) P (4) kinase, and the kinases that synthesize diphosphoinositol polyphosphates. Particular emphasis is placed upon data that are relevant to the situation in vivo. It will be shown that catalytic promiscuity towards different inositol phosphates is not typically an evolutionary compromise, bu...

  18. Isatin, a versatile molecule: studies in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Barbara, E-mail: barbara.iq@gmail.com [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil)

    2013-05-15

    Isatin is a small, versatile and widely applicable pharmacological molecule. These characteristics make isatin and its derivatives attractive to many research groups as resources for chemical and pharmacological studies. Although it has a relatively simple structure, isatin is a useful chemical scaffold for a variety of chemical transformations. This article discusses several studies performed by Brazilian groups, including investigations of its structural changes, biological assay designs and new methods for the synthesis of isatin. (author)

  19. Recent Advances and Strategies in Tumor Vasculature Targeted Nano-Drug Delivery Systems.

    Science.gov (United States)

    Ying, Man; Chen, Guanyu; Lu, Weiyue

    2015-01-01

    In recent decades, targeted nano-drug delivery systems have attracted extensive attention in cancer therapy for their efficient drug delivery and tumor site specificity. Tumor vasculature, including angiogenesis and vasculogenic mimicry is associated tightly with tumor growth, progression and metastasis. Therefore, nano-drug delivery systems targeting tumor vasculature are becoming a promising approach for tumor treatment. As complicated mechanisms and various factors are involved in the tumor vasculature, different ligands modified on the surface of nanocarriers acquire active targeting through binding to the receptors over-expressed by cancer cells or angiogenic endothelial cells. In this review, the tumor vasculature characteristics are briefly described and the recent advances and potential strategies in tumor vasculature targeted nano-drug delivery systems are introduced.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-10-09

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

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

    Directory of Open Access Journals (Sweden)

    Feng Jiang

    2015-10-01

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

  3. Adiponectin: a versatile player of innate immunity.

    Science.gov (United States)

    Luo, Yan; Liu, Meilian

    2016-04-01

    Adiponectin acts as a key regulator of the innate immune system and plays a major role in the progression of inflammation and metabolic disorders. Macrophages and monocytes are representative components of the innate immune system, and their proliferation, plasticity, and polarization are a key component of metabolic adaption. Innate-like lymphocytes such as group 2 innate lymphoid cells (ILC2s), natural killer T (NKT) cells, and gamma delta T (γδ T) cells are also members of the innate immune system and play important roles in the development of obesity and its related diseases. Adiponectin senses metabolic stress and modulates metabolic adaption by targeting the innate immune system under physiological and pathological conditions. Defining the mechanisms underlying the role of adiponectin in regulating innate immunity is crucial to adiponectin-based therapeutic intervention. © The Author (2016). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Wenjie Lang

    2015-01-01

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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Yaozhong Hu

    2017-11-01

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

  7. Design of a Compact and Versatile Bench Scale Tubular Reactor

    Directory of Open Access Journals (Sweden)

    R. Prasad

    2009-06-01

    Full Text Available A compact and versatile laboratory tubular reactor has been designed and fabricated keeping in view of reducing capital cost and minimising energy consumption for gas/vapor-phase heterogeneous catalytic reactions. The reactor is consisted of two coaxial corning glass tubes with a helical coil of glass tube in between the coaxial tubes serving as vaporiser and pre-heater, the catalyst bed is in the inner tube. A schematic diagram of the reactor with detailed dimensions and working principles are described. The attractive feature of the reactor is that the vaporiser, pre-heater and fixed bed reactor are merged in a single compact unit. Thus, the unit minimises separate vaporiser and pre-heater, also avoids separate furnaces used for them and eliminate auxiliary instrumentation such as temperature controller etc. To demonstrate the system operation and illustrate the key features, catalyst screening data and the efficient collection of complete, and accurate intrinsic kinetic data are provided for oxidation of CO over copper chromite catalyst. CO oxidation is an important reaction for auto-exhaust pollution control. The suitability of the versatile nature of the reactor has been ascertained for catalytic reactions where either volatile or vaporizable feeds can be introduced to the reaction zone, e.g. oxidation of iso-octane, reduction of nitric oxide, dehydrogenation of methanol, ethanol and iso-propanol, hydrogenation of nitrobenzene to aniline, etc. Copyright (c 2009 by BCREC. All Rights reserved.[Received: 10 February 2009, Accepted: 9 May 2009][How to Cite: R. Prasad, G. Rattan. (2009. Design of a Compact and Versatile Bench Scale Tubular Reactor. Bulletin of Chemical Reaction Engineering and Catalysis, 4(1: 5-9.  doi:10.9767/bcrec.4.1.1250.5-9][How to Link/ DOI: http://dx.doi.org/10.9767/bcrec.4.1.1250.5-9

  8. Submicron Lipid Emulsions: A Versatile Platform for Drug Delivery.

    Science.gov (United States)

    Zhang, Xingwang; Wu, Baojian

    2015-01-01

    Lipid emulsions have turned out to be a versatile tool for systemic delivery of poorly soluble drugs and cytotoxic drugs. Currently, the majority of marketed or developing drugs are recognized as BCS II and IV ones. How to solve the solubility and systemic administration that enables them access to clinical application is arising a great challenge in drug delivery systems. The key considerations for lipid emulsions are how to enhance the drug load, stability and reproducibility. Formulation and manufacture technique play the leading role in development of lipid emulsions. Understanding the biofate and characterization in vitro/vivo is suggestive to exploit the potential of lipid emulsions. This review discussed the manufacture techniques and in vivo behavior of lipid emulsions. Momentous interests were focused on their applications in drug delivery as well as the future evolution. Finally, we appreciated the methodologies of quality control and systemic risks associated with lipid emulsions.

  9. Experience upgrading 18F target and control system of an unshielded RDS112

    Science.gov (United States)

    Arenas, G.; Calderon, G.; Noya, E.

    2017-05-01

    The 18F target and the Control System of an unshielded CTI RDS112 cyclotron have been upgraded in order to increase 18F-fluoride production and meet new radioprotection requirements of the National Regulator, among other goals. At present, maximum capacity of 18F-fluoride production of the cyclotron is about 5 times bigger than originally with a higher reproducibility and more flexibility given by two targets with different rated filling capacities. Also, safety and procedure interlock systems have been integrated and validated in the new Control System.

  10. A monocular vision system based on cooperative targets detection for aircraft pose measurement

    Science.gov (United States)

    Wang, Zhenyu; Wang, Yanyun; Cheng, Wei; Chen, Tao; Zhou, Hui

    2017-08-01

    In this paper, a monocular vision measurement system based on cooperative targets detection is proposed, which can capture the three-dimensional information of objects by recognizing the checkerboard target and calculating of the feature points. The aircraft pose measurement is an important problem for aircraft’s monitoring and control. Monocular vision system has a good performance in the range of meter. This paper proposes an algorithm based on coplanar rectangular feature to determine the unique solution of distance and angle. A continuous frame detection method is presented to solve the problem of corners’ transition caused by symmetry of the targets. Besides, a displacement table test system based on three-dimensional precision and measurement system human-computer interaction software has been built. Experiment result shows that it has a precision of 2mm in the range of 300mm to 1000mm, which can meet the requirement of the position measurement in the aircraft cabin.

  11. Targeted Delivery System of Nanobiomaterials in Anticancer Therapy: From Cells to Clinics

    Directory of Open Access Journals (Sweden)

    Su-Eon Jin

    2014-01-01

    Full Text Available Targeted delivery systems of nanobiomaterials are necessary to be developed for the diagnosis and treatment of cancer. Nanobiomaterials can be engineered to recognize cancer-specific receptors at the cellular levels and to deliver anticancer drugs into the diseased sites. In particular, nanobiomaterial-based nanocarriers, so-called nanoplatforms, are the design of the targeted delivery systems such as liposomes, polymeric nanoparticles/micelles, nanoconjugates, norganic materials, carbon-based nanobiomaterials, and bioinspired phage system, which are based on the nanosize of 1–100 nm in diameter. In this review, the design and the application of these nanoplatforms are discussed at the cellular levels as well as in the clinics. We believe that this review can offer recent advances in the targeted delivery systems of nanobiomaterials regarding in vitro and in vivo applications and the translation of nanobiomaterials to nanomedicine in anticancer therapy.

  12. [The research on a pocket microcontroller system for target controlled infusion].

    Science.gov (United States)

    Cheng, Yu-Ke; Zhang, Xin-An; Zhang, Yan-Wu; Wu, Qun-Ling; Dou, Jian-Hong; Wang, Rou-Shong

    2005-05-01

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

  13. [High-speed target recognition positioning system based on multi-spectral radiation characteristics].

    Science.gov (United States)

    Li, Jian-Min; Wang, Gao

    2014-11-01

    In order to achieve quick recognition and positioning of the high-speed target, using multi-spectral radiation combined with acoustic positioning technology, in the passive state, the blast wave spectral characteristics and acoustic characteristics of the measured target were rapidly obtained, thus analysis was performed to determine the type, location and other important parameters. Multi-spectral radiation detection target recognition formula was deduced. The accuracy of the optical path length and the logical integration time was calculated by shock acoustic positioning method. Experiments used 5.56 mm NATO bullets, 7.62 mm 56-rifle bullets, 12.7 mm 54 type machine-gun bullets as a target identified projectile. Interference fringes were collected by the static Fourier transform interferometer system and ICX387AL type CCD, and the peak of sound pressure was collected using 2209 pulse sound pressure meter made by B & K Company from Denmark Experimental results show that for the 5.56 mm NATO bullets, the three characteristic wavelengths position amplitudes are close to each other, with the maximum amplitude at 966 nm; For the 7.62 mm 56-rifle bullets, 935 nm is the maximum amplitude position, while for 966 and 997 nm position the magnitudes are sunukar; For 12.7 mm 54 type machine-gun bullets, the three wavelengths show a ladder-like distribution. With the increase in the detection distance spectral radiation energy decreased. Meanwhile, with the decrease in the total radiation spectrum, the spectrum of target was affected strongly by background noise, and the SNR of system was decreased. But the spectral characteristics of different target still exist, the target species can be identified by the system with the ratio algorithm of characteristic peaks. Through spectral calibration and characteristic wavelengths extraction, the target can successfully identify the type of projectile and target position, and it meets the design requirements.

  14. Targeting the orexinergic system: Mainly but not only for sleep-wakefulness therapies

    Directory of Open Access Journals (Sweden)

    Abdelaziz Ghanemi

    2015-12-01

    Full Text Available Orexin receptors belong to the big family of G protein coupled receptors (GPCRs that constitute the main targets in the modern pharmacological approaches. Although the orexinergic system is involved in a variety of processes, treating sleep-wakefulness disorders such as narcolepsy and insomnia, remains the main therapeutic implication of targeting orexinergic receptors. After novel advances, such as the description of the binding pockets, and ligand developments, more researchers are focusing on orexin receptors as promising targets. Furthermore, targeting these receptors may provide therapeutic solutions for some health problems, other than sleep-wakefulness disorders including some psychiatric disorders and neurodegenerative diseases. Within this paper, we put a spotlight on the orexins’ physiology, pathophysiology and pharmacology of mainly sleep-wakefulness. We have also reviewed examples about other orexinergic system-related disorders. We further illustrated recent development in orexin receptors’ agonists and antagonists. In addition, we discussed selected progresses in orexinergic receptors’ ligands.

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

    Directory of Open Access Journals (Sweden)

    Jinjian Jiang

    2017-01-01

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

  16. Quantitating plant microRNA-mediated target repression using a dual-luciferase transient expression system.

    Science.gov (United States)

    Liu, Qikun; Axtell, Michael J

    2015-01-01

    microRNA (miRNA) mediated repression of target genes plays essential roles in a variety of functions in plants. An easy-to-use method that can effectively validate functional miRNA-target interactions in plants thus is of particular interest. Here, we describe an Agrobacterium tumefaciens-mediated in vivo assay utilizing a dual-luciferase reporter system. With this method, the strength of miRNA-mediated target repression can be quantified at both the mRNA (via qRT-PCR) and protein (via dual-luciferase assay) levels quickly and accurately.

  17. RNA-guided complex from a bacterial immune system enhances target recognition through seed sequence interactions

    OpenAIRE

    Wiedenheft, Blake; van Duijn, Esther; Bultema, Jelle; Waghmare, Sakharam; Zhou, Kaihong; Barendregt, Arjan; Westphal, Wiebke; Heck, Albert; Boekema, Egbert; Dickman, Mark; Doudna, Jennifer A.

    2011-01-01

    Prokaryotes have evolved multiple versions of an RNA-guided adaptive immune system that targets foreign nucleic acids. In each case, transcripts derived from clustered regularly interspaced short palindromic repeats (CRISPRs) are thought to selectively target invading phage and plasmids in a sequence-specific process involving a variable cassette of CRISPR-associated (cas) genes. The CRISPR locus in Pseudomonas aeruginosa (PA14) includes four cas genes that are unique to and conserved in micr...

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

    Science.gov (United States)

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

    2015-01-01

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

  19. Recent advances in brain tumor-targeted nano-drug delivery systems.

    Science.gov (United States)

    Liu, Yu; Lu, Weiyue

    2012-06-01

    Brain tumors represent one of the most challenging and difficult areas in unmet medical needs. Fortunately, the past decade has seen momentous developments in brain tumor research in terms of brain tumor-targeted novel nano-drug delivery systems with significant important superiority over conventional formulations with respect to decreased toxicity and improved pharmacokinetics/pharmacodynamics. This review first introduces the characteristics of the two major obstacles in brain-tumor targeted delivery, blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), and then reviews recent advances in brain tumor-targeted novel nano-drug delivery systems according to their targeting strategies aimed at different stages of brain tumor development and growth. Based on continuously changing vascular characteristics of brain tumors at different development and growth stages, we propose the concept of 'whole-process targeting' for brain tumor for nano-drug delivery systems, referring to a series of overall targeted drug delivery strategies aimed at key points during the whole development of brain tumors.

  20. Targeted Drug Delivery Systems and Their Therapeutic Applications in Cancer and Immune Pathological Conditions.

    Science.gov (United States)

    Iqbal, Jamshed; Anwar, Fareeha; Afridi, Saifullah

    2017-01-01

    More than a century ago, Paul Ehrlich proposed the idea of a drug working as a "magic bullet" that selectively eliminates diseased cells without harming the surrounding normal cells. Since then, much progress has been made in this field to broaden the scope for targeted delivery of drugs. A major problem remain the toxic effects of targeted drugs on healthy cells. In order to reduce the adverse effects of chemotherapy on healthy tissues, we survey the use of recent drug delivery systems for targeted therapy. The selective delivery of the drugs to specific diseased cells or tissues still is a daunting task. Ideally, for target drug delivery systems, the system should be made up of carriers and drugs, where carriers precisely target the desired drug. This issue covers the recent advancements in modern techniques for such purposes. It encompasses advances, benefits and limitations in state of art work of targeted drug delivery through hydrogels, microfluidics, nanoparticles, carbon nanotubes, polymeric micelles, liposomes, lipoprotein based drug carriers and dendrites. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    Science.gov (United States)

    2011-01-01

    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. PMID:21995320

  2. Effective and versatile software beamformation toolbox

    DEFF Research Database (Denmark)

    Kortbek, Jacob; Nikolov, Svetoslav; Jensen, Jørgen Arendt

    2007-01-01

    aperture to obtain a preferred constant F-number. An effective and versatile software toolbox for off-line beamformation designed to address all of these issues has been developed. It is capable of exploiting parallelization of computations on a Linux cluster and is written in C++ with a MATLAB (Math Works...... and stored in lookup-tables (LUT). Parametric beamforming can also be applied where calculations are done by demand, thus, reducing the storage demand dramatically. On a standard PC with a Pentium 4, 2.66 GHz processor running Linux the toolbox can beamform 100,000 points in lines of various directions in 20...

  3. Systems and methods for managing shared-path instrumentation and irradiation targets in a nuclear reactor

    Science.gov (United States)

    Heinold, Mark R.; Berger, John F.; Loper, Milton H.; Runkle, Gary A.

    2015-12-29

    Systems and methods permit discriminate access to nuclear reactors. Systems provide penetration pathways to irradiation target loading and offloading systems, instrumentation systems, and other external systems at desired times, while limiting such access during undesired times. Systems use selection mechanisms that can be strategically positioned for space sharing to connect only desired systems to a reactor. Selection mechanisms include distinct paths, forks, diverters, turntables, and other types of selectors. Management methods with such systems permits use of the nuclear reactor and penetration pathways between different systems and functions, simultaneously and at only distinct desired times. Existing TIP drives and other known instrumentation and plant systems are useable with access management systems and methods, which can be used in any nuclear plant with access restrictions.

  4. The renin-angiotensin system: a possible new target for depression.

    Science.gov (United States)

    Vian, João; Pereira, Círia; Chavarria, Victor; Köhler, Cristiano; Stubbs, Brendon; Quevedo, João; Kim, Sung-Wan; Carvalho, André F; Berk, Michael; Fernandes, Brisa S

    2017-08-01

    Depression remains a debilitating condition with an uncertain aetiology. Recently, attention has been given to the renin-angiotensin system. In the central nervous system, angiotensin II may be important in multiple pathways related to neurodevelopment and regulation of the stress response. Studies of drugs targeting the renin-angiotensin system have yielded promising results. Here, we review the potential beneficial effects of angiotensin blockers in depression and their mechanisms of action. Drugs blocking the angiotensin system have efficacy in several animal models of depression. While no randomised clinical trials were found, case reports and observational studies showed that angiotensin-converting enzyme inhibitors or angiotensin receptor blockers had positive effects on depression, whereas other antihypertensive agents did not. Drugs targeting the renin-angiotensin system act on inflammatory pathways implicated in depression. Both preclinical and clinical data suggest that these drugs possess antidepressant properties. In light of these results, angiotensin system-blocking agents offer new horizons in mood disorder treatment.

  5. Video camera system for locating bullet holes in targets at a ballistics tunnel

    Science.gov (United States)

    Burner, A. W.; Rummler, D. R.; Goad, W. K.

    1990-01-01

    A system consisting of a single charge coupled device (CCD) video camera, computer controlled video digitizer, and software to automate the measurement was developed to measure the location of bullet holes in targets at the International Shooters Development Fund (ISDF)/NASA Ballistics Tunnel. The camera/digitizer system is a crucial component of a highly instrumented indoor 50 meter rifle range which is being constructed to support development of wind resistant, ultra match ammunition. The system was designed to take data rapidly (10 sec between shoots) and automatically with little operator intervention. The system description, measurement concept, and procedure are presented along with laboratory tests of repeatability and bias error. The long term (1 hour) repeatability of the system was found to be 4 microns (one standard deviation) at the target and the bias error was found to be less than 50 microns. An analysis of potential errors and a technique for calibration of the system are presented.

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

    Directory of Open Access Journals (Sweden)

    Janel Kydd

    2017-10-01

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

  7. Versatile aggressive mimicry of cicadas by an Australian predatory katydid.

    Directory of Open Access Journals (Sweden)

    David C Marshall

    Full Text Available BACKGROUND: In aggressive mimicry, a predator or parasite imitates a signal of another species in order to exploit the recipient of the signal. Some of the most remarkable examples of aggressive mimicry involve exploitation of a complex signal-response system by an unrelated predator species. METHODOLOGY/PRINCIPAL FINDINGS: We have found that predatory Chlorobalius leucoviridis katydids (Orthoptera: Tettigoniidae can attract male cicadas (Hemiptera: Cicadidae by imitating the species-specific wing-flick replies of sexually receptive female cicadas. This aggressive mimicry is accomplished both acoustically, with tegminal clicks, and visually, with synchronized body jerks. Remarkably, the katydids respond effectively to a variety of complex, species-specific Cicadettini songs, including songs of many cicada species that the predator has never encountered. CONCLUSIONS/SIGNIFICANCE: We propose that the versatility of aggressive mimicry in C. leucoviridis is accomplished by exploiting general design elements common to the songs of many acoustically signaling insects that use duets in pair-formation. Consideration of the mechanism of versatile mimicry in C. leucoviridis may illuminate processes driving the evolution of insect acoustic signals, which play a central role in reproductive isolation of populations and the formation of species.

  8. Activation analysis of targets and lead in a lead slowing down spectrometer system

    Directory of Open Access Journals (Sweden)

    Yongdeok Lee

    2018-02-01

    Full Text Available A neutron generation system was developed to induce fissile fission in a lead slowing down spectrometer (LSDS system. The source neutron is one of the key factors for LSDS system work. The LSDS was developed to quantify the isotopic contents of fissile materials in spent nuclear fuel and recycled fuel. The source neutron is produced at a multilayered target by the (e,γ(γ,n reaction and slowed down at the lead medium. Activation analysis of the target materials is necessary to estimate the lifetime, durability, and safety of the target system. The CINDER90 code was used for the activation analysis, and it can involve three-dimensional geometry, position dependent neutron flux, and multigroup cross-section libraries. Several sensitivity calculations for a metal target with different geometries, materials, and coolants were done to achieve a high neutron generation rate and a low activation characteristic. Based on the results of the activation analysis, tantalum was chosen as a target material due to its better activation characteristics, and helium gas was suggested as a coolant. In addition, activation in a lead medium was performed. After a distance of 55 cm from the lead surface to the neutron incidence, the neutron intensity dramatically decreased; this result indicates very low activation.

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

    Science.gov (United States)

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

    2014-02-20

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

  10. RNA-guided complex from a bacterial immune system enhances target recognition through seed sequence interactions

    Science.gov (United States)

    Wiedenheft, Blake; van Duijn, Esther; Bultema, Jelle B.; Waghmare, Sakharam P.; Zhou, Kaihong; Barendregt, Arjan; Westphal, Wiebke; Heck, Albert J. R.; Boekema, Egbert J.; Dickman, Mark J.; Doudna, Jennifer A.

    2011-01-01

    Prokaryotes have evolved multiple versions of an RNA-guided adaptive immune system that targets foreign nucleic acids. In each case, transcripts derived from clustered regularly interspaced short palindromic repeats (CRISPRs) are thought to selectively target invading phage and plasmids in a sequence-specific process involving a variable cassette of CRISPR-associated (cas) genes. The CRISPR locus in Pseudomonas aeruginosa (PA14) includes four cas genes that are unique to and conserved in microorganisms harboring the Csy-type (CRISPR system yersinia) immune system. Here we show that the Csy proteins (Csy1–4) assemble into a 350 kDa ribonucleoprotein complex that facilitates target recognition by enhancing sequence-specific hybridization between the CRISPR RNA and complementary target sequences. Target recognition is enthalpically driven and localized to a “seed sequence” at the 5′ end of the CRISPR RNA spacer. Structural analysis of the complex by small-angle X-ray scattering and single particle electron microscopy reveals a crescent-shaped particle that bears striking resemblance to the architecture of a large CRISPR-associated complex from Escherichia coli, termed Cascade. Although similarity between these two complexes is not evident at the sequence level, their unequal subunit stoichiometry and quaternary architecture reveal conserved structural features that may be common among diverse CRISPR-mediated defense systems. PMID:21536913

  11. Efficient gene targeting in golden Syrian hamsters by the CRISPR/Cas9 system.

    Directory of Open Access Journals (Sweden)

    Zhiqiang Fan

    Full Text Available The golden Syrian hamster is the model of choice or the only rodent model for studying many human diseases. However, the lack of gene targeting tools in hamsters severely limits their use in biomedical research. Here, we report the first successful application of the CRISPR/Cas9 system to efficiently conduct gene targeting in hamsters. We designed five synthetic single-guide RNAs (sgRNAs--three for targeting the coding sequences for different functional domains of the hamster STAT2 protein, one for KCNQ1, and one for PPP1R12C--and demonstrated that the CRISPR/Cas9 system is highly efficient in introducing site-specific mutations in hamster somatic cells. We then developed unique pronuclear (PN and cytoplasmic injection protocols in hamsters and produced STAT2 knockout (KO hamsters by injecting the sgRNA/Cas9, either in the form of plasmid or mRNA, targeting exon 4 of hamster STAT2. Among the produced hamsters, 14.3% and 88.9% harbored germline-transmitted STAT2 mutations from plasmid and mRNA injection, respectively. Notably, 10.4% of the animals produced from mRNA injection were biallelically targeted. This is the first success in conducting site-specific gene targeting in hamsters and can serve as the foundation for developing other genetically engineered hamster models for human disease.

  12. Efficient gene targeting in golden Syrian hamsters by the CRISPR/Cas9 system.

    Science.gov (United States)

    Fan, Zhiqiang; Li, Wei; Lee, Sang R; Meng, Qinggang; Shi, Bi; Bunch, Thomas D; White, Kenneth L; Kong, Il-Keun; Wang, Zhongde

    2014-01-01

    The golden Syrian hamster is the model of choice or the only rodent model for studying many human diseases. However, the lack of gene targeting tools in hamsters severely limits their use in biomedical research. Here, we report the first successful application of the CRISPR/Cas9 system to efficiently conduct gene targeting in hamsters. We designed five synthetic single-guide RNAs (sgRNAs)--three for targeting the coding sequences for different functional domains of the hamster STAT2 protein, one for KCNQ1, and one for PPP1R12C--and demonstrated that the CRISPR/Cas9 system is highly efficient in introducing site-specific mutations in hamster somatic cells. We then developed unique pronuclear (PN) and cytoplasmic injection protocols in hamsters and produced STAT2 knockout (KO) hamsters by injecting the sgRNA/Cas9, either in the form of plasmid or mRNA, targeting exon 4 of hamster STAT2. Among the produced hamsters, 14.3% and 88.9% harbored germline-transmitted STAT2 mutations from plasmid and mRNA injection, respectively. Notably, 10.4% of the animals produced from mRNA injection were biallelically targeted. This is the first success in conducting site-specific gene targeting in hamsters and can serve as the foundation for developing other genetically engineered hamster models for human disease.

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

    Science.gov (United States)

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

    2017-11-27

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

  14. Target decoupling in a coupled optical system resistant to random perturbation

    CERN Document Server

    Yu, Sunkyu; Park, Namkyoo

    2016-01-01

    To suppress unwanted crosstalks between nearby optical elements, the decoupling technique for integrated systems has been desired for the target control of light flows. Although cloaking methods have enabled complete decoupling of optical elements by manipulating electromagnetic waves microscopically, it is neither feasible nor necessary to control each unit element in coupled systems when considering severe restrictions on material parameters for cloaking. Here we develop the macroscopic approach to design crosstalk-free regions in coupled optical systems. By inversely designing the eigenstate which encompasses target elements, the stable decoupling of the elements from the coupled system is achieved, being completely independent from the random alteration of the decoupled region, and at the same time, allowing coherent and scattering-free wave transport with desired spatial profiles. We also demonstrate the decoupling in disordered systems, overcoming the transport blockade from Anderson localization. Our r...

  15. Targeting the innate immune system as immunotherapy for Acute Myeloid Leukemia (AML

    Directory of Open Access Journals (Sweden)

    Emily Kathleen Curran

    2015-04-01

    Full Text Available Because of its disseminated nature and lack of tumor-draining lymph nodes, acute myeloid leukemia (AML likely employs unique immune evasion strategies as compared to solid malignancies. Targeting these unique mechanisms may result in improved immunotherapeutic approaches. Emerging data suggests that a specific dendritic cell (DC subset, CD8α DCs, may be responsible for mediating tolerance in AML and thus targeting the innate immune system may be of benefit in this disease. Promising immune targets include the Toll-like receptors (TLRs, calreticulin/CD47, the stimulator of interferon genes (STING pathway and signal transducer and activator of transcription 3 (STAT3. However, it is becoming clear that compensatory mechanisms may limit the efficacy of these agents alone and thus rationale combinations of immunotherapies are warranted. This review discusses the potential immune evasion strategies in AML, as well as discussion of the promising innate immune targets, both alone and in combination, for this disease.

  16. A versatile apparatus for two-dimensional atomtronic quantum simulation

    Science.gov (United States)

    Haase, T. A.; White, D. H.; Brown, D. J.; Herrera, I.; Hoogerland, M. D.

    2017-11-01

    We report on the implementation of a novel optical setup for generating high-resolution customizable potentials to address ultracold bosonic atoms in two dimensions. Two key features are developed for this purpose. The customizable potential is produced with a direct image of a spatial light modulator, conducted with an in-vacuum imaging system of high numerical aperture. Custom potentials are drawn over an area of 600 ×400 μ m with a resolution of 0.9 μm. The second development is a two-dimensional planar trap for atoms with an aspect ratio of 900 and spatial extent of Rayleigh range 1.6 × 1.6 mm, providing near-ballistic in-planar movement. We characterize the setup and present a brief catalog of experiments to highlight the versatility of the system.

  17. The Effusive-Flow Properties of Target/Vapor-Transport Systems for Radioactive Ion Beam Applications

    CERN Document Server

    Kawai, Yoko; Liu, Yuan

    2005-01-01

    Radioactive atoms produced by the ISOL technique must diffuse from a target, effusively flow to an ion source, be ionized, be extracted, and be accelerated to research energies in a time commensurate with the lifetime of the species of interest. We have developed a fast valve system (closing time ~100 us) that can be used to accurately measure the effusion times of chemically active or inactive species through arbitrary geometry and size vapor transport systems with and without target material in the reservoir. The effusive flow times are characteristic of the system and thus serve as figures of merit for assessing the quality of a given vapor transport system as well as for assessing the permeability properties of a given target design. This article presents effusive flow data for noble gases flowing through a target reservoir and ion source system routinely used to generate radioactive species at the HRIBF with and without disks of 6 times and 10 times compressed Reticulated Vitreous Carbon Foam (RVCF) with...

  18. Efficient Targeted Genome Modification in Maize Using CRISPR/Cas9 System.

    Science.gov (United States)

    Feng, Chao; Yuan, Jing; Wang, Rui; Liu, Yang; Birchler, James A; Han, Fangpu

    2016-01-20

    CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 system, which is a newly developed technology for targeted genome modification, has been successfully used in a number of species. In this study, we applied this technology to carry out targeted genome modification in maize. A marker gene Zmzb7 was chosen for targeting. The sgRNA-Cas9 construct was transformed into maize protoplasts, and indel (insertion and deletion) mutations could be detected. A mutant seedling with an expected albino phenotype was obtained from screening 120 seedlings generated from 10 callus events. Mutation efficiency in maize heterochromatic regions was also investigated. Twelve sites with different expression levels in maize centromeres or pericentromere regions were selected. The sgRNA-Cas9 constructs were transformed into protoplasts followed by sequencing the transformed protoplast genomic DNA. The results show that the genes in heterochromatic regions could be targeted by the CRISPR/Cas9 system efficiently, no matter whether they are expressed or not. Meanwhile, off-target mutations were not found in the similar sites having no PAM (protospacer adjacent motif) or having more than two mismatches. Together, our results show that the CRISPR/Cas9 system is a robust and efficient tool for genome modification in both euchromatic and heterochromatic regions in maize. Copyright © 2015 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

  19. Mid-infrared imaging system based on polarizers for detecting marine targets covered in sun glint.

    Science.gov (United States)

    Zhao, Huijie; Ji, Zheng; Zhang, Ying; Sun, Xiaofeng; Song, Pengfei; Li, Yansong

    2016-07-25

    When a marine target is detected by a mid-infrared detector on a sunny day, the target's information could be lost if it is located in sun glint. Therefore, we developed a new mid-infrared imaging system capable of effectively detecting marine targets in regions of strong sun glint, which is presented in this report. Firstly, the theory of the analysis methods employed in different detection scenarios is briefly described to establish whether one or two polarizers should be utilized to suppress further the p-polarized component of sun glint. Secondly, for the case in which a second polarizer is employed, the formula for the optimum angle between the two polarizers is given. Then, the results of our field experiment are presented, demonstrating that the developed system can significantly reduce sun glint and can enhance the contrast of target images. A commonly used image processing algorithm proved capable of identifying a target in sun glint, confirming the effectiveness of our proposed mid-infrared polarization imaging system.

  20. Development of a Versatile Ultrasonic Internal Pipe/Vessel Component Monitor for In-Service Inspection of Nuclear Reactor Components

    Energy Technology Data Exchange (ETDEWEB)

    Searfass, Clifford T. [Structural Integrity Associates, Inc., State College, PA (United States); Malinowski, Owen M. [Structural Integrity Associates, Inc., State College, PA (United States); Van Velsor, Jason K. [Structural Integrity Associates, Inc., State College, PA (United States)

    2015-03-22

    The stated goal of this work was to develop a versatile system which could accurately measure vessel and valve internal vibrations and cavitation formation under in-service conditions in nuclear power plants, ultrasonically. The developed technology will benefit the nuclear power generation industry by allowing plant operators to monitor valve and vessel internals during operation. This will help reduce planned outages and plant component failures. During the course of this work, Structural Integrity Associates, Inc. gathered information from industry experts that target vibration amplitudes to be detected should be in the range of 0.001-in to 0.005-in (0.025-mm to 0.127-mm) and target vibration frequency ranges which should be detected were found to be between 0-Hz and 300-Hz. During the performed work, an ultrasonic measuring system was developed which utilized ultrasonic pulse-echo time-of-flight measurements to measure vibration frequency and amplitude. The developed system has been shown to be able to measure vibration amplitudes as low as 0.0008-in (0.020-mm) with vibration frequencies in the range of 17-Hz to 1000-Hz. Therefore, the developed system was able to meet the industry needs for vibration measurement. The developed ultrasonic system was also to be able to measure cavitation formation by monitoring the received ultrasonic time- and frequency-domain signals. This work also demonstrated the survivability of commercially available probes at temperatures up to 300-F for several weeks.

  1. Improving oncology outcomes through targeted therapeutics will require electronic delivery systems.

    Science.gov (United States)

    van Rooij, Tibor; Marsh, Sharon

    2011-05-01

    Typically, chemotherapy selection takes into account patient demographic data, including disease symptoms, family history, environmental factors and concurrent medications. Although validated and approved genomics tests are available for targeted therapeutics, a major challenge facing healthcare is the ability to process the genomic data in the patient's context and to return clinically interpretable dosing guidance to the physician in a realistic time frame. Delivery of these targeted therapeutics, made possible by clinical decision support systems connected to an electronic health record may help drive both the acceptance and adaptation of an electronic health record system, as well as provide personalized information at point-of-care, as part of the routine workflow. The realization of targeted therapeutics will depend on the concerted efforts of stakeholder groups as they address political, ethical, socioeconomical and technical challenges to achieve personalized medicine adoption through real-world implementation.

  2. Multiplexed Targeted Genome Engineering Using a Universal Nuclease-Assisted Vector Integration System.

    Science.gov (United States)

    Brown, Alexander; Woods, Wendy S; Perez-Pinera, Pablo

    2016-07-15

    Engineered nucleases are capable of efficiently modifying complex genomes through introduction of targeted double-strand breaks. However, mammalian genome engineering remains limited by low efficiency of heterologous DNA integration at target sites, which is typically performed through homologous recombination, a complex, ineffective and costly process. In this study, we developed a multiplexable and universal nuclease-assisted vector integration system for rapid generation of gene knock outs using selection that does not require customized targeting vectors, thereby minimizing the cost and time frame needed for gene editing. Importantly, this system is capable of remodeling native mammalian genomes through integration of DNA, up to 50 kb, enabling rapid generation and screening of multigene knockouts from a single transfection. These results support that nuclease assisted vector integration is a robust tool for genome-scale gene editing that will facilitate diverse applications in synthetic biology and gene therapy.

  3. The endocannabinoid system: its roles in energy balance and potential as a target for obesity treatment.

    Science.gov (United States)

    André, Aurore; Gonthier, Marie-Paule

    2010-11-01

    Obesity and cardiometabolic risk continue to be major public health concerns. A better understanding of the physiopathological mechanisms leading to obesity may help to identify novel therapeutic targets. The endocannabinoid system discovered in the early 1990s is believed to influence body weight regulation and cardiometabolic risk factors. This article aims to review the literature on the endocannabinoid system including the biological roles of its major components, namely, the cannabinoid receptors, their endogenous ligands the endocannabinoids and the ligand-metabolising enzymes. The review also discusses evidence that the endocannabinoid system constitutes a new physiological pathway occurring in the central nervous system and peripheral tissues that has a key role in the control of food intake and energy expenditure, insulin sensitivity, as well as glucose and lipid metabolism. Based on the important finding that there is a close association between obesity and the hyperactivity of the endocannabinoid system, interest in blocking stimulation of this pathway to aid weight loss and reduce cardiometabolic risk factor development has become an important area of research. Among the pharmacological strategies proposed, the antagonism of the cannabinoid receptors has been particularly investigated and several clinical trials have been conducted. One challenging pharmacological task will be to target the endocannabinoid system in a more selective, and hence, safe way. As the management of obesity also requires lifestyle modifications in terms of healthy eating and physical activity, the targeting of the endocannabinoid system may represent a novel approach for a multifactorial therapeutic strategy. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Versatile and Extensible, Continuous-Thrust Trajectory Optimization Tool Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose to develop an innovative, versatile and extensible, continuous-thrust trajectory optimization tool for planetary mission design and optimization of...

  5. Targeted nanoparticulate drug-delivery systems for treatment of solid tumors: a review.

    Science.gov (United States)

    Bhattacharjee, Himanshu; Balabathula, Pavan; Wood, George C

    2010-11-01

    Technological advancements in the field of biomaterials, polymer chemistry and drug-delivery techniques have aided the development of a number of new drug-delivery systems for targeting to solid tumors. Numerous research groups have explored the possibility of utilizing tumor-specific drug-delivery systems using nanoparticles. In this review we have attempted to highlight the achievements of some research groups actively involved in nanoparticulate drug delivery systems. The manuscript presents an in-depth discussion for nanoparticle systems such as micelles, liposomes, dendrimers, nanoemulsion, solid lipid nanoparticles and carbon fullerenes as chemotherapeutic options. The review reiterates the importance of the basic fundamentals of targeted drug delivery using nanoparticles and the influence of physiological parameters on their efficacy.

  6. A numerical study of the target system of an ADSS with different flow ...

    Indian Academy of Sciences (India)

    solved numerically using the streamline upwind Petrov–Galerkin (SUPG) finite element. (FE) method. The target systems with a straight and a nozzle guide have been considered. The principal purpose of the analysis is to trace the flow and temperature distribution and thereby to check the suitability of the flow guide in ...

  7. Dissecting molecular interactions involved in recognition of target disulfides by the barley thioredoxin system

    DEFF Research Database (Denmark)

    Björnberg, Olof; Maeda, Kenji; Svensson, Birte

    2012-01-01

    Thioredoxin reduces disulfide bonds, thus regulating activities of target proteins in various biological systems, e.g., inactivation of inhibitors of starch hydrolases and proteases in germinating plant seeds. In the three-dimensional structure of a complex with barley α-amylase/subtilisin...

  8. Small-Medium Vessel Vasculitides: is the Complement System a Potential Forgotten Target?

    Science.gov (United States)

    Ballanti, Eleonora; Chimenti, Maria S; Perricone, Roberto

    2015-02-01

    Systemic vasculitides are a group of uncommon diseases characterized by blood vessel inflammation. The complement system is involved in the pathogenesis and clinical manifestations of several autoimmune diseases, including systemic vasculitides. This enzymatic system is a component of the innate immune system. Its main function was initially believed to be limited to the recognition and elimination of pathogens, but research in recent years has demonstrated the important role that complement proteins play in modulating adaptive immunity and in bridging innate and adaptive responses. Its activation is also critical for the development of T cell immunity and natural antibodies as well as for the regulation of autoreactive B cells. In systemic vasculitides, particularly small-medium vesselvasculitides, the complement system has been shown to contribute to the development of inflammatory damage. In view of these crucial functions, the complement system represents an attractive therapeutic target for a wide range of diseases. including vasculitic disorders.

  9. Targeting the Glutamatergic System to Develop Novel, Improved Therapeutics for Mood Disorders

    Science.gov (United States)

    Sanacora, Gerard; Zarate, Carlos A.; Krystal, John; Manji, Husseini K.

    2009-01-01

    PREFACE Mood disorders are common, chronic, recurrent mental illnesses that affect the lives of millions of individuals worldwide. To date, the monoaminergic systems (serotonergic, noradrenergic and dopaminergic) in the brain have received the greatest attention in neurobiological studies of mood disorders, and most therapeutics target these systems. However, there is growing evidence that the glutamatergic system is central to the neurobiology and treatment of these disorders. Here, we review data supporting the involvement of the glutamatergic system in mood disorder pathophysiology as well as the efficacy of glutamatergic agents in mood disorders. We also discuss exciting new prospects for the development of improved therapeutics for these devastating disorders. PMID:18425072

  10. Targeting the Cholinergic System to Develop a Novel Therapy for Huntington's Disease.

    Science.gov (United States)

    D'Souza, Gary X; Waldvogel, Henry J

    2016-12-15

    In this review, we outline the role of the cholinergic system in Huntington's disease, and briefly describe the dysfunction of cholinergic transmission, cholinergic neurons, cholinergic receptors and cholinergic survival factors observed in post-mortem human brains and animal models of Huntington's disease. We postulate how the dysfunctional cholinergic system can be targeted to develop novel therapies for Huntington's disease, and discuss the beneficial effects of cholinergic therapies in pre-clinical and clinical studies.

  11. CFD Analysis and Design of Detailed Target Configurations for an Accelerator-Driven Subcritical System

    Energy Technology Data Exchange (ETDEWEB)

    Kraus, Adam; Merzari, Elia; Sofu, Tanju; Zhong, Zhaopeng; Gohar, Yousry

    2016-08-01

    High-fidelity analysis has been utilized in the design of beam target options for an accelerator driven subcritical system. Designs featuring stacks of plates with square cross section have been investigated for both tungsten and uranium target materials. The presented work includes the first thermal-hydraulic simulations of the full, detailed target geometry. The innovative target cooling manifold design features many regions with complex flow features, including 90 bends and merging jets, which necessitate three-dimensional fluid simulations. These were performed using the commercial computational fluid dynamics code STAR-CCM+. Conjugate heat transfer was modeled between the plates, cladding, manifold structure, and fluid. Steady-state simulations were performed but lacked good residual convergence. Unsteady simulations were then performed, which converged well and demonstrated that flow instability existed in the lower portion of the manifold. It was established that the flow instability had little effect on the peak plate temperatures, which were well below the melting point. The estimated plate surface temperatures and target region pressure were shown to provide sufficient margin to subcooled boiling for standard operating conditions. This demonstrated the safety of both potential target configurations during normal operation.

  12. Urokinase plasminogen activator system-targeted delivery of nanobins as a novel ovarian cancer therapy.

    Science.gov (United States)

    Zhang, Yilin; Kenny, Hilary A; Swindell, Elden P; Mitra, Anirban K; Hankins, Patrick L; Ahn, Richard W; Gwin, Katja; Mazar, Andrew P; O'Halloran, Thomas V; Lengyel, Ernst

    2013-12-01

    The urokinase system is overexpressed in epithelial ovarian cancer cells and is expressed at low levels in normal cells. To develop a platform for intracellular and targeted delivery of therapeutics in ovarian cancer, we conjugated urokinase plasminogen activator (uPA) antibodies to liposomal nanobins. The arsenic trioxide-loaded nanobins had favorable physicochemical properties and the ability to bind specifically to uPA. Confocal microscopy showed that the uPA-targeted nanobins were internalized by ovarian cancer cells, whereas both inductively coupled plasma optical mass spectrometry (ICP-MS) and fluorescence-activated cell sorting (FACS) analyses confirmed more than four-fold higher uptake of targeted nanobins when compared with untargeted nanobins. In a coculture assay, the targeted nanobins showed efficient uptake in ovarian cancer cells but not in the normal primary omental mesothelial cells. Moreover, this uptake could be blocked by either downregulating uPA receptor expression in the ovarian cancer cells using short-hairpin RNA (shRNA) or by competition with free uPA or uPA antibody. In proof-of-concept experiments, mice bearing orthotopic ovarian tumors showed a greater reduction in tumor burden when treated with targeted nanobins than with untargeted nanobins (47% vs. 27%; P cancer cells could serve as the foundation for a new targeted cancer therapy using protease receptors. ©2013 AACR.

  13. Enhancing Targeted Genomic DNA Editing in Chicken Cells Using the CRISPR/Cas9 System

    Science.gov (United States)

    Wang, Ling; Yang, Likai; Guo, Yijie; Du, Weili; Yin, Yajun; Zhang, Tao; Lu, Hongzhao

    2017-01-01

    The CRISPR/Cas9 system has enabled highly efficient genome targeted editing for various organisms. However, few studies have focused on CRISPR/Cas9 nuclease-mediated chicken genome editing compared with mammalian genomes. The current study combined CRISPR with yeast Rad52 (yRad52) to enhance targeted genomic DNA editing in chicken DF-1 cells. The efficiency of CRISPR/Cas9 nuclease-induced targeted mutations in the chicken genome was increased to 41.9% via the enrichment of the dual-reporter surrogate system. In addition, the combined effect of CRISPR nuclease and yRad52 dramatically increased the efficiency of the targeted substitution in the myostatin gene using 50-mer oligodeoxynucleotides (ssODN) as the donor DNA, resulting in a 36.7% editing efficiency after puromycin selection. Furthermore, based on the effect of yRad52, the frequency of exogenous gene integration in the chicken genome was more than 3-fold higher than that without yRad52. Collectively, these results suggest that ssODN is an ideal donor DNA for targeted substitution and that CRISPR/Cas9 combined with yRad52 significantly enhances chicken genome editing. These findings could be extensively applied in other organisms. PMID:28068387

  14. Location Detection and Tracking of Moving Targets by a 2D IR-UWB Radar System

    Directory of Open Access Journals (Sweden)

    Van-Han Nguyen

    2015-03-01

    Full Text Available In indoor environments, the Global Positioning System (GPS and long-range tracking radar systems are not optimal, because of signal propagation limitations in the indoor environment. In recent years, the use of ultra-wide band (UWB technology has become a possible solution for object detection, localization and tracking in indoor environments, because of its high range resolution, compact size and low cost. This paper presents improved target detection and tracking techniques for moving objects with impulse-radio UWB (IR-UWB radar in a short-range indoor area. This is achieved through signal-processing steps, such as clutter reduction, target detection, target localization and tracking. In this paper, we introduce a new combination consisting of our proposed signal-processing procedures. In the clutter-reduction step, a filtering method that uses a Kalman filter (KF is proposed. Then, in the target detection step, a modification of the conventional CLEAN algorithm which is used to estimate the impulse response from observation region is applied for the advanced elimination of false alarms. Then, the output is fed into the target localization and tracking step, in which the target location and trajectory are determined and tracked by using unscented KF in two-dimensional coordinates. In each step, the proposed methods are compared to conventional methods to demonstrate the differences in performance. The experiments are carried out using actual IR-UWB radar under different scenarios. The results verify that the proposed methods can improve the probability and efficiency of target detection and tracking.

  15. Location Detection and Tracking of Moving Targets by a 2D IR-UWB Radar System

    Science.gov (United States)

    Nguyen, Van-Han; Pyun, Jae-Young

    2015-01-01

    In indoor environments, the Global Positioning System (GPS) and long-range tracking radar systems are not optimal, because of signal propagation limitations in the indoor environment. In recent years, the use of ultra-wide band (UWB) technology has become a possible solution for object detection, localization and tracking in indoor environments, because of its high range resolution, compact size and low cost. This paper presents improved target detection and tracking techniques for moving objects with impulse-radio UWB (IR-UWB) radar in a short-range indoor area. This is achieved through signal-processing steps, such as clutter reduction, target detection, target localization and tracking. In this paper, we introduce a new combination consisting of our proposed signal-processing procedures. In the clutter-reduction step, a filtering method that uses a Kalman filter (KF) is proposed. Then, in the target detection step, a modification of the conventional CLEAN algorithm which is used to estimate the impulse response from observation region is applied for the advanced elimination of false alarms. Then, the output is fed into the target localization and tracking step, in which the target location and trajectory are determined and tracked by using unscented KF in two-dimensional coordinates. In each step, the proposed methods are compared to conventional methods to demonstrate the differences in performance. The experiments are carried out using actual IR-UWB radar under different scenarios. The results verify that the proposed methods can improve the probability and efficiency of target detection and tracking. PMID:25808773

  16. Cat-eye target imaging system research and dual-channel DSP implementation

    Science.gov (United States)

    Zheng, Zheng; Zhang, Haiyang; Shi, Guang; Han, Lei; Zhao, Changming

    2013-09-01

    In modern warfare, well-equipped and trained snipers have become a mortal malady for the combat troops. How to accurately, timely and quickly find and destroy snipers becomes a research focus of national military experts. In order to effectively detect faint echo signal of cat-eye target and get the snipers' position information in the detection area, a small size of dual-channel active laser detection system with monochrome and color Charge-couple Devices(CCD) is designed, which is based on the laser imaging principle of cat-eye effect, associated tests are also conducted. The dual-channel video capture can obtain more information of target area, while taking advantage of the high sensitivity of monochrome CCD will also provide more accurate grayscale information for the video image processing. In order to achieve the miniaturization of system, we choose a video processing board whose size is only 54mm*90mm as hardware platform to complete the algorithm. For verifying the feasibility and accuracy of algorithm, we ultimately build a full set of experimental detection system. The test results show that the system can accurately detect and mark typical cat-eye target from background under different distances, which verifies the rationality and validity of the proposed system and has certain practicality and promotion in the active laser detection system research areas.

  17. A PC-based imaging system for the Naval Postgraduate School Infrared Search and Target Designation (NPS-IRSTD) system.

    OpenAIRE

    Engel, Raymond Charles

    1989-01-01

    Approved for public release; distribution is unlimited A system to display images from data generated by the Naval Postgraduate School Infrared Search and Target Designation (NPS-IRSTD) system (modified AN/SAR-8 ADM) was developed using an Intel 80386 CPU based desktop computer as the base platform. This computer was enhanced with a Metrabyte PDMA-16 Input/output board to facilitate data transfers and a Data Translation DT2861 framegrabber board for image processing. Images are displayed...

  18. Lead discovery and chemical biology approaches targeting the ubiquitin proteasome system.

    Science.gov (United States)

    Akinjiyan, Favour A; Carbonneau, Seth; Ross, Nathan T

    2017-10-15

    Protein degradation is critical for proteostasis, and the addition of polyubiquitin chains to a substrate is necessary for its recognition by the 26S proteasome. Therapeutic intervention in the ubiquitin proteasome system has implications ranging from cancer to neurodegeneration. Novel screening methods and chemical biology tools for targeting E1-activating, E2-conjugating and deubiquitinating enzymes will be discussed in this review. Approaches for targeting E3 ligase-substrate interactions as well as the proteasome will also be covered, with a focus on recently described approaches. Copyright © 2017. Published by Elsevier Ltd.

  19. Targeted HIV-1 Latency Reversal Using CRISPR/Cas9-Derived Transcriptional Activator Systems.

    Directory of Open Access Journals (Sweden)

    Julia K Bialek

    Full Text Available CRISPR/Cas9 technology is currently considered the most advanced tool for targeted genome engineering. Its sequence-dependent specificity has been explored for locus-directed transcriptional modulation. Such modulation, in particular transcriptional activation, has been proposed as key approach to overcome silencing of dormant HIV provirus in latently infected cellular reservoirs. Currently available agents for provirus activation, so-called latency reversing agents (LRAs, act indirectly through cellular pathways to induce viral transcription. However, their clinical performance remains suboptimal, possibly because reservoirs have diverse cellular identities and/or proviral DNA is intractable to the induced pathways. We have explored two CRISPR/Cas9-derived activator systems as targeted approaches to induce dormant HIV-1 proviral DNA. These systems recruit multiple transcriptional activation domains to the HIV 5' long terminal repeat (LTR, for which we have identified an optimal target region within the LTR U3 sequence. Using this target region, we demonstrate transcriptional activation of proviral genomes via the synergistic activation mediator complex in various in culture model systems for HIV latency. Observed levels of induction are comparable or indeed higher than treatment with established LRAs. Importantly, activation is complete, leading to production of infective viral particles. Our data demonstrate that CRISPR/Cas9-derived technologies can be applied to counteract HIV latency and may therefore represent promising novel approaches in the quest for HIV elimination.

  20. Efficient and Heritable Targeted Mutagenesis in Mosses Using the CRISPR/Cas9 System.

    Science.gov (United States)

    Nomura, Toshihisa; Sakurai, Tetsuya; Osakabe, Yuriko; Osakabe, Keishi; Sakakibara, Hitoshi

    2016-12-01

    Targeted genome modification by RNA-guided nucleases derived from the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9) system has seen rapid development in many organisms, including several plant species. In the present study, we succeeded in introducing the CRISPR/Cas9 system into the non-model organism Scopelophila cataractae, a moss that exhibits heavy metal tolerance, and the model organism Physcomitrella patens Utilizing the process by which moss plants regenerate from protoplasts, we conducted targeted mutagenesis by expression of single-chain guide RNA (sgRNA) and Cas9 in protoplasts. Using this method, the acquisition rate of strains exhibiting phenotypic changes associated with the target genes was approximately 45-69%, and strains with phenotypic changes exhibited various insertion and deletion mutations. In addition, we report that our method is capable of multiplex targeted mutagenesis (two independent genes) and also permits the efficient introduction of large deletions (∼3 kbp). These results demonstrate that the CRISPR/Cas9 system can be used to accelerate investigations of bryology and land plant evolution. © The Authors 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  1. Molecular pathology and targeted therapy of common tumors in central nervous system

    Directory of Open Access Journals (Sweden)

    Fei YANG

    2014-12-01

    Full Text Available It is difficult to cure central nervous system tumors using traditional method, due to chemotherapy drugs lack of specificity. They kill the tumor cells, and damage normal tissues and organs at the same time. The latest hotspot is targeted therapy on the specific molecules in the molecular pathway of central nervous system tumor cells. This review introduces the relationship between molecularly biological characteristics of medulloblastoma, oligodendrocytoma, glioblastoma and the prognosis in the view of critical intracellular pathway and genetic mutation. Furthermore, it reviews the current situation and progress of targeted therapy of tumors. As a consequence, it offers some new information for the individualized therapy of central nervous system tumors. doi: 10.3969/j.issn.1672-6731.2014.12.017

  2. The Innate and Adaptive Immune System as Targets for Biologic Therapies in Inflammatory Bowel Disease.

    Science.gov (United States)

    Holleran, Grainne; Lopetuso, Loris; Petito, Valentina; Graziani, Cristina; Ianiro, Gianluca; McNamara, Deirdre; Gasbarrini, Antonio; Scaldaferri, Franco

    2017-09-21

    Inflammatory bowel disease (IBD) is an immune-mediated inflammatory condition causing inflammation of gastrointestinal and systemic cells, with an increasing prevalence worldwide. Many factors are known to trigger and maintain inflammation in IBD including the innate and adaptive immune systems, genetics, the gastrointestinal microbiome and several environmental factors. Our knowledge of the involvement of the immune system in the pathophysiology of IBD has advanced rapidly over the last two decades, leading to the development of several immune-targeted treatments with a biological source, known as biologic agents. The initial focus of these agents was directed against the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) leading to dramatic changes in the disease course for a proportion of patients with IBD. However, more recently, it has been shown that a significant proportion of patients do not respond to anti-TNF-α directed therapies, leading a shift to other inflammatory pathways and targets, including those of both the innate and adaptive immune systems, and targets linking both systems including anti-leukocyte trafficking agents-integrins and adhesion molecules. This review briefly describes the molecular basis of immune based gastrointestinal inflammation in IBD, and then describes how several current and future biologic agents work to manipulate these pathways, and their clinical success to date.

  3. Polymeric colloidal particulate systems: intelligent tools for intracellular targeting of antileishmanial cargos.

    Science.gov (United States)

    Asthana, Shalini; Gupta, Pramod K; Chaurasia, Mohini; Dube, Anuradha; Chourasia, Manish K

    2013-12-01

    Targeted cargo delivery systems can overcome drawbacks associated with antileishmanials delivery, by defeating challenges of physiological barriers. Various colloidal particulate systems have been developed in the past; few of them even achieved success in the market, but still are limited in some ways. This review is focused on the pathobiology of leishmaniasis, interactions of particulate systems with biological environment, targeting strategies along with current conventional and vaccine therapies with special emphasis on polymeric nanotechnology for effective antileishmanial cargo delivery. The problems concerned with limited accessibility of chemotherapeutic cargos in conventional modes to Leishmania-harboring macrophages, their toxicity, and resistant parasitic strain development can be sorted out through target-specific delivery of cargos. Vaccination is another therapeutic approach employing antigen alone or adjuvant combinations delivered by means of a carrier, and can provide preventive measures against human leishmaniasis (HL). Therefore, there is an urgent need of designing site-specific antileishmanial cargo carriers for safe and effective management of HL. Among various colloidal carriers, polymeric particulate systems hold tremendous potential as an effective delivery tool by providing control over spatial and temporal distribution of cargos after systemic or localized administration along with enhancing their stability profile at a comparatively cost-effective price leading to improved chances of commercial applicability.

  4. Use of Admail and a geographic information system to send surveys to target populations.

    Science.gov (United States)

    Paller, Claire; Christidis, Tanya; Majowicz, Shannon; Aramini, Jeff; Law, Jane; Bigelow, Phil

    2016-01-01

    This paper briefly describes the use of Canada Post Unaddressed Admail and a geographic information system (GIS) for survey distribution to a specific target population in a large, sparsely populated geographic area, and the effectiveness of this approach. Surveys were sent as Unaddressed Admail via Canada Post to a target population of people living within 5 km of a wind turbine in southwestern Ontario. The overall response rate from 8 wind farms (in 8 counties) was 8.1%. This approach has the potential to save time and money, but low response rates are common, distribution is not precise and there is potential for selection bias. Despite these flaws, Unaddressed Admail is worth consideration for delivery of information, study-recruitment materials and surveys to rural, remote and specific target populations.

  5. A Hierarchical Target Extraction, Recognition, and Tracking (HiTert) System

    Science.gov (United States)

    1992-03-31

    Recognition, and Tracking (HiTert) System by Jun Lu Dominick Andrisani , II and M. Fernando Tenorio March 31,1992 TRIBOx.^M STATEMENT ’proved foi public...HiTert) System by Jun Lu Dominick Andrisani , II and M. Fernando Tenorio March 31, 1992 Final Report to the U. S. Army Research Office Contract No...SUBTITLE A Hierarchical Target Extraction, Recognition and Tracking (HiTert) System bflfiLoZ𔄂°i-k-ooH 6. AUTHOR(S) Jun Lu, Dominick Andrisani II, and

  6. A versatile method for cell-specific profiling of translated mRNAs in Drosophila.

    Directory of Open Access Journals (Sweden)

    Amanda Thomas

    Full Text Available In Drosophila melanogaster few methods exist to perform rapid cell-type or tissue-specific expression profiling. A translating ribosome affinity purification (TRAP method to profile actively translated mRNAs has been developed for use in a number of multicellular organisms although it has only been implemented to examine limited sets of cell- or tissue-types in these organisms. We have adapted the TRAP method for use in the versatile GAL4/UAS system of Drosophila allowing profiling of almost any tissue/cell-type with a single genetic cross. We created transgenic strains expressing a GFP-tagged ribosomal protein, RpL10A, under the control of the UAS promoter to perform cell-type specific translatome profiling. The GFP::RpL10A fusion protein incorporates efficiently into ribosomes and polysomes. Polysome affinity purification strongly enriches mRNAs from expected genes in the targeted tissues with sufficient sensitivity to analyze expression in small cell populations. This method can be used to determine the unique translatome profiles in different cell-types under varied physiological, pharmacological and pathological conditions.

  7. Image-Forming System Design of Dynamic Targets Based on Reflecting Mirror Splicing

    Directory of Open Access Journals (Sweden)

    Zhu Hong Mei

    2016-01-01

    Full Text Available In this paper, the author designed an area-scan CCD reflecting mirror splicing image-forming system with area-scan CCD ICX415AL as its transducer module and this system can be used for tracking dynamic targets. By analyzing the theory of vignetting generating, the author made mathematic model of vignetting and confirmed the splicing and overlapping pixel number of the optical system. What’s more, the sequential circuit and driving power circuit of ICX415AL was designed and the correlated noise in video signals was strained with CDS technology. Therefore, the signal-to-noise ratio (SNR of the system was elevated. With FPGA as its core controlling module, this system postponed the splicing image-forming system to a period during which a line of CCD data are read, thus the need of real-time tracking was completely met.

  8. Development of target ion source systems for radioactive beams at GANIL

    Energy Technology Data Exchange (ETDEWEB)

    Bajeat, O., E-mail: bajeat@ganil.fr [GANIL, BP 55027, 14076 CAEN Cedex 05 (France); Delahaye, P. [GANIL, BP 55027, 14076 CAEN Cedex 05 (France); Couratin, C. [GANIL, BP 55027, 14076 CAEN Cedex 05 (France); LPC Caen, 6 bd Maréchal Juin, 14050 CAEN Cedex (France); Dubois, M.; Franberg-Delahaye, H.; Henares, J.L.; Huguet, Y.; Jardin, P.; Lecesne, N.; Lecomte, P.; Leroy, R.; Maunoury, L.; Osmond, B.; Sjodin, M. [GANIL, BP 55027, 14076 CAEN Cedex 05 (France)

    2013-12-15

    Highlights: • For Spiral 1, a febiad ion source has been connected to a graphite target. • For Spiral 2, an oven made with a carbon resistor is under development. • We made some measurement of effusion in the Spiral 2 target. • A laser ion source is under construction. -- Abstract: The GANIL facility (Caen, France) is dedicated to the acceleration of heavy ion beams including radioactive beams produced by the Isotope Separation On-Line (ISOL) method at the SPIRAL1 facility. To extend the range of radioactive ion beams available at GANIL, using the ISOL method two projects are underway: SPIRAL1 upgrade and the construction of SPIRAL2. For SPIRAL1, a new target ion source system (TISS) using the VADIS FEBIAD ion source coupled to the SPIRAL1 carbon target will be tested on-line by the end of 2013 and installed in the cave of SPIRAL1 for operation in 2015. The SPIRAL2 project is under construction and is being design for using different production methods as fission, fusion or spallation reactions to cover a large area of the chart of nuclei. It will produce among others neutron rich beams obtained by the fission of uranium induced by fast neutrons. The production target made from uranium carbide and heated at 2000 °C will be associated with several types of ion sources. Developments currently in progress at GANIL for each of these projects are presented.

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

    Science.gov (United States)

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

    2014-01-01

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

  10. Scan statistics with local vote for target detection in distributed system

    Science.gov (United States)

    Luo, Junhai; Wu, Qi

    2017-12-01

    Target detection has occupied a pivotal position in distributed system. Scan statistics, as one of the most efficient detection methods, has been applied to a variety of anomaly detection problems and significantly improves the probability of detection. However, scan statistics cannot achieve the expected performance when the noise intensity is strong, or the signal emitted by the target is weak. The local vote algorithm can also achieve higher target detection rate. After the local vote, the counting rule is always adopted for decision fusion. The counting rule does not use the information about the contiguity of sensors but takes all sensors' data into consideration, which makes the result undesirable. In this paper, we propose a scan statistics with local vote (SSLV) method. This method combines scan statistics with local vote decision. Before scan statistics, each sensor executes local vote decision according to the data of its neighbors and its own. By combining the advantages of both, our method can obtain higher detection rate in low signal-to-noise ratio environment than the scan statistics. After the local vote decision, the distribution of sensors which have detected the target becomes more intensive. To make full use of local vote decision, we introduce a variable-step-parameter for the SSLV. It significantly shortens the scan period especially when the target is absent. Analysis and simulations are presented to demonstrate the performance of our method.

  11. Exploiting off-targeting in guide-RNAs for CRISPR systems for simultaneous editing of multiple genes

    DEFF Research Database (Denmark)

    Ferreira, Raphael; Gatto, Francesco; Nielsen, Jens

    2017-01-01

    Bioinformatics tools to design guide-RNAs (gRNAs) in Clustered Regularly Interspaced Short Palindromic Repeats systems mostly focused on minimizing off-targeting to enhance efficacy of genome editing. However, there are circumstances in which off-targeting might be desirable to target multiple ge...

  12. The innate and adaptive infiltrating immune systems as targets for breast cancer immunotherapy

    Science.gov (United States)

    Law, Andrew M K; Lim, Elgene; Ormandy, Christopher J

    2017-01-01

    A cancer cell-centric view has long dominated the field of cancer biology. Research efforts have focussed on aberrant cancer cell signalling pathways and on changes to cancer cell DNA. Mounting evidence demonstrates that many cancer-associated cell types within the tumour stroma co-evolve and support tumour growth and development, greatly modifying cancer cell behaviour, facilitating invasion and metastasis and controlling dormancy and sensitivity to drug therapy. Thus, these stromal cells represent potential targets for cancer therapy. Among these cell types, immune cells have emerged as a promising target for therapy. The adaptive and the innate immune system play an important role in normal mammary development and breast cancer. The number of infiltrating adaptive immune system cells with tumour-rejecting capacity, primarily, T lymphocytes, is lower in breast cancer compared with other cancer types, but infiltration occurs in a large proportion of cases. There is strong evidence demonstrating the importance of the immunosuppressive role of the innate immune system during breast cancer progression. A consideration of components of both the innate and the adaptive immune system is essential for the design and development of immunotherapies in breast cancer. In this review, we focus on the importance of immunosuppressive myeloid-derived suppressor cells (MDSCs) as potential targets for breast cancer therapy. PMID:28193698

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

    Directory of Open Access Journals (Sweden)

    Jia Wei Tang

    2016-01-01

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

  14. TargetVue: Visual Analysis of Anomalous User Behaviors in Online Communication Systems.

    Science.gov (United States)

    Cao, Nan; Shi, Conglei; Lin, Sabrina; Lu, Jie; Lin, Yu-Ru; Lin, Ching-Yung

    2016-01-01

    Users with anomalous behaviors in online communication systems (e.g. email and social medial platforms) are potential threats to society. Automated anomaly detection based on advanced machine learning techniques has been developed to combat this issue; challenges remain, though, due to the difficulty of obtaining proper ground truth for model training and evaluation. Therefore, substantial human judgment on the automated analysis results is often required to better adjust the performance of anomaly detection. Unfortunately, techniques that allow users to understand the analysis results more efficiently, to make a confident judgment about anomalies, and to explore data in their context, are still lacking. In this paper, we propose a novel visual analysis system, TargetVue, which detects anomalous users via an unsupervised learning model and visualizes the behaviors of suspicious users in behavior-rich context through novel visualization designs and multiple coordinated contextual views. Particularly, TargetVue incorporates three new ego-centric glyphs to visually summarize a user's behaviors which effectively present the user's communication activities, features, and social interactions. An efficient layout method is proposed to place these glyphs on a triangle grid, which captures similarities among users and facilitates comparisons of behaviors of different users. We demonstrate the power of TargetVue through its application in a social bot detection challenge using Twitter data, a case study based on email records, and an interview with expert users. Our evaluation shows that TargetVue is beneficial to the detection of users with anomalous communication behaviors.

  15. Targeting choroid plexus epithelia and ventricular ependyma for drug delivery to the central nervous system

    Directory of Open Access Journals (Sweden)

    Stopa Edward G

    2011-01-01

    Full Text Available Abstract Background Because the choroid plexus (CP is uniquely suited to control the composition of cerebrospinal fluid (CSF, there may be therapeutic benefits to increasing the levels of biologically active proteins in CSF to modulate central nervous system (CNS functions. To this end, we sought to identify peptides capable of ligand-mediated targeting to CP epithelial cells reasoning that they could be exploited to deliver drugs, biotherapeutics and genes to the CNS. Methods A peptide library displayed on M13 bacteriophage was screened for ligands capable of internalizing into CP epithelial cells by incubating phage with CP explants for 2 hours at 37C and recovering particles with targeting capacity. Results Three peptides, identified after four rounds of screening, were analyzed for specific and dose dependant binding and internalization. Binding was deemed specific because internalization was prevented by co-incubation with cognate synthetic peptides. Furthermore, after i.c.v. injection into rat brains, each peptide was found to target phage to epithelial cells in CP and to ependyma lining the ventricles. Conclusion These data demonstrate that ligand-mediated targeting can be used as a strategy for drug delivery to the central nervous system and opens the possibility of using the choroid plexus as a portal of entry into the brain.

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

    Science.gov (United States)

    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.

  17. Targeting cells of the immune system: mannosylated HPMA-LMA block-copolymer micelles for targeting of dendritic cells.

    Science.gov (United States)

    Mohr, Nicole; Kappel, Cinja; Kramer, Stefan; Bros, Matthias; Grabbe, Stephan; Zentel, Rudolf

    2016-10-01

    Successful tumor immunotherapy depends on the induction of strong and sustained tumor antigen-specific immune responses by activated antigen-presenting cells (APCs) such as dendritic cells (DCs). Since nanoparticles have the potential to codeliver tumor-specific antigen and DC-stimulating adjuvant in a DC-targeting manner, we wanted to assess the suitability of mannosylated HPMA-LMA block polymers for immunotherapy. Fluorescence-labeled block copolymer micelles derived from P(HPMA)-block-P(LMA) copolymers and according statistical copolymers were synthesized via RAFT polymerization, and loaded with the APC activator L18-MDP. Both types of copolymers were conjugated with D-mannose to target the mannose receptor as expressed by DCs and macrophages. The extent and specificity of micelle binding and activation of APCs was monitored using mouse spleen cells and bone marrow-derived DC (BMDC). Nontargeting HPMA-LMA statistical copolymers showed strong unspecific cell binding. HPMA-LMA block copolymers bound DC only when conjugated with mannose, and in a mannose receptor-specific manner. Mannosylated HPMA-LMA block copolymers were internalized by DC. DC-targeting HPMA-LMA block copolymers mediated DC activation when loaded with L18-MDP. Mannosylated HPMA-LMA block copolymers are a promising candidate for the delvopment of DC-targeting nanovaccines.

  18. Highly Efficient Targeted Mutagenesis of Drosophila with the CRISPR/Cas9 System

    Directory of Open Access Journals (Sweden)

    Andrew R. Bassett

    2013-07-01

    Full Text Available Here, we present a simple and highly efficient method for generating and detecting mutations of any gene in Drosophila melanogaster through the use of the CRISPR/Cas9 system (clustered regularly interspaced palindromic repeats/CRISPR-associated. We show that injection of RNA into the Drosophila embryo can induce highly efficient mutagenesis of desired target genes in up to 88% of injected flies. These mutations can be transmitted through the germline to make stable lines. Our system provides at least a 10-fold improvement in efficiency over previously published reports, enabling wider application of this technique. We also describe a simple and highly sensitive method of detecting mutations in the target gene by high-resolution melt analysis and discuss how the new technology enables the study of gene function.

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

    Science.gov (United States)

    Pritchard, Leighton; Birch, Paul

    2011-04-01

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

  20. Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting

    Directory of Open Access Journals (Sweden)

    Brian C. Palmer

    2016-12-01

    Full Text Available Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases.

  1. Communication systems in the genus Burkholderia: global regulators and targets for novel antipathogenic drugs.

    Science.gov (United States)

    Sokol, Pamela A; Malott, Rebecca J; Riedel, Kathrin; Eberl, Leo

    2007-10-01

    The genus Burkholderia not only contains the primary pathogens Burkholderia pseudomallei and Burkholderia mallei but also several species that have emerged as opportunistic pathogens in persons suffering from cystic fibrosis or chronic granulomatous disease and immunocompromised individuals. Burkholderia species utilize quorum-sensing (QS) systems that rely on N-acyl-homoserine lactone (AHL) signal molecules to express virulence factors and other functions in a population-density-dependent manner. Most Burkholderia species employ the CepIR QS system, which relies on N-octanoyl-homoserine lactone. However, some strains harbour multiple QS systems and produce numerous AHLs. QS systems have been demonstrated to be essential for full virulence in various infection models and, thus, these regulatory systems represent attractive targets for the development of novel therapeutics.

  2. Investigation of Lead Target Nuclei Used on Accelerator-Driven Systems for Tritium Production

    Science.gov (United States)

    Tel, E.; Aydin, A.

    2012-02-01

    High-current proton accelerators are being researched at Los Alamos National Laboratory and other laboratories for accelerator production of tritium, transmuting long-lived radioactive waste into shorter-lived products, converting excess plutonium, and producing energy. These technologies make use of spallation neutrons produced in ( p,xn) and ( n,xn) nuclear reactions on high-Z targets. Through ( p,xn) and ( n,xn) nuclear reactions, neutrons are produced and are moderated by heavy water. These moderated neutrons are subsequently captured on 3He to produce tritium via the ( n,p) reaction. Tritium self-sufficiency must be maintained for a commercial fusion power plant. Rubbia succeeded in a proposal of a full scale demonstration plant of the Energy Amplifier. This plant is to be known the accelerator-driven system (ADS). The ADS can be used for production of neutrons in spallation neutron source and they can act as an intense neutron source in accelerator-driven subcritical reactors, capable of incinerating nuclear waste and of producing energy. Thorium and Uranium are nuclear fuels and Lead, Bismuth, Tungsten are the target nuclei in these reactor systems. The spallation targets can be Pb, Bi, W, etc. isotopes and these target material can be liquid or solid. Naturally Lead includes the 204Pb (%1.42), 206Pb (%24.1), 207Pb (%22.1) and 208Pb (%52.3) isotopes. The design of ADS systems and also a fusion-fission hybrid reactor systems require the knowledge of a wide range of better data. In this study, by using Hartree-Fock method with an effective nucleon-nucleon Skyrme interactions rms nuclear charge radii, rms nuclear mass radii, rms nuclear proton, neutron radii and neutron skin thickness were calculated for the 204, 206, 208Pb isotopes . The calculated results have been compared with those of the compiled experimental and theoretical values of other studies.

  3. Targeted drug delivery system to neural cells utilizes the nicotinic acetylcholine receptor.

    Science.gov (United States)

    Huey, Rachel; O'Hagan, Barry; McCarron, Paul; Hawthorne, Susan

    2017-06-15

    Drug delivery to the brain is still a major challenge in the field of therapeutics, especially for large and hydrophilic compounds. In order to achieve drug delivery of therapeutic concentration in the central nervous system, the problematic blood brain barrier (BBB) must be overcome. This work presents the formulation of a targeted nanoparticle-based drug delivery system using a specific neural cell targeting ligand, rabies virus derived peptide (RDP). Characterization studies revealed that RDP could be conjugated to drug-loaded PLGA nanoparticles of average diameter 257.10±22.39nm and zeta potential of -5.51±0.73mV. In vitro studies showed that addition of RDP to nanoparticles enhanced drug accumulation in a neural cell line specifically as opposed to non-neural cell lines. It was revealed that this drug delivery system is reliant upon nicotinic acetylcholine receptor (nAChR) function for RDP-facilitated effects, supporting a cellular uptake mechanism of action. The specific neural cell targeting capabilities of RDP via the nAChR offers a non-toxic, non-invasive and promising approach to the delivery of therapeutics to the brain. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  4. Fluoroscopic freehand and electromagnetic-guided targeting system for distal locking screws of humeral intramedullary nail.

    Science.gov (United States)

    Persiani, P; Gurzi, M; Moreschini, O; Di Giacomo, G; Villani, C

    2017-04-01

    The current techniques used to lock distal screws for the nailing of long bone fractures expose the surgeons, radiologists and patients to a hearty dose of ionizing radiation. The Sureshot™ Distal Targeting System is a new technique that, with the same results, allows for shorter surgery times and, consequently, less exposure to radiation. The study was performed on 59 patients (34 males and 25 females) with a simple humerus fracture diagnosis, type 1.2.A according to the AO classification, who were divided into two groups. Group 1 was treated with ante-grade intramedullary nailing with distal locking screws inserted with a freehand technique. Group 2 was treated with the intramedullary nail using the Sureshot™ Distal Targeting System. Two intra-operative time parameters were evaluated in both groups: the time needed for the positioning of the distal locking screws and the time of exposure to ionizing radiations during this procedure. Group 2 showed a lower average distal locking time compared to group 1 (645.48″ vs. 1023.57″) and also a lower average time of exposure to ionizing radiation than in group 1 (4.35″ vs. 28.96″). The Sureshot™ Distal Targeting System has proven to be equally effective when compared to the traditional techniques, with the added benefits of a significant reduction in both surgical time and risk factors related to the exposure to ionizing radiation for all the operating room staff and the patient.

  5. Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors

    Science.gov (United States)

    Tosi, Umberto; Marnell, Christopher S.; Chang, Raymond; Cho, William C.; Ting, Richard; Maachani, Uday B.; Souweidane, Mark M.

    2017-01-01

    Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood–brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a “wait-and-see” approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents. PMID:28208698

  6. Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors

    Directory of Open Access Journals (Sweden)

    Umberto Tosi

    2017-02-01

    Full Text Available Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood–brain barrier (BBB renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a “wait-and-see” approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents.

  7. Nanomedicine strategies for sustained, controlled, and targeted treatment of cancer stem cells of the digestive system.

    Science.gov (United States)

    Xie, Fang-Yuan; Xu, Wei-Heng; Yin, Chuan; Zhang, Guo-Qing; Zhong, Yan-Qiang; Gao, Jie

    2016-10-15

    Cancer stem cells (CSCs) constitute a small proportion of the cancer cells that have self-renewal capacity and tumor-initiating ability. They have been identified in a variety of tumors, including tumors of the digestive system. CSCs exhibit some unique characteristics, which are responsible for cancer metastasis and recurrence. Consequently, the development of effective therapeutic strategies against CSCs plays a key role in increasing the efficacy of cancer therapy. Several potential approaches to target CSCs of the digestive system have been explored, including targeting CSC surface markers and signaling pathways, inducing the differentiation of CSCs, altering the tumor microenvironment or niche, and inhibiting ATP-driven efflux transporters. However, conventional therapies may not successfully eradicate CSCs owing to various problems, including poor solubility, stability, rapid clearance, poor cellular uptake, and unacceptable cytotoxicity. Nanomedicine strategies, which include drug, gene, targeted, and combinational delivery, could solve these problems and significantly improve the therapeutic index. This review briefly summarizes the ongoing development of strategies and nanomedicine-based therapies against CSCs of the digestive system.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-04-14

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

  10. AQUA Cloning: A Versatile and Simple Enzyme-Free Cloning Approach.

    Directory of Open Access Journals (Sweden)

    Hannes M Beyer

    Full Text Available Assembly cloning is increasingly replacing conventional restriction enzyme and DNA-ligase-dependent cloning methods for reasons of efficiency and performance. Here, we describe AQUA (advanced quick assembly, a simple and versatile seamless assembly cloning approach. We demonstrate the applicability and versatility of AQUA Cloning in selected proof-of-principle applications including targeted insertion-, deletion- and site-directed point-mutagenesis, and combinatorial cloning. Furthermore, we show the one pot de novo assembly of multiple DNA fragments into a single circular plasmid encoding a complex light- and chemically-regulated Boolean A NIMPLY B logic operation. AQUA Cloning harnesses intrinsic in vivo processing of linear DNA fragments with short regions of homology of 16 to 32 bp mediated by Escherichia coli. It does not require any kits, enzymes or preparations of reagents and is the simplest assembly cloning protocol to date.

  11. Target Selection for the LBTI Hunt for Observable Signatures of Terrestrial Planetary Systems

    Science.gov (United States)

    Roberge, A.; Weinberger, A.; Kennedy, G.; Defrère, D.; LBTI Instrument; Science Teams

    2014-03-01

    The Hunt for Observable Signatures of Terrestrial planetary Systems (HOSTS) on the Large Binocular Telescope Interferometer (LBTI) will survey nearby stars for faint exozodiacal dust (exozodi). This warm circumstellar dust, analogous to the interplanetary dust found in the vicinity of the Earth in our own system, is produced in comet breakups and asteroid collisions. Exozodi will be the major source of astrophysical noise for a future space telescope aimed at direct imaging and spectroscopy of habitable zone terrestrial planets (exo-Earths). About 20% of nearby field stars have cold dust coming from planetesimals at large distances from the stars (Eiroa et al. 2013). Much less is known about exozodi; current detection limits for individual stars are at best ~ 500 times our solar system's level (aka. 500 zodi). LBTI-HOSTS will be the first survey capable of measuring exozodi at the 10 zodi level (3s). Detections of warm dust will also reveal new information about planetary system architectures and evolution. We describe the target star selection by the LBTI Science Team to satisfy the goals of the HOSTS survey - to inform mission design and target selection for a future exo-Earth mission. We are interested in both 1) actual stars likely to be observed by such a mission and 2) stars whose observation will enable sensible extrapolations for stars that cannot be observed with LBTI. We integrated two approaches to generate the HOSTS target list. The mission-driven approach concentrates on F, G, and K-type stars that are the best targets for future direct observations of exo-Earths, thereby providing model-independent "ground truth" dust observations. However, not every potential target of a future exo-Earth mission can be observed with LBTI. The sensitivity-driven approach selects targets based on maximizing the exozodi sensitivity that can be achieved, without consideration of exo-Earth mission constraints. This naturally chooses more luminous stars (A and early F

  12. Target Tracking of a Linear Time Invariant System under Irregular Sampling

    Directory of Open Access Journals (Sweden)

    Jin Xue-Bo

    2012-11-01

    Full Text Available Due to event-triggered sampling in a system, or maybe with the aim of reducing data storage, tracking many applications will encounter irregular sampling time. By calculating the matrix exponential using an inverse Laplace transform, this paper transforms the irregular sampling tracking problem to the problem of tracking with time-varying parameters of a system. Using the common Kalman filter, the developed method is used to track a target for the simulated trajectory and video tracking. The results of simulation experiments have shown that it can obtain good estimation performance even at a very high irregular rate of measurement sampling time.

  13. Targeted gene modification in Fragaria vesca mediated by CRISPR/Cas9 system

    OpenAIRE

    Martín-Pizarro, Carmen; Posé, David

    2016-01-01

    Genome editing is becoming an important biotechnological tool for gene function analysis and crop improvement, being the CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeat-CRISPR associated protein 9) system the most widely used. The natural CRISPR/Cas9 system has been reduced to two components: a single-guide RNA (sgRNA) for target recognition via RNA-DNA base pairing, which is commonly expressed using a promoter for small-RNAs (U6 promoter), and the Cas9 endonuclease for ...

  14. miR-9: a versatile regulator of neurogenesis

    Directory of Open Access Journals (Sweden)

    Marion Coolen

    2013-11-01

    Full Text Available Soon after its discovery, microRNA-9 (miR-9 attracted the attention of neurobiologists, since it is one of the most highly expressed microRNAs in the developing and adult vertebrate brain. Functional analyses in different vertebrate species have revealed a prominent role of this microRNA in balancing proliferation in embryonic neural progenitor populations. Key transcriptional regulators such as FoxG1, Hes1 or Tlx, were identified as direct targets of miR-9, placing it at the core of the gene network controlling the progenitor state. Recent data also suggest that this function could extend to adult neural stem cells. Other studies point to a role of miR-9 in differentiated neurons. Moreover miR-9 has been implicated in human brain pathologies, either displaying a protective role, such as in Progeria, or participating in disease progression in brain cancers. Altogether functional studies highlight a prominent feature of this highly conserved microRNA, its functional versatility, both along its evolutionary history and across cellular contexts.

  15. Versatility of hydrocarbon production in cyanobacteria.

    Science.gov (United States)

    Xie, Min; Wang, Weihua; Zhang, Weiwen; Chen, Lei; Lu, Xuefeng

    2017-02-01

    Cyanobacteria are photosynthetic microorganisms using solar energy, H2O, and CO2 as the primary inputs. Compared to plants and eukaryotic microalgae, cyanobacteria are easier to be genetically engineered and possess higher growth rate. Extensive genomic information and well-established genetic platform make cyanobacteria good candidates to build efficient biosynthetic pathways for biofuels and chemicals by genetic engineering. Hydrocarbons are a family of compounds consisting entirely of hydrogen and carbon. Structural diversity of the hydrocarbon family is enabled by variation in chain length, degree of saturation, and rearrangements of the carbon skeleton. The diversified hydrocarbons can be used as valuable chemicals in the field of food, fuels, pharmaceuticals, nutrition, and cosmetics. Hydrocarbon biosynthesis is ubiquitous in bacteria, yeasts, fungi, plants, and insects. A wide variety of pathways for the hydrocarbon biosynthesis have been identified in recent years. Cyanobacteria may be superior chassis for hydrocabon production in a photosynthetic manner. A diversity of hydrocarbons including ethylene, alkanes, alkenes, and terpenes can be produced by cyanobacteria. Metabolic engineering and synthetic biology strategies can be employed to improve hydrocarbon production in cyanobacteria. This review mainly summarizes versatility and perspectives of hydrocarbon production in cyanobacteria.

  16. Plasmonic Biofoam: A Versatile Optically Active Material.

    Science.gov (United States)

    Tian, Limei; Luan, Jingyi; Liu, Keng-Ku; Jiang, Qisheng; Tadepalli, Sirimuvva; Gupta, Maneesh K; Naik, Rajesh R; Singamaneni, Srikanth

    2016-01-13

    Owing to their ability to confine and manipulate light at the nanoscale, plasmonic nanostructures are highly attractive for a broad range of applications. While tremendous progress has been made in the synthesis of size- and shape-controlled plasmonic nanostructures, their integration with other materials and application in solid-state is primarily through their assembly on rigid two-dimensional (2D) substrates, which limits the plasmonically active space to a few nanometers above the substrate. In this work, we demonstrate a simple method to create plasmonically active three-dimensional biofoams by integrating plasmonic nanostructures with highly porous biomaterial aerogels. We demonstrate that plasmonic biofoam is a versatile optically active platform that can be harnessed for numerous applications including (i) ultrasensitive chemical detection using surface-enhanced Raman scattering; (ii) highly efficient energy harvesting and steam generation through plasmonic photothermal heating; and (iii) optical control of enzymatic activity by triggered release of biomolecules encapsulated within the aerogel. Our results demonstrate that 3D plasmonic biofoam exhibits significantly higher sensing, photothermal, and loading efficiency compared to conventional 2D counterparts. The design principles and processing methodology of plasmonic aerogels demonstrated here can be broadly applied in the fabrication of other functional foams.

  17. Versatile microanalytical system with porous polypropylene capillary membrane for calibration gas generation and trace gaseous pollutants sampling applied to the analysis of formaldehyde, formic acid, acetic acid and ammonia in outdoor air.

    Science.gov (United States)

    Coelho, Lúcia H G; Melchert, Wanessa R; Rocha, Flavio R; Rocha, Fábio R P; Gutz, Ivano G R

    2010-11-15

    The analytical determination of atmospheric pollutants still presents challenges due to the low-level concentrations (frequently in the μg m(-3) range) and their variations with sampling site and time. In this work, a capillary membrane diffusion scrubber (CMDS) was scaled down to match with capillary electrophoresis (CE), a quick separation technique that requires nothing more than some nanoliters of sample and, when combined with capacitively coupled contactless conductometric detection (C(4)D), is particularly favorable for ionic species that do not absorb in the UV-vis region, like the target analytes formaldehyde, formic acid, acetic acid and ammonium. The CMDS was coaxially assembled inside a PTFE tube and fed with acceptor phase (deionized water for species with a high Henry's constant such as formaldehyde and carboxylic acids, or acidic solution for ammonia sampling with equilibrium displacement to the non-volatile ammonium ion) at a low flow rate (8.3 nL s(-1)), while the sample was aspirated through the annular gap of the concentric tubes at 2.5 mL s(-1). A second unit, in all similar to the CMDS, was operated as a capillary membrane diffusion emitter (CMDE), generating a gas flow with know concentrations of ammonia for the evaluation of the CMDS. The fluids of the system were driven with inexpensive aquarium air pumps, and the collected samples were stored in vials cooled by a Peltier element. Complete protocols were developed for the analysis, in air, of NH(3), CH(3)COOH, HCOOH and, with a derivatization setup, CH(2)O, by associating the CMDS collection with the determination by CE-C(4)D. The ammonia concentrations obtained by electrophoresis were checked against the reference spectrophotometric method based on Berthelot's reaction. Sensitivity enhancements of this reference method were achieved by using a modified Berthelot reaction, solenoid micro-pumps for liquid propulsion and a long optical path cell based on a liquid core waveguide (LCW). All

  18. Research on the image fusion and target extraction based on bionic compound eye system

    Science.gov (United States)

    Zhang, Shaowei; Hao, Qun; Song, Yong; Wang, Zihan; Zhang, Kaiyu; Zhang, Shiyu

    2015-08-01

    People attach more and more importance to bionic compound eye due to its advantages such as small volume, large field of view and sensitivity to high-speed moving objects. Small field of view and large volume are the disadvantages of traditional image sensor and in order to avoid these defects, this paper intends to build a set of compound eye system based on insect compound eye structure and visual processing mechanism. In the center of this system is the primary sensor which has high resolution ratio. The primary sensor is surrounded by the other six sensors which have low resolution ratio. Based on this system, this paper will study the target image fusion and extraction method by using plane compound eye structure. This paper designs a control module which can combine the distinguishing features of high resolution image with local features of low resolution image so as to conduct target detection, recognition and location. Compared with traditional ways, the way of high resolution in the center and low resolution around makes this system own the advantages of high resolution and large field of view and enables the system to detect the object quickly and recognize the object accurately.

  19. EGFR-Targeted Adenovirus Dendrimer Coating for Improved Systemic Delivery of the Theranostic NIS Gene

    Directory of Open Access Journals (Sweden)

    Geoffrey K Grünwald

    2013-01-01

    Full Text Available We recently demonstrated tumor-selective iodide uptake and therapeutic efficacy of combined radiovirotherapy after systemic delivery of the theranostic sodium iodide symporter (NIS gene using a dendrimer-coated adenovirus. To further improve shielding and targeting we physically coated replication-selective adenoviruses carrying the hNIS gene with a conjugate consisting of cationic poly(amidoamine (PAMAM dendrimer linked to the peptidic, epidermal growth factor receptor (EGFR-specific ligand GE11. In vitro experiments demonstrated coxsackie-adenovirus receptor-independent but EGFR-specific transduction efficiency. Systemic injection of the uncoated adenovirus in a liver cancer xenograft mouse model led to high levels of NIS expression in the liver due to hepatic sequestration, which were significantly reduced after coating as demonstrated by 123I-scintigraphy. Reduction of adenovirus liver pooling resulted in decreased hepatotoxicity and increased transduction efficiency in peripheral xenograft tumors. 124I-PET-imaging confirmed EGFR-specificity by significantly lower tumoral radioiodine accumulation after pretreatment with the EGFR-specific antibody cetuximab. A significantly enhanced oncolytic effect was observed following systemic application of dendrimer-coated adenovirus that was further increased by additional treatment with a therapeutic dose of 131I. These results demonstrate restricted virus tropism and tumor-selective retargeting after systemic application of coated, EGFR-targeted adenoviruses therefore representing a promising strategy for improved systemic adenoviral NIS gene therapy.

  20. EGFR-Targeted Adenovirus Dendrimer Coating for Improved Systemic Delivery of the Theranostic NIS Gene.

    Science.gov (United States)

    Grünwald, Geoffrey K; Vetter, Alexandra; Klutz, Kathrin; Willhauck, Michael J; Schwenk, Nathalie; Senekowitsch-Schmidtke, Reingard; Schwaiger, Markus; Zach, Christian; Wagner, Ernst; Göke, Burkhard; Holm, Per S; Ogris, Manfred; Spitzweg, Christine

    2013-11-05

    We recently demonstrated tumor-selective iodide uptake and therapeutic efficacy of combined radiovirotherapy after systemic delivery of the theranostic sodium iodide symporter (NIS) gene using a dendrimer-coated adenovirus. To further improve shielding and targeting we physically coated replication-selective adenoviruses carrying the hNIS gene with a conjugate consisting of cationic poly(amidoamine) (PAMAM) dendrimer linked to the peptidic, epidermal growth factor receptor (EGFR)-specific ligand GE11. In vitro experiments demonstrated coxsackie-adenovirus receptor-independent but EGFR-specific transduction efficiency. Systemic injection of the uncoated adenovirus in a liver cancer xenograft mouse model led to high levels of NIS expression in the liver due to hepatic sequestration, which were significantly reduced after coating as demonstrated by (123)I-scintigraphy. Reduction of adenovirus liver pooling resulted in decreased hepatotoxicity and increased transduction efficiency in peripheral xenograft tumors. (124)I-PET-imaging confirmed EGFR-specificity by significantly lower tumoral radioiodine accumulation after pretreatment with the EGFR-specific antibody cetuximab. A significantly enhanced oncolytic effect was observed following systemic application of dendrimer-coated adenovirus that was further increased by additional treatment with a therapeutic dose of (131)I. These results demonstrate restricted virus tropism and tumor-selective retargeting after systemic application of coated, EGFR-targeted adenoviruses therefore representing a promising strategy for improved systemic adenoviral NIS gene therapy.Molecular Therapy-Nucleic Acids (2013) 2, e131; doi:10.1038/mtna.2013.58; published online 5 November 2013.

  1. A systems biology approach to drug targets in Pseudomonas aeruginosa biofilm.

    Directory of Open Access Journals (Sweden)

    Gunnar Sigurdsson

    Full Text Available Antibiotic resistance is an increasing problem in the health care system and we are in a constant race with evolving bacteria. Biofilm-associated growth is thought to play a key role in bacterial adaptability and antibiotic resistance. We employed a systems biology approach to identify candidate drug targets for biofilm-associated bacteria by imitating specific microenvironments found in microbial communities associated with biofilm formation. A previously reconstructed metabolic model of Pseudomonas aeruginosa (PA was used to study the effect of gene deletion on bacterial growth in planktonic and biofilm-like environmental conditions. A set of 26 genes essential in both conditions was identified. Moreover, these genes have no homology with any human gene. While none of these genes were essential in only one of the conditions, we found condition-dependent genes, which could be used to slow growth specifically in biofilm-associated PA. Furthermore, we performed a double gene deletion study and obtained 17 combinations consisting of 21 different genes, which were conditionally essential. While most of the difference in double essential gene sets could be explained by different medium composition found in biofilm-like and planktonic conditions, we observed a clear effect of changes in oxygen availability on the growth performance. Eight gene pairs were found to be synthetic lethal in oxygen-limited conditions. These gene sets may serve as novel metabolic drug targets to combat particularly biofilm-associated PA. Taken together, this study demonstrates that metabolic modeling of human pathogens can be used to identify oxygen-sensitive drug targets and thus, that this systems biology approach represents a powerful tool to identify novel candidate antibiotic targets.

  2. A SYSTEM APPROACH TO ORGANISING PROTECTION FROM TARGETED INFORMATION IN SOCIAL NETWORKS

    Directory of Open Access Journals (Sweden)

    Marina V. Tumbinskaya

    2017-01-01

    Full Text Available Abstract. Objectives The aim of the study is to formalise a generalised algorithm for the distribution of targeted information in social networks, serving as the basis for a methodology for increasing personal information security. Method The research is based on the methodology of protection from unwanted information distributed across social network systems. Results The article presents the formalisation of an algorithm for the distribution of targeted information across social networks: input and output parameters are defined and the algorithm’s internal conditions are described, consisting of parameters for implementing attack scenarios, which variation would allow them to be detailed. A technique for protection from targeted information distributed across social networks is proposed, allowing the level of protection of personal data and information of social networks users to be enhanced, as well as the reliability of information increased. Conclusion The results of the research will help to prevent threats to information security, counteract attacks by intruders who often use methods of competitive intelligence and social engineering through the use of countermeasures. A model for protection against targeted information and implement special software for its integration into online social network social information systems is developed. The system approach will allow external monitoring of events in social networks to be carried out and vulnerabilities identified in the mechanisms of instant messaging, which provide opportunities for attacks by intruders. The results of the research make it possible to apply a network approach to the study of informal communities, which are actively developing today, at a new level. 

  3. An aptamer ligand based liposomal nanocarrier system that targets tumor endothelial cells.

    Science.gov (United States)

    Ara, Mst Naznin; Matsuda, Takashi; Hyodo, Mamoru; Sakurai, Yu; Hatakeyama, Hiroto; Ohga, Noritaka; Hida, Kyoko; Harashima, Hideyoshi

    2014-08-01

    The objective of this study was to construct our recently developed aptamer-modified targeted liposome nano-carrier (Apt-PEG-LPs) system to target primary cultured mouse tumor endothelial cells (mTEC), both in vitro and in vivo. We first synthesized an aptamer-polyethylene glycol 2000-distearoyl phosphoethanolamine (Apt-PEG2000-DSPE). The conjugation of the Apt-PEG2000-DSPE was confirmed by MALDI-TOF mass spectroscopy. A lipid hydration method was used to prepare Apt-PEG-LPs, in which the outer surface of the PEG-spacer was decorated with the aptamer. Apt-PEG-LPs were significantly taken up by mTECs. Cellular uptake capacity was observed both quantitatively and qualitatively using spectrofluorometry, and confocal laser scanning microscopy (CLSM), respectively. In examining the extent of localization of aptamer-modified liposomes that entered the cells, approximately 39% of the Apt-PEG-LPs were not co-localized with lysotracker, indicating that they had escaped from endosomes. The uptake route involved a receptor mediated pathway, followed by clathrin mediated endocytosis. This Apt-PEG-LP was also applied for in vivo research whether this system could target tumor endothelial cells. Apt-PEG-LP and PEG5000-DSPE modified Apt-PEG-LP (Apt/PEG5000-LP) were investigated by human renal cell carcinoma (OS-RC-2 cells) inoculating mice using CLSM. Apt-PEG-LP and Apt/PEG5000-LP showed higher accumulation on tumor vasculature compared to PEG-LP and the co-localization efficacy of Apt-PEG-LP and Apt/PEG5000-LP on TEC were quantified 16% and 25% respectively, which was also better than PEG-LP (3%). The findings suggest that this system is considerable promise for targeting tumor endothelial cells to deliver drugs or genes in vitro and in vivo. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Direct renin inhibition — a new way of targeting the renin system

    Directory of Open Access Journals (Sweden)

    Morris J Brown

    2006-06-01

    Full Text Available The renin system plays a key role in the pathology of hypertension and is influenced, both directly and indirectly, by most antihypertensive agents. The system is the target of several established classes of antihypertensive agents including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers. Of currently available drugs, only the beta-blockers suppress renin secretion, but these also reduce heart rate and cardiac output. Calcium channel blockers and diuretics cause a modest activation of the renin system secondary to the fall in renal afferent arteriolar pressure and reduction in filtered sodium load. Aliskiren is the first orally available direct inhibitor that blocks the renin system at its rate limiting step and is shown to reduce angiotensin I and II and plasma renin activity.

  5. Apelin/APJ system: A novel potential therapy target for kidney disease.

    Science.gov (United States)

    Huang, Zhen; Wu, Lele; Chen, Linxi

    2018-05-01

    Apelin is an endogenous ligand of seven-transmembrane G protein-coupled receptor APJ. Apelin and APJ are distributed in various tissues, including the heart, lung, kidney, and even in tumor tissues. Studies show that apelin mRNA is highly expressed in the inner stripe of kidney outer medulla, which plays an important role in process of water and sodium balance. Additionally, more studies also indicate that apelin/APJ system exerts a broad range of activities in kidney. Therefore, we review the role of apelin/APJ system in kidney diseases such as renal fibrosis, renal ischemia/reperfusion injury, diabetic nephropathy, polycystic kidney disease, and hemodialysis (HD). Apelin/APJ system can improve renal interstitial fibrosis by reducing the deposition of extracellular matrix. Apelin/APJ system significantly reduces renal ischemia/reperfusion injury by inhibiting renal cell death. Apelin/APJ system involves the progression of diabetic nephropathy (DN). Apelin/APJ system also predicts the process of polycystic kidney disease. Besides, apelin/APJ system prevents some dialysis complications in HD patients. And apelin/APJ system alleviates chronic kidney disease (CKD) by inhibiting vascular calcification (VC). Overall, apelin/APJ system plays diversified roles in kidney disease and may be a potential target for the treatment of kidney disease. © 2017 Wiley Periodicals, Inc.

  6. Data-Driven Approach To Determine Popular Proteins for Targeted Proteomics Translation of Six Organ Systems.

    Science.gov (United States)

    Lam, Maggie P Y; Venkatraman, Vidya; Xing, Yi; Lau, Edward; Cao, Quan; Ng, Dominic C M; Su, Andrew I; Ge, Junbo; Van Eyk, Jennifer E; Ping, Peipei

    2016-11-04

    Amidst the proteomes of human tissues lie subsets of proteins that are closely involved in conserved pathophysiological processes. Much of biomedical research concerns interrogating disease signature proteins and defining their roles in disease mechanisms. With advances in proteomics technologies, it is now feasible to develop targeted proteomics assays that can accurately quantify protein abundance as well as their post-translational modifications; however, with rapidly accumulating number of studies implicating proteins in diseases, current resources are insufficient to target every protein without judiciously prioritizing the proteins with high significance and impact for assay development. We describe here a data science method to prioritize and expedite assay development on high-impact proteins across research fields by leveraging the biomedical literature record to rank and normalize proteins that are popularly and preferentially published by biomedical researchers. We demonstrate this method by finding priority proteins across six major physiological systems (cardiovascular, cerebral, hepatic, renal, pulmonary, and intestinal). The described method is data-driven and builds upon the collective knowledge of previous publications referenced on PubMed to lend objectivity to target selection. The method and resulting popular protein lists may also be useful for exploring biological processes associated with various physiological systems and research topics, in addition to benefiting ongoing efforts to facilitate the broad translation of proteomics technologies.

  7. Phase calibration of sonar systems using standard targets and dual-frequency transmission pulses.

    Science.gov (United States)

    Islas-Cital, Alan; Atkins, Philip R; Foo, Kae Y; Picó, Ruben

    2011-10-01

    The phase angle component of the complex frequency response of a sonar system operating near transducer resonance is usually distorted. Interpretation and classification of the received sonar signal benefits from the preservation of waveform fidelity over the full bandwidth. A calibration process that measures the phase response in addition to the amplitude response is thus required. This paper describes an extension to the standard-target calibration method to include phase angle, without affecting the experimental apparatus, by using dual-frequency transmission pulses and frequency-domain data processing. This approach reduces the impact of unknown range and sound speed parameters upon phase calibration accuracy, as target phase is determined from the relationship of the two frequency components instead of relying on a local phase reference. Tungsten carbide spheres of various sizes were used to simultaneously calibrate the amplitude and phase response of an active sonar system in a laboratory tank. Experimental measurements of target phase spectra are in good agreement with values predicted from a theoretical model based upon full-wave analysis, over an operating frequency of 50-125 kHz. © 2011 Acoustical Society of America

  8. Study on the measurement system of the target polarization characteristics and test

    Science.gov (United States)

    Fu, Qiang; Zhu, Yong; Zhang, Su; Duan, Jin; Yang, Di; Zhan, Juntong; Wang, Xiaoman; Jiang, Hui-Lin

    2015-10-01

    The polarization imaging detection technology increased the polarization information on the basis of the intensity imaging, which is extensive application in the military and civil and other fields, the research on the polarization characteristics of target is particularly important. The research of the polarization reflection model was introduced in this paper, which describes the scattering vector light energy distribution in reflecting hemisphere polarization characteristics, the target polarization characteristics test system solutions was put forward, by the irradiation light source, measuring turntable and camera, etc, which illuminate light source shall direct light source, with laser light sources and xenon lamp light source, light source can be replaced according to the test need; Hemispherical structure is used in measuring circumarotate placed near its base material sample, equipped with azimuth and pitching rotation mechanism, the manual in order to adjust the azimuth Angle and high Angle observation; Measuring camera pump works, through the different in the way of motor control polaroid polarization test, to ensure the accuracy of measurement and imaging resolution. The test platform has set up by existing laboratory equipment, the laser is 532 nm, line polaroid camera, at the same time also set the sending and receiving optical system. According to the different materials such as wood, metal, plastic, azimuth Angle and zenith Angle in different observation conditions, measurement of target in the polarization scattering properties of different exposure conditions, implementation of hemisphere space pBRDF measurement.

  9. A human systems biology approach to discover new drug targets in epilepsy.

    Science.gov (United States)

    Loeb, Jeffery A

    2010-07-01

    One of the major challenges in developing novel therapeutics for human epileptic disorders comes from the wide range of brain abnormalities capable of producing epilepsy. In children and adults that undergo epilepsy surgery for treatment of refractory seizures, these abnormalities range from developmental defects to injuries, infections, tumors, and ischemia. Given the many molecular mechanisms likely involved in each of these, finding common therapeutic targets seems a futile task. However, patients undergoing surgery for neocortical seizures have surprisingly similar electrophysiologic abnormalities, which consist of the synchronous firing of large neuronal populations. Surgical removal of these regions is the only means at present time to permanently reduce or eliminate seizures. The precise locations of these hypersynchronous firing regions that produce seizures can be revealed using long-term subdural electrical high-density recordings. This therapeutic strategy not only can dramatically reduce seizures, but also offers the potential to generate molecular and cellular information that can be used to ask why certain regions of the cortex become and remain epileptic. We have taken advantage of these detailed clinical and electrophysiologic human studies by taking a "systems biology" approach to identify novel biomarkers and drug targets in neocortical human epilepsy. In this article, we describe our multidisciplinary systems approach that utilizes a relational database to interrelate clinical, quantitative electrophysiologic, pathologic, and gene expression profiling data together as a means to identify and validate new biomarkers and potential drug targets for human epilepsy.

  10. Development of an automated multiple-target mask CD disposition system to enable new sampling strategy

    Science.gov (United States)

    Ma, Jian; Farnsworth, Jeff; Bassist, Larry; Cui, Ying; Mammen, Bobby; Padmanaban, Ramaswamy; Nadamuni, Venkatesh; Kamath, Muralidhar; Buckmann, Ken; Neff, Julie; Freiberger, Phil

    2006-03-01

    Traditional mask critical dimension (CD) disposition systems with only one or two targets is being challenged by the new requirements from mask-users as the wafer process control becomes more complicated in the newer generation of technologies. Historically, the mask shop does not necessarily measure and disposition off the same kind of CD structures that wafer fabs do. Mask disposition specifications and structures come from the frame-design and the tapeout, while wafer-level CD dispositions are mainly based on the historical process window established per CD-skew experiments and EOL (end of line) yield. In the current high volume manufacturing environment, the mask CDs are mainly dispositioned off their mean-to-target (MTT) and uniformity (6sigma) on one or two types of pre-determined structures. The disposition specification is set to ensure the printed mask will meet the design requirements and to ensure minimum deviation from them. The CD data are also used to adjust the dose of the mask exposure tools to control CD MTT. As a result, the mask CD disposition automation system was built to allow only one or two kinds of targets at most. In contrast, wafer-fabs measure a fairly wide range of different structures to ensure their process is on target and in control. The number of such structures that are considered critical is increasing due the growing complexity of the technology. To fully comprehend the wafer-level requirements, it is highly desirable to align the mask CD sample site and disposition to be the same as that of the wafer-fabs, to measure the OPC (optical proximity correction) structures or equivalent whenever possible, and to establish the true correlation between mask CD measurements vs. wafer CD measurement. In this paper, the development of an automated multiple-target mask CD disposition system with the goal of enabling new sampling strategy is presented. The pros and cons of its implementation are discussed. The new system has been inserted in

  11. Targeted gene expression in transgenic Xenopus using the binary Gal4-UAS system.

    Science.gov (United States)

    Hartley, Katharine O; Nutt, Stephen L; Amaya, Enrique

    2002-02-05

    The transgenic technique in Xenopus allows one to misexpress genes in a temporally and spatially controlled manner. However, this system suffers from two experimental limitations. First, the restriction enzyme-mediated integration procedure relies on chromosomal damage, resulting in a percentage of embryos failing to develop normally. Second, every transgenic embryo has unique sites of integration and unique transgene copy number, resulting in variable transgene expression levels and variable phenotypes. For these reasons, we have adapted the Gal4-UAS method for targeted gene expression to Xenopus. This technique relies on the generation of transgenic lines that carry "activator" or "effector" constructs. Activator lines express the yeast transcription factor, Gal4, under the control of a desired promoter, whereas effector lines contain DNA-binding motifs for Gal4-(UAS) linked to the gene of interest. We show that on intercrossing of these lines, the effector gene is transcribed in the temporal and spatial manner of the activator's promoter. Furthermore, we use the Gal4-UAS system to misexpress Xvent-2, a transcriptional target of bone morphogenetic protein 4 (BMP4) signaling during early embryogenesis. Embryos inheriting both the Gal4 activator and Xvent-2 effector transgenes display a consistent microcephalic phenotype. Finally, we exploit this system to characterize the neural and mesodermal defects obtained from early misexpression of Xvent-2. These results emphasize the potential of this system for the controlled analyses of gene function in Xenopus.

  12. Thermal-hydraulic design concept of the solid-target system of spallation neutron source

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, F.; Hibiki, T.; Saito, Y.; Takeda, T.; Mishima, K. [Kyoto Univ., Research Reactor Institute (Japan)

    2001-07-01

    In relation to thermal-hydraulic design of the N-Arena solid-target system of the JHF project, heat transfer experiments were performed to obtain experimental data systematically on heat transfer coefficient and CHF for vertical upward and horizontal flows in a thin rectangular channel simulating a coolant channel of the proposed spallation neutron source. Thermal-hydraulic correlations which can be used for design calculations were proposed based on the obtained data. Finally tentative results of feasibility study on maximum beam power which could be attained with a solid target were presented. The result indicated that the condition for the onset of nucleate boiling is the most significant limiting factor to the maximum beam power. (author)

  13. A targeted drug delivery system based on dopamine functionalized nano graphene oxide

    Science.gov (United States)

    Masoudipour, Elham; Kashanian, Soheila; Maleki, Nasim

    2017-01-01

    The cellular targeting property of a biocompatible drug delivery system can widely increase the therapeutic effect against various diseases. Here, we report a dopamine conjugated nano graphene oxide (DA-nGO) carrier for cellular delivery of the anticancer drug, Methotrexate (MTX) into DA receptor positive human breast adenocarcinoma cell line. The material was characterized using scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy and UV-vis spectroscopy. Furthermore, the antineoplastic action of MTX loaded DA-nGO against DA receptor positive and negative cell lines were explored. The results presented in this article demonstrated that the application of DA functionalized GO as a targeting drug carrier can improve the drug delivery efficacy for DA receptor positive cancer cell lines and promise future designing of carrier conjugates based on it.

  14. Targeting the noradrenergic system for gender-sensitive medication development for tobacco dependence.

    Science.gov (United States)

    Verplaetse, Terril L; Weinberger, Andrea H; Smith, Philip H; Cosgrove, Kelly P; Mineur, Yann S; Picciotto, Marina R; Mazure, Carolyn M; McKee, Sherry A

    2015-04-01

    Tobacco use remains the leading cause of morbidity and mortality for both women and men in the United States, and women often experience poorer smoking cessation outcomes than men. Preliminary evidence suggests there are sex differences in medication effectiveness for smoking cessation. However, current medications do not take into account gender-sensitive treatment development and efficacy, underscoring the importance of this underdeveloped area of research. We reviewed preclinical and clinical evidence for gender differences in the inability to quit smoking by examining (a) the effect of increased negative affect and stress reactivity on smoking outcomes in women and (b) smoking for nicotine reinforcement in men. We also reviewed the current literature targeting the noradrenergic system as a novel gender-sensitive treatment strategy for tobacco dependence. We hypothesize that noradrenergic agents that normalize noradrenergic activity may differentially attenuate stress reactivity in women and nicotine-related reinforcement in men, indicating that targeting the noradrenergic system for smoking cessation may be effective for both genders, with benefits operating through sex-specific mechanisms. Converging lines of preclinical and clinical evidence suggest that gender-sensitive approaches to medication development for smoking cessation are a critical next step for addressing low quit rates and exacerbated health risks among women. Evidence reviewed indicates that smoking activates different brain systems modulated by noradrenergic activity in women versus men, and noradrenergic compounds may preferentially target these gender-sensitive systems. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. The trigger system for the external target experiment in the HIRFL cooling storage ring

    Science.gov (United States)

    Li, Min; Zhao, Lei; Liu, Jin-Xin; Lu, Yi-Ming; Liu, Shu-Bin; An, Qi

    2016-08-01

    A trigger system was designed for the external target experiment in the Cooling Storage Ring (CSR) of the Heavy Ion Research Facility in Lanzhou (HIRFL). Considering that different detectors are scattered over a large area, the trigger system is designed based on a master-slave structure and fiber-based serial data transmission technique. The trigger logic is organized in hierarchies, and flexible reconfiguration of the trigger function is achieved based on command register access or overall field-programmable gate array (FPGA) logic on-line reconfiguration controlled by remote computers. We also conducted tests to confirm the function of the trigger electronics, and the results indicate that this trigger system works well. Supported by the National Natural Science Foundation of China (11079003), the Knowledge Innovation Program of the Chinese Academy of Sciences (KJCX2-YW-N27), and the CAS Center for Excellence in Particle Physics (CCEPP).

  16. CB2 and GPR55 receptors as therapeutic targets for systemic immune dysregulation

    Directory of Open Access Journals (Sweden)

    Juan Zhou

    2016-08-01

    Full Text Available The endocannabinoid system (ECS is involved in many physiological processes and has been suggested to play critical roles in the immune response and the central nervous system (CNS. Therefore, ECS modulation has potential therapeutic effects on immune dysfunctional disorders, such as sepsis and CNS injury-induced immunodeficiency syndrome (CIDS. In sepsis, excessive release of pro- and anti-inflammatory mediators results in multi-organ dysfunction/failure and death. In CIDS, an acute CNS injury dysregulates a normally well-balanced interplay between the CNS and immune system, leading to increased patients’ susceptibility to infections. In this review, we will discuss potential therapeutic modulation of the immune response in sepsis and CNS injury by manipulation of the ECS representing a novel target for immunotherapy.

  17. Developing plan and pre-conceptual design of target system for JAERI`s high intensity neutron source

    Energy Technology Data Exchange (ETDEWEB)

    Hino, Ryutaro; Kaminaga, Masanori; Haga, Katsuhiro; Ishikura, Syuichi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Nakamura, Fumito; Uchida, Shoji

    1997-11-01

    This paper presents an outline of developing plan of a target system and topics obtained by a pre-conceptual design, which aims to establish a technology base of the target system and to make clear a system concept. In the plan, two types of target - solid and mercury targets - are to be developed for a neutron scattering facility. Information obtained through the development shall be applied to designs of an irradiation and a transmutation facilities. Through the pre-conceptual design, system arrangement, scale etc. were made clear: total weight will be 12000 ton, and 26 beam lines with beam shutters will be equipped for 4 moderators. Engineering problems were also made clear through the design; high flux heat removal, dynamic stress caused by thermal shock and pressure wave, loop technology for the mercury target and a slurry moderator consisting of methane pellets and liquefied hydrogen. We are now constructing new test apparatuses and arranging computer codes for solving these problems. (author)

  18. Sense and avoid requirements for unmanned aircraft systems using a target level of safety approach.

    Science.gov (United States)

    Melnyk, Richard; Schrage, Daniel; Volovoi, Vitali; Jimenez, Hernando

    2014-10-01

    One of the most critical challenges to full integration of unmanned aircraft systems (UAS) into the National Airspace System (NAS) is the requirement to comply with CFR 14 Part 91.113 to "see and avoid" other aircraft. Various attempts have been made to develop systems to "sense and avoid" other aircraft so UAS can comply with the intent of the regulation. This article proposes a framework to develop effectiveness requirements for any SAA system by linking UAS characteristics and operating environments to midair collision risk quantified by a fatality rate. The framework consists of a target level of safety (TLS) approach using an event tree format. Safety has been identified as the most important consideration in the UAS integration process. While safety can be defined in many ways, the authors propose using a fatality rate metric that follows other statistics used in the industry. This metric allows for the use of a TLS approach to the development of SAA requirements for system certification. Failure to adequately link system requirements to safety could result in the implementation of SAA systems that either do not adequately mitigate the risk associated with UAS operations or are overdesigned, resulting in increased cost and complexity. This article demonstrates the use of the proposed framework to develop specific SAA effectiveness standards based on UAS weight and airspace class combinations. © 2014 Society for Risk Analysis.

  19. Versatile transmission ellipsometry to study linear ferrofluid magneto-optics

    NARCIS (Netherlands)

    Kooij, Ernst S.; Galca, A.C.; Poelsema, Bene

    2006-01-01

    Linear birefringence and dichroism of magnetite ferrofluids are studied simultaneously using spectroscopic ellipsometry in transmission mode. It is shown that this versatile technique enables highly accurate characterisation of magneto-optical phenomena. Magnetic field-dependent linear birefringence

  20. A versatile hardware platform for brain computer interfaces.

    Science.gov (United States)

    Garcia, Pablo A; Haberman, Marcelo; Spinelli, Enrique M

    2010-01-01

    This article presents the development of a versatile hardware platform for brain computer interfaces (BCI). The aim of this work is to produce a small, autonomous and configurable BCI platform adaptable to the user's needs.

  1. Electrospun nanofibers as versatile interfaces for efficient gene delivery

    National Research Council Canada - National Science Library

    Lee, Slgirim; Jin, Gyuhyung; Jang, Jae-Hyung

    2014-01-01

    The integration of gene delivery technologies with electrospun nanofibers is a versatile strategy to increase the potential of gene therapy as a key platform technology that can be readily utilized...

  2. Off-target Effects in CRISPR/Cas9-mediated Genome Engineering

    Directory of Open Access Journals (Sweden)

    Xiao-Hui Zhang

    2015-01-01

    Full Text Available 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.

  3. Multigene knockout utilizing off-target mutations of the CRISPR/Cas9 system in rice.

    Science.gov (United States)

    Endo, Masaki; Mikami, Masafumi; Toki, Seiichi

    2015-01-01

    The clustered regularly interspaced short palindromic repeat (CRISPR)-associated endonuclease 9 (CRISPR/Cas9) system has been demonstrated to be a robust genome engineering tool in a variety of organisms including plants. However, it has been shown that the CRISPR/Cas9 system cleaves genomic DNA sequences containing mismatches to the guide RNA strand. We expected that this low specificity could be exploited to induce multihomeologous and multiparalogous gene knockouts. In the case of polyploid plants, simultaneous modification of multiple homeologous genes, i.e. genes with similar but not identical DNA sequences, is often needed to obtain a desired phenotype. Even in diploid plants, disruption of multiparalogous genes, which have functional redundancy, is often needed. To validate the applicability of the CRISPR/Cas9 system to target mutagenesis of paralogous genes in rice, we designed a single-guide RNA (sgRNA) that recognized 20 bp sequences of cyclin-dependent kinase B2 (CDKB2) as an on-target locus. These 20 bp possess similarity to other rice CDK genes (CDKA1, CDKA2 and CDKB1) with different numbers of mismatches. We analyzed mutations in these four CDK genes in plants regenerated from Cas9/sgRNA-transformed calli and revealed that single, double and triple mutants of CDKA2, CDKB1 and CDKB2 can be created by a single sgRNA. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.

  4. The control system of the polarized internal target of ANKE at COSY

    Energy Technology Data Exchange (ETDEWEB)

    Kleines, H. [Zentralinstitut fuer Elektronik, Forschungszentrum Juelich, 52425 Juelich (Germany); Sarkadi, J. [Zentralinstitut fuer Elektronik, Forschungszentrum Juelich, 52425 Juelich (Germany); Zwoll, K. [Zentralinstitut fuer Elektronik, Forschungszentrum Juelich, 52425 Juelich (Germany); Engels, R. [Institut fuer Kernphysik, Forschungszentrum Juelich, 52425 Juelich (Germany); Grigoryev, K. [Institut fuer Kernphysik, Forschungszentrum Juelich, 52425 Juelich (Germany); Mikirtychyants, M. [Institut fuer Kernphysik, Forschungszentrum Juelich, 52425 Juelich (Germany); Nekipelov, M. [Institut fuer Kernphysik, Forschungszentrum Juelich, 52425 Juelich (Germany); Rathmann, F. [Institut fuer Kernphysik, Forschungszentrum Juelich, 52425 Juelich (Germany); Seyfarth, H. [Institut fuer Kernphysik, Forschungszentrum Juelich, 52425 Juelich (Germany)]. E-mail: h.seyfarth@fz-juelich.de; Kravtsov, P. [St. Petersburg Nuclear Physics Institute, 188350 Gatchina (Russian Federation); Vasilyev, A. [St. Petersburg Nuclear Physics Institute, 188350 Gatchina (Russian Federation)

    2006-05-10

    The polarized internal target for the ANKE experiment at the Cooler Synchrotron COSY of the Forschungszentrum Juelich utilizes a polarized atomic beam source to feed a storage cell with polarized hydrogen or deuterium atoms. The nuclear polarization is measured with a Lamb-shift polarimeter. For common control of the two systems, industrial equipment was selected providing reliable, long-term support and remote control of the target as well as measurement and optimization of its operating parameters. The interlock system has been implemented on the basis of SIEMENS SIMATIC S7-300 family of programmable logic controllers. In order to unify the interfacing to the control computer, all front-end equipment is connected via the PROFIBUS DP fieldbus. The process control software was implemented using the Windows-based WinCC toolkit from SIEMENS. The variety of components, to be controlled, and the logical structure of the control and interlock system are described. Finally, a number of applications derived from the present development to other, new installations are briefly mentioned.

  5. The control system of the polarized internal target of ANKE at COSY

    Science.gov (United States)

    Kleines, H.; Sarkadi, J.; Zwoll, K.; Engels, R.; Grigoryev, K.; Mikirtychyants, M.; Nekipelov, M.; Rathmann, F.; Seyfarth, H.; Kravtsov, P.; Vasilyev, A.

    2006-05-01

    The polarized internal target for the ANKE experiment at the Cooler Synchrotron COSY of the Forschungszentrum Jülich utilizes a polarized atomic beam source to feed a storage cell with polarized hydrogen or deuterium atoms. The nuclear polarization is measured with a Lamb-shift polarimeter. For common control of the two systems, industrial equipment was selected providing reliable, long-term support and remote control of the target as well as measurement and optimization of its operating parameters. The interlock system has been implemented on the basis of SIEMENS SIMATIC S7-300 family of programmable logic controllers. In order to unify the interfacing to the control computer, all front-end equipment is connected via the PROFIBUS DP fieldbus. The process control software was implemented using the Windows-based WinCC toolkit from SIEMENS. The variety of components, to be controlled, and the logical structure of the control and interlock system are described. Finally, a number of applications derived from the present development to other, new installations are briefly mentioned.

  6. Targeted therapy for Hodgkin lymphoma and systemic anaplastic large cell lymphoma: focus on brentuximab vedotin

    Directory of Open Access Journals (Sweden)

    Chen X

    2013-12-01

    Full Text Available Xueyan Chen, Lorinda A Soma, Jonathan R FrommDepartment of Laboratory Medicine, University of Washington Medical Center, Seattle, WA, USAAbstract: Despite the relative success of chemotherapy for Hodgkin lymphoma (HL and systemic anaplastic large cell lymphoma (ALCL, novel therapeutic agents are needed for refractory or relapsed patients. Targeted immunotherapy has emerged as a novel treatment option for these patients. Although unconjugated anti-cluster of differentiation (CD30 antibodies showed minimal antitumor activity in early clinical trials, development of antibody–drug conjugates (ADCs appears promising. Brentuximab vedotin is an ADC composed of an anti-CD30 antibody linked to a potent microtubule-disrupting agent monomethyl auristatin E (MMAE. It has the ability to target CD30-positive tumor cells and, once bound to CD30, brentuximab vedotin is internalized and MMAE is released to induce cell cycle arrest and apoptosis. In two phase II trials, objective response was reported in 75% and 86% of patients with refractory or relapsed HL and systemic ALCL, respectively, with an acceptable toxicity profile. Based on these studies, the US Food and Drug Administration (FDA granted accelerated approval of brentuximab vedotin in August 2011 for the treatment of refractory and relapsed HL and ALCL. We review the key characteristics of brentuximab vedotin, clinical data supporting its therapeutic efficacy, and current ongoing trials to explore its utility in other CD30-positive malignancies.Keywords: classical Hodgkin lymphoma, systemic anaplastic large cell lymphoma, CD30, brentuximab vedotin, SGN-35

  7. Characterization of cubosomes as a targeted and sustained transdermal delivery system for capsaicin

    Directory of Open Access Journals (Sweden)

    Peng X

    2015-08-01

    Full Text Available Xinsheng Peng,1* Yanfang Zhou,1* Ke Han,2,3 Lingzhen Qin,3 Linghui Dian,1 Ge Li,4 Xin Pan,3 Chuanbin Wu3 1Guangdong Medical University, Dongguan, 2The Second Affiliated Hospital of Guangzhou Medical University, 3School of Pharmaceutical Sciences, Sun Yat-Sen University, 4Guangzhou Neworld Pharmaceuticals Co. Ltd., Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this work Abstract: Phytantriol- and glycerol monooleate-based cubosomes were produced and characterized as a targeted and sustained transdermal delivery system for capsaicin. The cubosomes were prepared by emulsification and homogenization of phytantriol (F1, glycerol monooleate (F2, and poloxamer dispersions, characterized for morphology and particle size distribution by transmission electron microscope and photon correlation spectroscopy. Their Im3m crystallographic space group was confirmed by small-angle X-ray scattering. An in vitro release study showed that the cubosomes provided a sustained release system for capsaicin. An in vitro diffusion study conducted using Franz diffusion cells indicated that the skin retention of capsaicin from cubosomes in the stratum corneum was much higher (2.75±0.22 µg versus 4.32±0.13 µg, respectively than that of capsaicin cream (0.72±0.13 µg. The stress testing showed that the cubosome formulations were stable under strong light and high temperature for up to 10 days. After multiapplications on mouse skin, the irritation of capsaicin cubosomes and cream was light with the least amount of side effects. Overall, the present study demonstrated that cubosomes may be a suitable skin-targeted and sustained delivery system for the transdermal administration of capsaicin. Keywords: cubosomes, skin-targeted delivery, capsaicin

  8. Construction of a CRISPR-Cas9 System for Pig Genome Targeting.

    Science.gov (United States)

    Su, Yu-Hsiu; Lin, Tai-Yun; Huang, Chung-Lin; Tu, Ching-Fu; Chuang, Chin-Kai

    2015-01-01

    A Cas9/sgRNA RNA-guided endonuclease expression system including a codon-optimized Streptococcus pyogenes A20 Cas9 recombinant protein expression vector and a spacer-guide chimeric RNA expression vector using the porcine U6 promoter was constructed for application in pigs. Only the Flag2-NLS1-Cas9-NLS2 recombinant protein in complex with sgRNA was translocated into the nucleus; the Flag2-NLS1-Cas9-NLS2 protein alone was excluded from the nucleus. Up to 13% of porcine PK1 cells targeted in vitro were observed, regardless of transfection efficiency.

  9. Sublethal effects of imidacloprid on interactions in a tritrophic system of non-target species.

    Science.gov (United States)

    Uhl, Philipp; Bucher, Roman; Schäfer, Ralf B; Entling, Martin H

    2015-08-01

    Imidacloprid is one of the most used insecticides worldwide, but is highly toxic to non-target arthropods. Effects of sublethal imidacloprid intoxication can potentially propagate in food webs, yet little is known about the impact on non-target populations and communities. We investigated short-term sublethal toxicity of imidacloprid in a tritrophic model system of wild strawberry Fragaria vesca, wood cricket Nemobius sylvestris and nursery web spider Pisaura mirabilis. Strawberries were treated two times with 0mg (control), 1mg (low rate) and 10mg (high rate) of Confidor® WG 70 and crickets were allowed to feed on them. In four lab experiments, we quantified the impact of imidacloprid on leaf damage, growth, behaviour and survival of crickets. The high imidacloprid rate reduced feeding, mass gain, thorax growth and mobility in crickets compared to the control, while mortality was similarly low in all treatments. The low rate reduced mass gain only. Cricket survival of spider predation was higher in the low rate treatment than in the control. Overall, herbivory and predation were reduced at sublethal imidacloprid rates in a non-target organism, three-level food chain, which demonstrates possible propagation of sublethal effects through trophic interactions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Impact of priming the infusion system on the performance of target-controlled infusion of remifentanil.

    Science.gov (United States)

    Kim, Jong-Yeop; Moon, Bong-Ki; Lee, Jong Hyuk; Jo, Youn Yi; Min, Sang-Kee

    2013-05-01

    The start-up behavior of syringe and syringe pump is known to be one of the causes of inaccurate intravenous infusion. This study evaluated the method of priming the infusion system (PRIMING), and its impact on the target-controlled infusion (TCI) of two remifentanil diluents. PRIMING was performed using an evacuation of 2.0 ml to the atmosphere prior to TCI. Forty-eight TCI, using 50 µg/ml (Remi50) or 20 µg/ml (Remi20) of diluents, were performed targeting 4.0 ng/ml of effect-site concentration (Ceff), with PRIMING or not. The gravimetrical measurements of the delivered infusates reproduced actual Ceff. The bolus amount and time to reach 95% target were compared. Without PRIMING, Remi50 infused less bolus (43 ± 23 %) than Remi20 (19 ± 9 %) (P = 0.003), and showed more delayed increase of Ceff (11.2 ± 4.0 min) than Remi20 (7.4 ± 0.4 min) (P = 0.028). However, PRIMING significantly decreased the deficit of the bolus (2 ± 1%), as well as the delay of the increase of Ceff in Remi50 (1.2 ± 0.2 min) (both P phase of infusion, or the infusion of a more concentrated diluent.

  11. Targetable genetic features of primary testicular and primary central nervous system lymphomas.

    Science.gov (United States)

    Chapuy, Bjoern; Roemer, Margaretha G M; Stewart, Chip; Tan, Yuxiang; Abo, Ryan P; Zhang, Liye; Dunford, Andrew J; Meredith, David M; Thorner, Aaron R; Jordanova, Ekaterina S; Liu, Gang; Feuerhake, Friedrich; Ducar, Matthew D; Illerhaus, Gerald; Gusenleitner, Daniel; Linden, Erica A; Sun, Heather H; Homer, Heather; Aono, Miyuki; Pinkus, Geraldine S; Ligon, Azra H; Ligon, Keith L; Ferry, Judith A; Freeman, Gordon J; van Hummelen, Paul; Golub, Todd R; Getz, Gad; Rodig, Scott J; de Jong, Daphne; Monti, Stefano; Shipp, Margaret A

    2016-02-18

    Primary central nervous system lymphomas (PCNSLs) and primary testicular lymphomas (PTLs) are extranodal large B-cell lymphomas (LBCLs) with inferior responses to current empiric treatment regimens. To identify targetable genetic features of PCNSL and PTL, we characterized their recurrent somatic mutations, chromosomal rearrangements, copy number alterations (CNAs), and associated driver genes, and compared these comprehensive genetic signatures to those of diffuse LBCL and primary mediastinal large B-cell lymphoma (PMBL). These studies identify unique combinations of genetic alterations in discrete LBCL subtypes and subtype-selective bases for targeted therapy. PCNSLs and PTLs frequently exhibit genomic instability, and near-uniform, often biallelic, CDKN2A loss with rare TP53 mutations. PCNSLs and PTLs also use multiple genetic mechanisms to target key genes and pathways and exhibit near-uniform oncogenic Toll-like receptor signaling as a result of MYD88 mutation and/or NFKBIZ amplification, frequent concurrent B-cell receptor pathway activation, and deregulation of BCL6. Of great interest, PCNSLs and PTLs also have frequent 9p24.1/PD-L1/PD-L2 CNAs and additional translocations of these loci, structural bases of immune evasion that are shared with PMBL. © 2016 by The American Society of Hematology.

  12. Smartphone-based portable wireless optical system for the detection of target analytes.

    Science.gov (United States)

    Gautam, Shreedhar; Batule, Bhagwan S; Kim, Hyo Yong; Park, Ki Soo; Park, Hyun Gyu

    2017-02-01

    Rapid and accurate on-site wireless measurement of hazardous molecules or biomarkers is one of the biggest challenges in nanobiotechnology. A novel smartphone-based Portable and Wireless Optical System (PAWS) for rapid, quantitative, and on-site analysis of target analytes is described. As a proof-of-concept, we employed gold nanoparticles (GNP) and an enzyme, horse radish peroxidase (HRP), to generate colorimetric signals in response to two model target molecules, melamine and hydrogen peroxide, respectively. The colorimetric signal produced by the presence of the target molecules is converted to an electrical signal by the inbuilt electronic circuit of the device. The converted electrical signal is then measured wirelessly via multimeter in the smartphone which processes the data and displays the results, including the concentration of analytes and its significance. This handheld device has great potential as a programmable and miniaturized platform to achieve rapid and on-site detection of various analytes in a point-of-care testing (POCT) manner. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. HOW BOXERS DECIDE TO PUNCH A TARGET: EMERGENT BEHAVIOUR IN NONLINEAR DYNAMICAL MOVEMENT SYSTEMS

    Directory of Open Access Journals (Sweden)

    Robert Hristovski

    2006-07-01

    Full Text Available Previous research has shown how dynamical systems theory provides a relevant framework for investigating decision-making behavior in sport. The aim of this study was to adopt concepts and tools from nonlinear dynamics in examining effects of boxer-target distance and perceived punching efficiency on emergent decision-making during a typical practice task in boxing. Results revealed the existence of critical values of scaled distances between boxers and targets for first time appearance and disappearance of a diverse range of boxing actions including jabs, hooks and uppercuts. Reasons for the diversity of actions were twofold: i abrupt (qualitative changes in the number of the possible punches, i.e. motor solutions to the hitting task; and ii, fine modification of the probabilities of selecting specific striking patterns. Boxers were able to exploit the emerging perception of strikeability, leading to a changing diversity of selected actions and a cascade of abrupt changes in the perceptual-motor work space of the task. Perceived efficiency of a punching action by the participants also changed as a function of the scaled distance to a target and was correlated with the probability of occurrence of specific boxing actions. Accordingly, scaled distance-dependent perceived efficiency seems an important perceptual constraint in the training task of punching a heavy bag in boxers

  14. Multi-target-qubit unconventional geometric phase gate in a multi-cavity system.

    Science.gov (United States)

    Liu, Tong; Cao, Xiao-Zhi; Su, Qi-Ping; Xiong, Shao-Jie; Yang, Chui-Ping

    2016-02-22

    Cavity-based large scale quantum information processing (QIP) may involve multiple cavities and require performing various quantum logic operations on qubits distributed in different cavities. Geometric-phase-based quantum computing has drawn much attention recently, which offers advantages against inaccuracies and local fluctuations. In addition, multiqubit gates are particularly appealing and play important roles in QIP. We here present a simple and efficient scheme for realizing a multi-target-qubit unconventional geometric phase gate in a multi-cavity system. This multiqubit phase gate has a common control qubit but different target qubits distributed in different cavities, which can be achieved using a single-step operation. The gate operation time is independent of the number of qubits and only two levels for each qubit are needed. This multiqubit gate is generic, e.g., by performing single-qubit operations, it can be converted into two types of significant multi-target-qubit phase gates useful in QIP. The proposal is quite general, which can be used to accomplish the same task for a general type of qubits such as atoms, NV centers, quantum dots, and superconducting qubits.

  15. Systemic coagulation parameters in mice after treatment with vascular targeting agents

    Directory of Open Access Journals (Sweden)

    Gottstein Claudia

    2005-12-01

    Full Text Available Abstract Background Vascular targeting of malignant tumors has become a clinically validated new treatment approach with clear patient benefit. However clinical studies have also revealed that some types of vascular targeting agents (VTAs are prone to coagulation system side effects. It is therefore essential to predetermine coagulation parameters in preclinical studies. As of to date, this has rarely been done, predominantly due to technical issues. The goal of this study was to establish and apply a standardized process, whereby systemic coagulation activation can be routinely measured in mice. Results We have evaluated a number of sampling techniques and coagulation tests regarding their suitability for this purpose. We were able to adapt two assays measuring soluble fibrin, a marker for a prethrombotic status. Thus, soluble fibrin could be measured for the first time in mice. All assays were validated in a positive control model for systemic coagulation activation, i.e. lipopolysaccharide-induced endotoxemia. Based on our results, we selected a panel of coagulation tests, which are both feasable and informative for preclinical testing of VTAs: soluble fibrin, thrombin-antithrombin complexes, free antithrombin III, white blood cell counts and platelet counts. The effect of tumor transplants on coagulation parameters was evaluated using this panel. We then applied this set of assays in treatment studies with a VTA developed in our laboratory to investigate a potential systemic coagulation activation. Conclusion We have established a standardized panel of assays that can be used to test murine blood samples for coagulation activation in preclinical studies. All tests are feasible to perform in any research laboratory without specialized equipment. In addition, this is the first report to measure soluble fibrin, an early marker of systemic coagulation activation, in mice. The panel was applied on tumor bearing mice and mice treated with a VTA

  16. Lymphatic drainage system of the brain: A novel target for intervention of neurological diseases.

    Science.gov (United States)

    Sun, Bao-Liang; Wang, Li-Hua; Yang, Tuo; Sun, Jing-Yi; Mao, Lei-Lei; Yang, Ming-Feng; Yuan, Hui; Colvin, Robert A; Yang, Xiao-Yi

    2017-09-10

    The belief that the vertebrate brain functions normally without classical lymphatic drainage vessels has been held for many decades. On the contrary, new findings show that functional lymphatic drainage does exist in the brain. The brain lymphatic drainage system is composed of basement membrane-based perivascular pathway, a brain-wide glymphatic pathway, and cerebrospinal fluid (CSF) drainage routes including sinus-associated meningeal lymphatic vessels and olfactory/cervical lymphatic routes. The brain lymphatic systems function physiological as a route of drainage for interstitial fluid (ISF) from brain parenchyma to nearby lymph nodes. Brain lymphatic drainage helps maintain water and ion balance of the ISF, waste clearance, and reabsorption of macromolecular solutes. A second physiological function includes communication with the immune system modulating immune surveillance and responses of the brain. These physiological functions are influenced by aging, genetic phenotypes, sleep-wake cycle, and body posture. The impairment and dysfunction of the brain lymphatic system has crucial roles in age-related changes of brain function and the pathogenesis of neurovascular, neurodegenerative, and neuroinflammatory diseases, as well as brain injury and tumors. In this review, we summarize the key component elements (regions, cells, and water transporters) of the brain lymphatic system and their regulators as potential therapeutic targets in the treatment of neurologic diseases and their resulting complications. Finally, we highlight the clinical importance of ependymal route-based targeted gene therapy and intranasal drug administration in the brain by taking advantage of the unique role played by brain lymphatic pathways in the regulation of CSF flow and ISF/CSF exchange. Copyright © 2017. Published by Elsevier Ltd.

  17. Car Alarm System Engineered In Arduino Environment

    OpenAIRE

    Järvelä, Sakari

    2014-01-01

    This thesis is targeting to develop and engineer a burglar alarm system prototype using the software and hardware environment Arduino, which is originally manufactured by Smart Projects. The system under development provides a versatile theft inhibition hardware configuration for the holder of the system. It also provides vehicle localization enabling features in case of theft. In the final project, the aim is not to reach commercial benefit. The aim is to get familiar with software libra...

  18. Medicine, material science and security: the versatility of the coded-aperture approach.

    Science.gov (United States)

    Munro, P R T; Endrizzi, M; Diemoz, P C; Hagen, C K; Szafraniec, M B; Millard, T P; Zapata, C E; Speller, R D; Olivo, A

    2014-03-06

    The principal limitation to the widespread deployment of X-ray phase imaging in a variety of applications is probably versatility. A versatile X-ray phase imaging system must be able to work with polychromatic and non-microfocus sources (for example, those currently used in medical and industrial applications), have physical dimensions sufficiently large to accommodate samples of interest, be insensitive to environmental disturbances (such as vibrations and temperature variations), require only simple system set-up and maintenance, and be able to perform quantitative imaging. The coded-aperture technique, based upon the edge illumination principle, satisfies each of these criteria. To date, we have applied the technique to mammography, materials science, small-animal imaging, non-destructive testing and security. In this paper, we outline the theory of coded-aperture phase imaging and show an example of how the technique may be applied to imaging samples with a practically important scale.

  19. An integrated structure- and system-based framework to identify new targets of metabolites and known drugs

    OpenAIRE

    Naveed, Hammad; Hameed, Umar S.; Harrus, Deborah; Bourguet, William; Arold, Stefan T.; Gao, Xin

    2015-01-01

    Motivation: The inherent promiscuity of small molecules towards protein targets impedes our understanding of healthy versus diseased metabolism. This promiscuity also poses a challenge for the pharmaceutical industry as identifying all protein targets is important to assess (side) effects and repositioning opportunities for a drug. Results: Here, we present a novel integrated structure- and system-based approach of drug-target prediction (iDTP) to enable the large-scale discovery of new targe...

  20. FIA versatile system for spectrophotometric determinations of vanadium and molybdenum exploring the catalytic activities of V(V) and Mo(VI); Sistema FIA polivalente para determinacoes espectrofotometricas de vanadio e molibdenio explorando as atividades cataliticas de V(V) e Mo(VI)

    Energy Technology Data Exchange (ETDEWEB)

    Luca, Gilmara Caseri de

    1996-02-01

    A versatile system for chemical analysis by flow injection analysis was developed and applied for catalytic spectrophotometric determination of vanadium or molybdenum in metallic alloys. The selected methods were based upon indicator reactions chromotropic (CS)-bromate acid or hydrogen iodide-peroxide, respectively. Initially, a model system was proposed, in which common parameters for methods were studied. This included a re-sampling process in which high degrees of samples dilution were obtained. Other parameters such as concentrations and reagents addition order, reaction medium Ph, temperature and ionic power, as well as procedures for sample solubilization, were studied relating to each method. A mini-column with cationic exchanger resin (Dowex 50W-X8, 50-100 mesh, H{sup +} form) was used. The system for vanadium determination processes 120 samples by hour, consuming 2,0 mg CS and 10 mg K Br O{sub 3b}y determination. Concerning the method for molybdenum, the reagents consumption was 2,0 mg KI and 1,0 {mu}L of solution 30% H{sub 2}O{sub 2} by determination, since the analytic velocity was the same, in relation to vanadium.

  1. Advances in oral nano-delivery systems for colon targeted drug delivery in inflammatory bowel disease: selective targeting to diseased versus healthy tissue.

    Science.gov (United States)

    Hua, Susan; Marks, Ellen; Schneider, Jennifer J; Keely, Simon

    2015-07-01

    Colon targeted drug delivery is an active area of research for local diseases affecting the colon, as it improves the efficacy of therapeutics and enables localized treatment, which reduces systemic toxicity. Targeted delivery of therapeutics to the colon is particularly advantageous for the treatment of inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease. Advances in oral drug delivery design have significantly improved the bioavailability of drugs to the colon; however in order for a drug to have therapeutic efficacy during disease, considerations must be made for the altered physiology of the gastrointestinal (GI) tract that is associated with GI inflammation. Nanotechnology has been used in oral dosage formulation design as strategies to further enhance uptake into diseased tissue within the colon. This review will describe some of the physiological challenges faced by orally administered delivery systems in IBD, the important developments in orally administered nano-delivery systems for colon targeting, and the future advances of this research. Inflammatory Bowel Disease (IBD) poses a significant problem for a large number of patients worldwide. Current medical therapy mostly aims at suppressing the active inflammatory episodes. In this review article, the authors described and discussed the various approaches current nano-delivery systems can offer in overcoming the limitations of conventional drug formulations. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Delivery of drugs to intracellular organelles using drug delivery systems: Analysis of research trends and targeting efficiencies.

    Science.gov (United States)

    Maity, Amit Ranjan; Stepensky, David

    2015-12-30

    Targeting of drug delivery systems (DDSs) to specific intracellular organelles (i.e., subcellular targeting) has been investigated in numerous publications, but targeting efficiency of these systems is seldom reported. We searched scientific publications in the subcellular DDS targeting field and analyzed targeting efficiency and major formulation parameters that affect it. We identified 77 scientific publications that matched the search criteria. In the majority of these studies nanoparticle-based DDSs were applied, while liposomes, quantum dots and conjugates were used less frequently. The nucleus was the most common intracellular target, followed by mitochondrion, endoplasmic reticulum and Golgi apparatus. In 65% of the publications, DDSs surface was decorated with specific targeting residues, but the efficiency of this surface decoration was not analyzed in predominant majority of the studies. Moreover, only 23% of the analyzed publications contained quantitative data on DDSs subcellular targeting efficiency, while the majority of publications reported qualitative results only. From the analysis of publications in the subcellular targeting field, it appears that insufficient efforts are devoted to quantitative analysis of the major formulation parameters and of the DDSs' intracellular fate. Based on these findings, we provide recommendations for future studies in the field of organelle-specific drug delivery and targeting. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Reuben B Vercoe

    2013-04-01

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

  5. Oral immune therapy: targeting the systemic immune system via the gut immune system for the treatment of inflammatory bowel disease

    OpenAIRE

    Ilan, Yaron

    2016-01-01

    Inflammatory bowel diseases (IBD) are associated with an altered systemic immune response leading to inflammation-mediated damage to the gut and other organs. Oral immune therapy is a method of systemic immune modulation via alteration of the gut immune system. It uses the inherit ability of the innate system of the gut to redirect the systemic innate and adaptive immune responses. Oral immune therapy is an attractive clinical approach to treat autoimmune and inflammatory disorders. It can in...

  6. Target motifs affecting natural immunity by a constitutive CRISPR-Cas system in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Cristóbal Almendros

    Full Text Available Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR and CRISPR associated (cas genes conform the CRISPR-Cas systems of various bacteria and archaea and produce degradation of invading nucleic acids containing sequences (protospacers that are complementary to repeat intervening spacers. It has been demonstrated that the base sequence identity of a protospacer with the cognate spacer and the presence of a protospacer adjacent motif (PAM influence CRISPR-mediated interference efficiency. By using an original transformation assay with plasmids targeted by a resident spacer here we show that natural CRISPR-mediated immunity against invading DNA occurs in wild type Escherichia coli. Unexpectedly, the strongest activity is observed with protospacer adjoining nucleotides (interference motifs that differ from the PAM both in sequence and location. Hence, our results document for the first time native CRISPR activity in E. coli and demonstrate that positions next to the PAM in invading DNA influence their recognition and degradation by these prokaryotic immune systems.

  7. Research on Key Technologies of Network Centric System Distributed Target Track Fusion

    Directory of Open Access Journals (Sweden)

    Yi Mao

    2017-01-01

    Full Text Available To realize common tactical picture in network-centered system, this paper proposes a layered architecture for distributed information processing and a method for distributed track fusion on the basis of analyzing the characteristics of network-centered systems. Basing on the noncorrelation of three-dimensional measurement of surveillance and reconnaissance sensors under polar coordinates, it also puts forward an algorithm for evaluating track quality (TQ using statistical decision theory. According to simulation results, the TQ value is associated with the measurement accuracy of sensors and the motion state of targets, which is well matched with the convergence process of tracking filters. Besides, the proposed algorithm has good reliability and timeliness in track quality evaluation.

  8. Connexin: a potential novel target for protecting the central nervous system?

    Directory of Open Access Journals (Sweden)

    Hong-yan Xie

    2015-01-01

    Full Text Available Connexin subunits are proteins that form gap junction channels, and play an important role in communication between adjacent cells. This review article discusses the function of connexins/hemichannels/gap junctions under physiological conditions, and summarizes the findings regarding the role of connexins/hemichannels/gap junctions in the physiological and pathological mechanisms underlying central nervous system diseases such as brain ischemia, traumatic brain and spinal cord injury, epilepsy, brain and spinal cord tumor, migraine, neuroautoimmune disease, Alzheimer′s disease, Parkinson′s disease, X-linked Charcot-Marie-Tooth disease, Pelizaeus-Merzbacher-like disease, spastic paraplegia and maxillofacial dysplasia. Connexins are considered to be a potential novel target for protecting the central nervous system.

  9. Purinergic System Dysfunction in Mood Disorders: A Key Target for Developing Improved Therapeutics

    Science.gov (United States)

    Ortiz, Robin; Ulrich, Henning; Zarate, Carlos A; Machado-Vieira, Rodrigo

    2014-01-01

    Uric acid and purines (such as adenosine) regulate mood, sleep, activity, appetite, cognition, memory, convulsive threshold, social interaction, drive, and impulsivity. A link between purinergic dysfunction and mood disorders was first proposed a century ago. Interestingly, a recent nationwide population-based study showed elevated risk of gout in subjects with bipolar disorder (BD), and a recent meta-analysis and systematic review of placebo-controlled trials of adjuvant purinergic modulators confirmed their benefits in bipolar mania. Uric acid may modulate energy and activity levels, with higher levels associated with higher energy and BD spectrum. Several recent genetic studies suggest that the purinergic system particularly the modulation of P1 and P2 receptor subtypes—plays a role in mood disorders, lending credence to this model. Nucleotide concentrations can be measured using brain spectroscopy, and ligands for in vivo positron emission tomography (PET) imaging of adenosine (P1) receptors have been developed, thus allowing potential target engagement studies. This review discusses the key role of the purinergic system in the pathophysiology of mood disorders. Focusing on this promising therapeutic target may lead to the development of therapies with antidepressant, mood stabilization, and cognitive effects. PMID:25445063

  10. Targeting CDK11 in osteosarcoma cells using the CRISPR-Cas9 system.

    Science.gov (United States)

    Feng, Yong; Sassi, Slim; Shen, Jacson K; Yang, Xiaoqian; Gao, Yan; Osaka, Eiji; Zhang, Jianming; Yang, Shuhua; Yang, Cao; Mankin, Henry J; Hornicek, Francis J; Duan, Zhenfeng

    2015-02-01

    Osteosarcoma is the most common type primary malignant tumor of bone. Patients with regional osteosarcoma are routinely treated with surgery and chemotherapy. In addition, many patients with metastatic or recurrent osteosarcoma show poor prognosis with current chemotherapy agents. Therefore, it is important to improve the general condition and the overall survival rate of patients with osteosarcoma by identifying novel therapeutic strategies. Recent studies have revealed that CDK11 is essential in osteosarcoma cell growth and survival by inhibiting CDK11 mRNA expression with RNAi. Here, we apply the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 system, a robust and highly efficient novel genome editing tool, to determine the effect of targeting endogenous CDK11 gene at the DNA level in osteosarcoma cell lines. We show that CDK11 can be efficiently silenced by CRISPR-Cas9. Inhibition of CDK11 is associated with decreased cell proliferation and viability, and induces cell death in osteosarcoma cell lines KHOS and U-2OS. Furthermore, the migration and invasion activities are also markedly reduced by CDK11 knockout. These results demonstrate that CRISPR-Cas9 system is a useful tool for the modification of endogenous CDK11 gene expression, and CRISPR-Cas9 targeted CDK11 knockout may be a promising therapeutic regimen for the treatment of osteosarcoma. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  11. Immune system of the inner ear as a novel therapeutic target for sensorineural hearing loss

    Directory of Open Access Journals (Sweden)

    Takayuki eOkano

    2014-09-01

    Full Text Available Sensorineural hearing loss (SNHL is a common clinical condition resulting from dysfunction in one or more parts in the auditory pathway between the inner ear and auditory cortex. Despite the prevalence of SNHL, little is known about its etiopathology, although several mechanisms have been postulated including ischemia, viral infection or reactivation, and microtrauma. Immune-mediated inner ear disease has been introduced and accepted as one SNHL pathophysiology; it responds to immunosuppressive therapy and is one of the few reversible forms of bilateral SNHL. The concept of immune-mediated inner ear disease is straightforward and comprehensible, but criteria for clinical diagnosis and the precise mechanism of hearing loss have not been determined. Moreover, the therapeutic mechanisms of corticosteroids are unclear, leading to several misconceptions by both clinicians and investigators concerning corticosteroid therapy. This review addresses our current understanding of the immune system in the inner ear and its involvement in the pathophysiology in SNHL. Treatment of SNHL, including immune-mediated inner ear disorder, will be discussed with a focus on the immune mechanism and immunocompetent cells as therapeutic targets. Finally, possible interventions modulating the immune system in the inner ear to repair the tissue organization and improve hearing in patients with SNHL will be discussed. Tissue macrophages in the inner ear appear to be a potential target for modulating the immune response in the inner ear in the pathophysiology of SNHL.

  12. Novel siRNA delivery system to target podocytes in vivo.

    Directory of Open Access Journals (Sweden)

    Peter V Hauser

    2010-03-01

    Full Text Available Podocytes are injured in several glomerular diseases. To alter gene expression specifically in podocytes in vivo, we took advantage of their active endocytotic machinery and developed a method for the targeted delivery of small interfering ribonucleic acids (siRNA. We generated an anti-mouse podocyte antibody that binds to rat and mouse podocytes in vivo. The polyclonal IgG antibody was cleaved into monovalent fragments, while preserving the antigen recognition sites. One Neutravidin molecule was linked to each monovalent IgG via the available sulfohydryl group. Protamine, a polycationic nuclear protein and universal adaptor for anionic siRNA, was linked to the neutravidin via biotin. The delivery system was named shamporter (sheep anti mouse podocyte transporter. Injection of shamporter coupled with either nephrin siRNA or TRPC6 siRNA via tail vein into normal rats substantially reduced the protein levels of nephrin or TRPC6 respectively, measured by western blot analysis and immunostaining. The effect was target specific because other podocyte-specific genes remained unchanged. Shamporter + nephrin siRNA induced transient proteinuria in rats. Control rats injected with shamporter coupled to control-siRNA showed no changes. These results show for the first time that siRNA can be delivered efficiently and specifically to podocytes in vivo using an antibody-delivery system.

  13. Targeting local vascular and systemic consequences of inflammation on vascular and cardiac valve calcification.

    Science.gov (United States)

    Hénaut, Lucie; Sanchez-Nino, Maria Dolores; Aldamiz-Echevarría Castillo, Gonzalo; Sanz, Ana B; Ortiz, Alberto

    2016-01-01

    Cardiac valve calcification and vascular calcification (VC) are associated with cardiovascular mortality in the general population and in patients with chronic kidney disease (CKD). CKD, diabetes mellitus, and atherosclerosis are among the causes of systemic inflammation that are associated with VC. This review collates clinical and experimental evidence that inflammation accelerates VC progression. Specifically, we review the actions of key pro-inflammatory cytokines and inflammation-related transcription factors on VC, and the role played by senescence. Inflammatory cytokines, such as the TNF superfamily and IL-6 superfamily, and inflammation-related transcription factor NF-κB promote calcification in cultured vascular smooth muscle cells, valvular interstitial cells, or experimental animal models through direct effects, but also indirectly by decreasing circulating Fetuin A or Klotho levels. Experimental evidence suggests a causal link between inflammation and VC that would change the clinical approach to prevention and treatment of VC. However, the molecular basis remains unclear and little is known about VC in humans treated with drugs targeting inflammatory cytokines. The effect of biologicals targeting TNF-α, RANKL, IL-6, and other inflammatory mediators on VC, in addition to the impact of dietary phosphate in patients with chronic systemic inflammation, requires study.

  14. Targeting the endocannabinoid system for the treatment of cancer--a practical view.

    Science.gov (United States)

    Fowler, Christopher J; Gustafsson, Sofia B; Chung, Sui Chu; Persson, Emma; Jacobsson, Stig O P; Bergh, Anders

    2010-01-01

    In recent years, considerable interest has been generated by findings that cannabinoids not only have useful palliative effects, but also can affect the viability and invasivity of a variety of different cancer cells. In the present review, the potential of targeting the cannabinoid system for the treatment of cancer is considered from a practical, rather than a mechanistic viewpoint, addressing questions such as whether human tumour cells express CB receptors; whether the potencies of action of cannabinoids in vitro match the potencies expected on the base of receptor theory; what is known about the in vivo effects of cannabinoids and cancer, and how relevant the experiments undertaken are to the clinical situation; and finally, what approaches can be taken to minimise unwanted effects of cannabinoid treatment. It is concluded that cannabinoids (or agents modulating the endogenous cannabinoid system) are an attractive target for drug development in the cancer area, but that more in vivo studies, particularly those investigating the potential of cannabinoids as an addition to current treatment strategies, are needed.

  15. The enteric nervous system is a potential autoimmune target in multiple sclerosis.

    Science.gov (United States)

    Wunsch, Marie; Jabari, Samir; Voussen, Barbara; Enders, Michael; Srinivasan, Shanthi; Cossais, François; Wedel, Thilo; Boettner, Martina; Schwarz, Anna; Weyer, Linda; Göcer, Oktay; Schroeter, Michael; Maeurer, Mathias; Woenckhaus, Matthias; Pollok, Karolin; Radbruch, Helena; Klotz, Luisa; Scholz, Claus-Jürgen; Nickel, Joachim; Friebe, Andreas; Addicks, Klaus; Ergün, Süleyman; Lehmann, Paul V; Kuerten, Stefanie

    2017-08-01

    Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) in young adults that has serious negative socioeconomic effects. In addition to symptoms caused by CNS pathology, the majority of MS patients frequently exhibit gastrointestinal dysfunction, which was previously either explained by the presence of spinal cord lesions or not directly linked to the autoimmune etiology of the disease. Here, we studied the enteric nervous system (ENS) in a B cell- and antibody-dependent mouse model of MS by immunohistochemistry and electron microscopy at different stages of the disease. ENS degeneration was evident prior to the development of CNS lesions and the onset of neurological deficits in mice. The pathology was antibody mediated and caused a significant decrease in gastrointestinal motility, which was associated with ENS gliosis and neuronal loss. We identified autoantibodies against four potential target antigens derived from enteric glia and/or neurons by immunoprecipitation and mass spectrometry. Antibodies against three of the target antigens were also present in the plasma of MS patients as confirmed by ELISA. The analysis of human colon resectates provided evidence of gliosis and ENS degeneration in MS patients compared to non-MS controls. For the first time, this study establishes a pathomechanistic link between the well-established autoimmune attack on the CNS and ENS pathology in MS, which might provide a paradigm shift in our current understanding of the immunopathogenesis of the disease with broad diagnostic and therapeutic implications.

  16. A novel real-time control system for plasma cutting robot with xPC target

    Directory of Open Access Journals (Sweden)

    Mustafa Soylak

    2016-04-01

    Full Text Available In this article, a novel inexpensive controller system for plasma cutting robots built based on MATLAB xPC is presented. The plasma cutting robot model with 5 degrees of freedom is constructed in the MATLAB/Simulink of the host machine, where the code is generated by real-time workshop and downloaded on the target machine. Two different types of proportional–integral–derivative controllers are applied on the experimental robot manipulator for the real-time plasma cutting process’s trajectory control using this hardware system. First, the performance of a standard proportional–integral–derivative controller is evaluated on this manipulator. Then, a novel proportional–integral–derivative controller structure is used to control the system, and it is compared with a standard proportional–integral–derivative controller. This study shows that the control system for a plasma cutting robot can be established inexpensively, and MATLAB xPC and different controllers can be applied on this system. Moreover, the study concludes that the novel proportional–integral–derivative controller used in this study gives better results for plasma cutting robots than the standard proportional–integral–derivative controller.

  17. Composite Petroleum System and Advantageous Exploration Targets in the Kongquehe Area of Tarim Basin

    Science.gov (United States)

    Tang, Dazhen; Xing, Weixin; Lin, Wenji; Kong, Fanjun; Li, Danmei; Xu, Hao; Tao, Shu; Gao, Guanfeng

    Guided by the description methods and evaluation routine for composite petroleum system in superimposed basins, the composite characteristics of the petroleum systems in the Kongquehe area of the Tarim basin was studied and the geological evolution processes of hydrocarbon from source to trap was revealed. The petroleum systems in the Kongquehe area, mainly through fault composite linkage combined with unconformity surface composite linkage, constitute the Cambrian € (!)-Lower Ordovician O 1 (!)-Carboniferous C (*)-Triassic T (*)-Jurassic J (*) + Cambrian € (!)-Lower Ordovician O 1 (*)-Silurian S (*)-Devonian D (*)-Jurassic J (*) modified composite petroleum systems (*). There are three critical periods for composite petroleum system, such as the end of Devonian for forming tectonic framework and paleoreservoir, the end of Jurassic and Cretaceous for hydrocarbon transformation, redistribution, and adjustment. The research area may be classified into three types — destroyed dissipation zone, transformed adjustment zone, and deeply-buried preservation zone, amongst which the latter two zones are favorable for hydrocarbon accumulation. Especially, the Upper Paleozoic and Mesozoic faulted anticline traps of the Longkou anticline and the Weimake-Kaiping anticline and the residual Lower Paleozoic fault paleo-anticline traps in the transformed adjustment zone are the best prospecting targets.

  18. Reproductive toxicity: Male and female reproductive systems as targets for chemical injury

    Energy Technology Data Exchange (ETDEWEB)

    Mattison, D.R.; Plowchalk, D.R.; Meadows, M.J.; Al-Juburi, A.Z.; Gandy, J.; Malek, A. (Univ. of Arkansas for Medical Sciences, Little Rock (USA))

    1990-03-01

    On the basis of current knowledge of reproductive biology and toxicology, it is apparent that chemicals affecting reproduction may elicit their effects at a number of sites in both the male and the female reproductive system. This multiplicity of targets is attributable to the dynamic nature of the reproductive system, in which the hypothalamic-pituitary-gonadal axis is controlled by precise positive and negative feedback mechanisms among its components. Interference by a xenobiotic at any level in either the male or the female reproductive system may ultimately impair hypothalamic or pituitary function. Normal gonadal processes such as spermatogenesis or oogenesis, ejaculation or ovulation, hormone production by Leydig or granulosa cells, and the structure or function of the accessory reproductive structures (e.g., epididymis, fallopian tube) also appear vulnerable to xenobiotics. The reproductive system is a complex one that requires local and circulating hormones for control. This brief review illustrates a system for characterizing the mechanism of action of reproductive toxicants, as well as for defining the sites available for disruption of reproduction. Unfortunately, at present, data addressing the actual vulnerability of reproduction are sorely lacking. However, when experiments have been conducted and combined with epidemiologic data or clinical observation, it has been possible to demonstrate impairment of reproductive processes by xenobiotics. The role of environmental exposure to xenobiotics in the increase in infertility that has been observed remains to be defined. 87 references.

  19. Mini-tablets: a contemporary system for oral drug delivery in targeted patient groups.

    Science.gov (United States)

    Aleksovski, Aleksandar; Dreu, Rok; Gašperlin, Mirjana; Planinšek, Odon

    2015-01-01

    Mini-tablets represent a new trend in solid dosage form design, with the main goal of overcoming some therapeutic obstacles such as impaired swallowing and polypharmacy therapy, and also offering some therapeutic benefits such as dose flexibility and combined release patterns. Mini-tablets are a promising patient-friendly drug delivery system. Mini-tablets are tablets with a diameter ≤ 3 mm produced on conventional tablet presses equipped with multiple tooling. Mini-tablet production is similar to the production of standard tablets but requires excellent powder flow due to the small dies, exact control of process parameters and special caution during tablet press assembly in order to avoid tool damage. Mini-tablets (coated or uncoated and single- or multiple-unit systems) are mainly developed as patient-friendly systems for pediatric and geriatric patients and also for personalized medicine because they offer improved swallowing and flexible dosing, combining various release kinetics, doses and active compounds in only one system. Mini-tablets may also be successfully used as multiple-unit modified release systems (extended release, delayed-colon release, pulsatile and bi-modal release and gastroretentive systems) providing improved drug bioavailability compared with single-unit systems. Mini-tablets used as single- or multiple-unit oral dosage forms have enormous potential as a patient-friendly drug delivery system for targeted populations, providing improved swallowing, flexible dosing and a combination of different release patterns and/or different active compounds (decreasing dosing frequency and/or polypharmacy therapy problems). In terms of complete expression of the benefits of mini-tablets over other oral dosage forms on the market, further investigation in formulation possibilities and development of suitable dosing devices is of essential importance.

  20. P2X receptors in the cardiovascular system and their potential as therapeutic targets in disease.

    Science.gov (United States)

    Ralevic, Vera

    2015-01-01

    This review considers the expression and roles of P2X receptors in the cardiovascular system in health and disease and their potential as therapeutic targets. P2X receptors are ligand gated ion channels which are activated by the endogenous ligand ATP. They are formed from the assembly of three P2X subunit proteins from the complement of seven (P2X1-7), which can associate to form homomeric or heteromeric P2X receptors. The P2X1 receptor is widely expressed in the cardiovascular system, being located in the heart, in the smooth muscle of the majority of blood vessels and in platelets. P2X1 receptors expressed in blood vessels can be activated by ATP coreleased with noradrenaline as a sympathetic neurotransmitter, leading to smooth muscle depolarisation and contraction. There is evidence that the purinergic component of sympathetic neurotransmission is increased in hypertension, identifying P2X1 receptors as a possible therapeutic target in this disorder. P2X3 and P2X2/3 receptors are expressed on cardiac sympathetic neurones and may, through positive feedback of neuronal ATP at this prejunctional site, amplify sympathetic neurotransmission. Activation of P2X receptors expressed in the heart increases cardiac myocyte contractility, and an important role of the P2X4 receptor in this has been identified. Deletion of P2X4 receptors in the heart depresses contractile performance in models of heart failure, while overexpression of P2X4 receptors has been shown to be cardioprotective, thus P2X4 receptors may be therapeutic targets in the treatment of heart disease. P2X receptors have been identified on endothelial cells. Although immunoreactivity for all P2X1-7 receptor proteins has been shown on the endothelium, relatively little is known about their function, with the exception of the endothelial P2X4 receptor, which has been shown to mediate endothelium-dependent vasodilatation to ATP released during shear stress. The potential of P2X receptors as therapeutic targets

  1. A Versatile Software Program for Sampling Sferics and More

    Science.gov (United States)

    Stanley, M. A.; Lyons, W. A.; Cummer, S. A.; Jaugey, N.

    2008-12-01

    In 2004, a data acquisition program was written to sample and store sferic waveforms for the upgraded Los Alamos Sferic Array (LASA). The program acquired data using the 20MHz PCI-DAS4020/12 Measurement Computing (MC) board on the stable Linux operating system. The capabilities of this original program have been described elsewhere [Stanley et al., 2004; Shao et al., 2006]. Starting in 2006, this program was modified and enhanced to support data acquisition for a new Charge Moment Change Network (CMCN) which detects and quantifies impulsive charge moment changes of potential sprite-producing lightning discharges in near real-time. Some of the more notable modifications included the addition of low-pass filtered continuous data output capabilities as well as support for National Instruments (NI) boards. The continuous data output was particularly well suited for the unambiguous detection of sferics with slow tails which are often found around the time of sprites and especially sprite halos. The program also utilizes a shared memory architecture which gives it even more versatility in real-time processing as well as enables other modes of data acquisition. In 2008, the program was updated to utilize the Linux Comedi drivers in place of the previous MC and NI drivers. With this modification, the program now supports an even wider variety of data acquisition boards and also runs on the latest Linux distributions.

  2. Sapporo2: a versatile direct N-body library

    Science.gov (United States)

    Bédorf, Jeroen; Gaburov, Evghenii; Portegies Zwart, Simon

    2015-10-01

    Astrophysical direct N-body methods have been one of the first production algorithms to be implemented using NVIDIA's CUDA architecture. Now, almost seven years later, the GPU is the most used accelerator device in astronomy for simulating stellar systems. In this paper we present the implementation of the Sapporo2 N-body library, which allows researchers to use the GPU for N-body simulations with little to no effort. The first version, released five years ago, is actively used, but lacks advanced features and versatility in numerical precision and support for higher order integrators. In this updated version we have rebuilt the code from scratch and added support for OpenCL, multi-precision and higher order integrators. We show how to tune these codes for different GPU architectures and present how to continue utilizing the GPU optimal even when only a small number of particles (N < 100) is integrated. This careful tuning allows Sapporo2 to be faster than Sapporo1 even with the added options and double precision data loads. The code runs on a range of NVIDIA and AMD GPUs in single and double precision accuracy. With the addition of OpenCL support the library is also able to run on CPUs and other accelerators that support OpenCL.

  3. Versatile genetic tool box for the crenarchaeote Sulfolobus acidocaldarius

    Directory of Open Access Journals (Sweden)

    Michaela eWagner

    2012-06-01

    Full Text Available For reverse genetic approaches inactivation or selective modification of genes are required to elucidate their putative function. Sulfolobus acidocaldarius is a thermoacidophilic Crenarchaeon which grows optimally at 76 °C and pH 3. As many antibiotics do not withstand these conditions the development of a genetic system in this organism is dependent on auxotrophies. Therefore we constructed a pyrE deletion mutant of S. acidocaldarius wild type strain DSM639 missing 322 bp called MW001. Using this strain as the base, we describe here different methods using single as well as double crossover events to obtain markerless deletion mutants, tag genes genomically and ectopically integrate foreign DNA into MW001. These methods enable us to construct single, double and triple deletions strains that can still be complemented with the pRN1 based expression vector. Taken together we have developed a versatile and robust genetic tool box for the crenarchaeote Sulfolobus acidocaldarius that will promote the study of unknown gene functions in this organism and makes this organism a suitable host for synthetic biology approaches.

  4. Zebrafish: A Versatile Animal Model for Fertility Research

    Directory of Open Access Journals (Sweden)

    Jing Ying Hoo

    2016-01-01

    Full Text Available The utilization of zebrafish in biomedical research is very common in the research world nowadays. Today, it has emerged as a favored vertebrate organism for the research in science of reproduction. There is a significant growth in amount numbers of scientific literature pertaining to research discoveries in reproductive sciences in zebrafish. It has implied the importance of zebrafish in this particular field of research. In essence, the current available literature has covered from the very specific brain region or neurons of zebrafish, which are responsible for reproductive regulation, until the gonadal level of the animal. The discoveries and findings have proven that this small animal is sharing a very close/similar reproductive system with mammals. More interestingly, the behavioral characteristics and along with the establishment of animal courtship behavior categorization in zebrafish have laid an even stronger foundation and firmer reason on the suitability of zebrafish utilization in research of reproductive sciences. In view of the immense importance of this small animal for the development of reproductive sciences, this review aimed at compiling and describing the proximate close similarity of reproductive regulation on zebrafish and human along with factors contributing to the infertility, showing its versatility and its potential usage for fertility research.

  5. A road to food? : efficacy of nutrient management options targeted to heterogeneous soilscapes in the Teso farming system, Uganda

    NARCIS (Netherlands)

    Ebanyat, P.

    2009-01-01

    Key words: Land use change; Heterogeneity in soil fertility; Targeting; Integrated soil fertility management; Nutrient use efficiencies; Rehabilitation of degraded fields; Fertiliser requirements, Finger millet; QUEFTS model; Smallholder systems; sub-Saharan Africa. Poor soil fertility in

  6. Targeting and Fire Control System Analysis of the New Turkish Attack Helicopter "The AH-1Z King Cobra"

    National Research Council Canada - National Science Library

    Reyhan, Gokhan

    2001-01-01

    .... Turkey has chosen Bell Helicopter's KingCobra as its attack helicopter. The major difference between the USMC version of AH-1Z and the Turkish version KingCobra is the Targeting and Fire Control System...

  7. RELAP5-3D thermal hydraulic analysis of the target cooling system in the SPES experimental facility

    Science.gov (United States)

    Giardina, M.; Castiglia, F.; Buffa, P.; Palermo, G.; Prete, G.

    2014-11-01

    The SPES (Selective Production of Exotic Species) experimental facility, under construction at the Italian National Institute of Nuclear Physics (INFN) Laboratories of Legnaro, Italy, is a second generation Isotope Separation On Line (ISOL) plant for advanced nuclear physic studies. The UCx target-ion source system works at temperature of about 2273 K, producing a high level of radiation (105 Sv/h), for this reason a careful risk analysis for the target chamber is among the major safety issues. In this paper, the obtained results of thermofluid-dynamics simulations of accidental transients in the SPES target cooling system are reported. The analysis, performed by using the RELAP5-3D 2.4.2 qualified thermal-hydraulic system code, proves good safety performance of this system during different accidental conditions.

  8. Hazard identification and risk assessment for biologics targeting the immune system.

    Science.gov (United States)

    Weir, Andrea B

    2008-01-01

    Biologic pharmaceuticals include a variety of products, such as monoclonal antibodies, fusion proteins and cytokines. Products in those classes include immunomodulatory biologics, which are intended to enhance or diminish the activity of the immune system. Immunomodulatory biologics have been approved by the U.S. FDA for a variety of indications, including cancer and inflammatory conditions. Prior to gaining approval for marketing, sponsoring companies for all types of products must demonstrate a product's safety in toxicology studies conducted in animals and show safety and efficacy in clinical trials conducted in patients. The overall goal of toxicology studies, which applies to immunomodulatory and other product types, is to identify the hazards that products pose to humans. Because biologics are generally highly selective for specific targets (receptors/epitopes), conducting toxicology studies in animal models with the target is essential. Such animals are referred to as pharmacologically relevant. Endpoints routinely included in toxicology studies, such as hematology, organ weight and histopathology, can be used to assess the effect of a product on the structure of the immune system. Additionally, specialized endpoints, such as immunophenotyping and immune function tests, can be used to define effects of immunomodulatory products on the immune system. Following hazard identification, risks posed to patients are assessed and managed. Risks can be managed through clinical trial design and risk communication, a practice that applies to immunomodulatory and other product types. Examples of risk management in clinical trial design include establishing a safe starting dose, defining the appropriate patient population and establishing appropriate patient monitoring. Risk communication starts during clinical trials and continues after product approval. A combination of hazard identification, risk assessment and risk management allows for drug development to proceed

  9. THE DEVELOPMENT OF THE EUROPEAN BANKING INDUSTRY THROUGH THE TARGET PAYMENTS SYSTEM

    Directory of Open Access Journals (Sweden)

    LUCIAN-ION MEDAR

    2017-12-01

    Full Text Available The creation of the Single Euro Payments Area is in full swing and the completion of the Economic and Monetary Union is the moment of consolidation, of preparing the conditions in all Member States to enable them to cope with the global financial challenges and prosper. The markets for small value payments in euro within the European Union have been very fragmented. There was a need for a project (SEPA with a major impact on national payment markets in order to unify and standardize them in a single domestic market. Trans-European Automated Realtime Gross Settlement Express Transfer System (TARGET is a trans-European automated real-time gross settlement system - which meets the needs of consumers by offering services at a harmonized level in the European Union. Now, however, the banking clientele needs some education about banking operations taking place at the level of the European banking system. The initial project was proposed and promoted by the European Central Bank together with the European Commission and supported by the central banks of the European Union. However, the implementation and continued development of the SEPA-Single Euro Payments Area process is the responsibility of the financial institutions, and the final beneficiaries are indisputably the individuals and legal entities that represent their "clientele". The Eurosystem has cooperated with national central banks to implement standards that facilitate the rapid automation of payment systems by offering TAREGET 2-Securities (T2S banking clients.

  10. The ocular renin-angiotensin system: a therapeutic target for the treatment of ocular disease.

    Science.gov (United States)

    Giese, Michael J; Speth, Robert C

    2014-04-01

    The renin-angiotensin system (RAS) is most well-known for its role in regulation and dysregulation of blood pressure as well as fluid and electrolyte homeostasis. Due to its ability to cause cardiovascular disease, the RAS is the target of a multitude of drugs that antagonize its pathophysiological effects. While the "classical" RAS is a systemic hormonal system, there is an increasing awareness of the existence and functional significance of local RASs in a number of organs, e.g., liver, kidney, heart, lungs, reproductive organs, adipose tissue and adrenal. The eye is one of these organs where a compelling body of evidence has demonstrated the presence of a local RAS. Individual components of the RAS have been shown to be present in many structures of the eye and their potential functional significance in ocular disease states is described. Because the eye is one of the most important and complex organs in the body, this review also discusses the implications of dysregulation of the systemic RAS on the pathogenesis of ocular diseases and how pharmacological manipulation of the RAS might lead to novel or adjunctive therapies for ocular disease states. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Lymphocyte antigens targetable by monoclonal antibodies in non-systemic vasculitic neuropathy.

    Science.gov (United States)

    Schneider, Christian; Wunderlich, Gilbert; Bleistein, Johannes; Fink, Gereon R; Deckert, Martina; Brunn, Anna; Lehmann, Helmar Christoph

    2017-09-01

    To identify the most relevant antigens for monoclonal antibodies in lymphocytic infiltrates in non-systemic vasculitic neuropathy (NSVN). Current immunosuppressive treatment for NSVN is insufficient. Monoclonal antibodies might be a treatment option, but the expression profile for targetable antigens on lymphocytic infiltrates in NSVN is unknown. Sural nerve biopsies from a cohort of patients with NSVN were immunohistochemically studied for the expression of potential candidate antigens in perivascular and intramural lymphocytic infiltrates and correlated with neurological and electrophysiological parameters. 20 patients with treatment naïve NSVN and 5 patients with idiopathic axonal neuropathy were included. The CD52, BAFF and CD49d antigens were expressed in epineurial, perivascular or intramural lymphocytes of all (20/20) patients. CD52 was most prominently expressed in 21.49% of all inflammatory infiltrates. BAFF and CD49d were detected in 11.25% and 10.99% of these lymphocytes, respectively. The CD20, CD25 and CD126 antigens were found less frequently and at low levels only (CD20: 10/20 patients, 5.84% of lymphocytes; CD25: 17/20 patients, 5.22% of lymphocytes; CD126: 3/20 patients, 0.15% of lymphocytes). This is the first study in NSVN that identifies antigens expressed by pathogenic lymphocytes, which are potential targets for future monoclonal antibody treatment. Our data suggest that NSVN is amenable to monoclonal antibodies and, moreover, that targeting CD52 may be particularly promising. Our results strongly warrant future clinical trials in NSVN with monoclonal antibodies. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. Aluminum-doped zinc oxide thin films grown on various substrates using facing target sputtering system

    Science.gov (United States)

    Kim, Hwa-Min; Lee, Chang Hyun; Shon, Sun Young; Kim, Bong Hwan

    2017-11-01

    Aluminum-doped zinc oxide (AZO) films were fabricated on various substrates, such as glass, polyethylene naphthalate (PEN), and polyethylene terephthalate (PET), at room temperature using a facing target sputtering (FTS) system with hetero ZnO and Al2O3 targets, and their electrical and optical properties were investigated. The AZO film on glass exhibited compressive stress while the films on the plastic substrates showed tensile stress. These stresses negatively affected the crystalline quality of the AZO films, and it is suggested that the poor crystalline quality of the films may be related to the neutral Al-based defect complexes formed in the films; these complexes act as neutral impurity scattering centers. AZO films with good optoelectronic properties could be formed on the glass and plastic substrates by the FTS technique using the hetero targets. The AZO films deposited on the glass, PEN, and PET substrates showed very low resistivities, of 5.0 × 10-4 Ω cm, 7.0 × 10-4 Ω cm, and 7.4 × 10-4 Ω cm, respectively. Further, the figure merit of the AZO film formed on the PEN substrate in the visible range (400-700 nm) was significantly higher than that of the AZO film on PET and similar to that of the AZO film on glass. Finally, the average transmittances of the films in the visible range (400-700 nm) were 83.16% (on glass), 76.3% (on PEN), and 78.16% (on PET).

  13. Ubiquitin-Like Proteasome System Represents a Eukaryotic-Like Pathway for Targeted Proteolysis in Archaea

    Directory of Open Access Journals (Sweden)

    Xian Fu

    2016-05-01

    Full Text Available The molecular mechanisms of targeted proteolysis in archaea are poorly understood, yet they may have deep evolutionary roots shared with the ubiquitin-proteasome system of eukaryotic cells. Here, we demonstrate in archaea that TBP2, a TATA-binding protein (TBP modified by ubiquitin-like isopeptide bonds, is phosphorylated and targeted for degradation by proteasomes. Rapid turnover of TBP2 required the functions of UbaA (the E1/MoeB/ThiF homolog of archaea, AAA ATPases (Cdc48/p97 and Rpt types, a type 2 JAB1/MPN/MOV34 metalloenzyme (JAMM/MPN+ homolog (JAMM2, and 20S proteasomes. The ubiquitin-like protein modifier small archaeal modifier protein 2 (SAMP2 stimulated the degradation of TBP2, but SAMP2 itself was not degraded. Analysis of the TBP2 fractions that were not modified by ubiquitin-like linkages revealed that TBP2 had multiple N termini, including Met1-Ser2, Ser2, and Met1-Ser2(p [where (p represents phosphorylation]. The evidence suggested that the Met1-Ser2(p form accumulated in cells that were unable to degrade TBP2. We propose a model in archaea in which the attachment of ubiquitin-like tags can target proteins for degradation by proteasomes and be controlled by N-terminal degrons. In support of a proteolytic mechanism that is energy dependent and recycles the ubiquitin-like protein tags, we find that a network of AAA ATPases and a JAMM/MPN+ metalloprotease are required, in addition to 20S proteasomes, for controlled intracellular proteolysis.

  14. Dry-Powder Inhaler Formulation of Rifampicin: An Improved Targeted Delivery System for Alveolar Tuberculosis.

    Science.gov (United States)

    Rawal, Tejal; Kremer, Laurent; Halloum, Iman; Butani, Shital

    2017-12-01

    The delivery of antitubercular drugs through direct lung targeting can lead to reduction in the dose as well as side effects of the drug. In the present investigation, carrier (lactose)-based dry-powder inhaler of rifampicin was prepared to achieve direct targeting of the drug into the lungs. The dry powder inhaler formulation was prepared by simply mixing micronized rifampicin with coarse and fine lactose preblend. Preliminary blends of the drug were prepared with various lactose grades (Inhalac ® , Respitose, ® and Lactohale ® ). Rotahaler ® and Revolizer ® were evaluated for the performance. The 3 2 factorial design was used to optimize the amount of drug (X 1 ) and amount of fine lactose (X 2 ). In vitro lung deposition was carried out using Andersen Cascade Impactor. The % cell viability studies of the formulation were carried out using murine macrophage J774 cell lines. The in vivo toxicity was determined using histopathology. Further in vivo pulmonary pharmacokinetics of the developed dry-powder inhaler (DPI) formulation was carried out in comparison to the marketed formulation in the rat lungs. Based on preliminary trials, Inhalac 230 and Inhalac 400 were selected as coarse and fine lactose grades, respectively. Rotahaler ® exhibited better DPI performance with the evaluated drug blends. The mass median aerodynamic diameter (MMAD) was in the range of 4.3-5.8 μm with the maximum fine particle fraction of 28.9%. The formulation exhibited negligible cytotoxicity on macrophage J774 cell lines with about 75%-80% cell viability at 6- and 12-hour exposure. The histopathological examination revealed negligible toxicity of DPI in comparison to the marketed formulation. The in vivo pulmonary pharmacokinetic studies of the DPI formulation in rats showed higher drug concentration in lungs in comparison to the marketed formulation. The carrier-mediated dry-powder inhaler of rifampicin could serve as an improved and efficient system for local targeting of drugs

  15. Curcumin targeting the thioredoxin system elevates oxidative stress in HeLa cells

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Wenqing; Zhang, Baoxin; Duan, Dongzhu [State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000 (China); Wu, Jincai [College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000 (China); Fang, Jianguo, E-mail: fangjg@lzu.edu.cn [State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000 (China); College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000 (China)

    2012-08-01

    The thioredoxin system, composed of thioredoxin reductase (TrxR), thioredoxin (Trx), and NADPH, is ubiquitous in all cells and involved in many redox-dependent signaling pathways. Curcumin, a naturally occurring pigment that gives a specific yellow color in curry food, is consumed in normal diet up to 100 mg per day. This molecule has also been used in traditional medicine for the treatment of a variety of diseases. Curcumin has numerous biological functions, and many of these functions are related to induction of oxidative stress. However, how curcumin elicits oxidative stress in cells is unclear. Our previous work has demonstrated the way by which curcumin interacts with recombinant TrxR1 and alters the antioxidant enzyme into a reactive oxygen species (ROS) generator in vitro. Herein we reported that curcumin can target the cytosolic/nuclear thioredoxin system to eventually elevate oxidative stress in HeLa cells. Curcumin-modified TrxR1 dose-dependently and quantitatively transfers electrons from NADPH to oxygen with the production of ROS. Also, curcumin can drastically down-regulate Trx1 protein level as well as its enzyme activity in HeLa cells, which in turn remarkably decreases intracellular free thiols, shifting the intracellular redox balance to a more oxidative state, and subsequently induces DNA oxidative damage. Furthermore, curcumin-pretreated HeLa cells are more sensitive to oxidative stress. Knockdown of TrxR1 sensitizes HeLa cells to curcumin cytotoxicity, highlighting the physiological significance of targeting TrxR1 by curcumin. Taken together, our data disclose a previously unrecognized prooxidant mechanism of curcumin in cells, and provide a deep insight in understanding how curcumin works in vivo. -- Highlights: ► Curcumin induces oxidative stress by targeting the thioredoxin system. ► Curcumin-modified TrxR quantitatively oxidizes NADPH to generate ROS. ► Knockdown of TrxR1 augments curcumin's cytotoxicity in HeLa cells.

  16. Versatile annotation and publication quality visualization of protein complexes using POLYVIEW-3D

    Directory of Open Access Journals (Sweden)

    Meller Jaroslaw

    2007-08-01

    Full Text Available Abstract Background Macromolecular visualization as well as automated structural and functional annotation tools play an increasingly important role in the post-genomic era, contributing significantly towards the understanding of molecular systems and processes. For example, three dimensional (3D models help in exploring protein active sites and functional hot spots that can be targeted in drug design. Automated annotation and visualization pipelines can also reveal other functionally important attributes of macromolecules. These goals are dependent on the availability of advanced tools that integrate better the existing databases, annotation servers and other resources with state-of-the-art rendering programs. Results We present a new tool for protein structure analysis, with the focus on annotation and visualization of protein complexes, which is an extension of our previously developed POLYVIEW web server. By integrating the web technology with state-of-the-art software for macromolecular visualization, such as the PyMol program, POLYVIEW-3D enables combining versatile structural and functional annotations with a simple web-based interface for creating publication quality structure rendering, as well as animated images for Powerpoint™, web sites and other electronic resources. The service is platform independent and no plug-ins are required. Several examples of how POLYVIEW-3D can be used for structural and functional analysis in the context of protein-protein interactions are presented to illustrate the available annotation options. Conclusion POLYVIEW-3D server features the PyMol image rendering that provides detailed and high quality presentation of macromolecular structures, with an easy to use web-based interface. POLYVIEW-3D also provides a wide array of options for automated structural and functional analysis of proteins and their complexes. Thus, the POLYVIEW-3D server may become an important resource for researches and educators in

  17. A Target Tracking System Based on Imaging Sensor Network with Wi-Fi

    Directory of Open Access Journals (Sweden)

    Aiqun Chen

    2014-05-01

    Full Text Available With the rapid development of network communication technology, a variety of network technology and communication technology has been integrated into our lives and work, bringing great convenience to our work and life. Current research in wireless sensor network technology in the field of communication technology is more popular because of the use of wireless sensor network technology can achieve the communication between objects and objects, people and things, the application of this technology has greatly expanded the ability for people to obtain information, have important significance to the development of people and society. Based on the powerful function of wireless sensor and bring the influence of people, this paper focuses on the design and implementation of the target tracking system based on image sensor networks with Wi-Fi.

  18. A Colon Targeted Delivery System for Resveratrol Enriching in pH Responsive-Model

    DEFF Research Database (Denmark)

    Andishmand, Hashem; Hamishehkar, Hamed; Mohammadifar, Mohammad Amin

    2017-01-01

    Background: Resveratrol effects on the prevention and treatment of colon cancer have been well documented recently, but low solubility, rapid absorption and metabolism of resveratrol limit its beneficial effects on colon cancer. Designing a formulation that enhances the solubility of resveratrol......, protects resveratrol from oxidation and isomerization, and delivers it to the colon is a priority of food and drug industry. In this study, resveratrol-polyethylene glycol (PEG)-loaded pectin-chitosan polyelectrolyte complex was designed as a colon targeted delivery system. Methods: The effects of adding...... PEG, ultra-sonication time, pH, and pectin to chitosan ratio were investigated on particle size, polydispersity index (PDI), zeta potential by particle size analyzer, and scanning electron microscopy (SEM). Encapsulation efficiency (EE), release of resveratrol in simulated gastrointestinal fluid...

  19. Gut-central nervous system axis is a target for nutritional therapies

    Directory of Open Access Journals (Sweden)

    Pimentel Gustavo D

    2012-04-01

    Full Text Available Abstract Historically, in the 1950s, the chemist Linus Pauling established a relationship between decreased longevity and obesity. At this time, with the advent of studies involving the mechanisms that modulate appetite control, some researchers observed that the hypothalamus is the "appetite centre" and that peripheral tissues have important roles in the modulation of gut inflammatory processes and levels of hormones that control food intake. Likewise, the advances of physiological and molecular mechanisms for patients with obesity, type 2 diabetes mellitus, inflammatory bowel diseases, bariatric surgery and anorexia-associated diseases has been greatly appreciated by nutritionists. Therefore, this review highlights the relationship between the gut-central nervous system axis and targets for nutritional therapies.

  20. Targeted and anonymized smartphone-based public health interventions in a participatory sensing system.

    Science.gov (United States)

    Clarke, Andrew; Steele, Robert

    2014-01-01

    Public health interventions comprising information dissemination to affect behavioral adjustment have long been a significant component of public health campaigns. However, there has been limited development of public health intervention systems to make use of advances in mobile computing and telecommunications technologies. Such developments pose significant challenges to privacy and security where potentially sensitive data may be collected. In our previous work we identified and demonstrated the feasibility of using mobile devices as anonymous public health data collection devices as part of a Health Participatory Sensing Network (HPSN). An advanced capability of these networks extended in this paper would be the ability to distribute, apply, report on and analyze the usage and effectiveness of targeted public health interventions in an anonymous way. In this paper we describe such a platform, its place in the HPSN and demonstrate its feasibility through an implementation.

  1. Targeting renin-angiotensin system in malignant hypertension in atypical hemolytic uremic syndrome

    Directory of Open Access Journals (Sweden)

    V Raghunathan

    2017-01-01

    Full Text Available Hypertension is common in hemolytic uremic syndrome (HUS and often difficult to control. Local renin-angiotensin activation is believed to be an important part of thrombotic microangiopathy, leading to a vicious cycle of progressive renal injury and intractable hypertension. This has been demonstrated in vitro via enhanced tissue factor expression on glomerular endothelial cells which is enhanced by angiotensin II. We report two pediatric cases of atypical HUS with severe refractory malignant hypertension, in which we targeted the renin-angiotensin system by using intravenous (IV enalaprilat, oral aliskiren, and oral enalapril with quick and dramatic response of blood pressure. Both drugs, aliskiren and IV enalaprilat, were effective in controlling hypertension refractory to multiple antihypertensive medications. These appear to be promising alternatives in the treatment of severe atypical HUS-induced hypertension and hypertensive emergency.

  2. Gut-central nervous system axis is a target for nutritional therapies.

    Science.gov (United States)

    Pimentel, Gustavo D; Micheletti, Thayana O; Pace, Fernanda; Rosa, José C; Santos, Ronaldo V T; Lira, Fabio S

    2012-04-10

    Historically, in the 1950s, the chemist Linus Pauling established a relationship between decreased longevity and obesity. At this time, with the advent of studies involving the mechanisms that modulate appetite control, some researchers observed that the hypothalamus is the "appetite centre" and that peripheral tissues have important roles in the modulation of gut inflammatory processes and levels of hormones that control food intake. Likewise, the advances of physiological and molecular mechanisms for patients with obesity, type 2 diabetes mellitus, inflammatory bowel diseases, bariatric surgery and anorexia-associated diseases has been greatly appreciated by nutritionists. Therefore, this review highlights the relationship between the gut-central nervous system axis and targets for nutritional therapies.

  3. Design of a novel curcumin-soybean phosphatidylcholine complex-based targeted drug delivery systems.

    Science.gov (United States)

    Xie, Jiajiang; Li, Yanxiu; Song, Liang; Pan, Zhou; Ye, Shefang; Hou, Zhenqing

    2017-11-01

    Recently, the global trend in the field of nanomedicine has been toward the design of combination of nature active constituents and phospholipid (PC) to form a therapeutic drug-phospholipid complex. As a particular amphiphilic molecular complex, it can be a unique bridge of traditional dosage-form and novel drug delivery system. In thisarticle, on the basis of drug-phospholipid complex technique and self-assembly technique, we chose a pharmacologically safe and low toxic drug curcumin (CUR) to increase drug-loading ability, achieve controlled/sustained drug release and improve anticancer activity. A novel CUR-soybean phosphatidylcholine (SPC) complex and CUR-SPC complex self-assembled nanoparticles (CUR-SPC NPs) were prepared by a co-solvent method and a nanoprecipitation method. DSPE-PEG-FA was further functionalized on the surface of PEG-CUR-SPC NPs (designed as FA-PEG-CUR-SPC NPs) to specifically increase cellular uptake and targetability. The FA-PEG-CUR-SPC NPs showed a spherical shape, a mean diameter of about 180 nm, an excellent physiological stability and pH-triggered drug release. The drug entrapment efficiency and drug-loading content was up to 92.5 and 16.3%, respectively. In vitro cellular uptake and cytotoxicity studies demonstrated that FA-PEG-CUR-SPC NPs and CUR-SPC NPs presented significantly stronger cellular uptake efficacy and anticancer activity against HeLa cells and Caco-2 cells compared to free CUR, CUR-SPC NPs and PEG-CUR-SPC NPs. More importantly, FA-PEG-CUR-SPC NPs showed the prolonged systemic circulation lifetime and enhanced tumor accumulation compared with free CUR and PEG-CUR-SPC NPs. These results suggest that the FA targeted PEGylated CUR-SPC complex self-assembled NPs might be a promising candidate in cancer therapy.

  4. B-cell targeted therapies in systemic lupus erythematosus: successes and challenges.

    Science.gov (United States)

    Harvey, Philip R; Gordon, Caroline

    2013-04-01

    Systemic lupus erythematosus is a multisystem autoimmune disease characterized by the formation of autoantibodies that target a variety of self antigens. B cells are fundamental to the development of these antibodies and are a target for intervention in the disease. This review discusses four therapies that target B cells by inducing B-cell depletion, reduction in B-cell proliferation and differentiation, or modulation of B-cell function. Rituximab is an anti-CD20 chimeric monoclonal antibody that depletes B cells but not plasma cells. Systematic reviews of open label studies, particularly in lupus patients refractory to conventional therapy, have suggested that rituximab can be an effective treatment for non-renal lupus and lupus nephritis. However, randomized, double-blind, controlled trials comparing rituximab with placebo in addition to standard of care therapy for non-renal lupus and lupus nephritis over 12 months failed to demonstrate efficacy using the planned primary endpoints, although there were some post-hoc analyses suggesting that rituximab may have beneficial effects that would be worthy of further study as no significant toxicity has been demonstrated. Treatment with belimumab, a humanized monoclonal antibody targeted against B lymphocyte stimulator (BLys), was more efficacious than placebo and had no significant increase in adverse events in two non-renal, phase III lupus trials when given in addition to standard of care therapy for 52 weeks. Belimumab is licensed for the management of lupus in the US and in Europe. Atacicept is a humanized fusion protein that binds BLys and APRIL (a proliferation-inducing ligand) that might be more effective than belimumab in the management of lupus. Unfortunately a phase II/III trial of atacicept in lupus nephritis had to be stopped due to the development of low immunoglobulin levels and pneumonias in some patients. However, in retrospect these complications may have been due to concomitant treatment with

  5. Uniform brain tumor distribution and tumor associated macrophage targeting of systemically administered dendrimers.

    Science.gov (United States)

    Zhang, Fan; Mastorakos, Panagiotis; Mishra, Manoj K; Mangraviti, Antonella; Hwang, Lee; Zhou, Jinyuan; Hanes, Justin; Brem, Henry; Olivi, Alessandro; Tyler, Betty; Kannan, Rangaramanujam M

    2015-06-01

    Effective blood-brain tumor barrier penetration and uniform solid tumor distribution can significantly enhance therapeutic delivery to brain tumors. Hydroxyl-functionalized, generation-4 poly(amidoamine) (PAMAM) dendrimers, with their small size, near-neutral surface charge, and the ability to selectively localize in cells associated with neuroinflammation may offer new opportunities to address these challenges. In this study we characterized the intracranial tumor biodistribution of systemically delivered PAMAM dendrimers in an intracranial rodent gliosarcoma model using fluorescence-based quantification methods and high resolution confocal microscopy. We observed selective and homogeneous distribution of dendrimer throughout the solid tumor (∼6 mm) and peritumoral area within fifteen minutes after systemic administration, with subsequent accumulation and retention in tumor associated microglia/macrophages (TAMs). Neuroinflammation and TAMs have important growth promoting and pro-invasive effects in brain tumors. The rapid clearance of systemically administered dendrimers from major organs promises minimal off-target adverse effects of conjugated drugs. Therefore, selective delivery of immunomodulatory molecules to TAM, using hydroxyl PAMAM dendrimers, may hold promise for therapy of glioblastoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Functions of flavonoids in the central nervous system: Astrocytes as targets for natural compounds.

    Science.gov (United States)

    Matias, Isadora; Buosi, Andrea Schmidt; Gomes, Flávia Carvalho Alcantara

    2016-05-01

    In the last decade, there have been major advances in the understanding of the role of glial cells as key elements in the formation, maintenance and refinement of synapses. Recently, the discovery of natural compounds capable of modulating nervous system function has revealed new perspectives on the restoration of the injured brain. Among these compounds, flavonoids stand out as molecules easily obtainable in the diet that have remarkable effects on cognitive performance and behavior. Nevertheless, little is known about the cellular and molecular mechanisms underlying the actions of flavonoids in the nervous system. The present review presents recent advances in the effects of natural compounds, particularly flavonoids, in the nervous system. We shed light on astrocytes as targets of flavonoids and discuss how this interaction might contribute to the effects of flavonoids on neuronal survival, differentiation and function. Finally, we discuss how the effects of flavonoids on astrocytes might contribute to the development of alternative therapeutic approaches to the treatment of neural diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Agroterrorism targeting livestock: a review with a focus on early detection systems.

    Science.gov (United States)

    Elbers, Armin; Knutsson, Rickard

    2013-09-01

    Agroterrorism targeting livestock can be described as the intentional introduction of an animal disease agent against livestock with the purpose of causing economic damage, disrupting socioeconomic stability of a country, and creating panic and distress. This type of terrorism can be alluring to terrorists because animal disease agents are easily available. This review addresses the vulnerabilities of the livestock industry to agroterrorism. However, we also show that early detection systems have recently been developed for agroterrorism and deliberate spread of animal pathogens in livestock, including an agroterrorism intelligence cycle, syndromic surveillance programs, and computer-based clinical decision support systems that can be used for early detection of notifiable animal diseases. The development of DIVA-vaccines in the past 10 to 15 years has created, in principle, an excellent response instrument to counter intentional animal disease outbreaks. These developments have made our animal agriculture less vulnerable to agroterrorism. But we cannot relax; there are still many challenges, in particular with respect to integration of first line of defense, law enforcement, and early detection systems for animal diseases.

  8. Modulation of the Endocannabinoid System: Vulnerability Factor and New Treatment Target for Stimulant Addiction.

    Directory of Open Access Journals (Sweden)

    Stéphanie eOlière

    2013-09-01

    Full Text Available Cannabis is one of the most widely used illicit substance among users of stimulants such as cocaine and amphetamine. Interestingly, recent accumulating evidence points toward the involvement of the endocannabinoid system (ECBS in the neurobiological processes related to stimulant addiction. This article presents an up-to-date review with deep-insights into the pivotal role of the ECBS in the neurobiology of stimulant addiction and the effects of its modulation on addictive behaviors. The aims of this article are to: 1 review the role of cannabis use and ECBS modulation in the neurobiological substrates of psychostimulant addiction and 2 evaluate the potential of cannabinoid-based pharmacological strategies to treat stimulant addiction. A growing number of studies support a critical role of the ECBS and its modulation by synthetic or natural cannabinoid in various neurobiological and behavioral aspects of stimulants addiction. Thus, cannabinoids modulate brain reward systems closely involved in stimulants addiction, and provide further evidence that the cannabinoid system could be explored as a potential drug discovery target for treating addiction across different classes of stimulants.

  9. Modulation of the endocannabinoid system: vulnerability factor and new treatment target for stimulant addiction.

    Science.gov (United States)

    Olière, Stéphanie; Joliette-Riopel, Antoine; Potvin, Stéphane; Jutras-Aswad, Didier

    2013-09-23

    Cannabis is one of the most widely used illicit substance among users of stimulants such as cocaine and amphetamines. Interestingly, increasing recent evidence points toward the involvement of the endocannabinoid system (ECBS) in the neurobiological processes related to stimulant addiction. This article presents an up-to-date review with deep insights into the pivotal role of the ECBS in the neurobiology of stimulant addiction and the effects of its modulation on addictive behaviors. This article aims to: (1) review the role of cannabis use and ECBS modulation in the neurobiological substrates of psychostimulant addiction and (2) evaluate the potential of cannabinoid-based pharmacological strategies to treat stimulant addiction. A growing number of studies support a critical role of the ECBS and its modulation by synthetic or natural cannabinoids in various neurobiological and behavioral aspects of stimulants addiction. Thus, cannabinoids modulate brain reward systems closely involved in stimulants addiction, and provide further evidence that the cannabinoid system could be explored as a potential drug discovery target for treating addiction across different classes of stimulants.

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

    Science.gov (United States)

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

    2017-11-01

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

  11. Autoantigen TRIM21/Ro52 as a Possible Target for Treatment of Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Ryusuke Yoshimi

    2012-01-01

    Full Text Available Systemic lupus erythematosus (SLE is a chronic, systemic, and autoimmune disease, whose etiology is still unknown. Although there has been progress in the treatment of SLE through the use of glucocorticoid and immunosuppressive drugs, these drugs have limited efficacy and pose significant risks of toxicity. Moreover, prognosis of patients with SLE has remained difficult to assess. TRIM21/Ro52/SS-A1, a 52-kDa protein, is an autoantigen recognized by antibodies in sera of patients with SLE and Sjögren's syndrome (SS, another systemic autoimmune disease, and anti-TRIM21 antibodies have been used as a diagnostic marker for decades. TRIM21 belongs to the tripartite motif-containing (TRIM super family, which has been found to play important roles in innate and acquired immunity. Recently, TRIM21 has been shown to be involved in both physiological immune responses and pathological autoimmune processes. For example, TRIM21 ubiquitylates proteins of the interferon-regulatory factor (IRF family and regulates type I interferon and proinflammatory cytokines. In this paper, we summarize molecular features of TRIM21 revealed so far and discuss its potential as an attractive therapeutic target for SLE.

  12. Autoantigen TRIM21/Ro52 as a Possible Target for Treatment of Systemic Lupus Erythematosus

    Science.gov (United States)

    Yoshimi, Ryusuke; Ishigatsubo, Yoshiaki; Ozato, Keiko

    2012-01-01

    Systemic lupus erythematosus (SLE) is a chronic, systemic, and autoimmune disease, whose etiology is still unknown. Although there has been progress in the treatment of SLE through the use of glucocorticoid and immunosuppressive drugs, these drugs have limited efficacy and pose significant risks of toxicity. Moreover, prognosis of patients with SLE has remained difficult to assess. TRIM21/Ro52/SS-A1, a 52-kDa protein, is an autoantigen recognized by antibodies in sera of patients with SLE and Sjögren's syndrome (SS), another systemic autoimmune disease, and anti-TRIM21 antibodies have been used as a diagnostic marker for decades. TRIM21 belongs to the tripartite motif-containing (TRIM) super family, which has been found to play important roles in innate and acquired immunity. Recently, TRIM21 has been shown to be involved in both physiological immune responses and pathological autoimmune processes. For example, TRIM21 ubiquitylates proteins of the interferon-regulatory factor (IRF) family and regulates type I interferon and proinflammatory cytokines. In this paper, we summarize molecular features of TRIM21 revealed so far and discuss its potential as an attractive therapeutic target for SLE. PMID:22701487

  13. Through-the-wall localization of a moving target by two independent ultra wideband (UWB) radar systems.

    Science.gov (United States)

    Kocur, Dušan; Svecová, Mária; Rovňáková, Jana

    2013-09-09

    In the case of through-the-wall localization of moving targets by ultra wideband (UWB) radars, there are applications in which handheld sensors equipped only with one transmitting and two receiving antennas are applied. Sometimes, the radar using such a small antenna array is not able to localize the target with the required accuracy. With a view to improve through-the-wall target localization, cooperative positioning based on a fusion of data retrieved from two independent radar systems can be used. In this paper, the novel method of the cooperative localization referred to as joining intersections of the ellipses is introduced. This method is based on a geometrical interpretation of target localization where the target position is estimated using a properly created cluster of the ellipse intersections representing potential positions of the target. The performance of the proposed method is compared with the direct calculation method and two alternative methods of cooperative localization using data obtained by measurements with the M-sequence UWB radars. The direct calculation method is applied for the target localization by particular radar systems. As alternative methods of cooperative localization, the arithmetic average of the target coordinates estimated by two single independent UWB radars and the Taylor series method is considered.

  14. Through-the-Wall Localization of a Moving Target by Two Independent Ultra Wideband (UWB Radar Systems

    Directory of Open Access Journals (Sweden)

    Jana Rovňáková

    2013-09-01

    Full Text Available In the case of through-the-wall localization of moving targets by ultra wideband (UWB radars, there are applications in which handheld sensors equipped only with one transmitting and two receiving antennas are applied. Sometimes, the radar using such a small antenna array is not able to localize the target with the required accuracy. With a view to improve through-the-wall target localization, cooperative positioning based on a fusion of data retrieved from two independent radar systems can be used. In this paper, the novel method of the cooperative localization referred to as joining intersections of the ellipses is introduced. This method is based on a geometrical interpretation of target localization where the target position is estimated using a properly created cluster of the ellipse intersections representing potential positions of the target. The performance of the proposed method is compared with the direct calculation method and two alternative methods of cooperative localization using data obtained by measurements with the M-sequence UWB radars. The direct calculation method is applied for the target localization by particular radar systems. As alternative methods of cooperative localization, the arithmetic average of the target coordinates estimated by two single independent UWB radars and the Taylor series method is considered.

  15. Targeting the oxidative stress response system of fungi with safe, redox-potent chemosensitizing agents

    Directory of Open Access Journals (Sweden)

    Jong H. eKim

    2012-03-01

    Full Text Available The cellular antioxidation system is a target in the antifungal action of amphotericin B (AMB and itraconazole (ITZ, in filamentous fungi. The sakAΔ mutant of Aspergillus fumigatus, a mitogen-activated protein kinase (MAPK gene deletion mutant in the antioxidation system, was found to be more sensitive to AMB or ITZ than other A. fumigatus strains, a wild type and a mpkCΔ mutant (MAPK gene deletion mutant in polyalcohol sugar utilization system. The sakAΔ mutant showed no growth at 0.5 μg mL-1 of ITZ or reduced growth at 1.0 to 2.0 μg mL-1 of AMB, while the other strains exhibited robust growth. Complete fungal kill (≥ 99.9% by ITZ or AMB was achieved by much lower dosages for the sakAΔ mutant than for the other strains. SakA and MpkC appear to have overlapping roles in marshalling the oxidative stress response under treatment by an organic peroxide, tert-butyl hydroperoxide (t-BuOOH, or hydrogen peroxide (H2O2. The SakA signalling pathway was found to be responsible for fungal tolerance to AMB or ITZ toxicity. It appears msnA, an Aspergillus ortholog to Saccharomyces cerevisiae MSN2 (encoding a stress-responsive C2H2-type zinc-finger regulator and sakA and/or mpkC (upstream MAPKs are in the same stress response network under t-BuOOH-, H2O2- or AMB-triggered toxicity. Of note is that ITZ-sensitive yeast pathogens (Candida krusei and Cryptococcus neoformans were also sensitive to t-BuOOH, showing a connection between ITZ toxicity and oxidative stress response. This was shown by enhanced antifungal activity of AMB or ITZ when co-applied with redox-potent natural compounds, 2,3-dihydroxybenzaldehyde, thymol or salicylaldehyde, as chemosensitizing agents. Hence, redox compounds, which target the antioxidation system in fungi, possess a potent chemosensitizing capacity to enhance efficacy of conventional drugs inducing oxidative stress. Such chemosensitization can reduce costs and alleviate negative side effects associated with current

  16. Conceptual design of the handling and storage system of the spent target vessel for neutron scattering facility 2

    Energy Technology Data Exchange (ETDEWEB)

    Adachi, Junichi; Kaminaga, Masanori; Sasaki, Shinobu; Haga, Katsuhiro; Aso, Tomokazu; Kinoshita, Hidetaka; Hino, Ryutaro [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    2002-01-01

    In designing the neutron scattering facility, a spent target vessel should be replaced with remote handling devices in order to protect radioactive exposure, since it would be highly activated through the high energy neutron irradiation caused by the spallation reaction between mercury of the target material and the MW-class proton beam. In the storage of the spent target vessel, it is necessary to consider decay heat of the target vessel and mercury contamination caused by vaporization of the residual mercury in the vessel. A conceptual design has been carried out to establish basic concept and to clarify its specification of main equipments on handling and storage systems for the spent target vessel. This report presents the basic concept and a system plot plan based on latest design works of remote handling devices such as a spent target vessel storage cask and a target vessel exchange trolley, which aim at reasonability and simplification. In addition, storage systems for the spent moderator vessel, the spent proton beam window and the spent reflector vessel are also investigated based on the plot plan. (author)

  17. A versatile nondestructive evaluation imaging workstation

    Science.gov (United States)

    Chern, E. James; Butler, David W.

    1994-01-01

    Ultrasonic C-scan and eddy current imaging systems are of the pointwise type evaluation systems that rely on a mechanical scanner to physically maneuver a probe relative to the specimen point by point in order to acquire data and generate images. Since the ultrasonic C-scan and eddy current imaging systems are based on the same mechanical scanning mechanisms, the two systems can be combined using the same PC platform with a common mechanical manipulation subsystem and integrated data acquisition software. Based on this concept, we have developed an IBM PC-based combined ultrasonic C-scan and eddy current imaging system. The system is modularized and provides capacity for future hardware and software expansions. Advantages associated with the combined system are: (1) eliminated duplication of the computer and mechanical hardware, (2) unified data acquisition, processing and storage software, (3) reduced setup time for repetitious ultrasonic and eddy current scans, and (4) improved system efficiency. The concept can be adapted to many engineering systems by integrating related PC-based instruments into one multipurpose workstation such as dispensing, machining, packaging, sorting, and other industrial applications.

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

    Science.gov (United States)

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

    2014-08-01

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

  19. A versatile miniature bioreactor and its application to bioelectrochemistry studies.

    Science.gov (United States)

    Kloke, A; Rubenwolf, S; Bücking, C; Gescher, J; Kerzenmacher, S; Zengerle, R; von Stetten, F

    2010-08-15

    Often, reproducible investigations on bio-microsystems essentially require a flexible but well-defined experimental setup, which in its features corresponds to a bioreactor. We therefore developed a miniature bioreactor with a volume in the range of a few millilitre that is assembled by alternate stacking of individual polycarbonate elements and silicone gaskets. All the necessary supply pipes are incorporated as bore holes or cavities within the individual elements. Their combination allows for a bioreactor assembly that is easily adaptable in size and functionality to experimental demands. It allows for controlling oxygen transfer as well as the monitoring of dissolved oxygen concentration and pH-value. The system provides access for media exchange or sterile sampling. A mass transfer coefficient for oxygen (k(L)a) of 4.3x10(-3) s(-1) at a flow rate of only 15 ml min(-1) and a mixing time of 1.5s at a flow rate of 11 ml min(-1) were observed for the modular bioreactor. Single reactor chambers can be interconnected via ion-conductive membranes to form a two-chamber test setup for investigations on electrochemical systems such as fuel cells or sensors. The versatile applicability of this modular and flexible bioreactor was demonstrated by recording a growth curve of Escherichia coli (including monitoring of pH and oxygen) saturation, and also as by two bioelectrochemical experiments. In the first electrochemical experiment the use of the bioreactor enabled a direct comparison of electrode materials for a laccase-catalyzed oxygen reduction electrode. In a second experiment, the bioreactor was utilized to characterize the influence of outer membrane cytochromes on the performance of Shewanella oneidensis in a microbial fuel cell. Copyright 2010 Elsevier B.V. All rights reserved.

  20. Phosphatidic acid, a versatile water-stress signal in roots

    Directory of Open Access Journals (Sweden)

    Fionn eMcLoughlin

    2013-12-01

    Full Text Available Adequate water supply is of utmost importance for growth and reproduction of plants. In order to cope with water deprivation, plants have to adapt their development and metabolism to ensure survival. To maximize water use efficiency, plants use a large array of signaling mediators such as hormones, protein kinases and phosphatases, Ca2+, reactive oxygen species and low abundant phospholipids that together form complex signaling cascades. Phosphatidic acid (PA is a signaling lipid that rapidly accumulates in response to a wide array of abiotic stress stimuli. PA formation provides the cell with spatial and transient information about the external environment by acting as a protein-docking site in cellular membranes. PA reportedly binds to a number of proteins that play a role during water limiting conditions, such as drought and salinity and has been shown to play an important r