WorldWideScience

Sample records for intein-mediated specific bioconjugation

  1. Semiconductor nanocrystal-aptamer bioconjugate probes for specific prostate carcinoma cell targeting

    Science.gov (United States)

    Shieh, Felice; Lavery, Laura; Chu, Chitai T.; Richards-Kortum, Rebecca; Ellington, Andrew D.; Korgel, Brian A.

    2005-04-01

    Cancer of the prostate affects approximately 1 in 11 men. Current early screening for prostate cancer utilizes digital rectal examinations to detect anomalies in the prostate gland and blood test screenings for upregulated levels of prostate specific antigen (PSA). Many of these tests are invasive and can often be inconclusive as PSA levels may be heightened due to benign factors. Prostate specific membrane antigen (PSMA), a well-characterized integral membrane protein, is expressed in virtually all prostate cancers and often correlates with cancer aggressiveness. Therefore, it may be used as an indicator of cancer growth and metastases. PSMA-specific antibodies have been identified and conjugated to fluorescent markers for cancer cell targeting; however, both the antibodies and markers possess significant limitations in their pharmaceutical and diagnostic value. Here we report the use of semiconductor nanocrystals bioconjugated to PSMA-specific aptamer recognition molecules for prostate carcinoma cell targeting. The nanocrystal/aptamer bioconjugates are small biocompatible probes with the potential for color-tunability for multicolor imaging. Ongoing in vitro and in vivo research seeks to introduce these nanoparticle bioconjugates into medical diagnostics.

  2. Bioconjugates to specifically render inhibitors water-soluble

    NARCIS (Netherlands)

    Hirsch, Anna K.H.; Diederich, François; Antonietti, Markus; Börner, Hans G.

    2010-01-01

    Polymer–peptide conjugates are utilised to render small-molecule inhibitors of the kinase IspE, a promising new antimalarial target, water-soluble. It is shown that the peptide sequence of poly(ethylene oxide)–peptide conjugates can be tailored to mediate specific interactions with the ligands,

  3. A chelating dendritic ligand capped quantum dot: preparation, surface passivation, bioconjugation and specific DNA detection

    Science.gov (United States)

    Zhou, Dejian; Li, Yang; Hall, Elizabeth A. H.; Abell, Chris; Klenerman, David

    2011-01-01

    Herein we report the synthesis of a new chelating dendritic ligand (CDL) and its use in the preparation a compact, stable and water-soluble quantum dot (QD), and further development of specific DNA sensor. The CDL, which contains a chelative dihydrolipoic acid moiety for strong QD surface anchoring and four dendritic carboxylic acidgroups, provides a stable, compact and entangled hydrophilic coating around the QD that significantly increases the stability of the resulting water-soluble QD. A CDL-capped CdSe/ZnS core/shell QD (CDL-QD) has stronger fluorescence than that capped by a monodendate single-chain thiol, 3-mercapto-propionic acid (MPA-QD). In addition, the fluorescence of the CDL-QD can be enhanced by 2.5-fold by treatments with Zn2+ or S2- ions, presumably due to effective passivation of the surface defects. This level of fluorescence enhancement obtained for the CDL-QD is much greater than that for the MPA-QD. Further, by coupling a short single-stranded DNA target to the QD via the CDL carboxylic acidgroup, a functional QD-DNA conjugate that can resist non-specific adsorption and hybridize quickly to its complementary DNAprobe has been obtained. This functional QD-DNA conjugate is suitable for specific quantification of short, labelled complementary probes at the low DNAprobe:QD copy numbers via a QD-sensitised dyefluorescence resonance energy transfer (FRET) response with 500 pM sensitivity on a conventional fluorimeter.Herein we report the synthesis of a new chelating dendritic ligand (CDL) and its use in the preparation a compact, stable and water-soluble quantum dot (QD), and further development of specific DNA sensor. The CDL, which contains a chelative dihydrolipoic acid moiety for strong QD surface anchoring and four dendritic carboxylic acidgroups, provides a stable, compact and entangled hydrophilic coating around the QD that significantly increases the stability of the resulting water-soluble QD. A CDL-capped CdSe/ZnS core/shell QD (CDL-QD) has

  4. Enzyme-mediated site-specific bioconjugation of metal complexes to proteins: sortase-mediated coupling of copper-64 to a single-chain antibody.

    Science.gov (United States)

    Paterson, Brett M; Alt, Karen; Jeffery, Charmaine M; Price, Roger I; Jagdale, Shweta; Rigby, Sheena; Williams, Charlotte C; Peter, Karlheinz; Hagemeyer, Christoph E; Donnelly, Paul S

    2014-06-10

    The enzyme-mediated site-specific bioconjugation of a radioactive metal complex to a single-chain antibody using the transpeptidase sortase A is reported. Cage amine sarcophagine ligands that were designed to function as substrates for the sortase A mediated bioconjugation to antibodies were synthesized and enzymatically conjugated to a single-chain variable fragment. The antibody fragment scFv(anti-LIBS) targets ligand-induced binding sites (LIBS) on the glycoprotein receptor GPIIb/IIIa, which is present on activated platelets. The immunoconjugates were radiolabeled with the positron-emitting isotope (64)Cu. The new radiolabeled conjugates were shown to bind selectively to activated platelets. The diagnostic potential of the most promising conjugate was demonstrated in an in vivo model of carotid artery thrombosis using positron emission tomography. This approach gives homogeneous products through site-specific enzyme-mediated conjugation and should be broadly applicable to other metal complexes and proteins. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Extending the scope of site-specific cysteine bioconjugation by appending a prelabeled cysteine tag to proteins using protein trans-splicing.

    Science.gov (United States)

    Dhar, Tulika; Kurpiers, Thomas; Mootz, Henning D

    2011-01-01

    Incorporating synthetic probes site-specifically into proteins is of central interest in several areas of biotechnology and protein chemistry. Bioconjugation techniques provide a simple and effective means of chemically modifying a protein. In particular, covalent chemical modifications of cysteine residues belong to one of the most important reactions due to the unique reactivity of its thiol moiety and the relatively low abundance of this amino acid in proteins. However, such types of modifications cannot be performed in a regioselective fashion when one or more additional cysteines are present. To address this limitation, we have developed an approach where a short cysteine-containing tag (Cys-Tag) fused to one part of a split intein and modified at its sulfhydryl group can be used to label proteins by trans-splicing with a protein of interest (POI) fused to the other half of the split intein. In this way, it is possible to selectively label a protein containing multiple cysteines. The artificially split Mycobacterium xenopi GyrA intein and the Synechocystis sp. DnaB intein were highly suitable for this purpose and were successfully used for the labeling of several proteins. This approach enables a simple route for labeling proteins by site-specific cysteine bioconjugation with any one of several commercially available cysteine-modifying probes.

  6. Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry.

    Science.gov (United States)

    Mason, Alexander F; Thordarson, Pall

    2016-07-20

    The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the development of antibody drug conjugates (ADCs) and nanomedicine, fluorescent microscopy and systems chemistry. For many of these applications, specificity of the bioconjugation method used is of prime concern. The Michael addition of maleimides with cysteine(s) on the target proteins is highly selective and proceeds rapidly under mild conditions, making it one of the most popular methods for protein bioconjugation. We demonstrate here the modification of the only surface-accessible cysteine residue on yeast cytochrome c with a ruthenium(II) bisterpyridine maleimide. The protein bioconjugation is verified by gel electrophoresis and purified by aqueous-based fast protein liquid chromatography in 27% yield of isolated protein material. Structural characterization with MALDI-TOF MS and UV-Vis is then used to verify that the bioconjugation is successful. The protocol shown here is easily applicable to other cysteine - maleimide coupling of proteins to other proteins, dyes, drugs or polymers.

  7. Bio-Conjugates for Nanoscale Applications

    DEFF Research Database (Denmark)

    Villadsen, Klaus

    Bio-conjugates for Nanoscale Applications is the title of this thesis, which covers three different projects in chemical bio-conjugation research, namely synthesis and applications of: Lipidated fluorescent peptides, carbohydrate oxime-azide linkers and N-aryl O-R2 oxyamine derivatives. Lipidated...

  8. Linkable thiocarbamoylbenzamidines as ligands for bioconjugation of Rhenium and Technetium

    International Nuclear Information System (INIS)

    Castillo Gomez, Juan Daniel

    2015-01-01

    Bioconjugation reactions with Rhenium and Technetium are of high importance for the development of novel radiopharmaceuticals for nuclear medicine. In this thesis the possibilities for bioconjugation using linkable Thiocarmbamoylbenzamidines as ligands for the complexation of Rhenium and Technetium were examined.

  9. Investigating bioconjugation by atomic force microscopy

    Science.gov (United States)

    2013-01-01

    Nanotechnological applications increasingly exploit the selectivity and processivity of biological molecules. Integration of biomolecules such as proteins or DNA into nano-systems typically requires their conjugation to surfaces, for example of carbon-nanotubes or fluorescent quantum dots. The bioconjugated nanostructures exploit the unique strengths of both their biological and nanoparticle components and are used in diverse, future oriented research areas ranging from nanoelectronics to biosensing and nanomedicine. Atomic force microscopy imaging provides valuable, direct insight for the evaluation of different conjugation approaches at the level of the individual molecules. Recent technical advances have enabled high speed imaging by AFM supporting time resolutions sufficient to follow conformational changes of intricately assembled nanostructures in solution. In addition, integration of AFM with different spectroscopic and imaging approaches provides an enhanced level of information on the investigated sample. Furthermore, the AFM itself can serve as an active tool for the assembly of nanostructures based on bioconjugation. AFM is hence a major workhorse in nanotechnology; it is a powerful tool for the structural investigation of bioconjugation and bioconjugation-induced effects as well as the simultaneous active assembly and analysis of bioconjugation-based nanostructures. PMID:23855448

  10. O6-alkylguanine-DNA transferase (SNAP) as capture module for site-specific covalent bioconjugation of targeting protein on nanoparticles

    Science.gov (United States)

    Mazzucchelli, Serena; Colombo, Miriam; Galbiati, Elisabetta; Corsi, Fabio; Montenegro, Josè M.; Parak, Wolfgang J.; Prosperi, Davide

    2013-02-01

    A bimodular genetic fusion comprising a delivery module (scFv) and a capture module (SNAP) is proposed as a novel strategy for the biologically mediated site-specific covalent conjugation of targeting proteins to nanoparticles. ScFv800E6, an scFv mutant selective for HER2 antigen overexpressed in breast cancer cells was chosen as targeting ligand. The fusion protein SNAP-scFv was irreversibly immobilized on magnetofluorescent nanoparticles through the recognition between SNAP module and pegylated O6-alkylguanine derivative. The targeting efficiency of the resulting nanoparticle against HER2-positive breast cancer cells was assessed by flow cytometry and immunofluorescence.

  11. Novel Bioconjugation Strategy Using Elevated Hydrostatic Pressure: A Case Study for the Site-Specific Attachment of Polyethylene Glycol (PEGylation) of Recombinant Human Ciliary Neurotrophic Factor.

    Science.gov (United States)

    Wang, Qi; Zhang, Chun; Guo, Fangxia; Li, Zenglan; Liu, Yongdong; Su, Zhiguo

    2017-11-15

    In this paper, we reported a novel strategy for the site-specific attachment of polyethylene glycol (PEGylation) of proteins using elevated hydrostatic pressure. The process was similar to the conventional one except the reactor was under elevated hydrostatic pressure. The model protein was recombinant human ciliary neurotrophic factor (rhCNTF), and the reagent was monomethoxy-polyethylene glycol-maleimide (mPEG-MAL). PEGylation with mPEG (40 kDa)-MAL at pH 7.0 under normal pressure for 5 h achieved a less than 5% yield. In comparison, when the pressure was elevated, the PEGylation yield was increased dramatically, reaching nearly 90% at 250 MPa. Furthermore, the following phenomena were observed: (1) high-hydrostatic-pressure PEGylation (HHPP) could operate at a low reactant ratio of 1:1.2 (rhCNTF to mPEG-MAL), while the conventional process needs a much-higher ratio. (2) Short and long chains of PEG gave a similar yield of 90% in HHPP, while the conventional yield for the short chain of the PEG was higher than that of the long chain. (3) The reaction pH in the range of 7.0 to 8.0 had almost no influence upon the yield of HHPP, while the PEGylation yield was significantly increased by a factor of three from pH 7.0 to 8.0 at normal pressure. Surface accessibility analysis was performed using GRASP2 software, and we found that Cys17 of rhCNTF was located at the concave patches, which may have steric hindrance for the PEG to approach. The speculated benefit of HHPP was the facilitation of target-site exposure, reducing the steric hindrance and making the reaction much easier. Structure and activity analysis demonstrated that the HHPP product was comparable to the PEGylated rhCNTF prepared through a conventional method. Overall, this work demonstrated that HHPP, as we proposed, may have application potentials in various conjugations of biomacromolecules.

  12. Organometallic palladium reagents for cysteine bioconjugation

    Science.gov (United States)

    Vinogradova, Ekaterina V.; Zhang, Chi; Spokoyny, Alexander M.; Pentelute, Bradley L.; Buchwald, Stephen L.

    2015-10-01

    Reactions based on transition metals have found wide use in organic synthesis, in particular for the functionalization of small molecules. However, there are very few reports of using transition-metal-based reactions to modify complex biomolecules, which is due to the need for stringent reaction conditions (for example, aqueous media, low temperature and mild pH) and the existence of multiple reactive functional groups found in biomolecules. Here we report that palladium(II) complexes can be used for efficient and highly selective cysteine conjugation (bioconjugation) reactions that are rapid and robust under a range of bio-compatible reaction conditions. The straightforward synthesis of the palladium reagents from diverse and easily accessible aryl halide and trifluoromethanesulfonate precursors makes the method highly practical, providing access to a large structural space for protein modification. The resulting aryl bioconjugates are stable towards acids, bases, oxidants and external thiol nucleophiles. The broad utility of the bioconjugation platform was further corroborated by the synthesis of new classes of stapled peptides and antibody-drug conjugates. These palladium complexes show potential as benchtop reagents for diverse bioconjugation applications.

  13. Synthesis and Bioconjugation of Gold Nanoparticles as Potential Molecular Probes for Light-Based Imaging Techniques

    Directory of Open Access Journals (Sweden)

    Raja Gopal Rayavarapu

    2007-01-01

    Full Text Available We have synthesized and characterized gold nanoparticles (spheres and rods with optical extinction bands within the “optical imaging window.” The intense plasmon resonant driven absorption and scattering peaks of these nanoparticles make them suitable as contrast agents for optical imaging techniques. Further, we have conjugated these gold nanoparticles to a mouse monoclonal antibody specific to HER2 overexpressing SKBR3 breast carcinoma cells. The bioconjugation protocol uses noncovalent modes of binding based on a combination of electrostatic and hydrophobic interactions of the antibody and the gold surface. We discuss various aspects of the synthesis and bioconjugation protocols and the characterization results of the functionalized nanoparticles. Some proposed applications of these potential molecular probes in the field of biomedical imaging are also discussed.

  14. Decarboxylative alkylation for site-selective bioconjugation of native proteins via oxidation potentials

    Science.gov (United States)

    Bloom, Steven; Liu, Chun; Kölmel, Dominik K.; Qiao, Jennifer X.; Zhang, Yong; Poss, Michael A.; Ewing, William R.; MacMillan, David W. C.

    2018-02-01

    The advent of antibody-drug conjugates as pharmaceuticals has fuelled a need for reliable methods of site-selective protein modification that furnish homogeneous adducts. Although bioorthogonal methods that use engineered amino acids often provide an elegant solution to the question of selective functionalization, achieving homogeneity using native amino acids remains a challenge. Here, we explore visible-light-mediated single-electron transfer as a mechanism towards enabling site- and chemoselective bioconjugation. Specifically, we demonstrate the use of photoredox catalysis as a platform to selectivity wherein the discrepancy in oxidation potentials between internal versus C-terminal carboxylates can be exploited towards obtaining C-terminal functionalization exclusively. This oxidation potential-gated technology is amenable to endogenous peptides and has been successfully demonstrated on the protein insulin. As a fundamentally new approach to bioconjugation this methodology provides a blueprint toward the development of photoredox catalysis as a generic platform to target other redox-active side chains for native conjugation.

  15. Choosing an effective protein bioconjugation strategy.

    Science.gov (United States)

    Stephanopoulos, Nicholas; Francis, Matthew B

    2011-11-15

    The collection of chemical techniques that can be used to attach synthetic groups to proteins has expanded substantially in recent years. Each of these approaches allows new protein targets to be addressed, leading to advances in biological understanding, new protein-drug conjugates, targeted medical imaging agents and hybrid materials with complex functions. The protein modification reactions in current use vary widely in their inherent site selectivity, overall yields and functional group compatibility. Some are more amenable to large-scale bioconjugate production, and a number of techniques can be used to label a single protein in a complex biological mixture. This review examines the way in which experimental circumstances influence one's selection of an appropriate protein modification strategy. It also provides a simple decision tree that can narrow down the possibilities in many instances. The review concludes with example studies that examine how this decision process has been applied in different contexts.

  16. Synthesis and use of 2-[18F]fluoromalondialdehyde, an accessible synthon for bioconjugation

    Energy Technology Data Exchange (ETDEWEB)

    Hooker, Jacob M. [Massachusetts General Hospital, Boston, MA (United States)

    2017-03-16

    We proposed methods for the synthesis and purification of 2-[18F]fluoromalondialdehyde, which will be a readily accessible synthon for bioconjugation. Our achievements in these areas will specifically address a stated goal of the DOE providing a transformational technology for macromolecule radiolabeling. Accomplishment of our aims will serve both DOE mission-related research as well as nuclear medicine research supported by the NIH and industry. At the heart of our proposal is the aim to “improve synthetic methodology for rapidly and efficiently incorporating radionuclides into a wide range of organic compounds.”

  17. General Dialdehyde Click Chemistry for Amine Bioconjugation.

    Science.gov (United States)

    Elahipanah, Sina; O'Brien, Paul J; Rogozhnikov, Dmitry; Yousaf, Muhammad N

    2017-05-17

    -conjugation strategy, we designed a straightforward scheme to synthesize a suite of dialdehyde reagents. The dialdehyde molecules were used for applications in cell-surface engineering and for tailoring surfaces for material science applications. We anticipate the broad utility of the general dialdehyde click chemistry to primary amines in all areas of chemical research, ranging from polymers and bioconjugation to material science and nanoscience.

  18. Overview of the main methods used to combine proteins with nanosystems: absorption, bioconjugation, and encapsulation

    Directory of Open Access Journals (Sweden)

    Mariagrazia Di Marco

    2009-12-01

    Full Text Available Mariagrazia Di Marco1, Shaharum Shamsuddin2, Khairunisak Abdul Razak3, Azlan Abdul Aziz4, Corinne Devaux1, Elsa Borghi1, Laurent Levy1, Claudia Sadun51Nanobiotix, Paris, France; 2School of Health Sciences, Health Campus Universiti Sains Malaysia, Kelantan, Malaysia; 3School of Materials and Mineral Resources Engineering, Engineering Campus, 4School of Physics, Universiti Sains Malaysia, Penang, Malaysia; 5Department of Chemistry, Sapienza, University of Rome, Rome, ItalyAbstract: The latest development of protein engineering allows the production of proteins having desired properties and large potential markets, but the clinical advances of therapeutical proteins are still limited by their fragility. Nanotechnology could provide optimal vectors able to protect from degradation therapeutical biomolecules such as proteins, enzymes or specific polypeptides. On the other hand, some proteins can be also used as active ligands to help nanoparticles loaded with chemotherapeutic or other drugs to reach particular sites in the body. The aim of this review is to provide an overall picture of the general aspects of the most successful approaches used to combine proteins with nanosystems. This combination is mainly achieved by absorption, bioconjugation and encapsulation. Interactions of nanoparticles with biomolecules and caveats related to protein denaturation are also pointed out. A clear understanding of nanoparticle-protein interactions could make possible the design of precise and versatile hybrid nanosystems. This could further allow control of their pharmacokinetics as well as activity, and safety.Keywords: nanoparticles, drug delivery, proteins, polypeptides, absorption, bioconjugation, encapsulation

  19. Bioconjugation of barium titanate nanocrystals with immunoglobulin G antibody for second harmonic radiation imaging probes.

    Science.gov (United States)

    Hsieh, Chia-Lung; Grange, Rachel; Pu, Ye; Psaltis, Demetri

    2010-03-01

    The second harmonic generation (SHG) active nanocrystals have been demonstrated as attractive imaging probes in nonlinear microscopy due to their coherent, non-bleaching and non-blinking signals with a broad flexibility in the choice of excitation wavelength. For the use of these nanocrystals as biomarkers, it is essential to prepare a chemical interface for specific labeling. We developed a specific labeling scheme for barium titanate (BaTiO3) nanocrystals which we use as second harmonic radiation imaging probes. The specificity was achieved by covalently coupling antibodies onto the nanocrystals. We demonstrate highly specific labeling of the nanocrystal conjugates in an antibody microarray and also the membrane proteins of live biological cells in vitro. The development of surface functionalization and bioconjugation of SHG active nanocrystals provides the opportunities of applying them to biological studies. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  20. Linkable thiocarbamoylbenzamidines as ligands for bioconjugation of Rhenium and Technetium; Kopplungsfaehige Thiocarbamoylbenzamidine als Liganden zur Biokonjugation von Rhenium und Technetium

    Energy Technology Data Exchange (ETDEWEB)

    Castillo Gomez, Juan Daniel

    2015-04-27

    Bioconjugation reactions with Rhenium and Technetium are of high importance for the development of novel radiopharmaceuticals for nuclear medicine. In this thesis the possibilities for bioconjugation using linkable Thiocarmbamoylbenzamidines as ligands for the complexation of Rhenium and Technetium were examined.

  1. Design, Synthesis and Applications of Hyaluronic Acid-Paclitaxel Bioconjugatesâ€

    Directory of Open Access Journals (Sweden)

    Rinaldo Marini Bettolo

    2008-02-01

    Full Text Available Paclitaxel (1a, a well known antitumor agent adopted mainly for the treatmentof breast and ovarian cancer, suffers from significant disadvantages such as low solubility,certain toxicity and specific drug-resistance of some tumor cells. To overcome theseproblems extensive research has been carried out. Among the various proposed strategies,the conjugation of paclitaxel (1a to a biocompatible polymer, such as hyaluronic acid(HA, 2, has also been considered. Coupling a bioactive compound to a biocompatiblepolymer offers, in general, many advantages such as better drug solubilization, betterstabilization, specific localization and controlled release. Hereafter the design, synthesisand applications of hyaluronic acid-paclitaxel bioconjugates are reviewed. An overview ofHA-paclitaxel combinations is also given.

  2. Collagen like peptide bioconjugates for targeted drug delivery applications

    Science.gov (United States)

    Luo, Tianzhi

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

  3. Thiol-ene click chemistry: a biocompatible way for orthogonal bioconjugation of colloidal nanoparticles.

    Science.gov (United States)

    Liu, Yuan; Hou, Weijia; Sun, Hao; Cui, Cheng; Zhang, Liqin; Jiang, Ying; Wu, Yongxiang; Wang, Yanyue; Li, Juan; Sumerlin, Brent S; Liu, Qiaoling; Tan, Weihong

    2017-09-01

    Bioconjugation based on crosslinking primary amines to carboxylic acid groups has found broad applications in protein modification, drug development, and nanomaterial functionalization. However, proteins, which are made up of amino acids, typically give nonselective bioconjugation when using primary amine-based crosslinking. In order to control protein orientation and activity after conjugation, selective bioconjugation is desirable. We herein report an efficient and cysteine-selective thiol-ene click reaction-based bioconjugation strategy using colloidal nanoparticles. The resulting thiol-ene based aptamer and enzyme nanoconjugates demonstrated excellent target binding ability and enzymatic activity, respectively. Thus, thiol-ene click chemistry can provide a stable and robust crosslinker in a biocompatible manner for bioconjugation of any thiol-containing biomolecule with nanomaterials. This will open more opportunities for applications of thiol-ene reactions and functional colloidal nanoparticles in chemical biology.

  4. A highly efficient catalyst for oxime ligation and hydrazone-oxime exchange suitable for bioconjugation.

    Science.gov (United States)

    Rashidian, Mohammad; Mahmoodi, Mohammad M; Shah, Rachit; Dozier, Jonathan K; Wagner, Carston R; Distefano, Mark D

    2013-03-20

    Imine-based reactions are useful for a wide range of bioconjugation applications. Although aniline is known to catalyze the oxime ligation reaction under physiological conditions, it suffers from slow reaction kinetics, specifically when a ketone is being used or when hydrazone-oxime exchange is performed. Here, we report on the discovery of a new catalyst that is up to 15 times more efficient than aniline. That catalyst, m-phenylenediamine (mPDA), was initially used to analyze the kinetics of oxime ligation on aldehyde- and ketone-containing small molecules. While mPDA is only modestly more effective than aniline when used in equal concentrations (~2-fold), its much greater aqueous solubility relative to aniline allows it to be used at higher concentrations, resulting in significantly more efficient catalysis. In the context of protein labeling, it was first used to site-specifically label an aldehyde-functionalized protein through oxime ligation, and its kinetics were compared to reaction with aniline. Next, a protein was labeled with an aldehyde-containing substrate in crude cell lysate, captured with hydrazide-functionalized beads and then the kinetics of immobilized protein release via hydrazone-oxime exchange were analyzed. Our results show that mPDA can release and label 15 times more protein than aniline can in 3 h. Then, using the new catalyst, ciliary neurotrophic factor, a protein with therapeutic potential, was successfully labeled with a fluorophore in only 5 min. Finally, a protein containing the unnatural amino acid, p-acetyl phenylalanine, a ketone-containing residue, was prepared and PEGylated efficiently via oxime ligation using mPDA. This new catalyst should have a significant impact on the field of bioconjugation, where oxime ligation and hydrazone-oxime exchange are commonly employed.

  5. A Highly Efficient Catalyst for Oxime Ligation and Hydrazone-Oxime Exchange Suitable for Bioconjugation

    Science.gov (United States)

    Rashidian, Mohammad; Mahmoodi, Mohammad M.; Shah, Rachit; Dozier, Jonathan K.; Wagner, Carston R.; Distefano, Mark D.

    2014-01-01

    Imine-based reactions are useful for a wide range of bioconjugation applications. Although aniline is known to catalyze the oxime ligation reaction under physiological conditions, it suffers from slow reaction kinetics, specifically when a ketone is being used or when hydrazone-oxime exchange is performed. Here, we report on the discovery of a new catalyst that is up to 15 times more efficient than aniline. That catalyst, m-phenylenediamine (mPDA), was initially used to analyze the kinetics of oxime ligation on aldehyde- and ketone-containing small molecules. While mPDA is only modestly more effective than aniline when used in equal concentrations (~ 2-fold), its much greater aqueous solubility relative to aniline allows it to be used at higher concentrations, resulting in significantly more efficient catalysis. In the context of protein labeling, it was first used to site-specifically label an aldehyde-functionalized protein through oxime ligation, and its kinetics were compared to reaction with aniline. Next, a protein was labeled with an aldehyde-containing substrate in crude cell lysate, captured with hydrazide-functionalized beads and then the kinetics of immobilized protein release via hydrazone-oxime exchange were analyzed. Our results show that mPDA can release and label 15 times more protein than aniline can in 3 h. Then, using the new catalyst, ciliary neurotrophic factor, a protein with therapeutic potential, was successfully labeled with a fluorophore in only 5 min. Finally, a protein containing the unnatural amino acid, p-acetyl phenylalanine, a ketone-containing residue, was prepared and PEGylated efficiently via oxime ligation using mPDA. This new catalyst should have a significant impact on the field of bioconjugation, where oxime ligation and hydrazone-oxime exchange are commonly employed. PMID:23425124

  6. Bioconjugation of gold and silver nanoparticles synthesized by Fusarium oxysporum and their use in rapid identification of Candida species by using bioconjugate-nano-polymerase chain reaction.

    Science.gov (United States)

    Bansod, Sunita; Bonde, Shital; Tiwari, Vaibhav; Bawaskar, Manisha; Deshmukh, Shivaji; Gaikwad, Swapnil; Gade, Aniket; Rai, Mahendra

    2013-12-01

    We developed a Bioconjugate-Nano-PCR as a rapid and specific method for identification of Candida species in less time. This requires very low concentration of master mix and DNA sample of Candida albicans in conjugation with gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs). We report a modification of the PCR assay with nanoparticles that allows the detection of high fidelity amplification of ITS-rDNA and beta (beta) tubulin gene of Candida species from low concentrated DNA in short period. We synthesized and characterized the covalently attached 34 nm (AuNPs) and 35 nm of (AgNPs) and conjugated with C. albicans DNA sample, which is used as a template for PCR. The use of this nanoparticle modified template improves the sensitivity and specificity of the traditional PCR assay with very low cycles which is very helpful in molecular diagnostics and therapeutics. It proves to be an effective method for identification of Candida species with low concentration of DNA. This type of PCR assay is useful for detection of target gene by enhancing the specificity of the target gene and is less time consuming.

  7. Nanostructure L-asparaginase-fatty acid bioconjugate: synthesis, preformulation study and biological assessment.

    Science.gov (United States)

    Ashrafi, Hajar; Amini, Mohsen; Mohammadi-Samani, Soliman; Ghasemi, Younes; Azadi, Amir; Tabandeh, Mohammad Reza; Kamali-Sarvestani, Eskandar; Daneshamouz, Saeid

    2013-11-01

    The present study aims to develop a novel L-asparaginase fatty acid bioconjugates and characterize their applicability for intravenous delivery of L-asparaginase. These bioconjugates were achieved by covalent linkage of fatty acids having different chain lengths (C12, C16 and C22) to the native enzyme. To determine the optimum conditions of bioconjugation, the effect of lipid:protein ratios, reaction time and medium composition on enzyme activity and conjugation degree were evaluated. The native and bioconjugates have been characterized by activity, conjugation degree, particle size, and zeta potential. The results showed that bioconjugated L-asparaginase were more resistant to proteolysis, more stable at different pH, and had prolonged plasma half-life, compared to the native form. From partition coefficient study, the modified enzymes showed approximately 15-fold increase in hydrophobicity. Secondary structure analysis using circular dichroism revealed alteration after lipid conjugation. In addition, the Michaelis constant of the native enzyme was 3.38 mM, while the bioconjugates showed the higher affinity to the substrate L-asparagine. These findings indicate that new lipid bioconjugation could be a very useful strategy for intravenous delivery of L-asparaginase. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. 3D NIR-II Molecular Imaging Distinguishes Targeted Organs with High-Performance NIR-II Bioconjugates.

    Science.gov (United States)

    Zhu, Shoujun; Herraiz, Sonia; Yue, Jingying; Zhang, Mingxi; Wan, Hao; Yang, Qinglai; Ma, Zhuoran; Wang, Yan; He, Jiahuan; Antaris, Alexander L; Zhong, Yeteng; Diao, Shuo; Feng, Yi; Zhou, Ying; Yu, Kuai; Hong, Guosong; Liang, Yongye; Hsueh, Aaron J; Dai, Hongjie

    2018-02-15

    Greatly reduced scattering in the second near-infrared (NIR-II) region (1000-1700 nm) opens up many new exciting avenues of bioimaging research, yet NIR-II fluorescence imaging is mostly implemented by using nontargeted fluorophores or wide-field imaging setups, limiting the signal-to-background ratio and imaging penetration depth due to poor specific binding and out-of-focus signals. A newly developed high-performance NIR-II bioconjugate enables targeted imaging of a specific organ in the living body with high quality. Combined with a home-built NIR-II confocal set-up, the enhanced imaging technique allows 900 µm-deep 3D organ imaging without tissue clearing techniques. Bioconjugation of two hormones to nonoverlapping NIR-II fluorophores facilitates two-color imaging of different receptors, demonstrating unprecedented multicolor live molecular imaging across the NIR-II window. This deep tissue imaging of specific receptors in live animals allows development of noninvasive molecular imaging of multifarious models of normal and neoplastic organs in vivo, beyond the traditional visible to NIR-I range. The developed NIR-II fluorescence microscopy will become a powerful imaging technique for deep tissue imaging without any physical sectioning or clearing treatment of the tissue. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Construction of polymer-protein bioconjugates with varying chain topologies: polymer molecular weight and steric hindrance effects.

    Science.gov (United States)

    Wan, Xuejuan; Zhang, Guoying; Ge, Zhishen; Narain, Ravin; Liu, Shiyong

    2011-10-04

    We report on the fabrication of well-defined polymer-protein bioconjugates with varying chain architectures, including star polymers, star block copolymers, and heteroarm star copolymers through the specific noncovalent interaction between avidin and biotinylated synthetic polymer precursors. Homopolymer and diblock precursors site-specifically labeled with a single biotin moiety at the chain terminal, chain middle, or diblock junction point were synthesized by a combination of atom-transfer radical polymerization (ATRP) and click reactions. By taking advantage of molecular recognition between avidin and biotin moieties, supramolecular star polymers, star block copolymers, and heteroarm star copolymers were successfully fabricated. This specific binding process was also assessed by using the diffraction optic technology (DOT) technique. We further investigated the effects of polymer molecular weights, location of biotin functionality within the polymer chain, and polymer chain conformations, that is, steric hindrance effects, on the binding numbers of biotinylated polymer chains per avidin within the polymer-protein bioconjugates, which were determined by the standard avidin/2-(4-hydroxyazobenzene)benzoic acid (HABA) assay. The binding numbers vary in the range of 1.9-3.3, depending on the molecular weights, locations of biotin functionality within synthetic polymer precursors, and polymer chain conformations. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Photochemical Synthesis of the Bioconjugate Folic Acid-Gold Nanoparticles

    DEFF Research Database (Denmark)

    León, John Jairo Castillo; Bertel, Linda; Páez-Mozo, Edgar

    2013-01-01

    In this paper we present a rapid and simple onepot method to obtain gold nanoparticles functionalized with folic acid using a photochemistry method. The bioconjugate folic acid-gold nanoparticle was generated in one step using a photo-reduction method, mixing hydrogen tetrachloroaurate with folic...... at 4°C prolongs the stability of folic acid-gold nanoparticle suspensions to up to 26 days. Ultraviolet visible and Fourier transform infrared spectroscopy showed a surface plasmon band of around 534nm and fluorescence spectroscopy exhibited a quenching effect on gold nanoparticles in the fluorescence...... emission of folic acid and thus confirmed the conjugation of folic acid to the surface of gold nanoparticles. In this study we demonstrate the use of a photochemistry method to obtain folic acid-gold nanoparticles in a simple and rapid way without the use of surfactants and long reaction times...

  11. Bioconjugation of quantum dot luminescent probes for Western blot analysis.

    Science.gov (United States)

    Makrides, Savvas C; Gasbarro, Christina; Bello, Job M

    2005-10-01

    Western blot analysis is a widely used technique for protein immunodetection. Its current format, however is unsuitable for multiplex detection of proteins, primarily due to intrinsic limitations of standard organic dyes employed as probes. Quantum dot (QD) semiconductor nanoparticles exhibit significant advantages over organic dyes, including their broad absorption bands, narrow, tunable, and symmetric emission spectra, large Stokes shifts, and excellent photostability. Here we describe a novel method for the functionalization of streptavidin-coated QDs with an in vivo biotinylated peptide (head-to-tail dimerized Z domain derived from protein A) that permits the facile conjugation of antibodies to QDs. In this study, we demonstrate the simultaneous detection of two different types of protein in a Western blot. The bioconjugation of QDs described here makes it possible to achieve multiplex detection of proteins in Western blot analysis in a more straightforward manner.

  12. Bioconjugates of PAMAM dendrimers with trans-retinal, pyridoxal, and pyridoxal phosphate

    Directory of Open Access Journals (Sweden)

    Filipowicz A

    2012-09-01

    Full Text Available A Filipowicz, S WołowiecDepartment of Cosmetology, University of Information Technology and Management in Rzeszów, Rzeszów, PolandBackground: Bioconjugates of a polyamidoamine (PAMAM G3 dendrimer and an aldehyde were synthesized as carriers for vitamins A and B6, and the bioavailability of these vitamins for skin nutrition was investigated.Methods: Nuclear magnetic resonance (NMR and ultraviolet-visible methods were used to characterize the structure of the bioconjugates and for monitoring release of pyridoxal (Pyr and pyridoxal phosphate (PLP from these bioconjugates in vitro. A skin model permeation of bioconjugates was also studied in a Franz chamber.Results: A transdermal G3 PAMAM dendrimer was used to synthesize bioconjugates with trans-retinal (Ret, pyridoxal (Pyr, or PLP. These nanomolecules, containing up to four covalently linked Ret, Pyr, or PLP (G34Ret, G34Pyr, and G34PLP, were able to permeate the skin, as demonstrated in vitro using a model skin membrane. PLP and Pyr bound to a macromolecular vehicle were active cofactors for glutamic pyruvic transaminase, as shown by 1H NMR spectral monitoring of the progress of the L-alanine + α-ketoglutarate → glutamic acid + pyruvic acid reaction.Conclusion: PAMAM-PLP, PAMAM-Pyr, and PAMAM-Ret bioconjugates are able to permeate the skin. PLP and Pyr are available as cofactors for glutamic pyruvic transaminase.Keywords: PAMAM, trans-retinal, pyridoxal phosphate, pyridoxal, transamination

  13. The detection of platelet derived growth factor using decoupling of quencher-oligonucleotide from aptamer/quantum dot bioconjugates

    International Nuclear Information System (INIS)

    Kim, Gang-Il; Sung, Yun-Mo; Kim, Kyung-Woo; Oh, Min-Kyu

    2009-01-01

    High-sensitivity, high-specificity detection of platelet derived growth factor (PDGF)-BB was realized using the change in fluorescence resonance energy transfer (FRET) occurring between quantum dot (QD) donors and black hole quencher (BHQ) acceptors. CdSe/ZnS QD/mercaptoacetic acid (MAA)/PDGF aptamer bioconjugates were successfully synthesized using ligand exchange. Black hole quencher (BHQ)-bearing oligonucleotide molecules showing partial sequence matching to PDGF aptamer were attached to PDGF aptamers and photoluminescence (PL) quenching was obtained through FRET. By adding target PDGF-BB to the bioconjugates containing BHQs, PL recovery was detected due to detachment of BHQ-bearing oligonucleotide from the PDGF aptamer as a result of the difference in affinity to the PDGF aptamer. The detection limit of the sensor was ∼0.4 nM and the linearity was maintained up to 1.6 nM in the PL intensity versus concentration curve. Measurement of PL recovery was suggested as a strong tool for high-sensitivity detection of PDGF-BB. Epidermal growth factor (EGF), the negative control molecule, did not contribute to PL recovery due to lack of binding affinity to the PDGF aptamers, which demonstrates the selectivity of the biosensor.

  14. Detection of Salmonella typhi utilizing bioconjugated fluorescent polymeric nanoparticles

    International Nuclear Information System (INIS)

    Jain, Swati; Chattopadhyay, Sruti; Jackeray, Richa; Abid, Zainul; Singh, Harpal

    2016-01-01

    Present work demonstrates effective utilization of functionalized polymeric fluorescent nanoparticles as biosensing probe for the detection of Salmonella typhi bacteria on modified polycarbonate (PC) filters in about 3 h. Antibody modified-PC membranes were incubated with contaminated bacterial water for selective capturing which were detected by synthesized novel bioconjugate probe. Core–shell architecture of polymeric nanoparticles endows them with aqueous stabilization and keto-enolic functionalities making them usable for covalently linking S. typhi antibodies without any crosslinker or activator. Bradford analysis revealed that one nanoparticle has an average of 3.51 × 10 −19  g or 21 × 10 4 bound S. typhi Ab molecules. Analysis of the regions of interest (ROI) in fluorescent micrographs of modified fluoroimmunoassay showed higher detection sensitivity of 5 × 10 2  cells/mL due to signal amplification unlike conventional naked dye FITC-Ab conjugate. Fluorescence of pyrene dye remained same on immobilization of biomolecules and nanoparticles showed stable fluorescent intensity under prolong exposure to laser owing to protective polymeric layer allowing accurate identification of bacteria. Surface-functionalized PC matrix and fluorescent label NPs permit covalent interactions among biomolecules enhancing signal acquisitions showing higher detection efficiency as compared to conventional microtiter plate-based system. Our novel immunoassay has the potential to be explored as rapid detection method for identifying S. typhi contaminations in water.Graphical Abstract

  15. Detection of Salmonella typhi utilizing bioconjugated fluorescent polymeric nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Swati, E-mail: swatijain.iitd@gmail.com; Chattopadhyay, Sruti, E-mail: sruticiitd@gmail.com; Jackeray, Richa; Abid, Zainul; Singh, Harpal, E-mail: harpal2000@yahoo.com [Centre for Biomedical Engineering, Indian Institute of Technology-Delhi (India)

    2016-05-15

    Present work demonstrates effective utilization of functionalized polymeric fluorescent nanoparticles as biosensing probe for the detection of Salmonella typhi bacteria on modified polycarbonate (PC) filters in about 3 h. Antibody modified-PC membranes were incubated with contaminated bacterial water for selective capturing which were detected by synthesized novel bioconjugate probe. Core–shell architecture of polymeric nanoparticles endows them with aqueous stabilization and keto-enolic functionalities making them usable for covalently linking S. typhi antibodies without any crosslinker or activator. Bradford analysis revealed that one nanoparticle has an average of 3.51 × 10{sup −19} g or 21 × 10{sup 4} bound S. typhi Ab molecules. Analysis of the regions of interest (ROI) in fluorescent micrographs of modified fluoroimmunoassay showed higher detection sensitivity of 5 × 10{sup 2} cells/mL due to signal amplification unlike conventional naked dye FITC-Ab conjugate. Fluorescence of pyrene dye remained same on immobilization of biomolecules and nanoparticles showed stable fluorescent intensity under prolong exposure to laser owing to protective polymeric layer allowing accurate identification of bacteria. Surface-functionalized PC matrix and fluorescent label NPs permit covalent interactions among biomolecules enhancing signal acquisitions showing higher detection efficiency as compared to conventional microtiter plate-based system. Our novel immunoassay has the potential to be explored as rapid detection method for identifying S. typhi contaminations in water.Graphical Abstract.

  16. Topology-dependent swichability of peptide secondary structures in bioconjugates with complex architectures.

    Science.gov (United States)

    Börner, Hans G; Sütterlin, Romina I; Theato, Patrick; Wiss, Kerstin T

    2014-01-01

    Peptide sequences, which exhibit a reversible pH-responsive coil to α-helix secondary structure transition, are conjugated to polymer precursors to yield linear AB and graft ABA peptide-poly(ethylene oxide) conjugates. While the PEO B-block is comparable, the conjugates differ in topologies of the peptide bearing A-blocks. The influences of topology on the structure transitions in the peptide segments are investigated, comparing linear AB-bioconjugates with graft ABA-bioconjugates having multiple peptide segments combined in star or pom-pom topologies. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Bio-Conjugated Polycaprolactone Membranes: A Novel Wound Dressing

    Directory of Open Access Journals (Sweden)

    Elijah Zhengyang Cai

    2014-11-01

    Full Text Available BackgroundThe combination of polycaprolactone and hyaluronic acid creates an ideal environment for wound healing. Hyaluronic acid maintains a moist wound environment and accelerates the in-growth of granulation tissue. Polycaprolactone has excellent mechanical strength, limits inflammation and is biocompatible. This study evaluates the safety and efficacy of bio-conjugated polycaprolactone membranes (BPM as a wound dressing.Methods16 New Zealand white rabbits were sedated and local anaesthesia was administered. Two 3.0×3.0 cm full-thickness wounds were created on the dorsum of each rabbit, between the lowest rib and the pelvic bone. The wounds were dressed with either BPM (n=12 or Mepitel (n=12 (control, a polyamide-silicon wound dressing. These were evaluated macroscopically on the 7th, 14th, 21st, and 28th postoperative days for granulation, re-epithelialization, infection, and wound size, and histologically for epidermal and dermal regeneration.ResultsBoth groups showed a comparable extent of granulation and re-epithelialization. No signs of infection were observed. There was no significant difference (P>0.05 in wound size between the two groups. BPM (n=6: 8.33 cm2, 4.90 cm2, 3.12 cm2, 1.84 cm2; Mepitel (n=6: 10.29 cm2, 5.53 cm2, 3.63 cm2, 2.02 cm2; at the 7th, 14th, 21st, and 28th postoperative days. The extents of epidermal and dermal regeneration were comparable between the two groups.ConclusionsBPM is comparable to Mepitel as a safe and efficacious wound dressing.

  18. Development of bioconjugated dye-doped poly(styrene-co-maleimide) nanoparticles as a new bioprobe

    CSIR Research Space (South Africa)

    Swanepoel, A

    2015-02-01

    Full Text Available -1 Journal of Materials Chemistry B Development of bioconjugated dye-doped poly(styrene-co- maleimide) nanoparticles as a new bioprobe A. Swanepoel, I. du Preez, T. Mahlangu, A. Chetty and B. Klumperman Abstract Fluorescent dye-doped poly...

  19. Nanoparticle bioconjugates as "bottom-up" assemblies of artifical multienzyme complexes

    Science.gov (United States)

    Keighron, Jacqueline D.

    2010-11-01

    The sequential enzymes of several metabolic pathways have been shown to exist in close proximity with each other in the living cell. Although not proven in all cases, colocalization may have several implications for the rate of metabolite formation. Proximity between the sequential enzymes of a metabolic pathway has been proposed to have several benefits for the overall rate of metabolite formation. These include reduced diffusion distance for intermediates, sequestering of intermediates from competing pathways and the cytoplasm. Restricted diffusion in the vicinity of an enzyme can also cause the pooling of metabolites, which can alter reaction equilibria to control the rate of reaction through inhibition. Associations of metabolic enzymes are difficult to isolate ex vivo due to the weak interactions believed to colocalize sequential enzymes within the cell. Therefore model systems in which the proximity and diffusion of intermediates within the experiment system are controlled are attractive alternatives to explore the effects of colocalization of sequential enzymes. To this end three model systems for multienzyme complexes have been constructed. Direct adsorption enzyme:gold nanoparticle bioconjugates functionalized with malate dehydrogenase (MDH) and citrate synthase (CS) allow for proximity between to the enzymes to be controlled from the nanometer to micron range. Results show that while the enzymes present in the colocalized and non-colocalized systems compared here behaved differently overall the sequential activity of the pathway was improved by (1) decreasing the diffusion distance between active sites, (2) decreasing the diffusion coefficient of the reaction intermediate to prevent escape into the bulk solution, and (3) decreasing the overall amount of bioconjugate in the solution to prevent the pathway from being inhibited by the buildup of metabolite over time. Layer-by-layer (LBL) assemblies of MDH and CS were used to examine the layering effect of

  20. Intein-mediated Cre protein assembly for transgene excision in hybrid progeny of transgenic Arabidopsis.

    Science.gov (United States)

    Ge, Jia; Wang, Lijun; Yang, Chen; Ran, Lingyu; Wen, Mengling; Fu, Xianan; Fan, Di; Luo, Keming

    2016-10-01

    An approach for restoring recombination activity of complementation split-Cre was developed to excise the transgene in hybrid progeny of GM crops. Growing concerns about the biosafety of genetically modified (GM) crops has currently become a limited factor affecting the public acceptance. Several approaches have been developed to generate selectable-marker-gene-free GM crops. However, no strategy was reported to be broadly applicable to hybrid crops. Previous studies have demonstrated that complementation split-Cre recombinase restored recombination activity in transgenic plants. In this study, we found that split-Cre mediated by split-intein Synechocystis sp. DnaE had high recombination efficiency when Cre recombinase was split at Asp232/Asp233 (866 bp). Furthermore, we constructed two plant expression vectors, pCA-NCre-In and pCA-Ic-CCre, containing NCre866-In and Ic-CCre866 fragments, respectively. After transformation, parent lines of transgenic Arabidopsis with one single copy were generated and used for hybridization. The results of GUS staining demonstrated that the recombination activity of split-Cre could be reassembled in these hybrid progeny of transgenic plants through hybridization and the foreign genes flanked by two loxP sites were efficiently excised. Our strategy may provide an effective approach for generating the next generation of GM hybrid crops without biosafety concerns.

  1. Assessment of the systemic distribution of a bioconjugated anti-Her2 magnetic nanoparticle in a breast cancer model by means of magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Huerta-Núñez, L. F. E., E-mail: lidi-huerta@hotmail.com [Universidad del Ejercito y FAM/EMGS-Laboratorio Multidisciplinario de Investigación (Mexico); Villanueva-Lopez, G. Cleva, E-mail: villanuevacleva3@gmail.com [Instituto Politécnico Nacional-Escuela Superior de Medicina-Sección Investigación y Posgrado (Mexico); Morales-Guadarrama, A., E-mail: amorales@ci3m.mx [Centro Nacional de Investigacion en Imagenologia e Instrumentacion Medica-Universidad Autónoma (Mexico); Soto, S., E-mail: cuadrosdobles@hotmail.com; López, J., E-mail: jaimelocr@hotmail.com; Silva, J. G., E-mail: gabrielsilva173@gmail.com [Universidad del Ejercito y FAM/EMGS-Laboratorio Multidisciplinario de Investigación (Mexico); Perez-Vielma, N., E-mail: nadiampv@gmail.com [Instituto Politécnico Nacional - Centro Interdisciplinario de Ciencias de la Salud Unidad Santo Tomás (CICS-UST) (Mexico); Sacristán, E., E-mail: esacristan@ci3m.mx [Centro Nacional de Investigacion en Imagenologia e Instrumentacion Medica-Universidad Autónoma (Mexico); Gudiño-Zayas, Marco E., E-mail: gudino@unam.mx [UNAM, Departamento de Medicina Experimental, Facultad de Medicina (Mexico); González, C. A., E-mail: cgonzalezd@ipn.mx [Universidad del Ejercito y FAM/EMGS-Laboratorio Multidisciplinario de Investigación (Mexico)

    2016-09-15

    The aim of this study was to determine the systemic distribution of magnetic nanoparticles of 100 nm diameter (MNPs) coupled to a specific monoclonal antibody anti-Her2 in an experimental breast cancer (BC) model. The study was performed in two groups of Sprague–Dawley rats: control (n = 6) and BC chemically induced (n = 3). Bioconjugated “anti-Her2-MNPs” were intravenously administered, and magnetic resonance imaging (MRI) monitored its systemic distribution at seven times after administration. Non-heme iron presence associated with the location of the bioconjugated anti-Her2-MNPs in splenic, hepatic, cardiac and tumor tissues was detected by Perl’s Prussian blue (PPB) stain. Optical density measurements were used to semiquantitatively determine the iron presence in tissues on the basis of a grayscale values integration of T1 and T2 MRI sequence images. The results indicated a delayed systemic distribution of MNPs in cancer compared to healthy conditions with a maximum concentration of MNPs in cancer tissue at 24 h post-infusion.

  2. Recent developments in atom transfer radical polymerization initiators for development of polymer-protein bioconjugates

    Directory of Open Access Journals (Sweden)

    AKHILESH KUMAR SHAKYA

    2013-01-01

    Full Text Available One of the major challenges in modern synthetic polymer chemistry is to synthesize end defined polymers of different end functionality with predetermined uniform molecular weight. End functionalized polymers/copolymers basically in block and grafting form are having several potential applications in biomedical areas in the form of surface modifications, coatings, adhesives, and in order to increase the biocompatibility of polymeric blends. Among the existing controlled radical polymerization (CRP methods for synthesis of these functional polymers, the atom transfer radical polymerization (ATRP is one of the powerful techniques. The functional groups in these polymers can be easily introduced at the chain ends through functionalized ATRP initiators. A number of ATRP initiators have been developed in polymer science to develop defined polymer-protein bioconjugates. This critical review basically focuses on different types of ATRP initiators and their mechanisms used in the synthesis of polymer-protein bioconjugates.

  3. Quantum dot DNA bioconjugates: attachment chemistry strongly influences the resulting composite architecture.

    Science.gov (United States)

    Boeneman, Kelly; Deschamps, Jeffrey R; Buckhout-White, Susan; Prasuhn, Duane E; Blanco-Canosa, Juan B; Dawson, Philip E; Stewart, Michael H; Susumu, Kimihiro; Goldman, Ellen R; Ancona, Mario; Medintz, Igor L

    2010-12-28

    The unique properties provided by hybrid semiconductor quantum dot (QD) bioconjugates continue to stimulate interest for many applications ranging from biosensing to energy harvesting. Understanding both the structure and function of these composite materials is an important component in their development. Here, we compare the architecture that results from using two common self-assembly chemistries to attach DNA to QDs. DNA modified to display either a terminal biotin or an oligohistidine peptidyl sequence was assembled to streptavidin/amphiphilic polymer- or PEG-functionalized QDs, respectively. A series of complementary acceptor dye-labeled DNA were hybridized to different positions on the DNA in each QD configuration and the separation distances between the QD donor and each dye-acceptor probed with Förster resonance energy transfer (FRET). The polyhistidine self-assembly yielded QD-DNA bioconjugates where predicted and experimental separation distances matched reasonably well. Although displaying efficient FRET, data from QD-DNA bioconjugates assembled using biotin-streptavidin chemistry did not match any predicted separation distances. Modeling based upon known QD and DNA structures along with the linkage chemistry and FRET-derived distances was used to simulate each QD-DNA structure and provide insight into the underlying architecture. Although displaying some rotational freedom, the DNA modified with the polyhistidine assembles to the QD with its structure extended out from the QD-PEG surface as predicted. In contrast, the random orientation of streptavidin on the QD surface resulted in DNA with a wide variety of possible orientations relative to the QD which cannot be controlled during assembly. These results suggest that if a particular QD biocomposite structure is desired, for example, random versus oriented, the type of bioconjugation chemistry utilized will be a key influencing factor.

  4. Quantum Dot DNA Bioconjugates: Attachment Chemistry Strongly Influences the Resulting Composite Architecture

    Science.gov (United States)

    Boeneman, Kelly; Deschamps, Jeffrey R.; Buckhout-White, Susan; Prasuhn, Duane E.; Blanco-Canosa, Juan B.; Dawson, Philip E.; Stewart, Michael H.; Susumu, Kimihiro; Goldman, Ellen R.; Ancona, Mario; Medintz, Igor L.

    2010-01-01

    The unique properties provided by hybrid semiconductor quantum dot- (QD) bioconjugates continue to stimulate interest for many applications ranging from biosensing to energy harvesting. Understanding both the structure and function of these composite materials is an important component in their development. Here, we compare the architecture that results from using two common self-assembly chemistries to attach DNA to QDs. DNA modified to display either a terminal biotin or an oligohistidine peptidyl sequence was assembled to streptavidin/amphiphilic polymer- or PEG-functionalized QDs, respectively. A series of complementary acceptor dye-labeled DNA were hybridized to different positions on the DNA in each QD configuration and the separation distances between the QD donor and each dye-acceptor probed with Förster resonance energy transfer (FRET). The polyhistidine self-assembly yielded QD-DNA bioconjugates where predicted and experimental separation distances matched reasonably well. Although displaying efficient FRET, data from QD-DNA bioconjugates assembled using biotin-streptavidin chemistry did not match any predicted separation distances. Modeling based upon known QD and DNA structures along with the linkage chemistry and FRET-derived distances was used to simulate each QD-DNA structure and provide insight into the underlying architecture. Although displaying some rotational freedom, the DNA modified with the polyhistidine assembles to the QD with its structure extended out from the QD-PEG surface as predicted. In contrast, the random orientation of streptavidin on the QD surface resulted in DNA with a wide variety of possible orientations relative to the QD which cannot be controlled during assembly. These results suggest that if a particular QD-biocomposite structure is desired, for example, random versus oriented, the type of bioconjugation chemistry utilized will be a key influencing factor. PMID:21082822

  5. Bioconjugates of PAMAM dendrimers with trans-retinal, pyridoxal, and pyridoxal phosphate

    OpenAIRE

    Filipowicz, A; Wołowiec, S

    2012-01-01

    A Filipowicz, S WołowiecDepartment of Cosmetology, University of Information Technology and Management in Rzeszów, Rzeszów, PolandBackground: Bioconjugates of a polyamidoamine (PAMAM) G3 dendrimer and an aldehyde were synthesized as carriers for vitamins A and B6, and the bioavailability of these vitamins for skin nutrition was investigated.Methods: Nuclear magnetic resonance (NMR) and ultraviolet-visible methods were used to characterize the structure of the bioconjuga...

  6. In vitro cytotoxicity of the ternary PAMAM G3–pyridoxal–biotin bioconjugate

    Directory of Open Access Journals (Sweden)

    Uram Ł

    2013-12-01

    Full Text Available Łukasz Uram, Magdalena Szuster, Krzysztof Gargasz, Aleksandra Filipowicz, Elżbieta Wałajtys-Rode, Stanisław Wołowiec Cosmetology Department, University of Information Technology and Management in Rzeszów, Rzeszów, Poland Abstract: A third-generation polyamidoamine dendrimer (PAMAM G3 was used as a macromolecular carrier for pyridoxal and biotin. The binary covalent bioconjugate of G3, with nine molecules of biotin per one molecule of G3 (G39B, and the ternary covalent bioconjugate of G3, with nine biotin and ten pyridoxal molecules (G39B10P, were synthesized. The biotin and pyridoxal residues of the bioconjugate were available for carboxylase and transaminase enzymes, as demonstrated in the conversion of pyruvate to oxaloacetate and alanine to pyruvate, respectively, by in vitro monitoring of the reactions, using 1H nuclear magnetic resonance spectroscopy. The toxicity of the ternary bioconjugate (BC-PAMAM was studied in vitro on BJ human normal skin fibroblasts and human squamous cell carcinoma (SCC-15 cell cultures in comparison with PAMAM G3, using three cytotoxicity assays (XTT, neutral red, and crystal violet and an estimation of apoptosis by confocal microscopy detection. The tests have shown that BC-PAMAM has significantly lower cytotoxicity compared with PAMAM. Nonconjugated PAMAM was not cytotoxic at concentrations up to 5 µM (NR and 10 µM (XTT, and BC-PAMAM was not cytotoxic up to 50 µM (both assays for both cell lines. It has been also found that normal fibroblasts were more sensitive than SCC to both PAMAM and BC-PAMAM. The effect of PAMAM and BC-PAMAM on the initiation of apoptosis (PAMAM in fibroblasts at 5 µM and BC-PAMAM at 10 µM in both cell lines corresponded with cytotoxicity assays for both cell lines. We concluded that normal fibroblasts are more sensitive to the cytotoxic effects of the PAMAM G3 dendrimer and that modification of its surface cationic groups by substitution with biologically active molecules

  7. Purification, Characterization of Amylase from Indigenously Isolated Aureobasidium pullulans Cau 19 and Its Bioconjugates with Gold Nanoparticles.

    Science.gov (United States)

    Mulay, Y R; Deopurkar, R L

    2018-02-01

    The amylase from Aureobasidium pullulans Cau 19 was purified by ammonium sulfate precipitation and Sephadex G-100 chromatography with a 9.25-fold increase in specific activity as compared to crude enzyme. Km and turn over values of the enzyme were 6.25 mg/mL and 5.0 × 10 2 /min, respectively. Effect of different metal ions on the purified enzyme was investigated; 1 mM calcium (Ca) and cobalt (Co) enhanced enzyme activity by twofold; copper (Cu) had no effect on the activity of the enzyme. Mercury (Hg) 1 mM caused 90% inactivation whereas iron (Fe) and manganese (Mn) caused 10 to 16% inhibition. Amylase from A. pullulans Cau 19 was bioconjugated to gold nanoparticles synthesized using the biomass of A. pullulans Cau 19. Fourier transform infrared spectroscopy confirmed the conjugation of the enzyme to the gold nanoparticles. Though, only 20% of the added enzyme was adsorbed/conjugated on gold nanoparticles, 80% of the adsorbed activity could be estimated in the assay. The conjugated enzyme exhibited better tolerance to a broad pH range of 3.0-9.0 and higher temperatures compared with native enzyme.

  8. Nano-graphene oxide carboxylation for efficient bioconjugation applications: a quantitative optimization approach

    Energy Technology Data Exchange (ETDEWEB)

    Imani, Rana; Emami, Shahriar Hojjati, E-mail: semami@aut.ac.ir [Amirkabir University of Technology, Department of Biomedical Engineering (Iran, Islamic Republic of); Faghihi, Shahab, E-mail: shahabeddin.faghihi@mail.mcgill.ca, E-mail: sfaghihi@nigeb.ac.ir [National Institute of Genetic Engineering and Biotechnology, Tissue Engineering and Biomaterials Division (Iran, Islamic Republic of)

    2015-02-15

    A method for carboxylation of graphene oxide (GO) with chloroacetic acid that precisely optimizes and controls the efficacy of the process for bioconjugation applications is proposed. Quantification of COOH groups on nano-graphene oxide sheets (NGOS) is performed by novel colorimetric methylene blue (MB) assay. The GO is synthesized and carboxylated by chloroacetic acid treatment under strong basic condition. The size and morphology of the as-prepared NGOS are characterized by scanning electron microscopy, transmission electron microscopy (TEM), and atomic force microscopy (AFM). The effect of acid to base molar ratio on the physical, chemical, and morphological properties of NGOS is analyzed by Fourier-transformed infrared spectrometry (FTIR), UV–Vis spectroscopy, X-ray diffraction (XRD), AFM, and zeta potential. For evaluation of bioconjugation efficacy, the synthesized nano-carriers with different carboxylation ratios are functionalized by octaarginine peptide sequence (R8) as a biomolecule model containing amine groups. The quantification of attached R8 peptides to graphene nano-sheets’ surface is performed with a colorimetric-based assay which includes the application of 2,4,6-Trinitrobenzene sulfonic acid (TNBS). The results show that the thickness and lateral size of nano-sheets are dramatically decreased to 0.8 nm and 50–100 nm after carboxylation process, respectively. X-ray analysis shows the nano-sheets interlaying space is affected by the alteration of chloroacetic acid to base ratio. The MB assay reveals that the COOH groups on the surface of NGOS are maximized at the acid to base ratio of 2 which is confirmed by FTIR, XRD, and zeta potential. The TNBS assay also shows that bioconjugation of the optimized carboxylated NGOS sample with octaarginine peptide is 2.5 times more efficient compared to bare NGOS. The present work provides evidence that treatment of GO by chloroacetic acid under an optimized condition would create a functionalized high

  9. Quantum dots–DNA bioconjugates: synthesis to applications

    Science.gov (United States)

    2016-01-01

    Semiconductor nanoparticles particularly quantum dots (QDs) are interesting alternatives to organic fluorophores for a range of applications such as biosensing, imaging and therapeutics. Addition of a programmable scaffold such as DNA to QDs further expands the scope and applicability of these hybrid nanomaterials in biology. In this review, the most important stages of preparation of QD–DNA conjugates for specific applications in biology are discussed. Special emphasis is laid on (i) the most successful strategies to disperse QDs in aqueous media, (ii) the range of different conjugation with detailed discussion about specific merits and demerits in each case, and (iii) typical applications of these conjugates in the context of biology. PMID:27920898

  10. Safety and immunogenicity of a candidate bioconjugate vaccine against Shigella dysenteriae type 1 administered to healthy adults: A single blind, partially randomized Phase I study.

    Science.gov (United States)

    Hatz, Christoph F R; Bally, Bettina; Rohrer, Susanne; Steffen, Robert; Kramme, Stefanie; Siegrist, Claire-Anne; Wacker, Michael; Alaimo, Cristina; Fonck, Veronica Gambillara

    2015-08-26

    Shigellae cause severe disease in endemic countries, especially in children. Several efficacy trials have been conducted with candidate vaccines against Shigellae, but the lack of protection, the safety concerns, or manufacturing challenges hindered successful market approval. Conjugated vaccines have been shown to be safe and effective for different pathogens (i.e., Neisseria meningitidis, Shigella pneumonia, Haemophilus influenzae). The bio-conjugation technology, exploited here for the Shigella dysenteriae candidate vaccine, offers a novel and potentially simpler way to develop and produce vaccines against one of the major causes of morbidity and mortality in developing countries. A novel S. dysenteriae bioconjugate vaccine (GVXN SD133) made of the polysaccharide component of the Shigella O1 lipopolysaccharide, conjugated to the exotoxin protein A of Pseudomonas aeruginosa (EPA), was evaluated for immunogenicity and safety in healthy adults in a single blind, partially randomized Phase I study. Forty subjects (10 in each dose group; 2 μg or 10 μg with or without aluminium adjuvant) received two injections 60 days apart and were followed-up for 150 days. Both doses and formulations were well tolerated; the safety and reactogenicity profiles were consistent with that of other conjugated vaccines, adjuvanted or not, independent of the dose and the number of injections. The GVXN SD133 vaccine elicited statistically significant O1 specific humoral responses at all time points in all vaccination groups. Between-group comparisons did not show statistically significant differences in geometric mean titers of immunoglobulin G and A at any post-vaccination time point. This study demonstrated that the GVXN SD133 vaccine has a satisfactory safety profile. It elicited a significant humoral response to Shigella O1 polysaccharides at all doses tested. The protein carrier also elicited functional antibodies, showing the technology's advantages in preserving both sugar and

  11. Cyclic versus Noncyclic Chelating Scaffold for 89Zr-Labeled ZEGFR:2377 Affibody Bioconjugates Targeting Epidermal Growth Factor Receptor Overexpression.

    Science.gov (United States)

    Summer, Dominik; Garousi, Javad; Oroujeni, Maryam; Mitran, Bogdan; Andersson, Ken G; Vorobyeva, Anzhelika; Löfblom, John; Orlova, Anna; Tolmachev, Vladimir; Decristoforo, Clemens

    2018-01-02

    Zirconium-89 is an emerging radionuclide for positron emission tomography (PET) especially for biomolecules with slow pharmacokinetics as due to its longer half-life, in comparison to fluorine-18 and gallium-68, imaging at late time points is feasible. Desferrioxamine B (DFO), a linear bifunctional chelator (BFC) is mostly used for this radionuclide so far but shows limitations regarding stability. Our group recently reported on fusarinine C (FSC) with similar zirconium-89 complexing properties but potentially higher stability related to its cyclic structure. This study was designed to compare FSC and DFO head-to-head as bifunctional chelators for 89 Zr-radiolabeled EGFR-targeting ZEGFR:2377 affibody bioconjugates. 2377 and DFO-ZEGFR:2377 were evaluated regarding radiolabeling, in vitro stability, specificity, cell uptake, receptor affinity, biodistribution, and microPET-CT imaging. Both conjugates were efficiently labeled with zirconium-89 at room temperature but radiochemical yields increased substantially at elevated temperature, 85 °C. Both 89 Zr-FSC-ZEGFR:2377 and 89 Zr-DFO-ZEGFR:2377 revealed remarkable specificity, affinity and slow cell-line dependent internalization. Radiolabeling at 85 °C showed comparable results in A431 tumor xenografted mice with minor differences regarding blood clearance, tumor and liver uptake. In comparison 89 Zr-DFO-ZEGFR:2377, radiolabeled at room temperature, showed a significant difference regarding tumor-to-organ ratios. MicroPET-CT imaging studies of 89 Zr-FSC-ZEGFR:2377 as well as 89 Zr-DFO-ZEGFR:2377 confirmed these findings. In summary we were able to show that FSC is a suitable alternative to DFO for radiolabeling of biomolecules with zirconium-89. Furthermore, our findings indicate that 89 Zr-radiolabeling of DFO conjugates at higher temperature reduces off-chelate binding leading to significantly improved tumor-to-organ ratios and therefore enhancing image contrast.

  12. Synthesis of Aldehyde-Linked Nucleotides and DNA and Their Bioconjugations with Lysine and Peptides through Reductive Amination

    Czech Academy of Sciences Publication Activity Database

    Raindlová, Veronika; Pohl, Radek; Hocek, Michal

    2012-01-01

    Roč. 18, č. 13 (2012), s. 4080-4087 ISSN 0947-6539 R&D Projects: GA ČR GA203/09/0317 Institutional research plan: CEZ:AV0Z40550506 Keywords : nucleotides * aldehydes * DNA * reductive amination * bioconjugations Subject RIV: CC - Organic Chemistry Impact factor: 5.831, year: 2012

  13. Impact of Antibody Bioconjugation on Emission and Energy Band Profile of CdSeTe/ZnS Quantum Dots

    Science.gov (United States)

    Torchynska, T. V.; Gomez, J. A. Jaramillo; Polupan, G.; Macotela, L. G. Vega

    2018-03-01

    The variation of the photoluminescence (PL) and Raman scattering spectra of CdSeTe/ZnS quantum dots (QDs) on conjugation to an antibody has been investigated. Two types of CdSeTe/ZnS QD with different emission wavelength (705 nm and 800 nm) were studied comparatively before and after conjugation to anti-pseudorabies virus antibody (AB). Nonconjugated QDs were characterized by Gaussian-type PL bands. PL shifts to higher energy and asymmetric shape of PL bands was detected in PL spectra of bioconjugated QDs. The surface-enhanced Raman scattering effect was exhibited by the bioconjugated CdSeTe/ZnS QDs, indicating that the excitation light used in the Raman study generated electric dipoles in the AB molecules. The optical bandgap of the CdSeTe core was calculated numerically as a function of its radius based on an effective mass approximation model. The energy band diagrams for non- and bioconjugated CdSeTe/ZnS QDs were obtained, revealing a type II quantum well in the CdSeTe core. The calculations show that AB dipoles, excited in the bioconjugated QDs, stimulate a change in the energy band diagram of the QDs that alters the PL spectrum. These results could be useful for improving the sensitivity of QD biosensors.

  14. Organometallic-Peptide Bioconjugates: Synthetic Strategies and Medicinal Applications.

    Science.gov (United States)

    Albada, Bauke; Metzler-Nolte, Nils

    2016-10-12

    Peptides are important biological molecular entities in biomedical research. They can be prepared in a large variety of shapes, with a host of chemical functions, and tailored for specific applications. Organometallic medicinal chemistry is a relatively young field that explores biomedical and bioanalytical applications of organometallic complexes, that is, metal compounds with at least one direct, covalent metal-carbon bond. The conjugation of peptides to such medicinally active organometallic moieties started only about 20 years ago, and it has been very beneficial for the development of bioorganometallic chemistry in general. Similarly, the biomedical properties of peptides have been altered by their conjugation to organometallic (OM) moieties. In this review, synthetic methods by which OM moieties can be conjugated to peptides via a carbon-metal bond are described, and selected medicinal applications of such conjugates are discussed. Inorganic coordination complexes between metal ions and peptides are excluded from this review. Also, the labeling of peptides with radiometals and applications of radiolabeled peptides will not be treated herein. First, modifications of the peptide backbone (either N- or C-terminally, or both) with organometallic moieties will be described, including the insertion of OM moieties as part of the peptide backbone. Then side-chain modifications will be reported, among them the most recent strategies for chemoselective arene metalation on peptides. Finally, approaches by which multiple metalation can be achieved are explored. In each section, selected examples of biological applications are highlighted.

  15. Synthesis of linear polyether polyol derivatives as new materials for bioconjugation.

    Science.gov (United States)

    Li, Zhongyu; Chau, Ying

    2009-04-01

    Linear polyether polyol (PEP) consisting of glycidol as repeating units is a flexible hydrophilic aliphatic polymer. The polyether main chain is similar to the widely used, biocompatible polymer poly(ethylene glycol) (PEG). While linear PEG has one or two terminal hydroxyl group(s), linear PEP distinguishes itself by the large number of pendant hydroxyl groups along the polyether main chain. We propose that this property of PEP represents a major advantage over PEG, namely, by providing multiple anchorage points and increasing the possibility for introducing different functional groups. As a first step to establishing PEP as a bioconjugation material, we modified the pendant hydroxyl groups on PEP and prepared a series of mono- and heterobifunctional derivatives with the potential to join various drug entities and biomolecules. The synthesis methods and the results of characterization are reported here.

  16. Stable Poly(methacrylic acid Brush Decorated Silica Nano-Particles by ARGET ATRP for Bioconjugation

    Directory of Open Access Journals (Sweden)

    Marcello Iacono

    2015-08-01

    Full Text Available The synthesis of polymer brush decorated silica nano-particles is demonstrated by activator regeneration by electron transfer atom transfer radical polymerization (ARGET ATRP grafting of poly(tert-butyl methacrylate. ATRP initiator decorated silica nano-particles were obtained using a novel trimethylsiloxane derivatised ATRP initiator obtained by click chemistry. Comparison of de-grafted polymers with polymer obtained from a sacrificial initiator demonstrated good agreement up to 55% monomer conversion. Subsequent mild deprotection of the tert-butyl ester groups using phosphoric acid yielded highly colloidal and pH stable hydrophilic nano-particles comprising approximately 50% methacrylic acid groups. The successful bio-conjugation was achieved by immobilization of Horseradish Peroxidase to the polymer brush decorated nano-particles and the enzyme activity demonstrated in a conversion of o-phenylene diamine dihydrochloride assay.

  17. Bioconjugate techniques

    National Research Council Canada - National Science Library

    Hermanson, Greg T

    2013-01-01

    ... may be reproduced, stored in a retrieval system or transmitted in any form or by any means electronic, mechanical, photocopying, recording or otherwise without the prior written permission of the pu...

  18. Potentiometric Urea Biosensor Based on an Immobilised Fullerene-Urease Bio-Conjugate

    Directory of Open Access Journals (Sweden)

    Kasra Saeedfar

    2013-12-01

    Full Text Available A novel method for the rapid modification of fullerene for subsequent enzyme attachment to create a potentiometric biosensor is presented. Urease was immobilized onto the modified fullerene nanomaterial. The modified fullerene-immobilized urease (C60-urease bioconjugate has been confirmed to catalyze the hydrolysis of urea in solution. The biomaterial was then deposited on a screen-printed electrode containing a non-plasticized poly(n-butyl acrylate (PnBA membrane entrapped with a hydrogen ionophore. This pH-selective membrane is intended to function as a potentiometric urea biosensor with the deposition of C60-urease on the PnBA membrane. Various parameters for fullerene modification and urease immobilization were investigated. The optimal pH and concentration of the phosphate buffer for the urea biosensor were 7.0 and 0.5 mM, respectively. The linear response range of the biosensor was from 2.31 × 10−3 M to 8.28 × 10−5 M. The biosensor’s sensitivity was 59.67 ± 0.91 mV/decade, which is close to the theoretical value. Common cations such as Na+, K+, Ca2+, Mg2+ and NH4+ showed no obvious interference with the urea biosensor’s response. The use of a fullerene-urease bio-conjugate and an acrylic membrane with good adhesion prevented the leaching of urease enzyme and thus increased the stability of the urea biosensor for up to 140 days.

  19. Bioconjugation of lipase and cholesterol oxidase with graphene or graphene oxide

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Rubens A.; Souza, Michele L.; Bloisi, Georgia D.; Corio, Paolo; Petri, Denise F. S., E-mail: dfsp@iq.usp.br [Universidade de São Paulo, Instituto de Química (Brazil)

    2015-04-15

    The catalytic behavior of lipase and cholesterol oxidase (ChOx) in the absence and in the presence of graphene (G) or graphene oxide (GO) was investigated at 24 ± 1 °C and pH 6.5. GO flat sheets (0.5–2 μm) were ∼2-nm thick, while G formed aggregates. The maximum reaction velocity (V{sub max}) values and turnover numbers (k{sub cat}) determined for reactions catalyzed by physical mixtures of lipase (at 0.01 g l{sup −1}) or ChOx (at 0.03 g l{sup −1}) and G (0.012 g l{sup −1}) increased six-fold or doubled, respectively, in comparison to neat enzymes. Circular dichroism (CD) and photoluminescence (PL) spectroscopic measurements revealed the preservation of native secondary structures of enzymes and bioconjugation driven by hydrophobic interaction and energy transfer (redshift) between lipase or ChOx and G, corroborating with the enhanced catalytic behavior. On the other hand, the interactions between GO, which has hydrophilic moieties on the basal plane, and ChOx caused enzyme deactivation, as evidenced by the absence of typical CD signal. At low GO concentration (<0.012 g l{sup −1}), bioconjugates of lipases with GO led to V{sub max} and k{sub cat} values four-fold lower than their counterparts with G, but the GO hydrophilic groups probably favored the affinity for the substrate, because the Michaelis constant (K{sub m}) values decreased in comparison to that of neat lipase. Upon increasing the GO concentration, lipases lost secondary structure and the typical lipase PL bands disappeared.

  20. Protein–nanoparticle interaction in bioconjugated silver nanoparticles: A transmission electron microscopy and surface enhanced Raman spectroscopy study

    Energy Technology Data Exchange (ETDEWEB)

    Reymond-Laruinaz, Sébastien; Saviot, Lucien; Potin, Valérie; Marco de Lucas, María del Carmen, E-mail: delucas@u-bourgogne.fr

    2016-12-15

    Highlights: • Synthesis of protein-conjugated Ag nanoparticles (NPs) in absence of citrates. • NPs size and protein layer thickness determined by TEM. • SERS spectra showed the chemisorption of proteins on the surface of Ag-NPs. - Abstract: Understanding the mechanisms of interaction between proteins and noble metal nanoparticles (NPs) is crucial to extend the use of NPs in biological applications and nanomedicine. We report the synthesis of Ag-NPs:protein bioconjugates synthesized in total absence of citrates or other stabilizing agents in order to study the NP-protein interaction. Four common proteins (lysozyme, bovine serum albumin, cytochrome-C and hemoglobin) were used in this work. Transmission electron microscopy (TEM) and surface enhanced Raman spectroscopy (SERS) were mainly used to study these bioconjugated NPs. TEM images showed Ag NPs with sizes in the 5–40 nm range. The presence of a protein layer surrounding the Ag NPs was also observed by TEM. Moreover, the composition at different points of single bioconjugated NPs was probed by electron energy loss spectroscopy (EELS). The thickness of the protein layer varies in the 3–15 nm range and the Ag NPs are a few nanometers away. This allowed to obtain an enhancement of the Raman signal of the proteins in the analysis of water suspensions of bioconjugates. SERS results showed a broadening of the Raman bands of the proteins which we attribute to the contribution of different configurations of the proteins adsorbed on the Ag NPs surface. Moreover, the assignment of an intense and sharp peak in the low-frequency range to Ag–N vibrations points to the chemisorption of the proteins on the Ag-NPs surface.

  1. The mechanism of the photoluminescence changes in bio-conjugated CdSe/ZnS quantum dots

    Science.gov (United States)

    Borkovska, L.; Korsunska, N.; Stara, T.; Kolomys, O.; Strelchuk, V.; Rachkov, O.; Kryshtab, T.

    2013-09-01

    The change of the photoluminescence (PL) and optical characteristics in non-conjugated and conjugated with S6K2 antibody CdSe/ZnS core/shell quantum dots (QDs) during storage in air has been studied by the conventional PL, micro-PL and micro-Raman techniques. The QDs dried on a crystalline Si substrate were kept in the darkness and under illumination. In the PL spectra, the storage resulted in a blue shift of PL peak position, in the increasing of the full width at a half maximum (FWHM) of the PL band and in the decreasing of the PL intensity. In the Raman spectra, the shift of the CdSe LO peak position to the low frequency region and the increasing of its FWHM were observed. The transformations in the PL and optical characteristics correlate with each other and are found to be the largest in bio-conjugated QDs stored under illumination. The increase of the light intensity accelerated the changes occurred during storage. An oxidation of the QD core, which decreases the QD size, is supposed to be responsible for observed transformations. The bio-conjugation is assumed to promote QD oxidation that results in different PL peak position in stored non-conjugated and bio-conjugated QDs. The mechanism of the effect is discussed.

  2. Polyacrylamide gel electrophoresis of semiconductor quantum dots and their bioconjugates: materials characterization and physical insights from spectrofluorimetric detection.

    Science.gov (United States)

    Kim, Hyungki; Jeen, Tiffany; Tran, Michael V; Algar, W Russ

    2018-02-26

    Colloidal semiconductor quantum dot (QD) nanocrystals have ideal fluorescence properties for bioanalysis and bioimaging, but these materials must be functionalized with an inorganic shell, organic ligand or polymer coating, and conjugated with biomolecules to be useful in such applications. Several different analytical techniques are used to characterize QDs and their multiple layers of functionalization. Here, we revisit poly(acrylamide) gel electrophoresis (PAGE), which has been scarcely used for the characterization of QDs and their bioconjugates in deference to the routine use of agarose gel electrophoresis. We implemented PAGE in a novel "stubby" capillary format with spectrofluorimetric detection, the combination of which enabled more rapid and more detailed characterization of QDs than was possible with both poly(acrylamide) and agarose slab gels. Correlations between the peak photoluminescence (PL) emission wavelength and electropherogram peaks, especially when combined with Ferguson analysis, provided new and significant insight into the key factors that determine the electrophoretic mobility of QDs, and helped to resolve heterogeneity and sub-populations in ensembles of QDs. The method was useful for characterization of the inorganic core/shell nanocrystals, their organic ligand and polymer coatings, and their final bioconjugates, the latter of which were in the form of peptide and protein conjugates. With further development and optimization, we anticipate that capillary PAGE with spectrofluorimetric detection will become a valuable addition to the toolbox of characterization techniques suitable for QDs, their bioconjugates, and other nanoparticle materials as well.

  3. An optimized intein-mediated protein ligation approach for the efficient cyclization of cysteine-rich proteins.

    Science.gov (United States)

    Tarasava, Katsiaryna; Freisinger, Eva

    2014-12-01

    Head-to-tail backbone cyclization of proteins is a widely used approach for the improvement of protein stability. One way to obtain cyclic proteins via recombinant expression makes use of engineered Intein tags, which are self-cleaving protein domains. In this approach, pH-induced self-cleavage of the N-terminal Intein tag generates an N-terminal cysteine residue at the target protein, which then attacks in an intramolecular reaction the C-terminal thioester formed by the second C-terminal Intein tag resulting in the release of the cyclic target protein. In the current work we aimed to produce a cyclic analog of the small γ-Ec-1 domain of the wheat metallothionein, which contains six cysteine residues. During the purification process we faced several challenges, among them premature cleavage of one or the other Intein tag resulting in decreasing yields and contamination with linear species. To improve efficiency of the system we applied a number of optimizations such as the introduction of a Tobacco etch virus cleavage site and an additional poly-histidine tag. Our efforts resulted in the production of a cyclic protein in moderate yields without any contamination with linear protein species. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Polymerization of Ethylene Oxide, Propylene Oxide, and Other Alkylene Oxides: Synthesis, Novel Polymer Architectures, and Bioconjugation.

    Science.gov (United States)

    Herzberger, Jana; Niederer, Kerstin; Pohlit, Hannah; Seiwert, Jan; Worm, Matthias; Wurm, Frederik R; Frey, Holger

    2016-02-24

    The review summarizes current trends and developments in the polymerization of alkylene oxides in the last two decades since 1995, with a particular focus on the most important epoxide monomers ethylene oxide (EO), propylene oxide (PO), and butylene oxide (BO). Classical synthetic pathways, i.e., anionic polymerization, coordination polymerization, and cationic polymerization of epoxides (oxiranes), are briefly reviewed. The main focus of the review lies on more recent and in some cases metal-free methods for epoxide polymerization, i.e., the activated monomer strategy, the use of organocatalysts, such as N-heterocyclic carbenes (NHCs) and N-heterocyclic olefins (NHOs) as well as phosphazene bases. In addition, the commercially relevant double-metal cyanide (DMC) catalyst systems are discussed. Besides the synthetic progress, new types of multifunctional linear PEG (mf-PEG) and PPO structures accessible by copolymerization of EO or PO with functional epoxide comonomers are presented as well as complex branched, hyperbranched, and dendrimer like polyethers. Amphiphilic block copolymers based on PEO and PPO (Poloxamers and Pluronics) and advances in the area of PEGylation as the most important bioconjugation strategy are also summarized. With the ever growing toolbox for epoxide polymerization, a "polyether universe" may be envisaged that in its structural diversity parallels the immense variety of structural options available for polymers based on vinyl monomers with a purely carbon-based backbone.

  5. rDNA Mediated Bioconjugates: Fusion Proteins and their Intended Use in Medicine.

    Science.gov (United States)

    Kaya-Ozsan, Ayse Goksu; Oner, Ayse Filiz

    2017-01-01

    Protein bioconjugates can be synthesized by using chemical reactions, enzymatic reactions or genetic engineering technologies. Naturally occurred protein fusion event is used on purpose in the development of better biopharmaceuticals by applying genetic engineering methodologies. This review will mainly focus on the types of fusion proteins produced with the use of recombinant DNA technology, by combining genes or parts of genes from the same or different organisms, in order to be used in pharmaceutical applications for several purposes. Main concerns for the development of better biopharmaceuticals include quality, efficacy, safety, immunogenicity and toxicity issues. Extending half-life of the drug to increase patient compliance, targeting the drugs to reduce toxicity, improving the manufacturing environment to reduce the costs and revealing protein interaction technologies to find novel and superior drugs are the main aims of fusion protein production. Here, related tags and examples of fusion methods for different purposes will be explained precisely. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Bioconjugate functionalization of thermally carbonized porous silicon using a radical coupling reaction†

    Science.gov (United States)

    Sciacca, Beniamino; Alvarez, Sara D.; Geobaldo, Francesco; Sailor, Michael J.

    2011-01-01

    The high stability of Salonen’s thermally carbonized porous silicon (TCPSi) has attracted attention for environmental and biochemical sensing applications, where corrosion-induced zero point drift of porous silicon-based sensor elements has historically been a significant problem. Prepared by the high temperature reaction of porous silicon with acetylene gas, the stability of this silicon carbide-like material also poses a challenge—many sensor applications require a functionalized surface, and the low reactivity of TCPSi has limited the ability to chemically modify its surface. This work presents a simple reaction to modify the surface of TCPSi with an alkyl carboxylate. The method involves radical coupling of a dicarboxylic acid (sebacic acid) to the TCPSi surface using a benzoyl peroxide initiator. The grafted carboxylic acid species provides a route for bioconjugate chemical modification, demonstrated in this work by coupling propylamine to the surface carboxylic acid group through the intermediacy of pentafluorophenol and 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC). The stability of the carbonized porous Si surface, both before and after chemical modification, is tested in phosphate buffered saline solution and found to be superior to either hydrosilylated (with undecylenic acid) or thermally oxidized porous Si surfaces. PMID:20967329

  7. Universal method for protein bioconjugation with nanocellulose scaffolds for increased cell adhesion.

    Science.gov (United States)

    Kuzmenko, Volodymyr; Sämfors, Sanna; Hägg, Daniel; Gatenholm, Paul

    2013-12-01

    Bacterial nanocellulose (BNC) is an emerging biomaterial since it is biocompatible, integrates well with host tissue and can be biosynthesized in desired architecture. However, being a hydrogel, it exhibits low affinity for cell attachment, which is crucial for the cellular fate process. To increase cell attachment, the surface of BNC scaffolds was modified with two proteins, fibronectin and collagen type I, using an effective bioconjugation method applying 1-cyano-4-dimethylaminopyridinium (CDAP) tetrafluoroborate as the intermediate catalytic agent. The effect of CDAP treatment on cell adhesion to the BNC surface is shown for human umbilical vein endothelial cells and the mouse mesenchymal stem cell line C3H10T1/2. In both cases, the surface modification increased the number of cells attached to the surfaces. In addition, the morphology of the cells indicated more healthy and viable cells. CDAP activation of bacterial nanocellulose is shown to be a convenient method to conjugate extracellular proteins to the scaffold surfaces. CDAP treatment can be performed in a short period of time in an aqueous environment under heterogeneous and mild conditions preserving the nanofibrillar network of cellulose. © 2013.

  8. Fast Targeting and Cancer Cell Uptake of Luminescent Antibody-Nanozeolite Bioconjugates.

    Science.gov (United States)

    Marega, Riccardo; Prasetyanto, Eko Adi; Michiels, Carine; De Cola, Luisa; Bonifazi, Davide

    2016-10-01

    Understanding the targeted cellular uptake of nanomaterials is an essential step to engineer and program functional and effective biomedical devices. In this respect, the targeting and ultrafast uptake of zeolite nanocrystals functionalized with Cetuximab antibodies (Ctxb) by cells overexpressing the epidermal growth factor receptor are described here. Biochemical assays show that the cellular uptake of the bioconjugate in the targeted cancer cells already begins 15 min after incubation, at a rate around tenfold faster than that observed in the negative control cells. These findings further show the role of Ctxb exposed at the surfaces of the zeolite nanocrystals in mediating the targeted and rapid cellular uptake. By using temperature and pharmacological inhibitors as modulators of the internalization pathways, the results univocally suggest a dissipative uptake mechanism of these nanomaterials, which seems to occur using different internalization pathways, according to the targeting properties of these nanocrystals. Owing to the ultrafast uptake process, harmless for the cell viability, these results further pave the way for the design of novel theranostic tools based on nanozeolites. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Extracellular biosynthesis of gadolinium oxide (Gd2O3 nanoparticles, their biodistribution and bioconjugation with the chemically modified anticancer drug taxol

    Directory of Open Access Journals (Sweden)

    Shadab Ali Khan

    2014-03-01

    Full Text Available As a part of our programme to develop nanobioconjugates for the treatment of cancer, we first synthesized extracellular, protein-capped, highly stable and well-dispersed gadolinium oxide (Gd2O3 nanoparticles by using thermophilic fungus Humicola sp. The biodistribution of the nanoparticles in rats was checked by radiolabelling with Tc-99m. Finally, these nanoparticles were bioconjugated with the chemically modified anticancer drug taxol with the aim of characterizing the role of this bioconjugate in the treatment of cancer. The biosynthesized Gd2O3 nanoparticles were characterized by UV–vis spectroscopy, transmission electron microscopy (TEM, X-ray diffraction (XRD and X-ray photoemission spectroscopy (XPS. The Gd2O3–taxol bioconjugate was confirmed by UV–vis spectroscopy and fluorescence microscopy and was purified by using high performance liquid chromatography (HPLC.

  10. Asymmetric flow field-flow fractionation coupled to inductively coupled plasma mass spectrometry for the quantification of quantum dots bioconjugation efficiency.

    Science.gov (United States)

    Menéndez-Miranda, Mario; Encinar, Jorge Ruiz; Costa-Fernández, José M; Sanz-Medel, Alfredo

    2015-11-27

    Hyphenation of asymmetric flow field-flow fractionation (AF4) to an on-line elemental detection (inductively coupled plasma-mass spectrometry, ICP-MS) is proposed as a powerful diagnostic tool for quantum dots bioconjugation studies. In particular, conjugation effectiveness between a "model" monoclonal IgG antibody (Ab) and CdSe/ZnS core-shell Quantum Dots (QDs), surface-coated with an amphiphilic polymer, has been monitored here by such hybrid AF4-ICP-MS technique. Experimental conditions have been optimized searching for a proper separation between the sought bioconjugates from the eventual free reagents excesses employed during the bioconjugation (QDs and antibodies). Composition and pH of the carrier have been found to be critical parameters to ensure an efficient separation while ensuring high species recovery from the AF4 channel. An ICP-MS equipped with a triple quadropole was selected as elemental detector to enable sensitive and reliable simultaneous quantification of the elemental constituents, including sulfur, of the nanoparticulated species and the antibody. The hyphenated technique used provided nanoparticle size-based separation, elemental detection, and composition analysis capabilities that turned out to be instrumental in order to investigate in depth the Ab-QDs bioconjugation process. Moreover, the analytical strategy here proposed allowed us not only to clearly identify the bioconjugation reaction products but also to quantify nanoparticle:antibodies bioconjugation efficiency. This is a key issue in future development of analytical and bioanalytical photoluminescent QDs applications. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Sequence and Conformational Analysis of Peptide-Polymer Bioconjugates by Multidimensional Mass Spectrometry.

    Science.gov (United States)

    Sallam, Sahar; Dolog, Ivan; Paik, Bradford A; Jia, Xinqiao; Kiick, Kristi L; Wesdemiotis, Chrys

    2018-03-19

    The sequence and helical content of two alanine-rich peptides (AQK18 and GpAQK18, Gp: L-propargylglycine) and their conjugates with poly(ethylene glycol) (PEG) have been investigated by multidimensional mass spectrometry (MS), encompassing electrospray ionization (ESI) or matrix-assisted laser desorption/ionization (MALDI) interfaced with tandem mass spectrometry (MS 2 ) fragmentation and shape-sensitive separation via ion mobility mass spectrometry (IM-MS). The composition, sequence, and molecular weight distribution of the peptides and bioconjugates were identified by MS and MS 2 experiments, which also confirmed the attachment of PEG at the C-terminus of the peptides. ESI coupled with IM-MS revealed the existence of random coil and α-helical conformers for the peptides in the gas phase. More importantly, the proportion of the helical conformation increased substantially after PEG attachment, suggesting that conjugation adds stability to this conformer. The conformational assemblies detected in the gas phase were largely formed in solution, as corroborated by independent circular dichroism (CD) experiments. The collision cross-sections (rotationally averaged forward moving arears) of the random coil and helical conformers of the peptides and their PEG conjugates were simulated for comparison with the experimental values deduced by IM-MS in order to confirm the identity of the observed architectures and understand the stabilizing effect of the polymer chain. C-terminal PEGylation is shown to increase the positive charge density and to solvate intra-molecular positive charges at the conjugation site, thereby enhancing the stability of α-helices, preserving their conformation, and increasing helical propensity.

  12. Bioconjugation of gold-polymer core-shell nanoparticles with bovine serum amine oxidase for biomedical applications.

    Science.gov (United States)

    Venditti, I; Hassanein, T F; Fratoddi, I; Fontana, L; Battocchio, C; Rinaldi, F; Carafa, M; Marianecci, C; Diociaiuti, M; Agostinelli, E; Cametti, C; Russo, M V

    2015-10-01

    Core-shell gold nanoparticles [AuNPs], stabilized with a hydrophilic polymer, poly(3-dimethylammonium-1-propyne hydrochloride) [PDMPAHCl], have been used for the immobilization of bovine serum amine oxidase [BSAO]. The functionalized surface of the hybrid nanoparticles is pH responsive, due to the presence of aminic groups that carry out a double role: on one hand they act as ligands for the gold nanoparticle surface, allowing the colloidal stabilization and, on the other hand, they give a hydrophilic characteristic to the whole colloidal suspension. The core-shell nanoparticles [Au@PDMPAHCl] have been characterized by using UV-vis and X-ray photoelectron spectroscopy, DLS, ζ-potential measurements and by FE-TEM microscopy. BSAO enzyme can be loaded by non-covalent immobilization onto Au@PDMPAHCl nanoparticles up to 70% in weight, depending on the pH values of the environmental medium. Activity tests on Au@PDMPAHCl-BSAO bioconjugates confirm an enzymatic activity up to 40%, with respect to the free enzyme activity. Moreover, our results show that loading and enzymatic activity are rather interrelated characteristics and that, under appropriate polymer concentration and pH conditions, a satisfactory compromise can be reached. These results, as a whole, indicate that Au@PDMPAHCl-BSAO bioconjugate systems are promising for future biomedical applications. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Protein expression profile of HT-29 human colon cancer cells after treatment with a cytotoxic daunorubicin-GnRH-III derivative bioconjugate.

    Directory of Open Access Journals (Sweden)

    Verena Natalie Schreier

    Full Text Available Targeted delivery of chemotherapeutic agents is a new approach for the treatment of cancer, which provides increased selectivity and decreased systemic toxicity. We have recently developed a promising drug delivery system, in which the anticancer drug daunorubicin (Dau was attached via oxime bond to a gonadotropin-releasing hormone-III (GnRH-III derivative used as a targeting moiety (Glp-His-Trp-Lys(Ac-His-Asp-Trp-Lys(Da  = Aoa-Pro-Gly-NH2; Glp = pyroglutamic acid, Ac = acetyl; Aoa = aminooxyacetyl. This bioconjugate exerted in vitro cytostatic/cytotoxic effect on human breast, prostate and colon cancer cells, as well as significant in vivo tumor growth inhibitory effect on colon carcinoma bearing mice. In our previous studies, H-Lys(Dau = Aoa-OH was identified as the smallest metabolite produced in the presence of rat liver lysosomal homogenate, which was able to bind to DNA in vitro. To get a deeper insight into the mechanism of action of the bioconjugate, changes in the protein expression profile of HT-29 human colon cancer cells after treatment with the bioconjugate or free daunorubicin were investigated by mass spectrometry-based proteomics. Our results indicate that several metabolism-related proteins, molecular chaperons and proteins involved in signaling are differently expressed after targeted chemotherapeutic treatment, leading to the conclusion that the bioconjugate exerts its cytotoxic action by interfering with multiple intracellular processes.

  14. Synthesis of the copper chelator TGTA and evaluation of its ability to protect biomolecules from copper induced degradation during copper catalyzed azide-alkyne bioconjugation reactions.

    Science.gov (United States)

    Ekholm, F S; Pynnönen, H; Vilkman, A; Koponen, J; Helin, J; Satomaa, T

    2016-01-21

    One of the most successful bioconjugation strategies to date is the copper(I)-catalyzed cycloaddition reaction (CuAAC), however, the typically applied reaction conditions have been found to degrade sensitive biomolecules. Herein, we present a water soluble copper chelator which can be utilized to protect biomolecules from copper induced degradation.

  15. A Dual Bioconjugated Virus-Like Nanoparticle as a Drug Delivery System and Comparison with a pH-Responsive Delivery System

    Directory of Open Access Journals (Sweden)

    Roya Biabanikhankahdani

    2018-04-01

    Full Text Available Modifications of virus-like nanoparticles (VLNPs using chemical conjugation techniques have brought the field of virology closer to nanotechnology. The huge surface area to volume ratio of VLNPs permits multiple copies of a targeting ligand and drugs to be attached per nanoparticle. By exploring the chemistry of truncated hepatitis B core antigen (tHBcAg VLNPs, doxorubicin (DOX was coupled covalently to the external surface of these nanoparticles via carboxylate groups. About 1600 DOX molecules were conjugated on each tHBcAg VLNP. Then, folic acid (FA was conjugated to lysine residues of tHBcAg VLNPs to target the nanoparticles to cancer cells over-expressing folic acid receptor (FR. The result demonstrated that the dual bioconjugated tHBcAg VLNPs increased the accumulation and uptake of DOX in the human cervical and colorectal cancer cell lines compared with free DOX, resulting in enhanced cytotoxicity of DOX towards these cells. The fabrication of these dual bioconjugated nanoparticles is simple, and drugs can be easily conjugated with a high coupling efficacy to the VLNPs without any limitation with respect to the cargo’s size or charge, as compared with the pH-responsive system based on tHBcAg VLNPs. These dual bioconjugated nanoparticles also have the potential to be modified for other combinatorial drug deliveries.

  16. Controlled Release of Damascone from Poly(styrene-co-maleic anhydride-based Bioconjugates in Functional Perfumery

    Directory of Open Access Journals (Sweden)

    Andreas Herrmann

    2013-02-01

    Full Text Available Poly(styrene-co-maleic anhydrides were modified with poly(propylene oxide (PO-co-ethylene oxide (EO side chains (Jeffamine® with different EO/PO molar ratios, varying between 0.11 and 3.60. These copolymers were then further functionalized with a β-mercapto ketone of δ-damascone. The obtained poly(maleic acid monoamide-based β-mercapto ketones were then studied as delivery systems for the controlled release of δ-damascone by retro 1,4-addition. The release of δ-damascone, a volatile, bioactive molecule of the family of rose ketones, was studied by dynamic headspace analysis above a cotton surface after deposition of a cationic surfactant containing fabric softening formulation, as a function of the ethylene oxide (EO/propylene oxide (PO molar ratio of the grafted copolymer side chains. The polarity of the EO/PO side chain influenced the release efficiency of the damascone in a typical fabric softening application. PO-rich copolymers and the corresponding poly(styrene-co-maleic anhydride without Jeffamine® side chains were found to be less efficient for the desired fragrance release than the corresponding bioconjugate with a EO/PO ratio of 3.60 in the side chain. This copolymer conjugate seemed to represent a suitable balance between hydrophilicity and hydrophobicity to favor the release of the δ-damascone and to improve the deposition of the conjugate from an aqueous environment onto a cotton surface.

  17. Enhanced Biosensor Platforms for Detecting the Atherosclerotic Biomarker VCAM1 Based on Bioconjugation with Uniformly Oriented VCAM1-Targeting Nanobodies

    Directory of Open Access Journals (Sweden)

    Duy Tien Ta

    2016-07-01

    Full Text Available Surface bioconjugation of biomolecules has gained enormous attention for developing advanced biomaterials including biosensors. While conventional immobilization (by physisorption or covalent couplings using the functional groups of the endogenous amino acids usually results in surfaces with low activity, reproducibility and reusability, the application of methods that allow for a covalent and uniformly oriented coupling can circumvent these limitations. In this study, the nanobody targeting Vascular Cell Adhesion Molecule-1 (NbVCAM1, an atherosclerotic biomarker, is engineered with a C-terminal alkyne function via Expressed Protein Ligation (EPL. Conjugation of this nanobody to azidified silicon wafers and Biacore™ C1 sensor chips is achieved via Copper(I-catalyzed azide-alkyne cycloaddition (CuAAC “click” chemistry to detect VCAM1 binding via ellipsometry and surface plasmon resonance (SPR, respectively. The resulting surfaces, covered with uniformly oriented nanobodies, clearly show an increased antigen binding affinity, sensitivity, detection limit, quantitation limit and reusability as compared to surfaces prepared by random conjugation. These findings demonstrate the added value of a combined EPL and CuAAC approach as it results in strong control over the surface orientation of the nanobodies and an improved detecting power of their targets—a must for the development of advanced miniaturized, multi-biomarker biosensor platforms.

  18. Synthesis and structure-activity relationship study of organometallic bioconjugates of the cyclic octapeptide octreotate.

    Science.gov (United States)

    Gross, Annika; Habig, Daniel; Metzler-Nolte, Nils

    2013-12-16

    The chemically stabilized somatostatin-derived cyclic octapeptide octreotate has a number of interesting applications in medicinal chemistry. Here, a number of different organometallic derivatives of octreotate were prepared, and their properties were investigated. Specifically, we report the synthesis and characterization of ruthenocene, ferrocene, and cobaltocenium octreotate derivatives and their fluorophore-labeled conjugates as well as a dicobalt hexacarbonyl alkyne functionalized octreotate. To provide further insights into their characteristics, the log P values and electrochemical properties of the novel metal conjugates were compared. For biological activity, we determined their toxicity in three different cell lines. Cellular uptake and colocalization of selected compounds were studied by fluorescence microscopy with particular focus on efficiency and specificity of their uptake through the somatostatin receptor SSTR to elucidate the value of the metallocene head group for its potential use as a nontoxic and universal peptide label. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Transglutaminase-Catalyzed Bioconjugation Using One-Pot Metal-Free Bioorthogonal Chemistry.

    Science.gov (United States)

    Rachel, Natalie M; Toulouse, Jacynthe L; Pelletier, Joelle N

    2017-10-18

    General approaches for controlled protein modification are increasingly sought-after in the arena of chemical biology. Here, using bioorthogonal reactions, we present combinatorial chemoenzymatic strategies to effectuate protein labeling. A total of three metal-free conjugations were simultaneously or sequentially incorporated in a one-pot format with microbial transglutaminase (MTG) to effectuate protein labeling. MTG offers the particularity of conjugating residues within a protein sequence rather than at its extremities, providing a route to labeling the native protein. The reactions are rapid and circumvent the incompatibility posed by metal catalysts. We identify the tetrazine ligation as most-reactive for this purpose, as demonstrated by the fluorescent labeling of two proteins. The Staudinger ligation and strain-promoted azide-alkyne cycloaddition are alternatives. Owing to the breadth of labels that MTG can use as a substrate, our results demonstrate the versatility of this system, with the researcher being able to combine specific protein substrates with a variety of labels.

  20. Core/shell fluorescent magnetic silica-coated composite nanoparticles for bioconjugation

    Science.gov (United States)

    He, Rong; You, Xiaogang; Shao, Jun; Gao, Feng; Pan, Bifeng; Cui, Daxiang

    2007-08-01

    A new class of highly fluorescent, photostable, and magnetic core/shell nanoparticles has been synthesized from a reverse microemulsion method. The obtained bifunctional nanocomposites were characterized by transmission electron microscopy (TEM), ultraviolet-visible (UV-vis) spectrometry, photoluminescence (PL) spectrometry, and fluorescence microscopy in a magnetic field. To further improve their biocompatibility, the silica-coated nanoparticles were functionalized with amino groups. The fluorescent magnetic composite nanoparticles (FMCNPs) had a typical diameter of 50 ± 5 nm and a saturation magnetization of 3.21 emu g-1 at room temperature, and exhibited strong excitonic photoluminescence. Through activation with glutaraldehyde, the FMCNPs were successfully conjugated with goat anti-mouse immunoglobin G (GM IgG), and the bioactivity and binding specificity of the as-prepared FMCNPs-GM IgG were confirmed via immunofluorescence assays, commonly used in bioanalysis. So they are potentially useful for many applications in biolabelling, imaging, drug targeting, bioseparation and bioassays.

  1. Core/shell fluorescent magnetic silica-coated composite nanoparticles for bioconjugation

    International Nuclear Information System (INIS)

    He Rong; You Xiaogang; Shao Jun; Gao Feng; Pan Bifeng; Cui Daxiang

    2007-01-01

    A new class of highly fluorescent, photostable, and magnetic core/shell nanoparticles has been synthesized from a reverse microemulsion method. The obtained bifunctional nanocomposites were characterized by transmission electron microscopy (TEM), ultraviolet-visible (UV-vis) spectrometry, photoluminescence (PL) spectrometry, and fluorescence microscopy in a magnetic field. To further improve their biocompatibility, the silica-coated nanoparticles were functionalized with amino groups. The fluorescent magnetic composite nanoparticles (FMCNPs) had a typical diameter of 50 ± 5 nm and a saturation magnetization of 3.21 emu g -1 at room temperature, and exhibited strong excitonic photoluminescence. Through activation with glutaraldehyde, the FMCNPs were successfully conjugated with goat anti-mouse immunoglobin G (GM IgG), and the bioactivity and binding specificity of the as-prepared FMCNPs-GM IgG were confirmed via immunofluorescence assays, commonly used in bioanalysis. So they are potentially useful for many applications in biolabelling, imaging, drug targeting, bioseparation and bioassays

  2. A Nanodiamond-peptide Bioconjugate for Fluorescence and ODMR Microscopy of a Single Actin Filament.

    Science.gov (United States)

    Genjo, Takuya; Sotoma, Shingo; Tanabe, Ryotaro; Igarashi, Ryuji; Shirakawa, Masahiro

    2016-01-01

    Recently, the importance of conformational changes in actin filaments induced by mechanical stimulation of a cell has been increasingly recognized, especially in terms of mechanobiology. Despite its fundamental importance, however, long-term observation of a single actin filament by fluorescent microscopy has been difficult because of the low photostability of traditional fluorescent molecules. This paper reports a novel molecular labeling system for actin filaments using fluorescent nanodiamond (ND) particles harboring nitrogen-vacancy centers; ND has flexible chemical modifiability, extremely high photostability and biocompatibility, and provides a variety of physical information quantitatively via optically detected magnetic resonance (ODMR) measurements. We performed the chemical surface modification of an ND with the actin filament-specific binding peptide Lifeact and observed colocalization of pure Lifeact-modified ND and actin filaments by the ODMR selective imaging protocol, suggesting the capability of long-term observation and quantitative analysis of a single molecule by using an ND particle.

  3. Preparation of bioconjugates of CdTe nanocrystals for cancer marker detection

    Energy Technology Data Exchange (ETDEWEB)

    Hu Fengqin [Key Laboratory of Colloid, Interface Science and Chemical Thermodynamics, Molecular Science Center, Institute of Chemistry, Chinese Academy of Sciences, Zhong Guan Cun, Bei Yi Jie 2, Beijing 100080 (China); Ran Yuliang [Department of Cell and Molecular Biology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Pan Jia Yuan, Chao Yang Qu, Beijing 100021 (China); Zhou Zhuan [Department of Cell and Molecular Biology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Pan Jia Yuan, Chao Yang Qu, Beijing 100021 (China); Gao Mingyuan [Key Laboratory of Colloid, Interface Science and Chemical Thermodynamics, Molecular Science Center, Institute of Chemistry, Chinese Academy of Sciences, Zhong Guan Cun, Bei Yi Jie 2, Beijing 100080 (China)

    2006-06-28

    Highly fluorescent CdTe quantum dots (Q-dots) stabilized by 3-mercaptopropionic acid (MPA) were prepared by an aqueous solution approach and used as fluorescent labels in detecting a cancer marker, carcinoembryonic antigen (CEA), expressed on human colon carcinoma cell line LS 180. Nonspecific adsorptions of CdTe Q-dots on carcinoma cells were observed and effectively eliminated by replacing MPA with a thiolated PEG (poly(ethylene glycol), Mn = 750) synthesized according to literature. It was unexpectedly found out that the PEG-coated CdTe Q-dots exhibited very strong and specific affinity to anti-CEA monoclonal antibody rch 24 (rch 24 mAb). The resultant CdTe-(rch 24 mAb) conjugates were successfully used in detections of CEA expressed on the surface of cell line LS 180. Further experiments demonstrated that the fluorescent CdTe Q-dots exhibited much better photostability and a brighter fluorescence than FITC, which consequently led to a higher efficiency in the cancer marker detection.

  4. Sensitive prostate specific antigen quantification using dihydrolipoic acid surface-functionalized phosphorescent quantum dots.

    Science.gov (United States)

    García-Cortés, Marta; Fernández-Argüelles, María Teresa; Costa-Fernández, José M; Sanz-Medel, Alfredo

    2017-09-22

    Herein, high-quality Mn-doped ZnS quantum dots (QDs) have been synthesized using a facile approach directly in aqueous media. The surface of the obtained QDs was further modified by cap-exchange of the native cysteine shell with dihydrolipoic acid (DHLA) ligands resulting in nanocrystals with high water-stability having an intense phosphorescent signal. Covalent bioconjugation of the DHLA-coated nanoparticles with an anti-IgG antibody was then carried out. Interestingly the QD immunoprobe (QD-labelled antibodies) maintained an intense phosphorescence emission, without any significant spectral-shift (as compared to the free QDs). Coupling of an asymmetric flow field flow fractionation technique to an elemental mass spectrometry detection enabled the accurate determination of the efficiency of the bioconjugation reaction. The obtained nanoparticle-antibody bioconjugate was then applied to develop a quantitative sandwich-type phosphorescent immunoassay for Prostate Specific Antigen (PSA), and a limit of detection (LOD) of 17 pg mL -1 of PSA was achieved and allow to quantify such biomarker in samples within clinically relevant levels. Finally, the assay was validated for the quantification of PSA in the cellular media of prostate cancer cells. Obtained results proved the robustness of the proposed immunoassay based on long-lived phosphorescence measurements against eventual photoluminescent interferences significantly affecting the conventional short-lived fluorescence detection. Copyright © 2017. Published by Elsevier B.V.

  5. Different patterns of nuclear and mitochondrial penetration by the G3 PAMAM dendrimer and its biotin–pyridoxal bioconjugate BC-PAMAM in normal and cancer cells in vitro

    Directory of Open Access Journals (Sweden)

    Uram Ł

    2015-09-01

    Full Text Available Łukasz Uram,1 Magdalena Szuster,1 Aleksandra Filipowicz,2 Krzysztof Gargasz,3 Stanisław Wołowiec,3 Elżbieta Wałajtys-Rode4 1Bioorganic Chemistry Laboratory, Faculty of Chemistry, Rzeszow University of Technology, 2Cosmetology Department, University of Information Technology and Management in Rzeszow, 3Institute of Nursery and Health Sciences, Faculty of Medicine, University of Rzeszow, Rzeszow, 4Department of Drug Technology and Biotechnology, Faculty of Chemistry, Warsaw University of Technology, Warsaw, Poland Abstract: The intracellular localization and colocalization of a fluorescently labeled G3 amine-terminated cationic polyamidoamine (PAMAM dendrimer and its biotin–pyridoxal (BC-PAMAM bioconjugate were investigated in a concentration-dependent manner in normal human fibroblast (BJ and squamous epithelial carcinoma (SCC-15 cell lines. After 24 hours treatment, both cell lines revealed different patterns of intracellular dendrimer accumulation depending on their cytotoxic effects. Cancer cells exhibited much higher (20-fold tolerance for native PAMAM treatment than fibroblasts, whereas BC-PAMAM was significantly toxic only for fibroblasts at 50 µM concentration. Fibroblasts accumulated the native and bioconjugated dendrimers in a concentration-dependent manner at nontoxic range of concentration, with significantly lower bioconjugate loading. After reaching the cytotoxicity level, fluorescein isothiocyanate-PAMAM accumulation remains at high, comparable level. In cancer cells, native PAMAM loading at higher, but not cytotoxic concentrations, was kept at constant level with a sharp increase at toxic concentration. Mander’s coefficient calculated for fibroblasts and cancer cells confirmed more efficient native PAMAM penetration as compared to BC-PAMAM. Significant differences in nuclear dendrimer penetration were observed for both cell lines. In cancer cells, PAMAM signals amounted to ~25%–35% of the total nuclei area at all

  6. Nucleobases functionalized quantum dots and gold nanoparticles bioconjugates as a fluorescence resonance energy transfer (FRET) system - Synthesis, characterization and potential applications.

    Science.gov (United States)

    Rodzik-Czałka, Łucja; Lewandowska-Łańcucka, Joanna; Gatta, Viviana; Venditti, Iole; Fratoddi, Ilaria; Szuwarzyński, Michał; Romek, Marek; Nowakowska, Maria

    2018-03-15

    Fluorescence resonance energy transfer (FRET) system based on functionalized CdTe-guanine and AuNPs-cytosine bioconjugates for the model nucleobase - guanine detection was developed. Thioglycolic acid coated cadmium telluride quantum dots (QDs) conjugated with guanine and sodium 3-mercapto-1-propanesulfonate stabilized gold nanoparticles (AuNPs) capped by cytosine were obtained and fully characterized. Successful formation of the materials was confirmed by UV-Vis, fluorescence and FTIR spectroscopies. Composition of the conjugates was also characterized with elemental analysis and XPS. By employing a guanine-cytosine interaction the bonding between these complementary nucleobases attached to the nanoparticles leads to the formation of QDs-guanine-AuNPs-cytosine assembly, with the size about 7 nm as demonstrated using atomic force microscopy. That enables an effective FRET from functionalized QDs to AuNPs since both, the required distance and the spectral characteristics of donor-acceptor pair were secured. However, it was shown that in the presence of guanine-model molecule which inhibits the interaction between conjugated QDs and AuNPs the FRET is efficiently hampered. Thus monitoring the changes in the restoring fluorescence signal allows to assay the free guanine concentration. Importantly, we have demonstrated the sensitivity and selectivity of the obtained FRET-based system towards guanine. Moreover, in order to confirm the feasibility of the proposed material for nucleobase detection in the real biological samples the developed nanoparticles were also evaluated under simulated urine conditions. The presented strategy of FRET-based conjugated system preparation might be easily used for the development of another nucleobases selective detection and thus opens many possibilities for the determination of biomolecules in the real samples. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Evaluation of bio-conjugation methods for obtaining of synthetic positive control for IgM-capture ELISA

    Directory of Open Access Journals (Sweden)

    O. Y. Galkin

    2014-10-01

    Full Text Available The enzyme-linked immunosorbent assay (ELISA is the most informative and versatile method of serological diagnostics. The possibility of detecting by ELISA specific antibodies of different classes allow to differentiate primary infectious process and its remission, exacerbation and chronic disease (differential diagnosis. This approach is implemented in the methodology for evaluation of patients for the presence of humoral immune response to TORCH-infections pathogens (toxoplasmosis, rubella, cytomegalovirus, herpes simplex viruses’ infections, and some others. Therefore, testing for presence of specific IgG and IgM antibodies against TORCH-infections pathogens in blood serum is an important element of motherhood and childhood protection. The essential problem in the production of IgM-capture ELISA diagnostic kits is obtaining of positive control. The classic version of positive control is human blood serum (plasma containing specific antibodies. But specific IgM-positive sera are insignificant raw materials. This fact can seriously restrict the production of diagnostic kits, especially in the event of large-scale production. We have suggested the methodological approach to using of synthetic positive controls in IgM-capture ELISA kits based on conjugate of normal human IgM and monoclonal antibodies against horseradish peroxidase. It is found that this task can be fulfilled by means of NHS ester-maleimide-mediated conjugation (by sulfosuccinimidyl-4-(N-maleimidomethylcyclohexane-1-carboxylate, reductive amination-mediated conjugation (by sodium periodate and glutaraldehyde-mediated conjugation. It was found that conjugates of normal human IgM and monoclonal antibodies against horseradish peroxidase obtained using NHS ester-mediated maleimide conjugation and periodate method were similar by molecular weight, whereas conjugate synthesized by glutaraldehyde method comprised at least three types of biopolymers with close molecular weight. It was

  8. One-pot synthesis of polythiol ligand for highly bright and stable hydrophilic quantum dots toward bioconjugate formation

    Science.gov (United States)

    Dezhurov, Sergey V.; Krylsky, Dmitry V.; Rybakova, Anastasia V.; Ibragimova, Sagila A.; Gladyshev, Pavel P.; Vasiliev, Alexey A.; Morenkov, Oleg S.

    2018-03-01

    A fast and efficient one-pot synthesis of thiol-terminated poly(vinylpirrolidone-co-maleic anhydride-co-ethylene glycol dimethacrylate) based heterobifunctional polymer (PTVP) has been developed. The polymer was used for the modification of quantum dots (QDs) to prepare water soluble and stable QDs with emission quantum yield as high as 80%. Using carbodiimide method, PTVP-capped red light-emitting QDs were conjugated to model monoclonal antibodies specific to glycoprotein B (gB) of Aujeszky’s disease virus (ADV) and successfully used in the lateral flow assay (LFA) for the detection of ADV gB in biological fluids. A comparative analysis of the sensitivity of the method was carried out using three types of QDs emitting in the red and far-red region.

  9. Bio-conjugated luminescent quantum dots of doped ZnS: a cyto-friendly system for targeted cancer imaging

    International Nuclear Information System (INIS)

    Manzoor, Koyakutty; Johny, Seby; Thomas, Deepa; Setua, Sonali; Menon, Deepthy; Nair, Shantikumar

    2009-01-01

    A heavy-metal-free luminescent quantum dot (QD) based on doped zinc sulfide (ZnS), conjugated with a cancer-targeting ligand, folic acid (FA), is presented as a promising bio-friendly system for targeted cancer imaging. Doped QDs were prepared by a simple aqueous method at room temperature. X-ray diffraction and transmission electron microscopy studies showed the formation of monodisperse QDs of average size ∼4 nm with cubic (sphalerite) crystal structure. Doping of the QDs with metals (Al 3+ ), transition metals (Cu + , Mn 2+ ) and halides (F - ) resulted in multi-color emission with dopant-specific color tunability ranging from blue (480 nm) to red (622 nm). Luminescent centers in doped QDs could be excited using bio-friendly visible light >400 nm by directly populating the dopant centers, leading to bright emission. The cytotoxicity of bare and FA conjugated QDs was tested in vitro using normal lung fibroblast cell line (L929), folate-receptor-positive (FR+) nasopharyngeal epidermoid carcinoma cell line (KB), and FR-negative (FR-) lung cancer cell line (A549). Both bare and FA-conjugated ZnS QDs elicited no apparent toxicity even at high concentrations of ∼100 μM and 48 h of incubation. In contrast, CdS QDs prepared under identical conditions showed relatively high toxicity even at low concentrations of ∼0.1 μM and 24 h of incubation. Interaction of FA-QDs with different cell lines showed highly specific attachment of QDs in the FR+ cancer cell line, leaving others unaffected. The bright and stable luminescence of the QDs could be used to image both single cancer cells and colonies of cancer cells without affecting their metabolic activity and morphology. Thus, this study presents, for the first time, the use of non-toxic, Cd-, Te-, Se-, Pb- and Hg-free luminescent QDs for targeted cancer imaging.

  10. Quantum dot bio-conjugate: as a western blot probe for highly sensitive detection of cellular proteins

    Science.gov (United States)

    Kale, Sonia; Kale, Anup; Gholap, Haribhau; Rana, Abhimanyu; Desai, Rama; Banpurkar, Arun; Ogale, Satishchandra; Shastry, Padma

    2012-03-01

    In the present study, we report a quantum dot (QD)-tailored western blot analysis for a sensitive, rapid and flexible detection of the nuclear and cytoplasmic proteins. Highly luminescent CdTe and (CdTe)ZnS QDs are synthesized by aqueous method. High resolution transmission electron microscopy, Raman spectroscopy, fourier transform infrared spectroscopy, fluorescence spectroscopy and X-ray diffraction are used to characterize the properties of the quantum dots. The QDs are functionalized with antibodies of prostate apoptosis response-4 (Par-4), poly(ADP-ribose) polymerases and β actin to specifically bind with the proteins localized in the nucleus and cytoplasm of the cells, respectively. The QD-conjugated antibodies are used to overcome the limitations of conventional western blot technique. The sensitivity and rapidity of protein detection in QD-based approach is very high, with detection limits up to 10 pg of protein. In addition, these labels provide the capability of enhanced identification and localization of marker proteins in intact cells by confocal laser scanning microscopy.

  11. Terbium to Quantum Dot FRET Bioconjugates for Clinical Diagnostics: Influence of Human Plasma on Optical and Assembly Properties

    Directory of Open Access Journals (Sweden)

    Niko Hildebrandt

    2011-10-01

    Full Text Available Förster resonance energy transfer (FRET from luminescent terbium complexes (LTC as donors to semiconductor quantum dots (QDs as acceptors allows extraordinary large FRET efficiencies due to the long Förster distances afforded. Moreover, time-gated detection permits an efficient suppression of autofluorescent background leading to sub-picomolar detection limits even within multiplexed detection formats. These characteristics make FRET-systems with LTC and QDs excellent candidates for clinical diagnostics. So far, such proofs of principle for highly sensitive multiplexed biosensing have only been performed under optimized buffer conditions and interactions between real-life clinical media such as human serum or plasma and LTC-QD-FRET-systems have not yet been taken into account. Here we present an extensive spectroscopic analysis of absorption, excitation and emission spectra along with the luminescence decay times of both the single components as well as the assembled FRET-systems in TRIS-buffer, TRIS-buffer with 2% bovine serum albumin, and fresh human plasma. Moreover, we evaluated homogeneous LTC-QD FRET assays in QD conjugates assembled with either the well-known, specific biotin-streptavidin biological interaction or, alternatively, the metal-affinity coordination of histidine to zinc. In the case of conjugates assembled with biotin-streptavidin no significant interference with the optical and binding properties occurs whereas the histidine-zinc system appears to be affected by human plasma.

  12. Quantum dot bio-conjugate: as a western blot probe for highly sensitive detection of cellular proteins

    Energy Technology Data Exchange (ETDEWEB)

    Kale, Sonia [Agharkar Research Institute (India); Kale, Anup [University of Alabama, Center for Materials for Information Technology (United States); Gholap, Haribhau; Rana, Abhimanyu [National Chemical Laboratory, Physical and Materials Chemistry Division (India); Desai, Rama [National Centre for Cell Science (India); Banpurkar, Arun [University of Pune, Department of Physics (India); Ogale, Satishchandra, E-mail: sb.ogale@ncl.res.in [National Chemical Laboratory, Physical and Materials Chemistry Division (India); Shastry, Padma, E-mail: padma@nccs.res.in [National Centre for Cell Science (India)

    2012-03-15

    In the present study, we report a quantum dot (QD)-tailored western blot analysis for a sensitive, rapid and flexible detection of the nuclear and cytoplasmic proteins. Highly luminescent CdTe and (CdTe)ZnS QDs are synthesized by aqueous method. High resolution transmission electron microscopy, Raman spectroscopy, fourier transform infrared spectroscopy, fluorescence spectroscopy and X-ray diffraction are used to characterize the properties of the quantum dots. The QDs are functionalized with antibodies of prostate apoptosis response-4 (Par-4), poly(ADP-ribose) polymerases and {beta} actin to specifically bind with the proteins localized in the nucleus and cytoplasm of the cells, respectively. The QD-conjugated antibodies are used to overcome the limitations of conventional western blot technique. The sensitivity and rapidity of protein detection in QD-based approach is very high, with detection limits up to 10 pg of protein. In addition, these labels provide the capability of enhanced identification and localization of marker proteins in intact cells by confocal laser scanning microscopy.

  13. Segmental isotopic labeling by asparaginyl endopeptidase-mediated protein ligation.

    Science.gov (United States)

    Mikula, Kornelia M; Krumwiede, Luisa; Plückthun, Andreas; Iwaï, Hideo

    2018-03-13

    Segmental isotopic labeling can facilitate NMR studies of large proteins, multi-domain proteins, and proteins with repetitive sequences by alleviating NMR signal overlaps. Segmental isotopic labeling also allows us to investigate an individual domain in the context of a full-length protein by NMR. Several established methods are available for segmental isotopic labeling such as intein-mediated ligation, but each has specific requirements and limitations. Here, we report an enzymatic approach using bacterially produced asparagine endopeptidase from Oldenlandia affinis for segmental isotopic labeling of a protein with repetitive sequences, a designed armadillo repeat protein, by overcoming some of the shortcomings of enzymatic ligation for segmental isotopic labeling.

  14. A Nanoparticle Platform To Evaluate Bioconjugation and Receptor-Mediated Cell Uptake Using Cross-Linked Polyion Complex Micelles Bearing Antibody Fragments.

    Science.gov (United States)

    Florinas, Stelios; Liu, Marc; Fleming, Ryan; Van Vlerken-Ysla, Lilian; Ayriss, Joanne; Gilbreth, Ryan; Dimasi, Nazzareno; Gao, Changshou; Wu, Herren; Xu, Ze-Qi; Chen, Shaoyi; Dirisala, Anjaneyulu; Kataoka, Kazunori; Cabral, Horacio; Christie, R James

    2016-05-09

    Targeted nanomedicines are a promising technology for treatment of disease; however, preparation and characterization of well-defined protein-nanoparticle systems remain challenging. Here, we describe a platform technology to prepare antibody binding fragment (Fab)-bearing nanoparticles and an accompanying real-time cell-based assay to determine their cellular uptake compared to monoclonal antibodies (mAbs) and Fabs. The nanoparticle platform was composed of core-cross-linked polyion complex (PIC) micelles prepared from azide-functionalized PEG-b-poly(amino acids), that is, azido-PEG-b-poly(l-lysine) [N3-PEG-b-PLL] and azido-PEG-b-poly(aspartic acid) [N3-PEG-b-PAsp]. These PIC micelles were 30 nm in size and contained approximately 10 polymers per construct. Fabs were derived from an antibody binding the EphA2 receptor expressed on cancer cells and further engineered to contain a reactive cysteine for site-specific attachment and a cleavable His tag for purification from cell culture expression systems. Azide-functionalized micelles and thiol-containing Fab were linked using a heterobifunctional cross-linker (FPM-PEG4-DBCO) that contained a fluorophenyl-maleimide for stable conjugation to Fabs thiols and a strained alkyne (DBCO) group for coupling to micelle azide groups. Analysis of Fab-PIC micelle conjugates by fluorescence correlation spectroscopy, size exclusion chromatography, and UV-vis absorbance determined that each nanoparticle contained 2-3 Fabs. Evaluation of cellular uptake in receptor positive cancer cells by real-time fluorescence microscopy revealed that targeted Fab-PIC micelles achieved higher cell uptake than mAbs and Fabs, demonstrating the utility of this approach to identify targeted nanoparticle constructs with unique cellular internalization properties.

  15. Specific phobia.

    Science.gov (United States)

    Silverman, Wendy K; Moreno, Jacqueline

    2005-10-01

    This article describes specific phobia of childhood and its clinical presentation, discusses issues related to the differential diagnosis of specific phobia, considers the issue of comorbidity among phobic and anxiety disorders and developmental trends in the manifestation of fears, summarizes the epidemiology, causes, and course of specific phobia, and presents assessment and treatment issues. Finally, a case study is offered that serves to illuminate the major topics outlined in the article.

  16. Nonnatural amino acids for site-specific protein conjugation

    NARCIS (Netherlands)

    Graaf, Albert J. de; Kooijman, M.; Hennink, W.E.; Mastrobattista, E.

    2009-01-01

    Over the years, several chemical reactions have been developed that enable the covalent conjugation of synthetic molecules to natural proteins. The resulting bioconjugates have become important tools in the study of natural proteins. Furthermore, they form a new class of protein-based

  17. Expanding and exploring the bioconjugation toolbox

    NARCIS (Netherlands)

    Borrmann, A.

    2016-01-01

    A large variety of biomolecules such as lipids, DNA, carbohydrates and proteins exist inside cells. Every biomolecule fulfills a different type of function and it is highly relevant to study these functions to eventually understand the development of certain diseases. In order to study the role of a

  18. Click Chemistry in Complex Mixtures: Bioorthogonal Bioconjugation

    Science.gov (United States)

    McKay, Craig S.; Finn, M.G.

    2014-01-01

    The selective chemical modification of biological molecules drives a good portion of modern drug development and fundamental biological research. While a few early examples of reactions that engage amine and thiol groups on proteins helped establish the value of such processes, the development of reactions that avoid most biological molecules so as to achieve selectivity in desired bond-forming events has revolutionized the field. We provide an update on recent developments in bioorthogonal chemistry that highlights key advances in reaction rates, biocompatibility, and applications. While not exhaustive, we hope this summary allows the reader to appreciate the rich continuing development of good chemistry that operates in the biological setting. PMID:25237856

  19. Probe specificity

    International Nuclear Information System (INIS)

    Laget, J.M.

    1986-11-01

    Specificity and complementarity of hadron and electron probes must be systematically developed to answer three questions currently asked in intermediate energy nuclear physics: what is nucleus structure at short distances, what is nature of short range correlations, what is three body force nature [fr

  20. HRT Specification

    CERN Document Server

    Möller, M

    1996-01-01

    In the context of the AIS Project (Advanced Informatics Systems for administration and management) a study has been conducted that resulted in the definition of a high level information systems model. Thirteen proposed systems were defined for detailed analysis. The Finance, Foundation, Human Resources, Logistics and Purchasing areas have been studied in detail. These studies have lead to the purchase and implementation of the ORIAC and SIRIAC packages, the Foundation database, the Oracle HR package, the Triton package and EDH and BHT. This specification describes the Human Resources Toolkit (HRT) intended to be used for accessing data in the HR and Foundation systems. This toolkit should help the divisions carry out their Human Resource management, planning and follow-up. It will have extensive report generation capabilities and offer a variety of standard graphs. It should have an easy-to-use graphical user interface and run on the CERN standard desktop platforms.

  1. Prolactin Receptor-Mediated Internalization of Imaging Agents Detects Epithelial Ovarian Cancer with Enhanced Sensitivity and Specificity.

    Science.gov (United States)

    Sundaram, Karthik M; Zhang, Yilin; Mitra, Anirban K; Kouadio, Jean-Louis K; Gwin, Katja; Kossiakoff, Anthony A; Roman, Brian B; Lengyel, Ernst; Piccirilli, Joseph A

    2017-04-01

    Poor prognosis of ovarian cancer, the deadliest of the gynecologic malignancies, reflects major limitations associated with detection and diagnosis. Current methods lack high sensitivity to detect small tumors and high specificity to distinguish malignant from benign tissue, both impeding diagnosis of early and metastatic cancer stages and leading to costly and invasive surgeries. Tissue microarray analysis revealed that >98% of ovarian cancers express the prolactin receptor (PRLR), forming the basis of a new molecular imaging strategy. We fused human placental lactogen (hPL), a specific and tight binding PRLR ligand, to magnetic resonance imaging (gadolinium) and near-infrared fluorescence imaging agents. Both in tissue culture and in mouse models, these imaging bioconjugates underwent selective internalization into ovarian cancer cells via PRLR-mediated endocytosis. Compared with current clinical MRI techniques, this targeted approach yielded both enhanced signal-to-noise ratio from accumulation of signal via selective internalization and improved specificity conferred by PRLR upregulation in malignant ovarian cancer. These features endow PRLR-targeted imaging with the potential to transform ovarian cancer detection. Cancer Res; 77(7); 1684-96. ©2017 AACR . ©2017 American Association for Cancer Research.

  2. Dual Immunomagnetic Nanobeads-Based Lateral Flow Test Strip for Simultaneous Quantitative Detection of Carcinoembryonic Antigen and Neuron Specific Enolase

    Science.gov (United States)

    Lu, Wenting; Wang, Kan; Xiao, Kun; Qin, Weijian; Hou, Yafei; Xu, Hao; Yan, Xinyu; Chen, Yanrong; Cui, Daxiang; He, Jinghua

    2017-01-01

    A novel immunomagnetic nanobeads -based lateral flow test strip was developed for the simultaneous quantitative detection of neuron specific enolase (NSE) and carcinoembryonic antigen (CEA), which are sensitive and specific in the clinical diagnosis of small cell lung cancer. Using this nanoscale method, high saturation magnetization, carboxyl-modified magnetic nanobeads were successfully synthesized. To obtain the immunomagnetic probes, a covalent bioconjugation of the magnetic nanobeads with the antibody of NSE and CEA was carried out. The detection area contained test line 1 and test line 2 which captured the immune complexes sensitively and formed sandwich complexes. In this assay, cross-reactivity results were negative and both NSE and CEA were detected simultaneously with no obvious influence on each other. The magnetic signal intensity of the nitrocellulose membrane was measured by a magnetic assay reader. For quantitative analysis, the calculated limit of detection was 0.094 ng/mL for NSE and 0.045 ng/mL for CEA. One hundred thirty clinical samples were used to validate the test strip which exhibited high sensitivity and specificity. This dual lateral flow test strip not only provided an easy, rapid, simultaneous quantitative detection strategy for NSE and CEA, but may also be valuable in automated and portable diagnostic applications. PMID:28186176

  3. Site-specific Incorporation of Chemical Fluorescence on Live Enterovirus-71 Virion by Organometallic Palladium Reagent to Monitor Virus Entry.

    Science.gov (United States)

    Lou, Zhiyong; Wang, Yaxin; Liu, Jingwei; Cao, Lin; Wang, Wenjing; Sun, Yuna; Yin, Zheng

    2018-04-06

    Imaging live virus to monitor the viral entry process is essential to understand virus-host interactions during pathogen infection. However, methods for efficient labeling of live viruses, in particular labeling non-enveloped viruses and tracing virus entry processes, remains limited. Recently, labeling using organometallic palladium reagents has provided a highly efficient and a highly selective way to bioconjugate cysteines of virus proteins. Here, the site-specific bioorthogonal labeling mediated by an organometallic palladium reagent on the surface of live enterovirus-71 (EV71) was used to visualize its entry into live cells. In contrast to currently used immunofluorescence and membrane-anchored dyes, this site-specific and quantitative labeling of live EV71 virus allows temporal imaging on a seconds time scale of its entry into host cell membranes with little negative impact on the virulence. This method revealed details of EV71 virus entry and has broad applicability for monitoring virus entry that is difficult to assess using conventional protein labeling approaches. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. pH-sensitive inulin-based nanomicelles for intestinal site-specific and controlled release of celecoxib.

    Science.gov (United States)

    Mandracchia, Delia; Trapani, Adriana; Perteghella, Sara; Sorrenti, Milena; Catenacci, Laura; Torre, Maria Luisa; Trapani, Giuseppe; Tripodo, Giuseppe

    2018-02-01

    Aiming at a site-specific drug release in the lower intestinal tract, this paper deals with the synthesis and physicochemical/biological characterization of pH-sensitive nanomicelles from an inulin (INU) amphiphilic derivative. To allow an intestinal site specific release of the payload, INU-Vitamin E (INVITE) bioconjugates were functionalized with succinic anhydride to provide the system with pH-sensitive groups preventing a premature release of the payload into the stomach. The obtained INVITESA micelles resulted nanosized, with a low critical aggregation concentration and the release studies showed a marked pH-dependent release. The drug loading stabilized the micelles against the acidic hydrolysis. From transport studies on Caco-2 cells, resulted that INVITESA nanomicelles cross the cellular monolayer but are actively re-transported in the secretory (basolateral-apical) direction when loaded in apical side. It suggests that the entrapped drug could not be absorbed before the release from the micelles, enabling so a local release of the active. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Biofunctional quantum dots as fluorescence probe for cell-specific targeting

    OpenAIRE

    Ag, Didem; Bongartz, Rebecca; Dogan, Leyla Eral; Seleci, Muharrem; Walter, Johanna-Gabriela; Demirkol, Dilek Odaci; Stahl, Frank; Ozcelik, Serdar; Timur, Suna; Scheper, Thomas

    2014-01-01

    We describe here the synthesis, characterization, bioconjugation, and application of water-soluble thioglycolic acid TGA-capped CdTe/CdS quantum dots (TGA-QDs) for targeted cellular imaging. Anti-human epidermal growth factor receptor 2 (HER2) antibodies were conjugated to TGA-QDs to target HER2-overexpressing cancer cells. TGA-QDs and TGA-QDs/anti-HER2 bioconjugates were characterized by fluorescence and UV-Vis spectroscopy, X-ray diffraction (XRD), hydrodynamic sizing, electron microscopy, ...

  6. Cyclic peptide inhibitors of the β-sliding clamp in Staphylococcus aureus

    DEFF Research Database (Denmark)

    Kjelstrup, Susanne; Hansen, Paula Melo Paulon; Thomsen, Line Elnif

    2013-01-01

    Interaction between pairs of Staphylococcus aureus replication proteins was detected in an Escherichia coli based two-hybrid analysis. A reverse two-hybrid system was constructed for selection of compounds that hindered interaction between interacting protein pairs. A number of cyclic peptides......, from a library generated by the split intein-mediated circular ligation of peptides and proteins technology, were found to interfere with dimerization of the β-sliding clamp of the replisome. Two 8-mer peptides were analyzed in more detail. Both inhibited DNA replication, led to SOS induction, altered...... cell morphology and cell death. The peptides were active when added to bacterial cultures indicating that they could traverse the bacterial membrane to find their intracellular target. Peptide specificity was confirmed by overproduction of the putative target (DnaN) which resulted in resistance...

  7. Towards cancer cell-specific phototoxic organometallic rhenium(I) complexes.

    Science.gov (United States)

    Leonidova, Anna; Pierroz, Vanessa; Rubbiani, Riccardo; Heier, Jakob; Ferrari, Stefano; Gasser, Gilles

    2014-03-21

    Over the recent years, several Re(I) organometallic compounds have been shown to be toxic to various cancer cell lines. However, these compounds lacked sufficient selectivity towards cancer tissues to be used as novel chemotherapeutic agents. In this study, we probe the potential of two known N,N-bis(quinolinoyl) Re(I) tricarbonyl complex derivatives, namely Re(I) tricarbonyl [N,N-bis(quinolin-2-ylmethyl)amino]-4-butane-1-amine (Re-NH₂) and Re(I) tricarbonyl [N,N-bis(quinolin-2-ylmethyl)amino]-5-valeric acid (Re-COOH), as photodynamic therapy (PDT) photosensitizers. Re-NH₂ and Re-COOH proved to be excellent singlet oxygen generators in a lipophilic environment with quantum yields of about 75%. Furthermore, we envisaged to improve the selectivity of Re-COOH via conjugation to two types of peptides, namely a nuclear localization signal (NLS) and a derivative of the neuropeptide bombesin, to form Re-NLS and Re-Bombesin, respectively. Fluorescent microscopy on cervical cancer cells (HeLa) showed that the conjugation of Re-COOH to NLS significantly enhanced the compound's accumulation into the cell nucleus and more specifically into its nucleoli. Importantly, in view of PDT applications, the cytotoxicity of the Re complexes and their bioconjugates increased significantly upon light irradiation. In particular, Re-Bombesin was found to be at least 20-fold more toxic after light irradiation. DNA photo-cleavage studies demonstrated that all compounds damaged DNA via singlet oxygen and, to a minor extent, superoxide production.

  8. Specific Language Impairment

    Science.gov (United States)

    ... Home » Health Info » Voice, Speech, and Language Specific Language Impairment On this page: What is specific language ... percent of children in kindergarten. What is specific language impairment? Specific language impairment (SLI) is a language ...

  9. A Proposed Method for Thermal Specific Bioimaging and Therapy Technique for Diagnosis and Treatment of Malignant Tumors by Using Magnetic Nanoparticles

    Directory of Open Access Journals (Sweden)

    Iddo M. Gescheit

    2008-01-01

    Full Text Available The objective of this research program is to develop a novel, noninvasive, low-cost infrared (8–12 μm spectral range imaging technique that would improve upon current methods using nanostructured core/shell magnetic/noble metal-based imaging and therapies. The biocompatible magnetic nanoparticles are able to produce heat under AC magnetic field. This thermal radiation propagates along the tissue by thermal conduction reaching the medium's (tissue's surface. The surface temperature distribution is acquired by a thermal camera and can be analyzed to retrieve and reconstruct nanoparticles' temperature and location within the tissue. The technique may function as a diagnostic tool thanks to the ability of specific bioconjugation of these nanoparticles to tumor's outer surface markers. Hence, by applying a magnetic field, we could cause a selective elevation of temperature of the targeted nanoparticles up to 5∘C, which detects the tumor. Furthermore, elevating the temperature over 65∘C and up to 100∘C stimulates a thermo ablating interaction which causes a localized irreversible damage to the cancerous site with no harm to the surrounding tissue. While functioning as a diagnostic tool, this procedure may serve as a targeted therapeutic tool under thermal feedback control as well.

  10. Urine specific gravity test

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003587.htm Urine specific gravity test To use the sharing features on this page, please enable JavaScript. Urine specific gravity is a laboratory test that shows the concentration ...

  11. How specific is specific self-efficacy?

    DEFF Research Database (Denmark)

    Nielsen, Tine; Makransky, Guido; Vang, Maria Louison

    2017-01-01

    Self-efficacy is an important and much used construct in psychology and social science studies. The validity of the measurements used is not always sufficiently evaluated. The aim was to evaluate the psychometric properties of the Danish translation of the self-efficacy subscale of The Motivated...... academic learning self-efficacy (SAL-SE) and specific academic exam self-efficacy (SAE-SE), each scale being measurement invariant relative to age, Gender, admission method and specific course targeted. Furthermore, significant and relevant differences between the SAL-SE and SAE-SE scores dependent...... on university and admission method were found, and these results were replicated with two further samples. The SAL-SE and SAE-SE scales hold promise for more detailed studies of student self-efficacy....

  12. Introducing gold nanoparticle bioconjugates within the biological machinery

    OpenAIRE

    García Fernández, Lorena

    2013-01-01

    El rápido desarrollo de la Nanotecnología durante las últimas décadas ofrece amplias perspectivas en el uso de materiales a micro- y nanoescala en diferentes áreas de la industria, tecnología y medicina. Sin embargo, su uso y aplicación segura y eficaz en estas áreas requieren un control mucho mayor sobre sus propiedades físico-químicas y sus interacciones moleculares relacionadas con los seres vivos. El conocimiento actual de la comunidad científica está de acuerdo en que existe una brecha c...

  13. Click-generated triazole based ferrocene-carbohydrate bioconjugates

    Indian Academy of Sciences (India)

    Gokel G W 1992 Chem. Soc. Rev. 21 39. 12. Beer P D 1992 Adv. Inorg. Chem. 39 79. 13. Jorgensen T, Hansen T K and Becher J 1994 Chem. Soc. Rev. 23 41. 14. Fabrizzi L and Poggi A 1995 Chem. Soc. Rev. 197. 15. Kaifer A E and Mendoza S, 1996 1 701 In: Com- prehensive supramolecular chemistry: G W Gokel (ed).

  14. Neat Protein-Polymer Surfactant Bioconjugates as Universal Solvents.

    Science.gov (United States)

    Mukhopadhyay, Anasua; Das, Tarasankar; Datta, Anindya; Sharma, Kamendra P

    2018-02-23

    Solvents, particularly those having low volatility, are of great interest for the biocatalytic synthesis of utility chemicals and fuels. We show novel and universal solvent-like properties of a neat and water-less polymer surfactant-bovine serum albumin (BSA) conjugated material (WL-PSpBSA). This highly viscous, nonvolatile material behaves as a liquid above its solid-liquid transition temperature (∼25-27 °C) and can be used as a solvent for variety of completely dry solutes of different sizes and surface chemistries. We show using a combination of optical microscopy and steady -state and time-resolved fluorescence spectroscopy that dry and powdered dyes (hydrophobic Coumarin 153 (C153)), enzymes (α-chymotrypsin (α-Chy)), or even 1 μm microparticles (diffusion coefficient ca. three orders slower than C153), can be solubilized and completely dispersed in the WL-PSpBSA solvent above 25 °C. While C153, irrespective of its mode of addition to WL-PSpBSA, binds similarly to BSA, α-Chy can be stabilized and activated to perform its hydrolysis function, even at 100 °C. This work therefore provides insights into the form of universal solvent characteristic property for this new class of nonaqueous, nonvolatile, biodegradable protein-polymer surfactant-based conjugated materials and suggests potential new avenues that can have a huge impact on biocatalysis, bionanotechnology, drug delivery, and other applications.

  15. Dynamic light scattering on bioconjugated laser generated gold nanoparticles.

    Directory of Open Access Journals (Sweden)

    Massimo Zimbone

    Full Text Available Gold nanoparticles (AuNPs conjugated to DNA are widely used for biomedical targeting and sensing applications. DNA functionalization is easily reached on laser generated gold nanoparticles because of their unique surface chemistry, not reproducible by other methods. In this context, we present an extensive investigation concerning the attachment of DNA to the surface of laser generated nanoparticles using Dynamic Light Scattering and UV-Vis spectroscopy. The DNA conjugation is highlighted by the increase of the hydrodynamic radius and by the UV-Vis spectra behavior. Our investigation indicates that Dynamic Light Scattering is a suitable analytical tool to evidence, directly and qualitatively, the binding between a DNA molecule and a gold nanoparticle, therefore it is ideal to monitor changes in the conjugation process when experimental conditions are varied.

  16. Heterobifunctional PEG Ligands for Bioconjugation Reactions on Iron Oxide Nanoparticles

    Science.gov (United States)

    Bloemen, Maarten; Van Stappen, Thomas; Willot, Pieter; Lammertyn, Jeroen; Koeckelberghs, Guy; Geukens, Nick; Gils, Ann; Verbiest, Thierry

    2014-01-01

    Ever since iron oxide nanoparticles have been recognized as promising scaffolds for biomedical applications, their surface functionalization has become even more important. We report the synthesis of a novel polyethylene glycol-based ligand that combines multiple advantageous properties for these applications. The ligand is covalently bound to the surface via a siloxane group, while its polyethylene glycol backbone significantly improves the colloidal stability of the particle in complex environments. End-capping the molecule with a carboxylic acid introduces a variety of coupling chemistry possibilities. In this study an antibody targeting plasminogen activator inhibitor-1 was coupled to the surface and its presence and binding activity was assessed by enzyme-linked immunosorbent assay and surface plasmon resonance experiments. The results indicate that the ligand has high potential towards biomedical applications where colloidal stability and advanced functionality is crucial. PMID:25275378

  17. Bioconjugation and Applications of Amino Functional Fluorescence Polymers.

    Science.gov (United States)

    Geyik, Caner; Guler, Emine; Gumus, Zinar Pinar; Barlas, Firat Baris; Akbulut, Huseyin; Demirkol, Dilek Odaci; Timur, Suna; Yagci, Yusuf

    2017-03-01

    Synthesis and novel applications of biofunctional polymers for diagnosis and therapy are promising area involving various research domains. Herein, three fluorescent polymers, poly(p-phenylene-co-thiophene), poly(p-phenylene), and polythiophene with amino groups (PPT-NH 2 , PPP-NH 2 , and PT-NH 2 , respectively) are synthesized and investigated for cancer cell targeted imaging, drug delivery, and radiotherapy. Polymers are conjugated to anti-HER2 antibody for targeted imaging studies in nontoxic concentrations. Three cell lines (A549, Vero, and HeLa) with different expression levels of HER2 are used. In a model of HER2 expressing cell line (A549), radiotherapy experiments are carried out and results show that all three polymers increase the efficacy of radiotherapy. This effect is even more increased when conjugated to anti-HER2. In the second part of this work, one of the selected polymers (PT-NH 2 ) is conjugated with a drug model; methotrexate via pH responsive hydrazone linkage and a drug carrier property of PT-NH 2 is demonstrated on neuroblastoma (SH-SY5Y) cell model. Our results indicate that, PPT-NH 2 , PPP-NH 2 , and PT-NH 2 have a great potential as biomaterials for various bioapplications in cancer research. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Bioconjugated fluorescent zeolite L nanocrystals as labels in protein microarrays.

    Science.gov (United States)

    Li, Zhen; Luppi, Gianluigi; Geiger, Albert; Josel, Hans-Peter; De Cola, Luisa

    2011-11-18

    Zeolite L nanocrystals, as inorganic host material containing hydrophobic fluorophore N,N'-bis(2,6-dimethylphenyl)perylene-3,4,9,10-tetracarboxylic diimide in the unidirectional channels, are developed as new labels for biosensor systems. The external surface of the particles is modified with carboxylic acid groups for conjugation to primary amines of biomolecules such as antibodies. Anti-digoxigenin (anti-DIG) is selected to be immobilized on zeolite L via N-hydroxysulfosuccinimide ester linker. Together with DIG, it serves as a good universal binding pair for diverse analyte detection owing to the high binding affinity and low background noise. The conjugates are characterized by the dynamic light scattering technique for their hydrodynamic diameters and by enzyme-linked immunosorbent assay for antigen-antibody binding behavior. The characterizations prove that anti-DIG antibodies are successfully immobilized on zeolite L with their binding activities maintained. The microarray fluorescent sandwich immunoassay based on such nanocrystalline labels shows high sensitivity in a thyroid-stimulating hormone assay with the lower detection limit down to the femtomolar range. These new fluorescent labels possess great potential for in vitro diagnostics applications. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Click-generated triazole based ferrocene-carbohydrate bioconjugates

    Indian Academy of Sciences (India)

    implicated in inflammatory disorders5 and Alzheimer's disease.6 The Cu2+ proteins are involved in oxygen binding, electron transfer and the activation of small molecules.7 As a result, a strong interest exists in the development of selective Cu2+ sensors for biologi- cal and environmental applications. A variety of Cu2+.

  20. Development and Characterization of Reactive Triangulenium Chromophores for Bioconjugation Applications

    DEFF Research Database (Denmark)

    Bora, Ilkay

    With the continuing development of advanced fluorescence techniques such as single-molecule fluorescence, time-gated detection, multiple laser pulse excitation, anisotropy decay assays and quenching experiments, fluorescent dyes are needed whose focus does not only lie on classic emission amplitude.......66 in acetonitrile. Their saliently high lifetimes of up to 23 ns in acetonitrile allow for autofluorescence eliminating time-gated measurements; combined with their strongly polarized transitions they enable the measurement of slow protein dynamics. Synthetic strategies developed by Laursen and Krebs allow...... maleimides were introduced into the azadioxa- and diazaoxa-triangulenium chromophores. The effect of the linker rigidity on the local mobility of the fluorophore on protein surfaces and the resulting retardation of initial emission anisotropy loss in time-resolved experiments were then investigated...

  1. FOXP3-specific immunity

    OpenAIRE

    Andersen, Mads Hald

    2013-01-01

    Forkhead box P3 (FOXP3)-specific cytotoxic CD8+ T cells are present among human peripheral blood mononuclear cells (PBMCs), especially in cancer patients. Such T lymphocytes are able not only to specifically recognize dendritic cells (DCs) that have been exposed to recombinant FOXP3 and regulatory T cells, but also to kill FOXP3+ malignant T cells. The natural occurrence of FOXP3-specific cytotoxic T lymphocytes among human PBMCs suggests a general role for these cells in the complex network ...

  2. Review of technical specifications

    International Nuclear Information System (INIS)

    Bedrich, M.; Scholz, D.

    1980-01-01

    The present paper deals with position and function of technical specifications before and during the manufacturing of reactor components, their structure and reasons for specific regulations due to safety philosophy and explains the cooperation of supplier, manufacturer, utilities and supervisory organizations. (RW)

  3. Place-Specific Computing

    DEFF Research Database (Denmark)

    Messeter, Jörn

    2009-01-01

    An increased interest in the notion of place has evolved in interaction design based on the proliferation of wireless infrastructures, developments in digital media, and a ‘spatial turn’ in computing. In this article, place-specific computing is suggested as a genre of interaction design...... that addresses the shaping of interactions among people, place-specific resources and global socio-technical networks, mediated by digital technology, and influenced by the structuring conditions of place. The theoretical grounding for place-specific computing is located in the meeting between conceptions...... examples of place-specific computing are presented from a series of pilot studies, conducted in close collaboration with design students in Malmö, Berlin, Cape Town and Rome, that generated 36 design concepts in the genre. Reflecting on these examples, issues in the design of place-specific computing...

  4. FOXP3-specific immunity

    DEFF Research Database (Denmark)

    Andersen, Mads Hald

    2013-01-01

    Forkhead box P3 (FOXP3)-specific cytotoxic CD8(+) T cells are present among human peripheral blood mononuclear cells (PBMCs), especially in cancer patients. Such T lymphocytes are able not only to specifically recognize dendritic cells (DCs) that have been exposed to recombinant FOXP3...... and regulatory T cells, but also to kill FOXP3(+) malignant T cells. The natural occurrence of FOXP3-specific cytotoxic T lymphocytes among human PBMCs suggests a general role for these cells in the complex network of immune regulation....

  5. TWRSview system requirements specification

    International Nuclear Information System (INIS)

    Caldwell, J.A.; Lee, A.K.

    1995-12-01

    This document provides the system requirements specification for the TWRSview software system. The TWRSview software system is being developed to integrate electronic data supporting the development of the TWRS technical baseline

  6. Place-Specific Computing

    DEFF Research Database (Denmark)

    Messeter, Jörn; Johansson, Michael

    An increased interest in the notion of place has evolved in interaction design. Proliferation of wireless infrastructure, developments in digital media, and a ‘spatial turn’ in computing provides the base for place-specific computing as a suggested new genre of interaction design. In the REcult...... project place- specific computing is explored through design oriented research. This article reports six pilot studies where design students have designed concepts for place-specific computing in Berlin (Germany), Cape Town (South Africa), Rome (Italy) and Malmö (Sweden). Background and arguments...... for place-specific computing as a genre of interaction design are described. A total number of 36 design concepts designed for 16 designated zones in the four cities are presented. An analysis of the design concepts is presented indicating potentials, possibilities and problems as directions for future...

  7. Construction and material specification

    Science.gov (United States)

    2002-01-01

    These Construction and Material Specifications are written to the Bidder before award of the : Contract and to the Contractor after award of the Contract. The sentences that direct the Contractor to perform Work are written as commands. For example, ...

  8. Test Equipment Specifications Transistor

    OpenAIRE

    Didiek Andiana Ramadan; Drs. Linga Hermanto, MMSI Drs. Linga Hermanto, MMSI

    2005-01-01

    In this paper, we design a test apparatus Transistor Specification. Specification is atype of transistor is a transistor and common emitter current reinforcement value ( βDC ). The system will provide information in the form of an LED display emits greenlight when the tested types of NPN transistor and the second LED emits blue lightwhen the tested types of PNP transistors.To test the value of β, whose value is proportional to the display used by the collectorcurrent Ic.

  9. Domain-Specific Multimodeling

    DEFF Research Database (Denmark)

    Hessellund, Anders

    Enterprise systems are complex artifacts. They are hard to build, manage, understand, and evolve. Existing software development paradigms fail to properly address challenges such as system size, domain complexity, and software evolution when development is scaled to enterprise systems. We propose...... domain-specific multimodeling as a development paradigm to tackle these challenges in a language-oriented manner. The different concerns of a system are conceptually separated and made explicit as independent domain-specific languages. This approach increases productivity and quality by raising...... this coordination problem. By systematically identifying language interactions, we can specify a coordination model for the system. Specifically, we explicitly identify name bindings and references across language boundaries. We argue that such a coordination model facilitates consistency, navigation, and guidance...

  10. Comparative Test Case Specification

    DEFF Research Database (Denmark)

    Kalyanova, Olena; Heiselberg, Per

     This document includes a definition of the comparative test cases DSF200_3 and DSF200_4, which previously described in the comparative test case specification for the test cases DSF100_3 and DSF200_3 [Ref.1]....... This document includes a definition of the comparative test cases DSF200_3 and DSF200_4, which previously described in the comparative test case specification for the test cases DSF100_3 and DSF200_3 [Ref.1]....

  11. Specification of Nonmonotonic Reasoning.

    NARCIS (Netherlands)

    Engelfriet, J.; Treur, J.

    2000-01-01

    Two levels of description of nonmonotonic reasoning are distinguished. For these levels semantical formalizations are given. The first Level is defined semantically by the notion of belief state frame, the second Level by the notion of reasoning frame. We introduce two specification languages to

  12. Specification of Nonmonotonic Reasoning

    NARCIS (Netherlands)

    Engelfriet, J.; Treur, J.

    1996-01-01

    Two levels of description of nonmonotonic reasoning are distinguished. For these levels semantical formalizations are given. The first level is defined semantically by the notion of belief state frame, the second level by the notion of reasoning frame. We introduce two specification languages to

  13. Site-Specific Innovation

    DEFF Research Database (Denmark)

    Reeh, Henrik; Hemmersam, Peter

    2015-01-01

    Currently, cities across the Northern European region are actively redeveloping their former industrial harbours. Indeed, harbours areas are essential in the long-term transition from industrial to information and experience societies; harbours are becoming sites for new businesses and residences...... question is how innovation may contribute to urban life and site-specific qualities....

  14. IDC System Specification Document.

    Energy Technology Data Exchange (ETDEWEB)

    Clifford, David J.

    2014-12-01

    This document contains the system specifications derived to satisfy the system requirements found in the IDC System Requirements Document for the IDC Reengineering Phase 2 project. Revisions Version Date Author/Team Revision Description Authorized by V1.0 12/2014 IDC Reengineering Project Team Initial delivery M. Harris

  15. Experiences with effects specifications

    DEFF Research Database (Denmark)

    Simonsen, Jesper; Hertzum, Morten; Barlach, Anders

    2011-01-01

    We describe the effects-specification process from a project that was conducted during the fall 2010 and spring of 2011 in this chapter. The project configured and implemented an electronic patient record system at a maternity ward at a hospital located in a European region. The process comprised...... for measuring effects were designed. The project is analyzed and lessons learned are discussed....

  16. Specification of Concurrent Objects

    DEFF Research Database (Denmark)

    Sørensen, Morten U.

    relation over two objects and an event. In the model, objects can be composed by parallel composition, encapsulation, and hiding of operations. Refinement between objects is defined as fair trace inclusion.A specification language is presented where objects can be specified operationally by abstract...

  17. Acquiring specific interpreting competence

    Directory of Open Access Journals (Sweden)

    Jana Zidar Forte

    2012-12-01

    Full Text Available In postgraduate interpreter training, the main objective of the course is to help trainees develop various competences, from linguistic, textual and cultural competence, to professional and specific interpreting competence. For simultaneous interpreting (SI, the main focus is on mastering the SI technique and strategies as well as on developing and strengthening communicative skills, which is discussed and illustrated with examples in the present paper. First, a brief overview is given of all the necessary competences of a professional interpreter with greater emphasis on specific interpreting competence for SI. In the second part of the paper, various approaches are described in terms of acquiring specific skills and strategies, specifically through a range of exercises. Besides interpreting entire speeches, practical courses should also consist of targeted exercises, which help trainees develop suitable coping strategies and mechanisms (later on almost automatisms, while at the same time "force" them to reflect on their individual learning process and interpreting performance. This provides a solid base on which trained interpreters can progress and develop their skills also after joining the professional sphere.

  18. Testing abstract behavioral specifications

    NARCIS (Netherlands)

    P.Y.H. Wong; R. Bubel (Richard); F.S. de Boer (Frank); C.P.T. de Gouw (Stijn); M. Gómez-Zamalloa; R Haehnle; K. Meinke; M.A. Sindhu

    2015-01-01

    htmlabstractWe present a range of testing techniques for the Abstract Behavioral Specification (ABS) language and apply them to an industrial case study. ABS is a formal modeling language for highly variable, concurrent, component-based systems. The nature of these systems makes them susceptible to

  19. Sport-specific balance.

    Science.gov (United States)

    Zemková, Erika

    2014-05-01

    This review includes the latest findings based on experimental studies addressing sport-specific balance, an area of research that has grown dramatically in recent years. The main objectives of this work were to investigate the postural sway response to different forms of exercise under laboratory and sport-specific conditions, to examine how this effect can vary with expertise, and to provide examples of the association of impaired balance with sport performance and/or increasing risk of injury. In doing so, sports where body balance is one of the limiting factors of performance were analyzed. While there are no significant differences in postural stability between athletes of different specializations and physically active individuals during standing in a standard upright position (e.g., bipedal stance), they have a better ability to maintain balance in specific conditions (e.g., while standing on a narrow area of support). Differences in magnitude of balance impairment after specific exercises (rebound jumps, repeated rotations, etc.) and mainly in speed of its readjustment to baseline are also observed. Besides some evidence on an association of greater postural sway with the increasing risk of injuries, there are many myths related to the negative influence of impaired balance on sport performance. Though this may be true for shooting or archery, findings have shown that in many other sports, highly skilled athletes are able to perform successfully in spite of increased postural sway. These findings may contribute to better understanding of the postural control system under various performance requirements. It may provide useful knowledge for designing training programs for specific sports.

  20. Real-time specifications

    DEFF Research Database (Denmark)

    David, A.; Larsen, K.G.; Legay, A.

    2015-01-01

    , with the semantics expressed in terms of Timed I/O Transition Systems. We provide constructs for refinement, consistency checking, logical and structural composition, and quotient of specifications-all indispensable ingredients of a compositional design methodology. The theory is implemented in the new tool Ecdar....... We present symbolic versions of the algorithms used in Ecdar, and demonstrate the use of the tool using a small case study in compositional verification....

  1. Empirical Test Case Specification

    DEFF Research Database (Denmark)

    Kalyanova, Olena; Heiselberg, Per

    This document includes the empirical specification on the IEA task of evaluation building energy simulation computer programs for the Double Skin Facades (DSF) constructions. There are two approaches involved into this procedure, one is the comparative approach and another is the empirical one. I....... In the comparative approach the outcomes of different software tools are compared, while in the empirical approach the modelling results are compared with the results of experimental test cases....

  2. Comparative Test Case Specification

    DEFF Research Database (Denmark)

    Kalyanova, Olena; Heiselberg, Per

    This document includes the specification on the IEA task of evaluation building energy simulation computer programs for the Double Skin Facades (DSF) constructions. There are two approaches involved into this procedure, one is the comparative approach and another is the empirical one. In the comp....... In the comparative approach the outcomes of different software tools are compared, while in the empirical approach the modelling results are compared with the results of experimental test cases. The comparative test cases include: ventilation, shading and geometry....

  3. Allergen-specific immunotherapy

    Directory of Open Access Journals (Sweden)

    Moote William

    2011-11-01

    Full Text Available Abstract Allergen-specific immunotherapy is a potentially disease-modifying therapy that is effective for the treatment of allergic rhinitis/conjunctivitis, allergic asthma and stinging insect hypersensitivity. However, despite its proven efficacy in these conditions, it is frequently underutilized in Canada. The decision to proceed with allergen-specific immunotherapy should be made on a case-by-case basis, taking into account individual patient factors such as the degree to which symptoms can be reduced by avoidance measures and pharmacological therapy, the amount and type of medication required to control symptoms, the adverse effects of pharmacological treatment, and patient preferences. Since this form of therapy carries the risk of anaphylactic reactions, it should only be prescribed by physicians who are adequately trained in the treatment of allergy. Furthermore, injections must be given under medical supervision in clinics that are equipped to manage anaphylaxis. In this article, the authors review the indications and contraindications, patient selection criteria, and the administration, safety and efficacy of allergen-specific immunotherapy.

  4. Safety detaching hook specification.

    CSIR Research Space (South Africa)

    Roux, JD

    1999-05-01

    Full Text Available Single-sided Impact Tests 14 Appendix C Record of Amendments 15 5. REFERENCES 17 4 1. INTRODUCTION 1.1 Subiect The subject of this specification is safety detaching hooks for mine shaft conveyances. According to South African Law1 it is a legal... after a full detachment in the catch plate or bell. Engineer The Mine Engineer, or his authorised sub-ordinate, legally appointed in terms of an Act to be responsible for shaft equipment. NDE Non-Destructive Examination. OEM Original Equipment...

  5. Tendering specification and contracting

    International Nuclear Information System (INIS)

    Koch, E. von

    1975-01-01

    The lecture tendering, specification and contracting is prepared in two parts: This first part deals with technical aspects while part two features the commercial and legal situation in the partnership of two: the supplier of the fuel bundles and the utility. In this lecture a look is given on the way how a supplier can offer its fuel and some certain points are mentioned which are important to compare the bid of one competitor to the other. The major points are summarized which are or at least should be in an offer so as to find out which offer is the best. (orig./FW) [de

  6. Task Specific Tremors.

    Science.gov (United States)

    Friedman, Joseph H

    2015-07-01

    A patient reported bilateral hand tremors when writing but not with other tasks. These "task specific" tremors are considered subcategories of essential tremor. Primary writing tremor, in which the tremor occurs only with writing, is probably the most common. The important teaching point is that the "standard" tremor assessment, watching the patient holding a sustained posture and touching his finger to the examiner's and then back to the nose is not adequate. Patients should be tested doing the activity that causes them the most difficulty.

  7. [Pregnancy-specific dermatoses].

    Science.gov (United States)

    Soutou, B; Aractingi, S

    2015-03-01

    Pregnancy-specific dermatoses include polymorphic eruption of pregnancy, atopic eczema of pregnancy, and pemphigoid gestationis. Intrahepatic cholestasis of pregnancy and impetigo herpetiformis are not real pregnancy-specific dermatoses but they are important to know considering the fetal and maternal risks. Polymorphic eruption of pregnancy is a pruritic disease that usually occurs in primiparous women during the last trimester of pregnancy. Atopic eczema of pregnancy is still controversial as an entity covering conditions with eczematous lesions, prurigo, or folliculitis, and inconstantly associated with a personal history of atopy. Skin biopsy with direct immunofluorescence or search for serum anti-BPAg1 (180kD) NC16a antibodies is mandatory in pruritic dermatoses of pregnancy in order to rule out pemphigoid gestationis. Serum bile salts levels should be tested whenever a generalized pruritus develops during pregnancy in order to rule out intrahepatic cholestasis. Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  8. Disease specific protein corona

    Science.gov (United States)

    Rahman, M.; Mahmoudi, M.

    2015-03-01

    It is now well accepted that upon their entrance into the biological environments, the surface of nanomaterials would be covered by various biomacromolecules (e.g., proteins and lipids). The absorption of these biomolecules, so called `protein corona', onto the surface of (nano)biomaterials confers them a new `biological identity'. Although the formation of protein coronas on the surface of nanoparticles has been widely investigated, there are few reports on the effect of various diseases on the biological identity of nanoparticles. As the type of diseases may tremendously changes the composition of the protein source (e.g., human plasma/serum), one can expect that amount and composition of associated proteins in the corona composition may be varied, in disease type manner. Here, we show that corona coated silica and polystyrene nanoparticles (after interaction with in the plasma of the healthy individuals) could induce unfolding of fibrinogen, which promotes release of the inflammatory cytokines. However, no considerable releases of inflammatory cytokines were observed for corona coated graphene sheets. In contrast, the obtained corona coated silica and polystyrene nanoparticles from the hypofibrinogenemia patients could not induce inflammatory cytokine release where graphene sheets do. Therefore, one can expect that disease-specific protein coronas can provide a novel approach for applying nanomedicine to personalized medicine, improving diagnosis and treatment of different diseases tailored to the specific conditions and circumstances.

  9. Selective labelling of stromal cell-derived factor 1α with carboxyfluorescein to study receptor internalisation.

    Science.gov (United States)

    Bellmann-Sickert, Kathrin; Baumann, Lars; Beck-Sickinger, Annette G

    2010-10-01

    SDF1α plays an important role in the regeneration of injured tissue after ischemia or stroke by inducing the migration of progenitor cells. In order to study the function of this therapeutically relevant chemokine site-specific protein labelling is of great interest. However, modification of SDF1α is complicated because of its complex tertiary structure. Here, we describe the first site-specific fluorescent modification of SDF1α by EPL. We recombinantly expressed SDF1α (1-49) by intein-mediated protein expression. The C-terminal peptide SDF1α (50-68) was synthesised by SPPS and selectively labelled with carboxyfluorescein at Lys(56). In a cell migration assay, M-[K(56)(CF)]SDF1α showed a clear potency to induce chemotaxis of human T-cell leukaemia cells. Microscopic analysis on HEK293 cells transfected with the CXCR4 revealed specific binding of the fluorescent ligand. Furthermore, receptor-induced internalisation of the ligand could be visualised. These results show that site-specific modification of SDF1α yields in a biologically functional molecule that allows the characterisation of CXCR4 production of cells on a molecular level. © 2010 European Peptide Society and John Wiley & Sons, Ltd.

  10. Site specific plan

    International Nuclear Information System (INIS)

    Hutchison, J.; Jernigan, G.

    1989-12-01

    The Environmental Restoration and Waste Management Five-Year Plan (FYP) covers the period for FY 1989 through FY 1995. The plan establishes a Department of Energy -- Headquarters (DOE-HQ) agenda for cleanup and compliance against which overall progress can be measured. The FYP covers three areas: Corrective Activities, Environmental Restoration, and Waste Management Operations. Corrective Activities are those activities necessary to bring active or standby facilities into compliance with local, state, and federal environmental regulations. Environmental restoration activities include the assessment and cleanup of surplus facilities and inactive waste sites. Waste management operations includes the treatment, storage, and disposal of wastes which are generated as a result of ongoing operations. This Site Specific Plan (SSP) has been prepared by the Savannah River Site (SRS) in order to show how environmental restoration and waste management activities that were identified during the preparation of the FYP will be implemented, tracked, and reported. The SSP describes DOE Savannah River (DOE-SR) and operating contractor, Westinghouse Savannah River Company (WSRC), organizations that are responsible, for undertaking the activities identified in this plan. The SSP has been prepared in accordance with guidance received from DOE-HQ. DOE-SR is accountable to DOE-HQ for the implementation of this plan. 8 refs., 46 figs., 23 tabs

  11. ADANS database specification

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-01-16

    The purpose of the Air Mobility Command (AMC) Deployment Analysis System (ADANS) Database Specification (DS) is to describe the database organization and storage allocation and to provide the detailed data model of the physical design and information necessary for the construction of the parts of the database (e.g., tables, indexes, rules, defaults). The DS includes entity relationship diagrams, table and field definitions, reports on other database objects, and a description of the ADANS data dictionary. ADANS is the automated system used by Headquarters AMC and the Tanker Airlift Control Center (TACC) for airlift planning and scheduling of peacetime and contingency operations as well as for deliberate planning. ADANS also supports planning and scheduling of Air Refueling Events by the TACC and the unit-level tanker schedulers. ADANS receives input in the form of movement requirements and air refueling requests. It provides a suite of tools for planners to manipulate these requirements/requests against mobility assets and to develop, analyze, and distribute schedules. Analysis tools are provided for assessing the products of the scheduling subsystems, and editing capabilities support the refinement of schedules. A reporting capability provides formatted screen, print, and/or file outputs of various standard reports. An interface subsystem handles message traffic to and from external systems. The database is an integral part of the functionality summarized above.

  12. [Dermatomyositis-specific antibodies].

    Science.gov (United States)

    Bodoki, L; Nagy-Vincze, M; Griger, Z; Dankó, K

    2015-05-01

    Idiopathic inflammatory myopathies are chronic systemic autoimmune diseases characterized by symmetrical proximal muscle weakness. The clinicopathological subdivision nowadays appears to be obsolete which is why the immunoserological classification has been developed. Dermatomyositis represents one the most important subsets of idiopathic inflammatory myopathy and dermatomyositis-specific autoantibodies play a significant role in this subset. The aim of this article was to present these autoantibodies with the help of the literature. This article presents the most important information about dermatomyositis including not only the classical anti-Mi-2 autoantibody but also the recently detected anti-TIF1γ, anti-NXP2, anti-SAE and anti-MDA5 autoantibodies. The focus is on the frequency of these autoantibodies, the associated symptoms in adult and juvenile dermatomyositis cases and some special aspects from the literature. All of the studies confirmed that these autoantibodies are particularly detectable in dermatomyositis. The results from the literature have recently shown that the frequency of the autoantibodies detected in juvenile cases is higher than the frequency of traditional autoantibodies (e.g. anti-Jo-1, anti-Mi-2 and anti-SRP). It is useful to detect these autoantibodies in order to be able to make a better assessment of the clinical symptoms and prognosis during the course of the disease.

  13. Intent Specifications: An Approach to Building Human-Centered Specifications

    Science.gov (United States)

    Leveson, Nancy G.

    1999-01-01

    This paper examines and proposes an approach to writing software specifications, based on research in systems theory, cognitive psychology, and human-machine interaction. The goal is to provide specifications that support human problem solving and the tasks that humans must perform in software development and evolution. A type of specification, called intent specifications, is constructed upon this underlying foundation.

  14. Application of Quantum-Dot Conjugates for Detection and Subspecies Differentiation of Vibrio cholerae by Optical Methods

    Science.gov (United States)

    Erohin, P. S.; Utkin, D. V.; Kouklev, V. E.; Ossina, N. A.; Miheeva, E. A.; Alenkina, T. V.

    2016-03-01

    The application of bioconjugates of specific antibodies and CdSe quantum dots to identify two serovariants of Vibrio cholerae using fluorescence microscopy and optical spectroscopy is considered. It is found that a mixture of different bioconjugates with different emission maxima can be used without affecting the specificity of the method. Different V. cholerae serovariants are colored differently in fl uorescence microscopy (bright green and bright yellow), thereby allowing subspecies differentiation. The absorption spectrum of the bacterial suspension changed with homologous antigens in the sample and did not change with heterologous antigens. It is shown that the quantum-dot bioconjugates can serve as an alternative to the traditional fluorescence and agglutination diagnostics.

  15. Specification-Based Testing Via Domain Specific Language

    Science.gov (United States)

    Sroka, Michal; Nagy, Roman; Fisch, Dominik

    2014-12-01

    The article presents tCF (testCaseFramework) - a domain specific language with corresponding toolchain for specification-based software testing of embedded software. tCF is designed for efficient preparation of maintainable and intelligible test cases and for testing process automation, as it allows to generate platform specific test cases for various testing levels. The article describes the essential parts of the tCF meta-model and the applied concept of platform specific test cases generators.

  16. Adequate procedures for specific exams

    International Nuclear Information System (INIS)

    Staevie, G.L.G.; Gattringer, D.K.; Dal Mas, C.R.; Tessman, M.

    1996-01-01

    Some ideal procedures for specific radiographic exams are briefly presented. The aim is to improve the quality standard, establishing a specific method for each exam in order to decrease films waste and reduce the patient dose exposure

  17. VHDL Specification Methodology from High-level Specification

    OpenAIRE

    M. Benmohammed; S. Merniz

    2005-01-01

    Design complexity has been increasing exponentially this last decade. In order to cope with such an increase and to keep up designers' productivity, higher level specifications were required. Moreover new synthesis systems, starting with a high level specification, have been developed in order to automate and speed up processor design. This study presents a VHDL specification methodology aimed to extend structured design methodologies to the behavioral level. The goal is t...

  18. In vitro and in vivo evaluation of the bifunctional chelator NODIA-Me in combination with a prostate-specific membrane antigen targeting vector.

    Science.gov (United States)

    Läppchen, Tilman; Kiefer, Yvonne; Holland, Jason P; Bartholomä, Mark D

    2018-03-10

    We recently developed a chelating platform based on the macrocycle 1,4,7-triazacyclononane with up to three five-membered azaheterocyclic arms for complexation of the PET nuclides gallium-68 and copper-64. The main objective of this study was to evaluate the stability and pharmacokinetics of 68 Ga- and 64 Cu-complexes of the bifunctional chelator NODIA-Me 1 covalently bound to a PSMA targeting vector in vivo. NODIA-Me 1 was conjugated to the PSMA targeting Glu-NH-CO-NH-Lys moiety to give the bioconjugate NODIA-Me-NaI-Ahx-PSMA 4. The stability of [ 68 Ga]4 and [ 64 Cu]4 was assessed in vitro by serum stability studies. The PSMA binding affinity was determined in competitive cell experiments in LNCaP cells using 68 Ga-PSMA-HBED-CC as radioligand. The stability and pharmacokinetics of [ 68 Ga]4 and [ 64 Cu]4 was evaluated by PET imaging and ex vivo biodistribution studies in mice bearing subcutaneous LNCaP tumors. In human serum, [ 68 Ga]4 and [ 64 Cu]4 remained intact to 85% (3 h) and 92% (24 h), respectively. Nature of the metal chelate influenced PSMA binding affinity with IC 50 of 233 ± 10 nM for uncomplexed 4, 681 ± 7 nM for Cu-4 and 176 ± 10 nM for Ga-4. In animal studies, [ 68 Ga]4 and [ 64 Cu]4 revealed low uptake (≤1% IA g -1 ) in the majority of organs. Kidney uptake at 1 h p.i. was 6.28 ± 0.92% IA g -1 and 4.96 ± 0.79% IA g -1 and specific tumor uptake was 1.33 ± 0.46% IA g -1 and 2.15 ± 0.38% IA g -1 for [ 68 Ga]4 and [ 64 Cu]4, respectively. The bifunctional chelator NODIA-Me 1 was successfully conjugated to a PSMA targeting moiety. In small-animal PET imaging and ex vivo biodistribution studies, 68 Ga- and 64 Cu-labelled conjugates specifically delineated PSMA-positive LNCaP tumors and exhibited rapid renal clearance from non-target tissues with no significant demetallation/transchelation in vivo. The results support further development of this novel chelating platform for production of 68 Ga- and 64 Cu

  19. Specification-Based Testing Via Domain Specific Language

    Directory of Open Access Journals (Sweden)

    Sroka Michal

    2014-12-01

    Full Text Available The article presents tCF (testCaseFramework - a domain specific language with corresponding toolchain for specification-based software testing of embedded software. tCF is designed for efficient preparation of maintainable and intelligible test cases and for testing process automation, as it allows to generate platform specific test cases for various testing levels. The article describes the essential parts of the tCF meta-model and the applied concept of platform specific test cases generators.

  20. Age-specific serum prostate specific antigen ranges among ...

    African Journals Online (AJOL)

    Introduction: Serum prostate specific antigen (PSA) levels increase with age and varies among different races and communities. The study was aimed at defining the age-specific reference ranges of serum PSA in our environment. Methods: We evaluated the relationship between age and serum PSA levels and the ...

  1. The Order Specification Decoupling Line

    DEFF Research Database (Denmark)

    Hansen, Benjamin Loer; Hvam, Lars

    2004-01-01

    This paper discusses the important issue in build-to-order production of separating innovative long term engineering processes from day-to-day variant specification processes, i.e. the processes creating specifications such as bill-of-materials, drawings, text descriptions, routings etc. The paper...... find some welding specifications or product descriptions which are standard for every order, while there may be other specifications, such as bill-of-materials and drawings, which are customized. Through a use of this concept it becomes possible to discuss different levels of OSDL and different variant...

  2. [Multilingualism and specific language impairment].

    Science.gov (United States)

    Arkkila, Eva; Smolander, Sini; Laasonen, Marja

    2013-01-01

    Specific language impairment is one of the most common developmental disturbances in childhood. With the increase of the foreign language population group an increasing number of children assimilating several languages and causing concern in language development attend clinical examinations. Knowledge of factors underlying the specific language impairment and the specific impairment in general, special features of language development of those learning several languages, as well as the assessment and support of the linguistic skills of a multilingual child is essential. The risk of long-term problems and marginalization is high for children having specific language impairment.

  3. Hanford Site environmental management specification

    Energy Technology Data Exchange (ETDEWEB)

    Grygiel, M.L.

    1998-06-10

    The US Department of Energy, Richland Operations Office (RL) uses this Hanford Site Environmental Management Specification (Specification) to document top-level mission requirements and planning assumptions for the prime contractors involved in Hanford Site cleanup and infrastructure activities under the responsibility of the US Department of Energy, Office of Environmental Management. This Specification describes at a top level the activities, facilities, and infrastructure necessary to accomplish the cleanup of the Hanford Site and assigns this scope to Site contractors and their respective projects. This Specification also references the key National Environmental Policy Act of 1969 (NEPA), Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA), and safety documentation necessary to accurately describe the cleanup at a summary level. The information contained in this document reflects RL`s application of values, priorities, and critical success factors expressed by those involved with and affected by the Hanford Site project. The prime contractors and their projects develop complete baselines and work plans to implement this Specification. These lower-level documents and the data that support them, together with this Specification, represent the full set of requirements applicable to the contractors and their projects. Figure 1-1 shows the relationship of this Specification to the other basic Site documents. Similarly, the documents, orders, and laws referenced in this specification represent only the most salient sources of requirements. Current and contractual reference data contain a complete set of source documents.

  4. Measuring wood specific gravity, correctly

    Science.gov (United States)

    G. Bruce Williamson; Michael C. Wiemann

    2010-01-01

    The specific gravity (SG) of wood is a measure of the amount of structural material a tree species allocates to support and strength. In recent years, wood specific gravity, traditionally a forester’s variable, has become the domain of ecologists exploring the universality of plant functional traits and conservationists estimating global carbon stocks. While these...

  5. A parallel approach for subwavelength molecular surgery using gene-specific positioned metal nanoparticles as laser light antennas.

    Science.gov (United States)

    Csaki, Andrea; Garwe, Frank; Steinbrück, Andrea; Maubach, Gunter; Festag, Grit; Weise, Anja; Riemann, Iris; König, Karsten; Fritzsche, Wolfgang

    2007-02-01

    An optical technique for the parallel manipulation of nanoscale structures with molecular resolution is presented. Bioconjugated metal nanoparticles are thereby positioned at the location of interest, such as, e.g., certain DNA sequences along metaphase chromosomes, prior to pulsed laser light irradiation of the whole sample. The nanoparticles are designed to absorb the introduced energy highly efficiently, in that way acting as nanoantenna. As result of the interaction, structural changes of the sample with subwavelength dimensions and nanoscale precision are observed at the location of the particles. The process leading to the nanolocalized destruction is caused by particle ablation as well as thermal damage of the surrounding material.

  6. Standard technical specifications, Westinghouse Plants: Specifications. Volume 1, Revision 1

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-04-01

    This NUREG contains the improved Standard Technical Specifications (STS) for Westinghouse plants. Revision 1 incorporates the cumulative changes to Revision 0, which was published in September 1992. The changes reflected in Revision 1 resulted from the experience gained from license amendment applications to convert to these improved STS or to adopt partial improvements to existing technical specifications. This NUREG is the result of extensive public technical meetings and discussions between the Nuclear Regulatory Commission (NRC) staff and various nuclear power plant licensees, Nuclear Steam Supply System (NSSS) Owners Groups, specifically the Westinghouse Owners Group (WOG), NSSS vendors, and the Nuclear Energy Institute (NEI). The improved STS were developed based on the criteria in the Final Commission Policy Statement on Technical Specifications Improvements for Nuclear Power Reactors, dated July 22, 1993 (58 FR 39132). Licensees are encouraged to upgrade their technical specifications consistent with those criteria and conforming, to the extent practical and consistent with the licensing basis for the facility, to Revision 1 to the improved STS. The Commission continues to place the highest priority on requests for complete conversions to the improved STS. Licensees adopting portions of the improved STS to existing technical specifications should adopt all related requirements, as applicable, to achieve a high degree of standardization and consistency.

  7. Patient-Specific Computational Modeling

    CERN Document Server

    Peña, Estefanía

    2012-01-01

    This book addresses patient-specific modeling. It integrates computational modeling, experimental procedures, imagine clinical segmentation and mesh generation with the finite element method (FEM) to solve problems in computational biomedicine and bioengineering. Specific areas of interest include cardiovascular problems, ocular and muscular systems and soft tissue modeling. Patient-specific modeling has been the subject of serious research over the last seven years and interest in the area is continually growing and this area is expected to further develop in the near future.

  8. Specificity of immunoassays. Pt. 2

    International Nuclear Information System (INIS)

    Pratt, J.J.; Woldring, M.G.; Boonman, R.; Kittikool, J.

    1979-01-01

    Practical aspects of the measurement of the specificity of immunoassay are reviewed. Antibody heterogeneity in an antiserum makes a pragmatic rather than a theoretical approach necessary. A new method for the measurement of immunoassay specificity is described. This method is based on the errors caused by the cross-reacting antigens and is directly relevant to the validity of results obtained by immunoassay methods. The effect of selectively blocking the least specific antibodies in antisera raised against steroid haptens is tested. The practical consequences of these considerations are tested using steroid radioimmunoassay and enzyme-immunoassay. (orig.) [de

  9. Bid specifications and bid evaluations

    International Nuclear Information System (INIS)

    Zijl, N.A. van

    1977-01-01

    Bid specifications are in view of the size of these projects important and comprehensive documents. The basic content and set up of the specifications are discussed such as: 1) Bid invitation letter, 2) instruction to bidders, 3) draft contract (terms and conditions), 4) technical specifications, 5) side data and information. - The evaluations of bids for nuclear power stations is due to the complexity of such bids a difficult undertaking. Evaluation methods and approaches which can be applied for such bid evaluations are discussed as well as the preparations which are required for carrying out such evaluations. (orig.) [de

  10. Youth job market specific features

    Directory of Open Access Journals (Sweden)

    Evgeniya Yu. Zhuravleva

    2011-05-01

    Full Text Available The article considers youth job market peculiarities, its specific features and regulation means, determines theoretical and application tasks of qualitative and quantitative comparison of vocations, which are highly in demand at the job market.

  11. GPS Civil Monitoring Performance Specification

    Science.gov (United States)

    2009-02-10

    This Civil Monitoring Performance Specification (CMPS) is published and maintained at : the direction of the Program Manager for Civil Applications, Global Positioning Systems : Wing (GPSW). The purpose of this document is to provide a comprehensive ...

  12. Grade 6 Science Curriculum Specifications.

    Science.gov (United States)

    Alberta Dept. of Education, Edmonton. Curriculum Branch.

    This material describes curriculum specifications for grade 6 science in Alberta. Emphases recommended are: (1) process skills (50%); (2) psychomotor skills (10%); (3) attitudes (10%); and (4) subject matter (30%). Priorities within each category are identified. (YP)

  13. [Specific immunotherapy in allergic asthma].

    Science.gov (United States)

    Bergmann, K-Ch

    2003-02-01

    Asthma is a chronic inflammatory disease of the airways considered as the result of a deregulated immune response, with a pivotal role played the TH2 cytokine phenotype. The treatment of allergic asthma is based on allergen avoidance, pharmacotherapy, allergen-specific immunotherapy, and patient education. Specific immunotherapy is able to normalize the upraised TH2 cytokine phenotype and indicated for patients who have demonstrable evidence of IgE-mediated clinically relevant sensitisation to pollens, house-dust mites and cat or dog allergens. The exposure to the allergens must be related to the appearance of symptoms. Randomised controlled trials in asthma have found that immunotherapy was effective (evidence 1a, strength of recommendation A) in reducing specific and non-specific bronchial hyperreactivity, asthmatic symptoms, and medication requirements. Patient selection is important and efficacy must be balanced against the risk of side effects. Immunotherapy should be used by pneumologists with a training in allergology in patients with mild asthma.

  14. ATR Technical Specification Upgrade Program

    International Nuclear Information System (INIS)

    McCracken, R.T.; Durney, J.L.; Freund, G.A.

    1990-01-01

    The Advanced Test Reactor (ATR) is a 250 MW, uranium-aluminum fueled test reactor which began full power operation in 1969. The initial operation was controlled by an Operating Limits document based on the original Safety Analysis Report. Additional safety bases were later developed to support Technical Specifications which were approved and implemented in 1977. The Technical Specifications which were initially developed with content and format specified in ANSI/ANS--15.1, ''The Development of Technical Specifications for Research Reactors.'' The safety basis documentation and the Technical Specifications have been updated as required to maintain them current with the ATR facility configuration. All revisions have been made with a content, format and style consistent with the original. A major, two-phase program to upgrade the content, format and style is in progress. This paper describes the first phase of this program

  15. ATR technical specification upgrade program

    International Nuclear Information System (INIS)

    McCraken, R.T.; Durney, J.L.; Freund, G.A.

    1990-01-01

    The Advanced Test Reactor (ATR) is a 250 MW, uranium-aluminum fueled test reactor which began full power operation in 1969. The initial operation was controlled by an Operating Limits document based on the original Safety Analysis Report. Additional safety bases were later developed to support Technical Specifications which were approved and implemented in 1977. The Technical Specifications were initially developed with the content and format specified in ANSI/ANS-15.1, The Development of Technical Specifications for Research Reactors. The safety basis documentation and the Technical Specifications have been updated as required to maintain them current with the ATR facility configuration. All revisions have been made with a content, format and style consistent with the original. A major, two-phase program to upgrade the content, format and style is in progress. This paper describes the first phase of this program

  16. GFF Specification for SAR Systems

    Energy Technology Data Exchange (ETDEWEB)

    Sweet, Nathan [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bielek, Timothy P. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Matthews, John D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Coakley, Henry John [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Pan, Len [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-08-01

    This document provides the basic GFF format definition for a GFF file. This document covers the contents of the main header and the basic GFF file structure. The contents of specific extensions are covered in a separate document.

  17. Patient-specific surgical simulation.

    Science.gov (United States)

    Soler, Luc; Marescaux, Jacques

    2008-02-01

    Technological innovations of the twentieth century have provided medicine and surgery with new tools for education and therapy definition. Thus, by combining Medical Imaging and Virtual Reality, patient-specific applications providing preoperative surgical simulation have become possible.

  18. Base compaction specification feasibility analysis.

    Science.gov (United States)

    2012-12-01

    The objective of this research is to establish the technical engineering and cost : analysis concepts that will enable WisDOT management to objectively evaluate the : feasibility of switching construction specification philosophies for aggregate base...

  19. CCL22-specific T Cells

    DEFF Research Database (Denmark)

    Martinenaite, Evelina; Munir Ahmad, Shamaila; Hansen, Morten

    2016-01-01

    Tumor cells and tumor-infiltrating macrophages produce the chemokine CCL22, which attracts regulatory T cells (Tregs) into the tumor microenvironment, decreasing anticancer immunity. Here, we investigated the possibility of targeting CCL22-expressing cells by activating specific T cells. We...... analyzed the CCL22 protein signal sequence, identifying a human leukocyte antigen A2- (HLA-A2-) restricted peptide epitope, which we then used to stimulate peripheral blood mononuclear cells (PMBCs) to expand populations of CCL22-specific T cells in vitro. T cells recognizing an epitope derived from...... the signal-peptide of CCL22 will recognize CCL22-expressing cells even though CCL22 is secreted out of the cell. CCL22-specific T cells recognized and killed CCL22-expressing cancer cells. Furthermore, CCL22-specific T cells lysed acute monocytic leukemia cells in a CCL22 expression-dependent manner. Using...

  20. XML specifications DanRIS

    DEFF Research Database (Denmark)

    2009-01-01

    XML specifications for DanRIS (Danish Registration- og InformationsSystem), where the the aim is: Improved exchange of data Improved data processing Ensuring future access to all gathered data from the year 1999 until now......XML specifications for DanRIS (Danish Registration- og InformationsSystem), where the the aim is: Improved exchange of data Improved data processing Ensuring future access to all gathered data from the year 1999 until now...

  1. CASL, the Common Algebraic Specification Language

    DEFF Research Database (Denmark)

    Mossakowski, Till; Haxthausen, Anne Elisabeth; Sannella, Donald

    2008-01-01

    CASL is an expressive specification language that has been designed to supersede many existing algebraic specification languages and provide a standard. CASL consists of several layers, including basic (unstructured) specifications, structured specifications and architectural specifications...

  2. Technical specification for vacuum systems

    International Nuclear Information System (INIS)

    Khaw, J.

    1987-01-01

    The vacuum systems at the Stanford Linear Accelerator Center (SLAC) are primarily of all-metal construction and operate at pressures from 10 -5 to 10 -11 Torr. The primary gas loads during operation result from thermal desorption and beam-induced desorption from the vacuum chamber walls. These desorption rates can be extremely high in the case of hydrocarbons and other contaminants. These specifications place a major emphasis on eliminating contamination sources. The specifications and procedures have been written to insure the cleanliness and vacuum integrity of all SLAC vacuum systems, and to assist personnel involved with SLAC vacuum systems in choosing and designing components that are compatible with existing systems and meet the quality and reliability of SLAC vacuum standards. The specification includes requirements on design, procurement, fabrication, chemical cleaning, clean room practices, welding and brazing, helium leak testing, residual gas analyzer testing, bakeout, venting, and pumpdown. Also appended are specifications regarding acceptable vendors, isopropyl alcohol, bakeable valve cleaning procedure, mechanical engineering safety inspection, notes on synchrotron radiation, and specifications of numerous individual components

  3. Industry specific financial distress modeling

    Directory of Open Access Journals (Sweden)

    Naz Sayari

    2017-01-01

    Full Text Available This study investigates uncertainty levels of various industries and tries to determine financial ratios having the greatest information content in determining the set of industry characteristics. It then uses these ratios to develop industry specific financial distress models. First, we employ factor analysis to determine the set of ratios that are most informative in specified industries. Second, we use a method based on the concept of entropy to measure the level of uncertainty in industries and also to single out the ratios that best reflect the uncertainty levels in specific industries. Finally, we conduct a logistic regression analysis and derive industry specific financial distress models which can be used to judge the predictive ability of selected financial ratios for each industry. The results show that financial ratios do indeed echo industry characteristics and that information content of specific ratios varies among different industries. Our findings show diverging impact of industry characteristics on companies; and thus the necessity of constructing industry specific financial distress models.

  4. Standard Technical Specifications, Westinghouse plants

    International Nuclear Information System (INIS)

    1992-09-01

    This NUREG contains improved Standard Technical Specifications (STS) for Westinghouse Plants and documents the positions of the Nuclear Regulatory Commission based on the Westinghouse Owners Group's proposed STS. This document is the result of extensive technical meetings and discussions among the NRC staff, the Nuclear Steam Supply System (NSSS) Owners Groups, the NSSS vendors, and the Nuclear Management and Resources Council (NUMARC). The improved STS were developed based on the criteria in the interim Commission Policy Statement on Technical Specification Improvements for Nuclear Power Reactors, dated February 6, 1987. The improved STS will be used as the basis for individual nuclear power plant licensees to develop improved plant-specific technical specifications. This report contains three volumes. This document, Volume 1, contains the Specifications for all chapters and sections of the improved STS. Volume 2 contains the Bases for Chapters 2.0 and 3.0, and Sections 3.1--3.3 of the improved STS. Volume 3 contains the Bases for Sections 3.4--3.9 of the improved STS

  5. Technical specification for vacuum systems

    Energy Technology Data Exchange (ETDEWEB)

    Khaw, J. (ed.)

    1987-01-01

    The vacuum systems at the Stanford Linear Accelerator Center (SLAC) are primarily of all-metal construction and operate at pressures from 10/sup -5/ to 10/sup -11/ Torr. The primary gas loads during operation result from thermal desorption and beam-induced desorption from the vacuum chamber walls. These desorption rates can be extremely high in the case of hydrocarbons and other contaminants. These specifications place a major emphasis on eliminating contamination sources. The specifications and procedures have been written to insure the cleanliness and vacuum integrity of all SLAC vacuum systems, and to assist personnel involved with SLAC vacuum systems in choosing and designing components that are compatible with existing systems and meet the quality and reliability of SLAC vacuum standards. The specification includes requirements on design, procurement, fabrication, chemical cleaning, clean room practices, welding and brazing, helium leak testing, residual gas analyzer testing, bakeout, venting, and pumpdown. Also appended are specifications regarding acceptable vendors, isopropyl alcohol, bakeable valve cleaning procedure, mechanical engineering safety inspection, notes on synchrotron radiation, and specifications of numerous individual components. (LEW)

  6. Age‑specific Serum Prostate Specific Antigen Ranges Among ...

    African Journals Online (AJOL)

    ethnic differences.[16] Although similar studies have been presented for a number of different groups of men and few studies have looked at the pattern of serum PSA among Nigerians[17‑20] but no such studies on normal serum PSA ranges and the age‑specific pattern have been carried out among healthy Nigerian men.

  7. Compiler writing system detail design specification. Volume 1: Language specification

    Science.gov (United States)

    Arthur, W. J.

    1974-01-01

    Construction within the Meta language for both language and target machine specification is reported. The elements of the function language as a meaning and syntax are presented, and the structure of the target language is described which represents the target dependent object text representation of applications programs.

  8. ROS signalling - specificity is required

    DEFF Research Database (Denmark)

    Møller, Ian M; Sweetlove, Lee J

    2010-01-01

    Reactive oxygen species (ROS) production increases in plants under stress. ROS can damage cellular components, but they can also act in signal transduction to help the cell counteract the oxidative damage in the stressed compartment. H2O2 might induce a general stress response, but it does not have...... the required specificity to selectively regulate nuclear genes required for dealing with localized stress, e.g. in chloroplasts or mitochondria. Here we argue that peptides deriving from proteolytic breakdown of oxidatively damaged proteins have the requisite specificity to act as secondary ROS messengers...... and regulate source-specific genes and in this way contribute to retrograde ROS signalling during oxidative stress. Likewise, unmodified peptides deriving from the breakdown of redundant proteins could help coordinate organellar and nuclear gene expression...

  9. Methylation-Specific PCR Unraveled

    Directory of Open Access Journals (Sweden)

    Sarah Derks

    2004-01-01

    Full Text Available Methylation‐specific PCR (MSP is a simple, quick and cost‐effective method to analyze the DNA methylation status of virtually any group of CpG sites within a CpG island. The technique comprises two parts: (1 sodium bisulfite conversion of unmethylated cytosine's to uracil under conditions whereby methylated cytosines remains unchanged and (2 detection of the bisulfite induced sequence differences by PCR using specific primer sets for both unmethylated and methylated DNA. This review discusses the critical parameters of MSP and presents an overview of the available MSP variants and the (clinical applications.

  10. 76 FR 7482 - Operations Specifications

    Science.gov (United States)

    2011-02-10

    ...: The final rule provides administrative process for a an administrative appeals process foreign... administrative appeals process, the rule may result in some benefits to foreign air carriers and foreign persons... will apply for operations specifications. Furthermore, it creates an administrative appeals process...

  11. Human-Specific Endogenous Retroviruses

    Directory of Open Access Journals (Sweden)

    Anton Buzdin

    2007-01-01

    Full Text Available This review focuses on a small family of human-specific genomic repetitive elements, presented by 134 members that shaped ~330 kb of the human DNA. Although modest in terms of its copy number, this group appeared to modify the human genome activity by endogenizing ~50 functional copies of viral genes that may have important implications in the immune response, cancer progression, and antiretroviral host defense. A total of 134 potential promoters and enhancers have been added to the human DNA, about 50% of them in the close gene vicinity and 22% in gene introns. For 60 such human-specific promoters, their activity was confirmed by in vivo assays, with the transcriptional level varying ~1000-fold from hardly detectable to as high as ~3% of β-actin transcript level. New polyadenylation signals have been provided to four human RNAs, and a number of potential antisense regulators of known human genes appeared due to human-specific retroviral insertional activity. This information is given here in the context of other major genomic changes underlining differences between human and chimpanzee DNAs. Finally, a comprehensive database, is available for download, of human-specific and polymorphic endogenous retroviruses is presented, which encompasses the data on their genomic localization, primary structure, encoded viral genes, human gene neighborhood, transcriptional activity, and methylation status.

  12. THE SPECIFICITY OF INTRACOMMUNITY TRANSACTIONS

    Directory of Open Access Journals (Sweden)

    PALIU-POPA LUCIA

    2011-09-01

    Full Text Available Considered from the perspective of Romania's accession to the European Union, we can say that starting with 1 January 2007, foreign trade transactions were delimited in relation to the customs borders in intra-Community transactions and international transactions. In this context, the way of conducting these operations is influenced by both the economic and financial features specific to both categories of transactions, that relate to the economic character of the activity, the diversity and specificity of the foreign trade activity, transport of goods, the complexity and regulation of intra-Community and international commercial transactions, and by the specific features of each category of transaction. Starting from the consideration that the economic and financial characteristics of foreign trade activity, specific to intra-Community commercial transactions, have a significant influence in the organization and management of accounting of the entities involved in such transactions, determining in a greater or lesser extent, the way of capitalization of the financial and accounting information in the processes of analysis, decision and control, in this paper we proposed to address the features of intra-Community trade.

  13. [Specificities in children wound healing].

    Science.gov (United States)

    Sanchez, J; Antonicelli, F; Tuton, D; Mazouz Dorval, S; François, C

    2016-10-01

    Children have specific characteristics of wound healing. The aim of this study was to describe the specific clinical characteristics of wounds healing in children and to present the current knowledge on the specific mechanisms with regard to infant age. The tissue insult or injury in fetus can heal without scar, mainly due to reduced granulation tissue associated to diminished or even no inflammatory phase, modified extracellular matrix such as the concentration of hyaluronic acid in amniotic liquid, expression and arrangement of collagen and tenascin. Thickness of children skin is a serious negative factor in case of trauma, whereas poor co-morbidities and efficient growth tissue mechanisms are beneficial to good evolution, even in cases of extensive damage and loss of tissue. The subsequent tissue mechanical forces, wound healing during childhood, spanning from the age of 2 until the end of puberty, is associated with more hypertrophic scars, both in duration and in intensity. Consequently, unnecessary surgery has to be avoided during this period when possible, and children with abnormal or pathologic wound healing should benefit from complementary treatments (hydration, massage, brace, silicone, hydrotherapy…), which represent efficient factors to minimize tissue scarring. After wound healing, the growth body rate can be responsible for specific complications, such as contractures, alopecia, and scar intussusceptions. Its evolutionary character implies the need of an attentive follow-up until adult age. Psychologic repercussions, as a consequence of pathologic scars, must be prevented and investigated by the surgeon. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. Lightweight Specifications for Parallel Correctness

    Science.gov (United States)

    2012-12-05

    that typically no pro- grammer specification is needed. However, manually determining which reported races are benign and which are bugs can be time...marked by the pro- grammer , but no statement is enclosed with if(true∗) — i.e., the set S∗ is empty. We are given a set T of parallel execution traces, and

  15. Final Empirical Test Case Specification

    DEFF Research Database (Denmark)

    Kalyanova, Olena; Heiselberg, Per

    This document includes the empirical specification on the IEA task of evaluation building energy simulation computer programs for the Double Skin Facades (DSF) constructions. There are two approaches involved into this procedure, one is the comparative approach and another is the empirical one....

  16. Vibrio chromosome-specific families

    DEFF Research Database (Denmark)

    Lukjancenko, Oksana; Ussery, David

    2014-01-01

    We have compared chromosome-specific genes in a set of 18 finished Vibrio genomes, and, in addition, also calculated the pan- and core-genomes from a data set of more than 250 draft Vibrio genome sequences. These genomes come from 9 known species and 2 unknown species. Within the finished...

  17. Specificity of Cardiovascular Endurance Training.

    Science.gov (United States)

    Riley, Calberth B., Jr.; Johnson, James H.

    This study determined the specificity of cardiovascular endurance training on a bicycle ergometer. Eighteen male subjects were tested on a heart rate response test of 150 beats per minute on a bicycle ergometer at the pace of 50 revolutions per minute (rpm) and at 160 beats per minute at 60 and 80 rpm, with the resistance equal to the force of…

  18. LOTOS specification style for OSI

    NARCIS (Netherlands)

    Turner, K.J.; van Sinderen, Marten J.; Bolognesi, T.; van de Lagemaat, J.; Vissers, C.A.

    1995-01-01

    The architecture of OSI is used to derive guidelines for writing LOTOS specifications of distributed systems. In particular, the architectural concepts that underlie service and protocol designs are examined in detail. For each of these concepts a representation in LOTOS is given. Examples are

  19. LOTOS specification style for OSI

    NARCIS (Netherlands)

    Brinksma, Hendrik; Turner, K.J.; Bolognesi, T.; van Sinderen, Marten J.; Vissers, C.A.

    1992-01-01

    The architecture of OSI is used to derive guidelines for writing LOTOS specifications of distributed systems. In particular, the architectural concepts that underlie service and protocol designs are examined in detail. For each of these concepts a representation in LOTOS is given. Examples are

  20. Niche-specific cognitive strategies

    DEFF Research Database (Denmark)

    Hulgard, K.; Ratcliffe, J. M.

    2014-01-01

    Related species with different diets are predicted to rely on different cognitive strategies: those best suited for locating available and appropriate foods. Here we tested two predictions of the niche-specific cognitive strategies hypothesis in bats, which suggests that predatory species should ...... the niche-specific cognitive strategies hypothesis and suggest that for gleaning and clutter-resistant aerial hawking bats, learning to associate shape with food interferes with subsequent spatial memory learning.......Related species with different diets are predicted to rely on different cognitive strategies: those best suited for locating available and appropriate foods. Here we tested two predictions of the niche-specific cognitive strategies hypothesis in bats, which suggests that predatory species should...... rely more on object memory than on spatial memory for finding food and that the opposite is true of frugivorous and nectivorous species. Specifically, we predicted that: (1) predatory bats would readily learn to associate shapes with palatable prey and (2) once bats had made such associations...

  1. Isotope specific arbitrary material sorter

    Science.gov (United States)

    Barty, Christopher P.J.

    2015-12-08

    A laser-based mono-energetic gamma-ray source is used to provide a rapid and unique, isotope specific method for sorting materials. The objects to be sorted are passed on a conveyor in front of a MEGa-ray beam which has been tuned to the nuclear resonance fluorescence transition of the desired material. As the material containing the desired isotope traverses the beam, a reduction in the transmitted MEGa-ray beam occurs. Alternately, the laser-based mono-energetic gamma-ray source is used to provide non-destructive and non-intrusive, quantitative determination of the absolute amount of a specific isotope contained within pipe as part of a moving fluid or quasi-fluid material stream.

  2. Certifying Domain-Specific Policies

    Science.gov (United States)

    Lowry, Michael; Pressburger, Thomas; Rosu, Grigore; Koga, Dennis (Technical Monitor)

    2001-01-01

    Proof-checking code for compliance to safety policies potentially enables a product-oriented approach to certain aspects of software certification. To date, previous research has focused on generic, low-level programming-language properties such as memory type safety. In this paper we consider proof-checking higher-level domain -specific properties for compliance to safety policies. The paper first describes a framework related to abstract interpretation in which compliance to a class of certification policies can be efficiently calculated Membership equational logic is shown to provide a rich logic for carrying out such calculations, including partiality, for certification. The architecture for a domain-specific certifier is described, followed by an implemented case study. The case study considers consistency of abstract variable attributes in code that performs geometric calculations in Aerospace systems.

  3. Specific bibliography on Anastrepha fraterculus

    International Nuclear Information System (INIS)

    Salles, L.A.; Jaldo, H.

    1999-01-01

    Most publications on Anastrepha fraterculus are in the literature sources from South America, and papers were published in Spanish or Portuguese. Many literature sources mentioned in this list are not indexed in entomological abstracts and, consequently, are not easily available outside their home state or country. Due to this fact, the inclusion of a list of specific bibliography on A. fraterculus could be a help for researchers and students interested in fruit flies. In this list are included only references directly dealing with Anastrepha fraterculus. Obviously, many more references exist that consider this species, but general or non-specific work or data concerning A. fraterculus were not included in the present list. (author)

  4. UNBIASED ESTIMATORS OF SPECIFIC CONNECTIVITY

    Directory of Open Access Journals (Sweden)

    Jean-Paul Jernot

    2011-05-01

    Full Text Available This paper deals with the estimation of the specific connectivity of a stationary random set in IRd. It turns out that the "natural" estimator is only asymptotically unbiased. The example of a boolean model of hypercubes illustrates the amplitude of the bias produced when the measurement field is relatively small with respect to the range of the random set. For that reason unbiased estimators are desired. Such an estimator can be found in the literature in the case where the measurement field is a right parallelotope. In this paper, this estimator is extended to apply to measurement fields of various shapes, and to possess a smaller variance. Finally an example from quantitative metallography (specific connectivity of a population of sintered bronze particles is given.

  5. UTM UAS Service Supplier Specification

    Science.gov (United States)

    Rios, Joseph Lucio

    2017-01-01

    Within the Unmanned Aircraft Systems (UAS) Traffic Management (UTM) system, the UAS Service Supplier (USS) is a key component. The USS serves several functions. At a high level, those include the following: Bridging communication between UAS Operators and Flight Information Management System (FIMS) Supporting planning of UAS operations Assisting strategic deconfliction of the UTM airspace Providing information support to UAS Operators during operations Helping UAS Operators meet their formal requirements This document provides the minimum set of requirements for a USS. In order to be recognized as a USS within UTM, successful demonstration of satisfying the requirements described herein will be a prerequisite. To ensure various desired qualities (security, fairness, availability, efficiency, maintainability, etc.), this specification relies on references to existing public specifications whenever possible.

  6. Multilingualism and Specific Language Impairment

    OpenAIRE

    Engel de Abreu, Pascale

    2014-01-01

    Is a multilingual education beneficial for children? What are the optimal conditions under which a child can become perfectly multilingual? When should we be concerned about a multilingual child's language skills? What are the signs of Specific Language Impairment in a child who speaks more than one language? Developmental psychologist and Associate Professor in multilingual cognitive development at the University of Luxembourg Pascale Engel de Abreu will address these questions based on what...

  7. Technical specifications, Hanford production reactors

    Energy Technology Data Exchange (ETDEWEB)

    Gilbert, W.D. [comp.

    1962-06-25

    These technical specifications are applicable to the eight operating production reactor facilities, B, C, D, DR, F, H, KE, and KW. Covered are operating and performance restrictions and administrative procedures. Areas covered by the operating and performance restrictions are reactivity, reactor control and safety elements, power level, temperature and heat flux, reactor fuel loadings, reactor coolant systems, reactor confinement, test facilities, code compliance, and reactor scram set points. Administrative procedures include process control procedures, training programs, audits and inspections, and reports and records.

  8. Genre specificity of political discourse

    OpenAIRE

    Aleshina E. Yu.

    2016-01-01

    The problem of political discourse genre specificity has been in the center of attention of Russian and foreign scholars, which is determined by the relevance of political discourse as a multidimensional object of study with its linguistic properties in particular. The ambiguity of principles for genre gradation of political discourse is linked to the variability of understanding genre proper. The definition of genre as goal-oriented text characteristics allows accentuating some genres of pol...

  9. Nanobody Based Dual Specific CARs

    Directory of Open Access Journals (Sweden)

    Stijn De Munter

    2018-01-01

    Full Text Available Recent clinical trials have shown that adoptive chimeric antigen receptor (CAR T cell therapy is a very potent and possibly curative option in the treatment of B cell leukemias and lymphomas. However, targeting a single antigen may not be sufficient, and relapse due to the emergence of antigen negative leukemic cells may occur. A potential strategy to counter the outgrowth of antigen escape variants is to broaden the specificity of the CAR by incorporation of multiple antigen recognition domains in tandem. As a proof of concept, we here describe a bispecific CAR in which the single chain variable fragment (scFv is replaced by a tandem of two single-antibody domains or nanobodies (nanoCAR. High membrane nanoCAR expression levels are observed in retrovirally transduced T cells. NanoCARs specific for CD20 and HER2 induce T cell activation, cytokine production and tumor lysis upon incubation with transgenic Jurkat cells expressing either antigen or both antigens simultaneously. The use of nanobody technology allows for the production of compact CARs with dual specificity and predefined affinity.

  10. Nanobody Based Dual Specific CARs.

    Science.gov (United States)

    De Munter, Stijn; Ingels, Joline; Goetgeluk, Glenn; Bonte, Sarah; Pille, Melissa; Weening, Karin; Kerre, Tessa; Abken, Hinrich; Vandekerckhove, Bart

    2018-01-30

    Recent clinical trials have shown that adoptive chimeric antigen receptor (CAR) T cell therapy is a very potent and possibly curative option in the treatment of B cell leukemias and lymphomas. However, targeting a single antigen may not be sufficient, and relapse due to the emergence of antigen negative leukemic cells may occur. A potential strategy to counter the outgrowth of antigen escape variants is to broaden the specificity of the CAR by incorporation of multiple antigen recognition domains in tandem. As a proof of concept, we here describe a bispecific CAR in which the single chain variable fragment (scFv) is replaced by a tandem of two single-antibody domains or nanobodies (nanoCAR). High membrane nanoCAR expression levels are observed in retrovirally transduced T cells. NanoCARs specific for CD20 and HER2 induce T cell activation, cytokine production and tumor lysis upon incubation with transgenic Jurkat cells expressing either antigen or both antigens simultaneously. The use of nanobody technology allows for the production of compact CARs with dual specificity and predefined affinity.

  11. JBK-75 microstructure specification recommendation

    International Nuclear Information System (INIS)

    Brewer, A.W.

    1977-01-01

    Since the ASTM-E-45 standard for microcleanliness is not applicable to superalloys like JBK-75 stainless steel (Modified A-286), Rocky Flats should adopt the Ladish microcleanliness standard (APML Cleanliness Classification of High Temperature Alloys Chart, 1971), as a guide for setting material acceptance specifications for JBK-75. Inclusion ratings of S-2, N-2, C-2, and M-2 should be acceptable. The microstructure should have a grain size of 5 or finer, but not smaller than 9, and microsegregation (banding) should be kept to a minimum

  12. Specific circuit design: electrocardiogram amplifier

    International Nuclear Information System (INIS)

    Laribiere, Laurent

    1991-01-01

    The electrocardiogram amplifier is a specific integrated circuit. It is based on a linear array of Raytheon. This circuit is fitted with the following functions and characteristics: - electrocardiogram signals amplification, - pacemaker detection, - electrode un-sticking detection, - defibrillator overload protection, - battery-powered, - internal regulation 5 V, - low supply current 2.5 mA, - according to French norms on electrocardiogram surveillance devices - 28 pin package, available in CMS version It can be used for any surveillance device, requiring an analog processing of cardiac signals. (author) [fr

  13. Central Solenoid Insert Technical Specification

    Energy Technology Data Exchange (ETDEWEB)

    Martovetsky, Nicolai N [ORNL; Smirnov, Alexandre [ORNL

    2011-09-01

    The US ITER Project Office (USIPO) is responsible for the ITER central solenoid (CS) contribution to the ITER project. The Central Solenoid Insert (CSI) project will allow ITER validation the appropriate lengths of the conductors to be used in the full-scale CS coils under relevant conditions. The ITER Program plans to build and test a CSI to verify the performance of the CS conductor. The CSI is a one-layer solenoid with an inner diameter of 1.48 m and a height of 4.45 m between electric terminal ends. The coil weight with the terminals is approximately 820 kg without insulation. The major goal of the CSI is to measure the temperature margin of the CS under the ITER direct current (DC) operating conditions, including determining sensitivity to load cycles. Performance of the joints, ramp rate sensitivity, and stability against thermal or electromagnetic disturbances, electrical insulation, losses, and instrumentation are addressed separately and therefore are not major goals in this project. However, losses and joint performance will be tested during the CSI testing campaign. The USIPO will build the CSI that will be tested at the Central Solenoid Model Coil (CSMC) Test Facility at the Japan Atomic Energy Agency (JAEA), Naka, Japan. The industrial vendors (the Suppliers) will report to the USIPO (the Company). All approvals to proceed will be issued by the Company, which in some cases, as specified in this document, will also require the approval of the ITER Organization. Responsibilities and obligations will be covered by respective contracts between the USIPO, called Company interchangeably, and the industrial Prime Contractors, called Suppliers. Different stages of work may be performed by more than one Prime Contractor, as described in this specification. Technical requirements of the contract between the Company and the Prime Contractor will be covered by the Fabrication Specifications developed by the Prime Contractor based on this document and approved by

  14. Gender specific determinants of goitre

    International Nuclear Information System (INIS)

    Jamshid, F.; Kerstin, C.; Elena, G.; Wilhelm, O.; Karl, W.; Hwe, M.

    2004-01-01

    Despite the strong implications of differences between females and males in the risk of goitre, gender-specific issues have not been extensively addressed in investigations of goitre prevalence. The Objective of our analysis was to investigate the gender-specific determinants of goitre. Methods: A total of 853 healthy employees from 4 institutions in western part of Germany aged between 18 and 68 years were examined by ultrasound of the neck to determine the thyroid volume between April 2001 and April 2002. Information on sex, age, daily use of iodised salt, the history of goitre in the first degree relatives, type and amount of' smoking, oral contraceptives and number of pregnancies were assessed by standardised questionnaires. Gender-specific predictors of goitre prevalence were assessed by multivariate logistic regression. Results: The overall prevalence of goitre among study subjects was (204/853) 23.9%. Goitre was present in 80 out of 370 females (21.6%) vs. 124/483 (25.7%) in males.In general smoking (<0.0001), increasing age (p<0.0001) and lack of daily intake of iodised salt (p=0.004) associated with goitre prevalence, but not sex (0.4) and family history of goitre (p=0.2). In 370 females, parity (p=0.004) and lack of daily intake of iodised salt (p=0.01) were the major determinants for goitre, whereas, age (p=0.2), oral contraceptives (p=0.8), family history of goitre (p=0.3), and smoking (p=0.1) did not affect the goitre prevalence. In 483 males, smoking (p<0.0001) and age (p<0.001) affected the goitre prevalence, but not family history of goitre (p=0.4) and the iodine status failed just to reach the significant level (p=0.08) in this analysis. Conclusions: Gender specific determinants of goitre are parity and iodine status in females and smoking and increasing age in males. (authors)

  15. 100 Areas water treatment specifications

    Energy Technology Data Exchange (ETDEWEB)

    Greninger, A.B.

    1952-07-11

    This memorandum discussed review of the data from tests using alum in the treatment of pile process water, and using activated silica as a coagulant aid during period of low water temperature, which shows that this method should be substituted for the present method of treating pile process water in all 100 Areas. It was recommended that the water treatment procedures and specifications attached to this memorandum be initiated as standard practice in all 100 Areas as soon as it is possible to make the necessary equipment modifications and installations.

  16. Food Odours Direct Specific Appetite

    Directory of Open Access Journals (Sweden)

    Harriët F. A. Zoon

    2016-02-01

    Full Text Available Olfactory food cues were found to increase appetite for products similar in taste. We aimed to replicate this phenomenon for taste (sweet/savoury, determine whether it extends to energy density (high/low as well, and uncover whether this effect is modulated by hunger state. Twenty-nine healthy-weight females smelled four odours differing in the energy density and taste they signalled, one non-food odour, and one odourless solution (control, in random order, for three minutes each. Appetite for 15 food products was rated in the following two minutes. Mixed model analyses revealed that exposure to an odour signalling a specific taste (respectively sweet, savoury led to a greater appetite for congruent food products (sweet/savoury compared to incongruent food products (savoury p < 0.001; sweet p < 0.001 or neutral food products (p = 0.02; p = 0.003. A similar pattern was present for the energy-density category (respectively high-energy dense, low-energy dense signalled by the odours (low-energy products p < 0.001; high-energy products p = 0.008. Hunger state did not have a significant impact on sensory-specific appetite. These results suggest that exposure to food odours increases appetite for congruent products, in terms of both taste and energy density, irrespective of hunger state. We speculate that food odours steer towards intake of products with a congruent macronutrient composition.

  17. Hanford Site Environmental Management Specification

    International Nuclear Information System (INIS)

    DAILY, J.L.

    2001-01-01

    The US Department of Energy, Richland Operations Office (RL) has established a document hierarchy as part of its integrated management system. The Strategic Plan defines the vision, values, missions, strategic goals, high-level outcomes, and the basic strategies in achieving those outcomes. As shown in Figure 1-1, the Site Specification derives requirements from the Strategic Plan and documents the top-level mission technical requirements for the work involved in the RL Hanford Site cleanup and infrastructure activities under the responsibility of the U.S. Department of Energy, Office of Environmental Management (EM). It also provides the basis for all contract technical requirements. Since this is limited to the EM work, neither the Fast Flux Test Facility (FFTF) nor the Pacific Northwest National Laboratory (PNNL) non-EM science activities are included. Figure 1-1 also shows the relationship between this Site Specification and the other Site management and planning documents. Similarly, the documents, orders, and laws referenced in this document represent only the most salient sources of requirements. Current and contractual reference data contain a complete set of source documents

  18. Is sexual victimization gender specific?

    DEFF Research Database (Denmark)

    Sundaram, Vanita; Laursen, Bjarne; Helweg-Larsen, Karin

    2008-01-01

    The present study investigates the prevalence of sexual victimization and correlations between sexual victimization and indicators of poor health in two representative samples of men and women in Denmark. Specifically, the authors explore the prevalence of self-reported victimization among...... adolescents (N = 5,829) and adults (N = 3,932) and analyze differences in self-reported health outcomes between male and female victims and corresponding controls. Gender differences are found in the reported prevalence of sexual victimization. Significantly more females than males reported forced sexual...... experiences in both samples. Associations between sexual victimization and poor health outcomes are found for both genders. Comparable patterns of association for men and women are found on a number of variables, particularly those pertaining to risk behavior....

  19. The Specificity of Human Aesthetics

    DEFF Research Database (Denmark)

    Bouchet, Dominique

    2015-01-01

    Today, humankind is being reintroduced within nature. Humankind is no longer presented as supernatural to nature. There is no longer a clear divide between animal and human. What makes us human is neither culture, nor language nor labor, nor art, but the degree of complexity those products and ca...... creativity. Art is fundamentally about shaping visions and very closely related to this specific human ability to make projects. Especially in times of crisis, when the old sources of meaning hardly can make sense in a new context, imagination must be used in order to survive........ Today, what is regarded as the essential characteristic of humankind is the ability to use a complex articulated language, to have thoughts entailing abstraction and conceptualization. It is the ability to operate with deferred representations, the necessity to relate to inner worlds of representation...

  20. Testing of badminton specific endurance

    DEFF Research Database (Denmark)

    Madsen, Christian Møller; Højlyng, Mads; Nybo, Lars

    2016-01-01

    In the present study, a novel intermittent badminton endurance test (B-ENDURANCE) was developed and tested in elite (n=17) and skilled (n=9) badminton players as well as in age-matched physically active men (non-badminton players; n=8). In addition, B-ENDURANCE test-retest reproducibility...... was evaluated in nine badminton players.B-ENDURANCE is an incremental test where each level consists of repeated sequences of badminton specific actions towards the four corners on the court. The subject starts in the center of the court in front of a computer screen and within each sequence he must...... decreases until the subjects cannot follow the dictated tempo.B-ENDURANCE performance for elite players was better (PENDURANCE performance correlated (r=0.8; P

  1. Domain specific MT in use

    DEFF Research Database (Denmark)

    Offersgaard, Lene; Povlsen, Claus; Almsten, Lisbeth Kjeldgaard

    2008-01-01

    point scale evaluate the sentence from the point of view of the post-editor. The post-editor profile defined by the LSP is based on the experiences of introducing MT in the LSP workflow. The relation between the Translation Edit Rate (TER) scores and “Usability” scores is tested. We find TER a candidate...... for an automatic metric simulating the post-editors’ usability judgements. LSP tests show 67% saved time in post-editing for the tested domain. Finally, the use of weighted sub-domain phrase tables in a SMT system is shown to improve translation quality.......The paper focuses on domain specific use of MT with a special focus on SMT in the workflow of a Language Service Provider (LSP). We report on the feedback of post-editors using fluency/adequacy evaluation and the evaluation metric ’Usability’, understood in this context as where users on a three...

  2. Formal specification of human-computer interfaces

    Science.gov (United States)

    Auernheimer, Brent

    1990-01-01

    A high-level formal specification of a human computer interface is described. Previous work is reviewed and the ASLAN specification language is described. Top-level specifications written in ASLAN for a library and a multiwindow interface are discussed.

  3. FY97 ICCS prototype specification

    International Nuclear Information System (INIS)

    Woodruff, J.

    1997-01-01

    The ICCS software team will implement and test two iterations of their software product during FY97. This document specifies the products to be delivered in that first prototype and projects the direction that the second prototype will take. Detailed specification of the later iteration will be written when the results of the first iteration are complete. The selection of frameworks to be implemented early is made on a basis of risk analysis from the point of view of future development in the ICCS project. The prototype will address risks in integration of object- oriented components, in refining our development process, and in emulation testing for FEP devices. This document is a specification that identifies products and processes to undertake for resolving these risks. The goals of this activity are to exercise our development process at a modest scale and to probe our architecture plan for fundamental limits and failure modes. The product of the iterations will be the framework software which will be useful in future ICCS code. Thus the FY97 products are intended for internal usage by the ICCS team and for demonstration to the FEP software developers of the strategy for integrating supervisory software with FEP computers. This will be the first of several expected iterations of the software development process and the performance measurements that ICCS will demonstrate, intended to support confidence in our ability to meet project RAM goals. The design of the application software is being carried out in a separate WBS 1.5.2 activity. The design activity has as its FY97 product a series of Software Design Documents that will specify the functionality of the controls software of ICCS. During the testing of this year''s prototypes, the application functionality needed for test will be provided by sample maintenance controls. These are early precursors of controls that can be used for low level device control. Since the devices under test will be represented by

  4. 31 CFR 596.309 - Specific license.

    Science.gov (United States)

    2010-07-01

    ... FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TERRORISM LIST GOVERNMENTS SANCTIONS REGULATIONS General Definitions § 596.309 Specific license. The term specific license means any license or...

  5. Advances in bacterial specific imaging

    Directory of Open Access Journals (Sweden)

    David Wareham

    2005-10-01

    Full Text Available Nuclear medicine is a powerful diagnostic technique able to detect inflammatory foci in human disease. A wide range of agents have been evaluated for their ability to distinguish lesions due to microbial infection from those due to sterile inflammation. Advances continue to be made on the use of radiolabelled antibiotics which as well as being highly specific in the diagnosis of infection may be useful in monitoring the treatment and course of disease. Here we provide an update on in-vitro and clinical studies with a number of established and novel radiopharmaceuticalsA medicina nuclear é uma técnica poderosa de diagnóstico capaz de detectar focos inflamatórios em doenças humanas. Uma ampla gama de agentes tem sido avaliada em sua capacidade de distinguir lesões, devidas a infecções microbianas daquelas causadas por inflamações estéreis. Avanços continuam sendo realizados no uso de antibióticos radiomarcados que, da mesma forma que têm sido usados no diagnóstico altamente específico de infecções, podem ser úteis na monitoração do tratamento e do curso da doença. Neste estudo, nós apresentamos uma atualização sobre estudos in vitro e clínicos, com alguns novos radiofármacos e outros já consagrados.

  6. Specificities of sustainable tourism planning

    Directory of Open Access Journals (Sweden)

    Jegdić Vaso

    2013-01-01

    Full Text Available In the past two decades, companies have been mentioning achievement of sustainability in their activities as a target of companies, governments and non-profit organizations, although measuring the degree to which an organization conducts its activities in a sustainable manner, can be very difficult. Sustainable tourism development requires a process of planning and management that will unite the interests of various stakeholders in a sustainable and strategic way. It requires an understanding of the meaning of sustainable development and guiding values for promoting sustainable tourism. The paper points to the importance of cross-sector partnerships and the roles of different stakeholders in the planning of sustainable tourism projects. Special importance is given to the community of which a willingness to understand the impacts of tourism industry is expected, as well as various procedures of engagement in participatory planning, consensus building and conflict resolution among all stakeholders. The aim of this research is to find an optimal model of planning of sustainable tourism projects that would take into consideration the interests of all stakeholders and reflect the specificities imposed by the acceptance of the concept of sustainable development by all participants in the project.

  7. Are specific emotions narrated differently?

    Science.gov (United States)

    Habermas, Tilmann; Meier, Michaela; Mukhtar, Barbara

    2009-12-01

    Two studies test the assertion that anger, sadness, fear, pride, and happiness are typically narrated in different ways. Everyday events eliciting these 5 emotions were narrated by young women (Study 1) and 5- and 8-year-old girls (Study 2). Negative narratives were expected to engender more effort to process the event, be longer, more grammatically complex, more often have a complication section, and use more specific emotion labels than global evaluations. Narratives of Hogan's (2003) juncture emotions anger and fear were expected to focus more on action and to contain more core narrative sections of orientation, complication, and resolution than narratives of the outcome emotions sadness and happiness. Hypotheses were confirmed for adults except for syntactic complexity, whereas children showed only some of these differences. Hogan's theory that juncture emotions are restricted to the complication section was not confirmed. Finally, in adults, indirect speech was more frequent in anger narratives and internal monologue in fear narratives. It is concluded that different emotions should be studied in how they are narrated, and that narratives should be analyzed according to qualitatively different emotions.

  8. [Amusia and its topic specification].

    Science.gov (United States)

    Buklina, S B; Skvortsova, V B

    2007-01-01

    A historical development of views on amusia and its clinical phenomenology is reviewed. The authors present a case of atypical amusia in a patient aged 32 years with glioma of the right temporal lobe including the upper temporal gyrus. Amusia was combined with euphoria and disturbances of evaluation of speech intonation. It has been assumed that different mechanisms implicated with different regions of both brain hemispheres may underlie amusia. Sometimes these mechanisms appear to be universal, e.g. disorders of symbolic gnosis in posterior hemisphere lesions, being comorbid with amusia as disturbances in reading music and letter agnosia. In our case, the right temporal lobe lesion, especially with involvement of the upper temporal gyrus, caused specific music agnosia with disturbances of perception of some notes and duration of their phonation or a musical contour of the whole melody. Motor amusia is developed due to additional disturbances of motor and premotor brain functions, with significant contribution of the Broca's speech area. Music may be a model for investigation into processes of multimodal integration and hemisphere interaction.

  9. Design, preparation and use of ligated phosphoproteins: a novel approach to study protein phosphatases by dot blot array, ELISA and Western blot assays.

    Science.gov (United States)

    Sun, Luo; Ghosh, Inca; Barshevsky, Tanya; Kochinyan, Samvel; Xu, Ming-Qun

    2007-07-01

    The study of substrate specificity of protein phosphatases (PPs) is very challenging since it is difficult to prepare a suitable phosphorylated substrate. Phosphoproteins, phosphorylated by a protein kinase, or chemically synthesized phosphopeptides are commonly used substrates for PPs. Both types of these substrates have their advantages and limitations. Phosphoproteins mimic more closely the physiologically relevant PP substrates, but their preparation is technically demanding. Synthetic phosphopeptides present advantages over proteins because they can be easily produced in large quantity and their amino acid sequence can be designed to contain potential determinants of substrate specificity. However, short peptides are less optimal compared to in vivo PP substrates and often display poor and variable binding to different matrices, resulting in low sensitivity in analysis of PP activity on solid support. In this work we utilize the intein-mediated protein ligation (IPL) technique to generate substrates for PPs, combining the advantages of proteins and synthetic peptides in one molecule. The ligation of a synthetic phosphopeptide to an intein-generated carrier protein (CP) with a one-to-one stoichiometry results in the formation of a ligated phosphoprotein (LPP). Three widely used assays, dot blot array, Western blot and ELISA were employed to study the PP activity on LPP substrates. Dephosphorylation was measured by detection of the remaining phosphorylation, or lack of it, with a phospho-specific antibody. The data show the advantage of LPPs over free peptides in assays on solid supports. LPPs exhibited enhanced binding to the matrices used in the study, which significantly improved sensitivity and consistency of the assays. In addition, saturation of the signal was circumvented by serial dilution of the assay samples. This report describes detailed experimental procedures for preparation of LPP substrates and their use in PP assays based on immobilization on

  10. THE SYNTHESIS OF BIOCONJUGATE BASED ON RHENIUM(I CARBONYL COMPLEX FOR VISUALIZATION OF PATHOLOGICAL PROCESS

    Directory of Open Access Journals (Sweden)

    K. O. Piletska

    2017-03-01

    Full Text Available Tricarbonyl rhenium(I complexes have a great potential like biomarkers. It is caused their biological stability, low toxicity, large Stokes shifts, and long luminescence lifetimes. Rhenium tricarbonyl complexes fac-[Re(CO3(N^N], where N^N is a ligand with low π* orbitals are excellent candidates as imaging dyes. The method of obtaining potential biomarkers based on tricarbonyl rhenium(I complex with a 4-methyl-2,2’-bipyridine-4’-carboxylate by the addition of biomolecules by peptide synthesis was developed. The new complex [Re(CO3MebpyCOOHBr] was synthesized, composition and structure of which were established by mass spectrometry, IR and NMR spectroscopy. A selective attachment of receptor peptide enkephalin to complex [Re(CO3(MebpyCOOHBr] was performed. The formation of a new compound and its structure has been confirmed by HPLC and mass spectral analysis. The method which has been developed allows to connect various peptides to rhenium(I complex in the solution.

  11. Assembly of catalase-based bioconjugates for enhanced anticancer efficiency of photodynamic therapy in vitro.

    Science.gov (United States)

    Zhao, Jie; Fei, Jinbo; Du, Cuiling; Cui, Wei; Ma, Hongchao; Li, Junbai

    2013-11-25

    An oxygen generation core-shell structure uploading rose bengal has been fabricated by covalent assembly of catalase and alginate dialdehyde via Schiff's base. The composite can catalyze the decomposition of intracellular H2O2 to increase the concentration of O2, which effectively enhances the anticancer efficiency of photodynamic therapy in vitro.

  12. Bioconjugated graphene oxide hydrogel as an effective adsorbent for cationic dyes removal.

    Science.gov (United States)

    Soleimani, Khadijeh; Tehrani, Abbas Dadkhah; Adeli, Mohsen

    2018-01-01

    In this study, graphene oxide - cellulose nanowhiskers nanocomposite hydrogel was easily synthesized through covalent functionalization of cellulose nanowhiskers with graphene oxide via a facile approach. The nitrene chemistry applied for covalent functionalization of graphene oxide sheets. The surface morphology and chemical structure of the nanocomposite hydrogel were characterized by FTIR, TGA, Raman, XRD, elemental analysis and SEM. The UV/Visible absorption spectrum revealed that the obtained porous nanocomposite hydrogel can efficiently remove cationic dyes such as methylene blue (MB) and Rhodamine B (RhB) from wastewater with high absorption power. The adsorption process showed that 100% of MB and 90% of RhB have been removed and the equilibrium state has been reached in 15min for low concentration solutions in accordance with the pseudo-second-order model. Moreover, the sample exhibited stable performance after being used several times. High adsorption capacity and easy recovery are the efficient factors making these materials as good adsorbent for water pollutants and wastewater treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Synthesis and bioconjugation of gold nanoparticles as potential molecular probes for light-based imaging techniques

    NARCIS (Netherlands)

    Rayavarapu, R.G.; Petersen, Wilhelmina; Ungureanu, C.; Post, Janine Nicole; van Leeuwen, Ton; Manohar, Srirang

    2007-01-01

    We have synthesized and characterized gold nanoparticles (spheres and rods) with optical extinction bands within the “optical imaging window.” The intense plasmon resonant driven absorption and scattering peaks of these nanoparticles make them suitable as contrast agents for optical imaging

  14. Synthesis and bioconjugation of gold nanoparticles as potential molecular probes for light-based imaging techniques

    NARCIS (Netherlands)

    Rayavarapu, Raja Gopal; Petersen, Wilma; Ungureanu, Constantin; Post, Janine N.; van Leeuwen, Ton G.; Manohar, Srirang

    2007-01-01

    We have synthesized and characterized gold nanoparticles (spheres and rods) with optical extinction bands within the "optical imaging window." The intense plasmon resonant driven absorption and scattering peaks of these nanoparticles make them suitable as contrast agents for optical imaging

  15. Dynamic Combinatorial Chemistry and Organocatalysis with Thiosemicarbazones and Organocatalysts for Hydrazone and Oxime Bioconjugations

    DEFF Research Database (Denmark)

    Larsen, Dennis

    The first part of this thesis describes the use of thiosemicarbazones for dynamic combinatorial chemistry. Building blocks incorporating thiosemicarbazides and acetalprotected aldehydes were synthesised and conditions where these building blocks formed dynamic combinatorial libraries under...

  16. Modular Bioconjugates to Study Herceptin Resistance: A Structural and Functional Approach

    Science.gov (United States)

    2015-10-01

    sequential anion exchange chromatography, ammonium sulfate precipitation, and size exclusion chromatography. These capsids are first functionalized on...1a,b on page 1591 of Appendix A) . Upon completion of the reaction , the solution is treated with sodium dithionite (Na2S2O4) to chemoselectively...MS2 capsids in a 3:1 ratio of 5 antibody to capsids and treated with sodium periodate (NaIO4) to promote the oxidative coupling reaction , which we

  17. Modular Bioconjugates to Study Herceptin Resistance: A Structural and Functional Approach

    Science.gov (United States)

    2016-10-01

    River Laboratories (Hollister, CA). For tumor inoculation, the cells were implanted in the number 4 mammary fat pad (β-estradiol pellets were also...PA). The list mode data were acquired from the time of injection to 1 h postinjection, and dynamic multiframe reconstruction was performed to capture...scan to provide anatomical localization of radio- nuclide data, as well as photon attenuation map for attenuation- corrected PET reconstruction

  18. The discovery of pyridinium 1,2,4-triazines with enhanced performance in bioconjugation reactions

    Czech Academy of Sciences Publication Activity Database

    Siegl, Sebastian J.; Dzijak, Rastislav; Vázquez, Arcadio; Pohl, Radek; Vrábel, Milan

    2017-01-01

    Roč. 8, č. 5 (2017), s. 3593-3598 ISSN 2041-6520 R&D Projects: GA ČR GJ15-06020Y Institutional support: RVO:61388963 Keywords : Diels-Alder reaction s * trans-cyclooctene ligation * living cells Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 8.668, year: 2016 http://pubs.rsc.org/en/content/articlehtml/2017/sc/c6sc05442k

  19. Preparation of bioconjugates by solid-phase conjugation to ion exchange matrix-adsorbed carrier proteins

    DEFF Research Database (Denmark)

    Houen, G.; Olsen, D.T.; Hansen, P.R.

    2003-01-01

    of ovalbumin and various peptides were prepared in a similar manner and used for production of peptide antisera by direct immunization with the conjugates bound to the ion exchanger. Advantages of the method are its solid-phase nature, allowing fast and efficient reactions and intermediate washings......, and immunization experiments with the eluted conjugates showed that the more substituted conjugates gave rise to the highest titers of glutathione antibodies. Direct immunization with the conjugates adsorbed to the ion exchange matrix was possible and gave rise to high titers of glutathione antibodies. Conjugates...

  20. Metallothionein bioconjugates as delivery vehicles for bismuth-212 alpha particle therapy

    International Nuclear Information System (INIS)

    Macklis, R.M.; Morris, C.; Humm, J.; Hines, J.; Atcher, R.

    1991-01-01

    Metallothioneins (MTHs) are small cysteine-rich polypeptides that binds cationic metals at physiologic pH ranges through noncovalent -SH ligand interactions. Some leucine-rich renal MTHs have a particular avidity for bismuth. The authors have examined the ability of MTHs to selectively incorporate Bi-212, a short-lived high-energy alpha particle emitter currently under exploration as a potential therapeutic radiolabel for use in molecularly targeted cancer therapy. They find that under physiologic conditions, MTH will selectively incorporate Bi-212 after incubation with an equilibrium mixture of its upstream and downstream parents. The MTH moieties may be linked to tumor-binding macromolecules such as antibodies via thiolation reactions using SPDP, and the resultant Bismuth-avid molecules may be used either as primary delivery vehicles for the Bi-212 or as part of a 2-step release-and-catch isotope localization system in which the MTH-antibody conjugate is pre-localized at the tumor site and the radiometal is then administered and chelated in situ. They present the chemistry, dosimetry and potential clinical applications of this system

  1. Overview of the main methods used to combine proteins with nanosystems: absorption, bioconjugation, and encapsulation

    OpenAIRE

    Di Marco, Maria

    2009-01-01

    Mariagrazia Di Marco1, Shaharum Shamsuddin2, Khairunisak Abdul Razak3, Azlan Abdul Aziz4, Corinne Devaux1, Elsa Borghi1, Laurent Levy1, Claudia Sadun51Nanobiotix, Paris, France; 2School of Health Sciences, Health Campus Universiti Sains Malaysia, Kelantan, Malaysia; 3School of Materials and Mineral Resources Engineering, Engineering Campus, 4School of Physics, Universiti Sains Malaysia, Penang, Malaysia; 5Department of Chemistry, Sapienza, University of Rome, Rome, ItalyAbstract: The latest d...

  2. Completely monodisperse, highly repetitive proteins for bioconjugate capillary electrophoresis: development and characterization.

    Science.gov (United States)

    Lin, Jennifer S; Albrecht, Jennifer Coyne; Meagher, Robert J; Wang, Xiaoxiao; Barron, Annelise E

    2011-06-13

    Protein-based polymers are increasingly being used in biomaterial applications because of their ease of customization and potential monodispersity. These advantages make protein polymers excellent candidates for bioanalytical applications. Here we describe improved methods for producing drag-tags for free-solution conjugate electrophoresis (FSCE). FSCE utilizes a pure, monodisperse recombinant protein, tethered end-on to a ssDNA molecule, to enable DNA size separation in aqueous buffer. FSCE also provides a highly sensitive method to evaluate the polydispersity of a protein drag-tag and thus its suitability for bioanalytical uses. This method is able to detect slight differences in drag-tag charge or mass. We have devised an improved cloning, expression, and purification strategy that enables us to generate, for the first time, a truly monodisperse 20 kDa protein polymer and a nearly monodisperse 38 kDa protein. These newly produced proteins can be used as drag-tags to enable longer read DNA sequencing by free-solution microchannel electrophoresis.

  3. Lactoferrin bioconjugated solid lipid nanoparticles: a new drug delivery system for potential brain targeting.

    Science.gov (United States)

    Singh, Indu; Swami, Rajan; Pooja, Deep; Jeengar, Manish Kumar; Khan, Wahid; Sistla, Ramakrishna

    2016-01-01

    Delivery of drugs to brain is a subtle task in the therapy of many severe neurological disorders. Solid lipid nanoparticles (SLN) easily diffuse the blood-brain barrier (BBB) due to their lipophilic nature. Furthermore, ligand conjugation on SLN surface enhances the targeting efficiency. Lactoferin (Lf) conjugated SLN system is first time attempted for effective brain targeting in this study. Preparation of Lf-modified docetaxel (DTX)-loaded SLN for proficient delivery of DTX to brain. DTX-loaded SLN were prepared using emulsification and solvent evaporation method and conjugation of Lf on SLN surface (C-SLN) was attained through carbodiimide chemistry. These lipidic nanoparticles were evaluated by DLS, AFM, FTIR, XRD techniques and in vitro release studies. Colloidal stability study was performed in biologically simulated environment (normal saline and serum). These lipidic nanoparticles were further evaluated for its targeting mechanism for uptake in brain tumour cells and brain via receptor saturation studies and distribution studies in brain, respectively. Particle size of lipidic nanoparticles was found to be optimum. Surface morphology (zeta potential, AFM) and surface chemistry (FTIR) confirmed conjugation of Lf on SLN surface. Cytotoxicity studies revealed augmented apoptotic activity of C-SLN than SLN and DTX. Enhanced cytotoxicity was demonstrated by receptor saturation and uptake studies. Brain concentration of DTX was elevated significantly with C-SLN than marketed formulation. It is evident from the cytotoxicity, uptake that SLN has potential to deliver drug to brain than marketed formulation but conjugating Lf on SLN surface (C-SLN) further increased the targeting potential for brain tumour. Moreover, brain distribution studies corroborated the use of C-SLN as a viable vehicle to target drug to brain. Hence, C-SLN was demonstrated to be a promising DTX delivery system to brain as it possessed remarkable biocompatibility, stability and efficacy than other reported delivery systems.

  4. Photophysical Studies of Bioconjugated Ruthenium Metal-Ligand Complexes Incorporated in Phospholipid Membrane Bilayers

    Science.gov (United States)

    Sharmin, Ayesha; Salassa, Luca; Rosenberg, Edward; Ross, J. B. Alexander; Abbott, Geoffrey; Black, Labe; Terwilliger, Michelle; Brooks, Robert

    2013-01-01

    Luminescent, mono-diimine, ruthenium complexes, [(H)Ru(CO)(PPh3)2(dcbpy)][PF6] (1, dcbpy = 4,4′-dicarboxy bipyridyl) and [(H)Ru(CO)(dppene)(5-amino-1,10-phen)][PF6] (2, dppene = bis diphenylphosphino-ethylene, phen = 9,10-phenanthroline), have been conjugated with 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine (DPPE) and with cholesterol in the case of 2. Compound 1 gives the bis-lipid derivative [(H)Ru(CO)(PPh3)2(dcbpy-N-DPPE2)][PF6] (3), while 2 provides the mono-lipid conjugate [(H)Ru(CO)(dppene)(1,10-phen-5-NHC(S)-N-DPPE)][ PF6] (4), and the cholesterol derivative [(H)Ru(CO)(dppene)(1,10-phen-5-NHC(O)OChol)][PF6] (5, Chol = cholesteryl), using standard conjugation techniques. These compounds were characterized by spectroscopic methods, and their photophysical properties were measured in organic solvents. The luminescence of lipid conjugates 3 and is quenched in organic solvents while compound 4 a weak, short-lived, blue-shifted emission in solution. The cholesterol conjugate shows the long-lived, microsecond-timescale emission associated with triplet metal-to-ligand charge-transfer (3MLCT) excited states. Incorporation of conjugate 3 in lipid bilayer vesicles restores the luminescence, but with blue shifts (~80 nm) accompanied by nanosecond-timescale lifetimes. In the vesicles conjugate 4 shows a similar short-lived and blue-shifted emission to that observed in solution but with increased intensity. Conjugation of the complex [(H)Ru(CO)(PhP2C2H4C(O)O-N-succinimidyl)2(bpy)][PF6] (6”) with DPPE gives the phosphine-conjugated complex [(H)Ru(CO)(PhP2C2H4C(O)-N-DPPE)2(bpy)][PF6] (7). Complex 7 also exhibits a short-lived and blue-shifted emission in solution and in vesicles as observed for 3 and 4. We have also conjugated the complex [Ru(bpy)2(5-amino-1,10-phenanthroline)][PF6]2 (8) with both cholesterol (9) and DPPE (10). Neither 9 nor the previously reported 10 exhibited the blue shifts observed for 3 and 4 when incorporated into LUVs. The anisotropies of the emissions of 3, 4 and 7 were also measured in LUVs and of 5 in both glycerol and LUVs. High fundamental anisotropies were observed for 3 and 4 and 7. PMID:24063694

  5. Enhancement of the detection limit for lateral flow immunoassays: evaluation and comparison of bioconjugates.

    Science.gov (United States)

    Linares, Elisângela M; Kubota, Lauro T; Michaelis, Jens; Thalhammer, Stefan

    2012-01-31

    There is an increasing demand for convenient and accurate point-of-care tools that can detect and diagnose different stages of a disease in remote or impoverished settings. In recent years, lateral flow immunoassays (LFIA) have been indicated as a suitable medical diagnostic tool for these environments because they require little or no sample preparation, provide rapid and reliable results with no electronic components and thus can be manufactured at low costs and operated by unskilled personnel. However, even though they have been successfully applied to acute and chronic disease detection, LFIA based on gold nanoparticles, the standard marker, show serious limitations when high sensitivity is needed, such as early stage disease detection. Moreover, based on the lack of comparative information for label performance, significant optimization of the systems that are currently in use might be possible. To this end, in the presented work, we compare the detection limit between the four most used labels: colloidal-gold, silver enhanced gold, blue latex bead and carbon black nanoparticles. Preliminary results were obtained by using the biotin-streptavidin coupling as a model system and showed that carbon black had a remarkably low detection limit of 0.01 μg/mL in comparison to 0.1 μg/mL, 1 μg/mL and 1mg/mL for silver-coated gold nanoparticles, gold nanoparticles and polystyrene beads, respectively. Therefore, as a proof of concept, carbon black was used in a detection system for Dengue fever. This was achieved by immobilizing monoclonal antibodies for the nonstructural glycoprotein (NS1) of the Dengue virus to carbon black. We found that the colorimetric detection limit of 57 ng/mL for carbon black was ten times lower than the 575 ng/mL observed for standard gold nanoparticles; which makes it sensitive enough to diagnose a patient on the first days of infection. We therefore conclude that, careful screening of detection labels should be performed as a necessary step during LFIA development in order to enhance the detection limit in a final test system. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Synthesis and Biological Evaluation of Triazolyl 13α-Estrone–Nucleoside Bioconjugates

    Directory of Open Access Journals (Sweden)

    Brigitta Bodnár

    2016-09-01

    Full Text Available 2′-Deoxynucleoside conjugates of 13α-estrone were synthesized by applying the copper-catalyzed alkyne–azide click reaction (CuAAC. For the introduction of the azido group the 5′-position of the nucleosides and a propargyl ether functional group on the 3-hydroxy group of 13α-estrone were chosen. The best yields were realized in our hands when the 3′-hydroxy groups of the nucleosides were protected by acetyl groups and the 5′-hydroxy groups were modified by the tosyl–azide exchange method. The commonly used conditions for click reaction between the protected-5′-azidonucleosides and the steroid alkyne was slightly modified by using 1.5 equivalent of Cu(I catalyst. All the prepared conjugates were evaluated in vitro by means of MTT assays for antiproliferative activity against a panel of human adherent cell lines (HeLa, MCF-7 and A2780 and the potential inhibitory activity of the new conjugates on human 17β-hydroxysteroid dehydrogenase 1 (17β-HSD1 was investigated via in vitro radiosubstrate incubation. Some protected conjugates displayed moderate antiproliferative properties against a panel of human adherent cancer cell lines (the protected cytidine conjugate proved to be the most potent with IC50 value of 9 μM. The thymidine conjugate displayed considerable 17β-HSD1 inhibitory activity (IC50 = 19 μM.

  7. Highly cytotoxic bioconjugated gold(I) complexes with cysteine-containing dipeptides.

    Science.gov (United States)

    Gutiérrez, Alejandro; Marzo, Isabel; Cativiela, Carlos; Laguna, Antonio; Gimeno, M Concepción

    2015-07-27

    Several gold(I) complexes with cysteine-containing dipeptides have been prepared starting from cystine by coupling different amino acids and using several orthogonal protections. The first step is the reaction of cystine, where the sulfur centre is protected as disulfide, with Boc2 O in order to protect the amino group, followed by coupling of an amino acid ester; finally the disulfide bridge is broken with mercaptoethanol to afford the dipeptide derivative. Further reaction with [AuCl(PPh3 )] gives the gold-dipeptide-phosphine species. Starting from these formally gold(I) thiolate-dipeptide phosphine complexes with the general formula [Au(SR)(PR3 )] different structural modifications, such as change in the type of the amino protecting group, the type of phosphine, the number of gold(I) atoms per molecule, or the use of a non-proteinogenic conformationally restricted amino acid ester, were introduced in order to evaluate their influence in the biological activity of the final complexes. The cytotoxic activity, in vitro, of these complexes was evaluated against different tumour human cell lines (A549, MiaPaca2 and Jurkat). The complexes show an outstanding cytotoxic activity with IC50 values in the very low micromolar range. Structure-activity relationship studies from the complexes open the possibility of designing more potent and promising gold(I) anticancer agents. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Peptide binding specificity of the chaperone calreticulin

    DEFF Research Database (Denmark)

    Sandhu, N.; Duus, K.; Jorgensen, C.S.

    2007-01-01

    Calreticulin is a molecular chaperone with specificity for polypeptides and N-linked monoglucosylated glycans. In order to determine the specificity of polypeptide binding, the interaction of calreticulin with polypeptides was investigated using synthetic peptides of different length and composit...

  9. Model Commissioning Plan and Guide Specifications

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    The objectives of Model Commissioning Plan and Guide Specifications are to ensure that the design team applies commissioning concepts to the design and prepares commissioning specifications and a commission plan for inclusion in the bid construction documents.

  10. Genre-Specific Semantic Video Indexing

    NARCIS (Netherlands)

    Wu, J.; Worring, M.

    2010-01-01

    In many applications, we find large video collections from different genres where the user is often only interested in one or two specific video genres. So, when users are querying the system with a specific semantic concept, they are likely aiming a genre specific instantiation of this concept.

  11. 42 CFR 37.203 - Autopsy specifications.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Autopsy specifications. 37.203 Section 37.203... EXAMINATIONS SPECIFICATIONS FOR MEDICAL EXAMINATIONS OF UNDERGROUND COAL MINERS Autopsies § 37.203 Autopsy specifications. (a) Every autopsy for which a claim for payment is submitted pursuant to this part: (1) Shall be...

  12. Low back pain (non-specific).

    NARCIS (Netherlands)

    Krismer, M.; van Tulder, M.W.

    2007-01-01

    Low back pain (LBP) is defined as pain localised between the 12th rib and the inferior gluteal folds, with or without leg pain. Most cases are non-specific, but in about 10% of cases a specific cause is identified. Red flags are typical signs or symptoms that are frequently associated with specific

  13. Isothermal Gravitational Segregation: Algorithms and Specifications

    DEFF Research Database (Denmark)

    Halldórsson, Snorri; Stenby, Erling Halfdan

    2000-01-01

    New algorithms for calculating the isothermal equilibrium state of reservoir fluids under the influence of gravity are presented. Two types of specifications are considered: the specification of pressure and composition at a reference depth; and the specification of the total overall content of t...

  14. Task-specific dystonia : pathophysiology and management

    NARCIS (Netherlands)

    Sadnicka, Anna; Kassavetis, Panagiotis; Parees, Isabel; Meppelink, Anne; Butler, Katherine; Edwards, Mark

    Task-specific dystonia is a form of isolated focal dystonia with the peculiarity of being displayed only during performance of a specific skilled motor task. This distinctive feature makes task-specific dystonia a particularly mysterious and fascinating neurological condition. In this review, we

  15. Technical specification improvement through safety margin considerations

    International Nuclear Information System (INIS)

    Howard, R.C.; Jansen, R.L.

    1986-01-01

    Westinghouse has developed an approach for utilizing safety analysis margin considerations to improve plant operability through technical specification revision. This approach relies on the identification and use of parameter interrelations and sensitivities to identify acceptable operating envelopes. This paper summarizes technical specification activities to date and presents the use of safety margin considerations as another viable method to obtain technical specification improvement

  16. Standard technical specifications combustion engineering plants

    International Nuclear Information System (INIS)

    1992-09-01

    This report documents the results of the combined effort of the NRC and the industry to produce improved Standard Technical Specifications (STS) for Combustion Engineering Plants. The improved STS wee developed based on the criteria in the interim Commission Policy Statement on Technical Specification Improvements for Nuclear Power Reactors, dated February 6, 1987. The improved STS will be used as the basis for individual nuclear power plant licensees to develop improved plant-specific technical specifications. This report contains three volumes. This document, Volume 1, contains the Specifications for all chapters and sections of the improved STS. Volume 2 contains the Bases for Sections 3.4--3.9 of the improved STS

  17. Specific phobia predicts psychopathology in young women

    Science.gov (United States)

    Margraf, Jürgen; Vriends, Noortje; Meyer, Andrea H.; Becker, Eni S.

    2009-01-01

    Background Although specific phobia is characterized by an early age at onset and by high rates of comorbidity, few studies have examined comorbid relationships prospectively. Objectives The present study investigated the association between specific phobia and the risk of a broad range of psychopathology among young women in the community. Method Data came from the Dresden Predictor Study in which 1,538 German women (18–25 years) completed a diagnostic interview at two time points. Results Women with specific phobia had a twofold increase in odds of developing any anxiety disorder, generalized anxiety disorder, depression, and any somatoform disorder during 17 months, compared to women without specific phobia. Except for depression, these associations persisted after adjustment for all comorbid mental disorders. Conclusions Specific phobia thus appears to be a risk factor for a variety of problems. The result further underpins the necessity for early intervention for specific phobia to prevent later mental health problems. PMID:19888542

  18. Towards a theory of product design specifications

    DEFF Research Database (Denmark)

    Hansen, Claus Thorp; Andreasen, Mogens Myrup

    2004-01-01

    , which express the customers¿ need and perception of value. In this paper we will scrutinize this assumption. We outline the roles and tasks of the product design specification in order to identify the requirements on a theory of product design specifications and we identify existing theory elements......The product design specification is an important element in a product development project because it defines the target to be met. One requirement on the product design specification is to articulate and communicate the aspects, which makes the product attractive seen from the users' viewpoint....... In the design methodology literature we find guidelines and methods to compile a product design specification. The contributions are based on the common underlying assumption that it is meaningful and the only feasible approach to interpret the result of a need analysis into a set of technical specifications...

  19. SOFTWARE REQUIREMENTS SPECIFICATION SINAPRA BERBASIS SISTEM INFORMASI

    Directory of Open Access Journals (Sweden)

    Nur Hadi Waryanto

    2015-07-01

    Full Text Available Sistem Informasi Sarana dan Prasarana (SINAPRA merupakan bagian dari beberapa sistem informasi yang dipakai oleh Univeristas Negeri Yogyakarta. SINAPRA merupakan salah satu sistem yang akan dikembangkan dalam Sistem Informasi Terpadu (SIPADU. Software Requirements Specification SINAPRA merupakan acuan teknis developer dalam mengembangkan sistem untuk tahap selanjutnya. Software Requirements Specification SINAPRA dikembangkan menggunakan model WSU-TC CptS 322  dengan berbasis sistem informasi terpadu UNY Kata Kunci : Software Requirements Specification, WSU-TC CptS 322, SINAPRA

  20. An Algebraic Specification of the Semantic Web

    OpenAIRE

    Ksystra, Katerina; Triantafyllou, Nikolaos; Stefaneas, Petros; Frangos, Panayiotis

    2011-01-01

    We present a formal specification of the Semantic Web, as an extension of the World Wide Web using the well known algebraic specification language CafeOBJ. Our approach allows the description of the key elements of the Semantic Web technologies, in order to give a better understanding of the system, without getting involved with their implementation details that might not yet be standardized. This specification is part of our work in progress concerning the modeling the Social Semantic Web.

  1. Embedded systems specification and design languages

    CERN Document Server

    Villar, Eugenio

    2008-01-01

    This book is the latest contribution to the Chip Design Languages series and it consists of selected papers presented at the Forum on Specifications and Design Languages (FDL'07), in September 2007. The book represents the state-of-the-art in research and practice, and it identifies new research directions. It highlights the role of specification and modelling languages, and presents practical experiences with specification and modelling languages.

  2. Map Specifications and Exchange of Geographical Information

    DEFF Research Database (Denmark)

    Frederiksen, Poul

    1999-01-01

    Specifications for Technical Maps 1993 – 99 are described giving an overview of the specification structure including the object description of the latest version: TK99.The technical map specifications are related to the standards for topographical maps - especially the TOP10DK standard. Common...... object definitions are essential for the standards. Technical as well as topographical map information is exchangeable through the Danish developed “Standard for Exchange of Digital Map Information”, known as the DSFL-format....

  3. Improved technical specifications for Korean NPP

    International Nuclear Information System (INIS)

    Ryu, J. D.; Lee, D. H.; Seong, C. K.

    2002-01-01

    PWRs use Technical Specifications(Tech. Spec.) to ensure safe operation of the plant. Recently, many efforts were made to improve Tech. Spec. and as a result, Improved Standard Technical Specifications(ISTS) have been developed. Korean NPP technical specifications were converted to ISTS format. KAERI also provided supporting documents for technical specification conversion including mark-up's and description of changes. This paper describes and summarizes the results of implementation of ISTS for Korean NPP. The new Tech. Spec. will improve safety of Korean NPP

  4. User Interface Technology for Formal Specification Development

    Science.gov (United States)

    Lowry, Michael; Philpot, Andrew; Pressburger, Thomas; Underwood, Ian; Lum, Henry, Jr. (Technical Monitor)

    1994-01-01

    Formal specification development and modification are an essential component of the knowledge-based software life cycle. User interface technology is needed to empower end-users to create their own formal specifications. This paper describes the advanced user interface for AMPHION1 a knowledge-based software engineering system that targets scientific subroutine libraries. AMPHION is a generic, domain-independent architecture that is specialized to an application domain through a declarative domain theory. Formal specification development and reuse is made accessible to end-users through an intuitive graphical interface that provides semantic guidance in creating diagrams denoting formal specifications in an application domain. The diagrams also serve to document the specifications. Automatic deductive program synthesis ensures that end-user specifications are correctly implemented. The tables that drive AMPHION's user interface are automatically compiled from a domain theory; portions of the interface can be customized by the end-user. The user interface facilitates formal specification development by hiding syntactic details, such as logical notation. It also turns some of the barriers for end-user specification development associated with strongly typed formal languages into active sources of guidance, without restricting advanced users. The interface is especially suited for specification modification. AMPHION has been applied to the domain of solar system kinematics through the development of a declarative domain theory. Testing over six months with planetary scientists indicates that AMPHION's interactive specification acquisition paradigm enables users to develop, modify, and reuse specifications at least an order of magnitude more rapidly than manual program development.

  5. Shape configuration and category-specificity

    DEFF Research Database (Denmark)

    Gerlach, Christian; Law, Ian; Paulson, Olaf B.

    2006-01-01

    a recent account of category-specificity and lends support to the notion that category-specific impairments can occur for both natural objects and artefacts following damage to pre-semantic stages in visual object recognition. The implications of the present findings are discussed in relation to theories...

  6. The Logic of the RAISE Specification Language

    DEFF Research Database (Denmark)

    George, Chris; Haxthausen, Anne Elisabeth

    2003-01-01

    This paper describes the logic of the RAISE Specification Language, RSL. It explains the particular logic chosen for RAISE, and motivates this choice as suitable for a wide spectrum language to be used for designs as well as initial specifications, and supporting imperative and concurrent...

  7. The Logic of the RAISE Specification Language

    DEFF Research Database (Denmark)

    George, Chris; Haxthausen, Anne Elisabeth

    2008-01-01

    This chapter describes the logic of the RAISE Specification Language, RSL. It explains the particular logic chosen for RAISE, and motivates this choice as suitable for a wide spectrum language to be used for designs as well as initial specifications, and supporting imperative and concurrent...

  8. Domain-specific languages in perspective

    NARCIS (Netherlands)

    J. Heering (Jan); M. Mernik (Marjan)

    2007-01-01

    textabstractDomain-specific languages (DSLs) are languages tailored to a specific application domain. They offer substantial gains in expressiveness and ease of use compared with general-purpose languages in their domain of application. Although the use of DSLs is by no means new, it is receiving

  9. Site-specific photochemical RNA editing.

    Science.gov (United States)

    Fujimoto, Kenzo; Konishi-Hiratsuka, Kaoru; Sakamoto, Takashi; Yoshimura, Yoshinaga

    2010-10-28

    Photo-induced artificial RNA editing was demonstrated using photo-reactive oligonucleotides containing 3-cyanovinylcarbazole nucleoside. This non-enzymatic and sequence-specific methodology will make a major contribution to the elucidation of RNA functions including non-coding RNAs and to the development of drugs based on sequence-specific RNA editing.

  10. SPECIFIC SKILLS AND SOCIAL COMPETENCE IN SCHIZOPHRENIA

    NARCIS (Netherlands)

    APPELO, MT; WOONINGS, FMJ; VANNIEUWENHUIZEN, CJ; EMMELKAMP, PMG; SLOOFF, CJ; LOUWERENS, JW

    Generalization of skills is a major problem in social skills training for schizophrenic patients. Assessment of skills is mostly not based on objective indices of specific skill deficits. The results of this study show that global competence of schizophrenics can be differentiated from specific

  11. ITER ISS system alternative specification study

    International Nuclear Information System (INIS)

    Kveton, O.K.

    1990-08-01

    Recent comments suggested that the fuel systems, in particular the ISS, could be simplified if the ITER specifications were relaxed from the data specified for ITER. This interim report addresses the first part of the analysis, which considers the impact of design specifications on fuel systems design

  12. Specific and social phobias in ICD-11

    NARCIS (Netherlands)

    Emmelkamp, P.M.G.

    2012-01-01

    The purpose of this article is to discuss the current status of research with respect to specific phobias and social phobia as defined in the ICD-10 and DSM-IV, and to provide op- tions for their classification in the ICD-11. Both ICD-10 and DSM-IV identify three main classes of phobias: specific

  13. Building finite automata from DI specifications

    NARCIS (Netherlands)

    Udding, J.T

    1998-01-01

    Numerous formalisms exist to specify delay-insensitive computations and their implementations. It is not always straightforward to compare specifications in the different formalisms. One way of comparing specifications is transforming them to automata in which nodes are annotated with progress

  14. Plutonium Immobilization Can Loading Preliminary Specifications

    Energy Technology Data Exchange (ETDEWEB)

    Kriikku, E.

    1998-11-25

    This report discusses the Plutonium Immobilization can loading preliminary equipment specifications and includes a process block diagram, process description, equipment list, preliminary equipment specifications, plan and elevation sketches, and some commercial catalogs. This report identifies loading pucks into cans and backfilling cans with helium as the top priority can loading development areas.

  15. PCR specific for Actinobacillus pleuropneumoniae serotype 3

    DEFF Research Database (Denmark)

    Zhou, L.; Jones, S.C.P.; Angen, Øystein

    2008-01-01

    , but the method has liminations, for example, cross-reactions between serotypes 3, 6, and 8. This study describes the development of a serotype 3-specific PCR, based on the capsule locus, which can be used in a multiplex format with the organism's specific gene apxIV. The PCR test was evaluated on 266 strains...

  16. Cell-Type-Specific Optogenetics in Monkeys.

    Science.gov (United States)

    Namboodiri, Vijay Mohan K; Stuber, Garret D

    2016-09-08

    The recent advent of technologies enabling cell-type-specific recording and manipulation of neuronal activity spurred tremendous progress in neuroscience. However, they have been largely limited to mice, which lack the richness in behavior of primates. Stauffer et al. now present a generalizable method for achieving cell-type specificity in monkeys. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Efficient genre-specific semantic video indexing

    NARCIS (Netherlands)

    Wu, J.; Worring, M.

    2012-01-01

    Large video collections such as YouTube contain many different video genres, while in many applications the user might be interested in one or two specific video genres only. Thus, when users are querying the system with a specific semantic concept like AnchorPerson, and MovieStars, they are likely

  18. 324 and 327 Facilities Environmental Effluent Specifications

    International Nuclear Information System (INIS)

    JOHNSON, D.L.

    1999-01-01

    These effluent specifications address requirements for the 324/321 Facilities, which are undergoing stabilization activities. Effluent specifications are imposed to protect personnel, the environment and the public, by ensuring adequate implementation and compliance with federal and state regulatory requirements and Hanford programs

  19. Specific elements of thoracic wound management.

    Science.gov (United States)

    Avaro, J-P; De Lesquen, H; Beranger, F; Cotte, J; Natale, C

    2017-12-01

    Damage control for thoracic trauma combines definitive and temporary surgical gestures specifically adapted to the lesions present. A systematic assessment of all injuries to prioritize the specific lesions and their treatments constitutes the first operative stage. Packing and temporary closure have a place in the care of chest injuries. Copyright © 2017. Published by Elsevier Masson SAS.

  20. Motorcycle Education Curriculum Specifications. Final Report.

    Science.gov (United States)

    McKnight, A. James; And Others

    This report contains specifications for a motorcycle safety education curriculum designed to reduce the incidence and severity of motorcycle accidents. The specifications prescribe objectives, prerequisites, methods, materials, equipment, facilities, and proficiency measures for six units of instruction: (1) basic riding skills, (2) street riding…

  1. 10 CFR 55.11 - Specific exemptions.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Specific exemptions. 55.11 Section 55.11 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) OPERATORS' LICENSES Exemptions § 55.11 Specific exemptions. The Commission... the requirements of the regulations in this part as it determines are authorized by law and will not...

  2. 10 CFR 26.9 - Specific exemptions.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Specific exemptions. 26.9 Section 26.9 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Administrative Provisions § 26.9 Specific exemptions. Upon... the requirements of the regulations in this part as it determines are authorized by law and will not...

  3. 10 CFR 35.19 - Specific exemptions.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Specific exemptions. 35.19 Section 35.19 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL General Information § 35.19 Specific exemptions. The... the regulations in this part that it determines are authorized by law and will not endanger life or...

  4. 10 CFR 60.43 - License specification.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false License specification. 60.43 Section 60.43 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DISPOSAL OF HIGH-LEVEL RADIOACTIVE WASTES IN GEOLOGIC REPOSITORIES Licenses License Issuance and Amendment § 60.43 License specification. (a) A license issued under this part shall...

  5. Determining the specific electric resistance of rock

    Energy Technology Data Exchange (ETDEWEB)

    Persad' ko, V.Ia.

    1982-01-01

    Data are presented on perfecting the method of laboratory determination of the specific electric resistance of a rock formation. The average error in determining the specific electric resistance of the core at various locations is no more than two percent with low resistance values (2-5 ohms).

  6. Specific skills and social competence in schizophrenia

    NARCIS (Netherlands)

    Appelo, M.T.; van Nieuwenhuizen, C.J.; Emmelkamp, P.M.G.; Slooff, C.J.; Louwerens, J.W.

    1992-01-01

    Generalization of skills is a major problem in social skills training for schizophrenic patients. Assessment of skills is mostly not based on objective indices of specific skill deficits. The results of this study show that global competence of schizophrenics can be differentiated from specific

  7. Light Rail Transit Car Specification Guide

    Science.gov (United States)

    1981-12-01

    This Light Rail Transit Car Specification Guide is not a procurement document in itself. It is intended to be used as a guide by light rail transit operators and purchasers of such equipment in the preparation of technical specifications. Because of ...

  8. Graphical And Textual Notations In Formal Specification

    Energy Technology Data Exchange (ETDEWEB)

    Bove, Rocco; Dipoppa, Giovanni; Groven, Arne-Kristian; Sivertsen, Terje

    1996-07-01

    The present report describes the current status of the co-operative project between ENEA and the OECD Halden Reactor Project on graphical and formal methods for software specification. The aim of this project is to contribute to a clarification of the relationship between graphical descriptions and formal specifications, and to provide guidelines for how they can be combined in order to utilize the strengths of' each approach. The overall aim of such a combination is to improve the formal basis of graphical descriptions and make formal specifications more generally comprehensible. The research reported includes the application of the IPTES technology on the APRM case example, an approach to the translation of Petri nets into algebraic specification, and the specification of real-time distributed systems using time-extended LOTOS. (author)

  9. Fundamental Characteristics of Industrial Variant Specification Systems

    DEFF Research Database (Denmark)

    Hansen, Benjamin Loer; Hvam, Lars

    2004-01-01

    This paper focuses on the operational task of creating customised variants of industrial specifications (e.g. drawings, routings and bill-of-materials). Rooted in a lack of existing literature on the subject the paper describes the nature of variant specification systems. It introduces some...... fundamental concepts related to this task, which are relevant to understand for academia and practitioners working with the subject. This is done through a description of variant specification tasks and typical aspects of system solutions. To support the description of variant specification tasks and systems...... examples. In general the paper discusses an important focus area within mass customization and build-to-order production: the nature of industrial variant specification systems....

  10. Development of industrial variant specification systems

    DEFF Research Database (Denmark)

    Hansen, Benjamin Loer

    With globalisation and increased competition industrial companies must be prepared to satisfy individual customer needs and still stay competitive with regards to lead times, quality, and prices. These factors require companies to be better prepared to handle specification activities during order...... to the four research tasks of the Ph.D. project: • Define and describe the variant specification system. • Create a procedure for the development of variant specification systems. • Create concepts, methods and tools to support the analysis and determination of the variant specification task. • Identify...... are presented for analysing and determining the variant specification task. These are grouped in external and internal task variables. Additionally functional characteristics, which can be used for defining performance measures, are defined. Based in the concept of “focus” different levels of tasks...

  11. Standard Technical Specifications, Babcock and Wilcox plants

    International Nuclear Information System (INIS)

    1992-09-01

    This NUREG contains improved Standard Technical Specifications (STS) for Babcock and Wilcox (B ampersand W) Plants and documents the positions of the Nuclear Regulatory Commission based on the B ampersand W Owners Group's proposed STS. This document is the result of extensive technical meetings and discussions among the NRC staff, the Nuclear Steam Supply System (NSSS) Owners Groups, the NSSS vendors, and the Nuclear Management and Resources Council (NUMARC). The unproved STS were developed based on the, criteria in the interim Commission Policy Statement on Technical Specification Improvements for Nuclear Power Reactors, dated February 6, 1987. The improved STS will be used as the basis for individual nuclear power plant licensees to develop proved plant-specific technical specifications. This report contains three volumes. This document, Volume 1 contains the Specifications for all chapters and sections of the improved STS

  12. Screening specifications for Gulf Coast salt domes

    International Nuclear Information System (INIS)

    Brunton, G.D.; Laughon, R.B.; McClain, W.C.

    1978-01-01

    A reconnaissance survey of the salt domes of Mississippi, Louisiana, and east Texas is being planned to identify study areas for potential sites for radioactive waste disposal. Preliminary screening specifications were derived for each of the geological evaluation criteria by application of the significant factors that will have an impact on the reconnaissance survey. The procedure for the derivation of each screening specification is discussed. The screening specifications are the official OWI values to be used for the first-cut acceptance for salt dome study areas along the Gulf Coast. The derivation of the screening specifications is illustrated by (1) a statement of the geological evaluation criterion, (2) a discussion of the pertinent factors affecting the criterion, and (3) the evaluation of the value of the specification

  13. CMV-specific T cell therapy.

    Science.gov (United States)

    Einsele, Hermann; Kapp, Markus; Grigoleit, Götz Ulrich

    2008-01-01

    Human cytomegalovirus (CMV) infection continues to be one of the most important and life threatening complications after allogeneic stem cell transplantation (SCT). The reconstitution of CMV-specific T cell responses after SCT has been demonstrated to be protective against the development of CMV disease. To improve T cell immunity against CMV in bone marrow transplant patients, different strategies were explored. On one hand, CMV-specific T cells can be selected from the donor, and can be transferred to the patient without any further in vitro expansion. On the other hand, CMV-specific T cells can be activated and expanded in vitro by stimulation with antigen presenting cells (APCs) loaded with specific proteins or peptides. Here, we review the therapeutic application of CMV-specific T cells to fight CMV infection.

  14. Specificity of transmembrane protein palmitoylation in yeast.

    Directory of Open Access Journals (Sweden)

    Ayelén González Montoro

    Full Text Available Many proteins are modified after their synthesis, by the addition of a lipid molecule to one or more cysteine residues, through a thioester bond. This modification is called S-acylation, and more commonly palmitoylation. This reaction is carried out by a family of enzymes, called palmitoyltransferases (PATs, characterized by the presence of a conserved 50- aminoacids domain called "Asp-His-His-Cys- Cysteine Rich Domain" (DHHC-CRD. There are 7 members of this family in the yeast Saccharomyces cerevisiae, and each of these proteins is thought to be responsible for the palmitoylation of a subset of substrates. Substrate specificity of PATs, however, is not yet fully understood. Several yeast PATs seem to have overlapping specificity, and it has been proposed that the machinery responsible for palmitoylating peripheral membrane proteins in mammalian cells, lacks specificity altogether.Here we investigate the specificity of transmembrane protein palmitoylation in S. cerevisiae, which is carried out predominantly by two PATs, Swf1 and Pfa4. We show that palmitoylation of transmembrane substrates requires dedicated PATs, since other yeast PATs are mostly unable to perform Swf1 or Pfa4 functions, even when overexpressed. Furthermore, we find that Swf1 is highly specific for its substrates, as it is unable to substitute for other PATs. To identify where Swf1 specificity lies, we carried out a bioinformatics survey to identify amino acids responsible for the determination of specificity or Specificity Determination Positions (SDPs and showed experimentally, that mutation of the two best SDP candidates, A145 and K148, results in complete and partial loss of function, respectively. These residues are located within the conserved catalytic DHHC domain suggesting that it could also be involved in the determination of specificity. Finally, we show that modifying the position of the cysteines in Tlg1, a Swf1 substrate, results in lack of palmitoylation, as

  15. Validating Avionics Conceptual Architectures with Executable Specifications

    Directory of Open Access Journals (Sweden)

    Nils Fischer

    2012-08-01

    Full Text Available Current avionics systems specifications, developed after conceptual design, have a high degree of uncertainty. Since specifications are not sufficiently validated in the early development process and no executable specification exists at aircraft level, system designers cannot evaluate the impact of their design decisions at aircraft or aircraft application level. At the end of the development process of complex systems, e. g. aircraft, an average of about 65 per cent of all specifications have to be changed because they are incorrect, incomplete or too vaguely described. In this paper, a model-based design methodology together with a virtual test environment is described that makes complex high level system specifications executable and testable during the very early levels of system design. An aircraft communication system and its system context is developed to demonstrate the proposed early validation methodology. Executable specifications for early conceptual system architectures enable system designers to couple functions, architecture elements, resources and performance parameters, often called non-functional parameters. An integrated executable specification at Early Conceptual Architecture Level is developed and used to determine the impact of different system architecture decisions on system behavior and overall performance.

  16. Position paper: the science of deep specification.

    Science.gov (United States)

    Appel, Andrew W; Beringer, Lennart; Chlipala, Adam; Pierce, Benjamin C; Shao, Zhong; Weirich, Stephanie; Zdancewic, Steve

    2017-10-13

    We introduce our efforts within the project 'The science of deep specification' to work out the key formal underpinnings of industrial-scale formal specifications of software and hardware components, anticipating a world where large verified systems are routinely built out of smaller verified components that are also used by many other projects. We identify an important class of specification that has already been used in a few experiments that connect strong component-correctness theorems across the work of different teams. To help popularize the unique advantages of that style, we dub it deep specification , and we say that it encompasses specifications that are rich , two-sided , formal and live (terms that we define in the article). Our core team is developing a proof-of-concept system (based on the Coq proof assistant) whose specification and verification work is divided across largely decoupled subteams at our four institutions, encompassing hardware microarchitecture, compilers, operating systems and applications, along with cross-cutting principles and tools for effective specification. We also aim to catalyse interest in the approach, not just by basic researchers but also by users in industry.This article is part of the themed issue 'Verified trustworthy software systems'. © 2017 The Author(s).

  17. Non-specific immunization against babesiosis

    International Nuclear Information System (INIS)

    Cox, F.E.G.

    1980-01-01

    The rodent babesias, Babesia rodhaini and the less virulent B. microti, are useful models with which to study immunity to and immunization against babesiosis. In contrast with the difficulty in inducing specific immunity to these parasites it is comparatively easy to induce non-specific immunity by prior exposure to related and unrelated intra-erythrocytic protozoa, micro-organisms such as Mycobacterium bovis (BCG) and Corynebacterium parvum, microbial extracts and muramyl dipeptide. This non-specific immunity is long lasting and extremely effective. It is characterized by the facts that (a) it occurs early in the infection at the height of the first peak of parasitaemia, and (b) it involves the intra-erythrocytic death of the parasites. After the primary parasitaemia has resolved, some parasites continue to persist at a low level and when introduced into clean mice produce only low-level 'attenuated' infections in these. Non-specific immunity is not equally effective in all strains of mice. It is suggested that immunity to babesiosis, and infections caused by other intra-erythrocytic protozoa, involves two mechanisms, the first non-specific and the second specific. The actual balance between these two mechanisms varies from parasite to parasite and from host to host. An effective vaccine would have to be based on an understanding of the roles of non-specific immunity in the actual disease under consideration, and would ideally combine an adjuvant that would also stimulate non-specific immunity and an attenuated strain of parasite that would induce a specific response. (author)

  18. Autoethnographic Mother-Writing: Advocating Radical Specificity

    Directory of Open Access Journals (Sweden)

    Patty Sotirin

    2010-01-01

    Full Text Available In considering the similarities between "momoirs"--popular memoirs written by mothers about motherhood experiences--and evocative autoethnographic mother-writing, I argue that differentiating these two forms of intimate observation and personal narrative requires a rethinking of autoethnographic practice. Specifically, I draw on the work of Gilles Deleuze to advocate for a radical specificity in autoethnographic writing. Thinking the autoethnographic narrative in terms of specificities and differences encourages us to think creatively about personal experiences and cultural relations beyond what is shared and communicable.

  19. Table of specific activities of selected isotopes

    International Nuclear Information System (INIS)

    Shipley, G.

    The bulk of this publication consists of a table of the half-lives, decay modes, and specific activities of isotopes selected for their particular interest to the Environmental Health and Safety Department, LBL. The specific activities were calculated with a PDP 9/15 computer. Also included in the report is a table of stable isotopes, the Th and U decay chains, a chart of the nuclides for elements 101 through 106, the heavy element region of the periodic table, and a specific activity monograph. 5 figures, 2 tables

  20. Technical specification optimization program - engineered safety features

    International Nuclear Information System (INIS)

    Andre, G.R.; Jansen, R.L.

    1986-01-01

    The Westinghouse Technical Specification Program (TOP) was designed to evaluate on a quantitative basis revisions to Nuclear Power Plant Technical Specifications. The revisions are directed at simplifying plant operation, and reducing unnecessary transients, shutdowns, and manpower requirements. In conjunction with the Westinghouse Owners Group, Westinghouse initiated a program to develop a methodology to justify Technical Specification revisions; particularly revisions related to testing and maintenance requirements on plant operation for instrumentation systems. The methodology was originally developed and applied to the reactor trip features of the reactor protection system (RPS). The current study further refined the methodology and applied it to the engineered safety features of the RPS

  1. Mining software specifications methodologies and applications

    CERN Document Server

    Lo, David

    2011-01-01

    An emerging topic in software engineering and data mining, specification mining tackles software maintenance and reliability issues that cost economies billions of dollars each year. The first unified reference on the subject, Mining Software Specifications: Methodologies and Applications describes recent approaches for mining specifications of software systems. Experts in the field illustrate how to apply state-of-the-art data mining and machine learning techniques to address software engineering concerns. In the first set of chapters, the book introduces a number of studies on mining finite

  2. Specific Developmental Disorders of Scholastic Skills

    Directory of Open Access Journals (Sweden)

    Beena Johnson

    2015-07-01

    Full Text Available Several factors contribute to scholastic backwardness in children. Causes include specific developmental disorders of scholastic skills, low intelligence, chronic illnesses, family dysfunction, social problems, attention deficits, and emotional disorders. Children with specific developmental disorders of scholastic skills experience significant impairment in the acquisition of reading, writing and mathematical skills. If not remedied at the earliest, these children are at risk of developing severe stress related disorders. There is high comorbidity of behaviour disorders and emotional disorders in these children. Hence early intensive remedial education is essential in the management of children with specific developmental disorders of scholastic skills.

  3. Specifications in early conceptual design work

    DEFF Research Database (Denmark)

    Hansen, Claus Thorp; Andreasen, Mogens Myrup

    2007-01-01

    In early conceptual design the design team is working in an uncertain situation, where the understanding of a need is limited and not much is known about the solution space. In this situation the design team has to both analyse need and explore solution space. Thus, the team has to formulate design...... the structure and content of design specifications during early ideation activities, where initial design specifications are formulated and a product idea is synthesised. We have analysed specification documents of 19 teams of novice designers. Our analysis indicates that a productive product design...

  4. PD-L1-specific T cells

    DEFF Research Database (Denmark)

    Ahmad, Shamaila Munir; Borch, Troels Holz; Hansen, Morten

    2016-01-01

    -specific T cells that recognize both PD-L1-expressing immune cells and malignant cells. Thus, PD-L1-specific T cells have the ability to modulate adaptive immune reactions by reacting to regulatory cells. Thus, utilization of PD-L1-derived T cell epitopes may represent an attractive vaccination strategy...... for targeting the tumor microenvironment and for boosting the clinical effects of additional anticancer immunotherapy. This review summarizes present information about PD-L1 as a T cell antigen, depicts the initial findings about the function of PD-L1-specific T cells in the adjustment of immune responses...

  5. Breckinridge Project, initial effort. Report III, Volume 2. Specifications

    Energy Technology Data Exchange (ETDEWEB)

    None

    1982-01-01

    Report III, Volume 2 contains those specifications numbered K through Y, as follows: Specifications for Compressors (K); Specifications for Piping (L); Specifications for Structures (M); Specifications for Insulation (N); Specifications for Electrical (P); Specifications for Concrete (Q); Specifications for Civil (S); Specifications for Welding (W); Specifications for Painting (X); and Specifications for Special (Y). The standard specifications of Bechtel Petroleum Incorporated have been amended as necessary to reflect the specific requirements of the Breckinridge Project and the more stringent specifications of Ashland Synthetic Fuels, Inc. These standard specifications are available for the Initial Effort (Phase Zero) work performed by all contractors and subcontractors.

  6. Cancer Chemotherapy Specific to Acidic Nests.

    Science.gov (United States)

    Kobayashi, Hiroshi

    2017-04-20

    The realization of cancer therapeutics specific to cancer cells with less of an effect on normal tissues is our goal. Many trials have been carried out for this purpose, but this goal is still far from being realized. It was found more than 80 years ago that solid cancer nests are acidified, but in vitro studies under acidic conditions have not been extensively studied. Recently, in vitro experiments under acidic conditions were started and anti-cancer drugs specific to acidic areas have been identified. Many genes have been reported to be expressed at a high level under acidic conditions, and such genes may be potent targets for anti-cancer drugs specific to acidic nests. In this review article, recent in vitro, in vivo, and clinical achievements in anti-cancer drugs with marked efficacy under acidic conditions are summarized, and the clinical use of anti-cancer drugs specific to acidic nests is discussed.

  7. Disease specific therapies in leukodystrophies and leukoencephalopathies

    NARCIS (Netherlands)

    Helman, Guy; van Haren, Keith; Bonkowsky, Joshua L.; Bernard, Genevieve; Pizzino, Amy; Braverman, Nancy; Suhr, Dean; Patterson, Marc C.; Ali Fatemi, S.; Leonard, Jeff; van der Knaap, Marjo S.; Back, Stephen A.; Damiani, Stephen; Goldman, Steven A.; Takanohashi, Asako; Petryniak, Magdalena; Rowitch, David; Messing, Albee; Wrabetz, Lawrence; Schiffmann, Raphael; Eichler, Florian; Escolar, Maria L.; Vanderver, Adeline

    2015-01-01

    Leukodystrophies are a heterogeneous, often progressive group of disorders manifesting a wide range of symptoms and complications. Most of these disorders have historically had no etiologic or disease specific therapeutic approaches. Recently, a greater understanding of the pathologic mechanisms

  8. Thermodynamic stability contributes to immunoglobulin specificity.

    Science.gov (United States)

    Dimitrov, Jordan D; Kaveri, Srinivas V; Lacroix-Desmazes, Sébastien

    2014-05-01

    Antigen-binding specificity of immunoglobulins is important for their function in immune defense. However, immune repertoires contain a considerable fraction of immunoglobulins with promiscuous binding behavior, the physicochemical basis of which is not well understood. Evolution of immunoglobulin specificity occurs through iterative processes of mutation and selection, referred to as affinity maturation. Recent studies reveal that some somatic mutations could compromise the thermodynamic stability of the variable regions of immunoglobulins. By integrating this observation with the wealth of data on the evolution of novel enzyme activities, we propose that antibody specificity is linked to the thermodynamic stability of the antigen-binding regions, which provides a quantitative distinction between highly specific and promiscuous antibodies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. UPC Language Specifications V1.2

    Energy Technology Data Exchange (ETDEWEB)

    UPC Consortium

    2005-05-31

    UPC is an explicitly parallel extension to the ISO C 99Standard. UPC follows the partitioned global address space programming model. This document is the formal specification for the UPC language syntax and semantics.

  10. Gender-Specific Health Challenges Facing Women

    Science.gov (United States)

    ... East and North Africa South and Central Asia Sub-Saharan Africa The Americas and the Caribbean Questions & Answers Resources Women's Health Research Overview Gender-Specific Health Challenges Facing Women ...

  11. Development of industrial variant specification systems

    DEFF Research Database (Denmark)

    Hansen, Benjamin Loer

    acquisition and order fulfilment, i.e. the creation of drawings, bill-of-materials, routings, product descriptions, quote letters etc. The present thesis is rooted in the assumption that variant specification systems supporting the cross-functional processes of order acquisition and order fulfilment must...... be developed from a holistic and strategically anchored point of view. Another assumption is that this is a challenge for many industrial companies. Even though the literature presents many considerations on general issues covering new information technology, little work is found on the business perspectives...... to the four research tasks of the Ph.D. project: • Define and describe the variant specification system. • Create a procedure for the development of variant specification systems. • Create concepts, methods and tools to support the analysis and determination of the variant specification task. • Identify...

  12. Customized atomicity specification for transactional workflows

    NARCIS (Netherlands)

    Derks, W.L.A.; Dehnert, Juliane; Grefen, P.W.P.J.; Jonker, Willem

    2000-01-01

    This paper introduces a new approach for specifying transaction management requirements for workflow applications. We propose independent models for the specification of workflow and transaction properties. Although we distinguish multiple transaction properties in our approach, we focus on

  13. Customized Atomicity Specification for Transactional Workflows

    NARCIS (Netherlands)

    Derks, W.L.A.; Dehnert, Juliane; Grefen, P.W.P.J.; Jonker, Willem

    This paper introduces a new approach for specifying transaction management requirements for workflow applications. We propose independent models for the specification of workflow and transaction properties. Although we distinguish multiple transaction properties in our approach, we focus on

  14. Analyzing Security-Enhanced Linux Policy Specifications

    National Research Council Canada - National Science Library

    Archer, Myla

    2003-01-01

    NSA's Security-Enhanced (SE) Linux enhances Linux by providing a specification language for security policies and a Flask-like architecture with a security server for enforcing policies defined in the language...

  15. Specification Editing and Discovery Assistant Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The project will prototype a specification editing and discovery tool (SPEEDY) for C/C++ that will assist software developers with modular formal verification tasks...

  16. Modal Specifications for Probabilistic Timed Systems

    Directory of Open Access Journals (Sweden)

    Tingting Han

    2013-06-01

    Full Text Available Modal automata are a classic formal model for component-based systems that comes equipped with a rich specification theory supporting abstraction, refinement and compositional reasoning. In recent years, quantitative variants of modal automata were introduced for specifying and reasoning about component-based designs for embedded and mobile systems. These respectively generalize modal specification theories for timed and probabilistic systems. In this paper, we define a modal specification language for combined probabilistic timed systems, called abstract probabilistic timed automata, which generalizes existing formalisms. We introduce appropriate syntactic and semantic refinement notions and discuss consistency of our specification language, also with respect to time-divergence. We identify a subclass of our models for which we define the fundamental operations for abstraction, conjunction and parallel composition, and show several compositionality results.

  17. Cdc42-mediated tubulogenesis controls cell specification

    DEFF Research Database (Denmark)

    Kesavan, Gokul; Sand, Fredrik Wolfhagen; Greiner, Thomas Uwe

    2009-01-01

    Understanding how cells polarize and coordinate tubulogenesis during organ formation is a central question in biology. Tubulogenesis often coincides with cell-lineage specification during organ development. Hence, an elementary question is whether these two processes are independently controlled......, or whether proper cell specification depends on formation of tubes. To address these fundamental questions, we have studied the functional role of Cdc42 in pancreatic tubulogenesis. We present evidence that Cdc42 is essential for tube formation, specifically for initiating microlumen formation and later...... for maintaining apical cell polarity. Finally, we show that Cdc42 controls cell specification non-cell-autonomously by providing the correct microenvironment for proper control of cell-fate choices of multipotent progenitors. For a video summary of this article, see the PaperFlick file with the Supplemental Data...

  18. Specification For ST-5 Li Ion Battery

    Science.gov (United States)

    Castell, Karen D.; Day, John H. (Technical Monitor)

    2000-01-01

    This Specification defines the general requirements for rechargeable Space Flight batteries intended for use in the ST-5 program. The battery chemistry chosen for this mission is lithium ion (Li-Ion).

  19. Technical requirements specification for tank waste retrieval

    Energy Technology Data Exchange (ETDEWEB)

    Lamberd, D.L.

    1996-09-26

    This document provides the technical requirements specification for the retrieval of waste from the underground storage tanks at the Hanford Site. All activities covered by this scope are conducted in support of the Tank Waste Remediation System (TWRS) mission.

  20. Interior Design's Role in Educational Specifications.

    Science.gov (United States)

    Keller, Mary Ann

    1986-01-01

    An experienced interior designer, equipped with a well-written educational specification, will specify the best materials and coordinate colors, materials, and furnishings in line with the district's budget. (MLF)

  1. DRUG DELIVERY BY ORGAN-SPECIFIC IMMUNOLIPOSOMES

    NARCIS (Netherlands)

    MARUYAMA, K; MORI, A; KENNEL, SJ; WAALKES, MVB; SCHERPHOF, GL; HUANG, L

    1991-01-01

    Monoclonal antibodies highly specific to the mouse pulmonary endothelial cells were conjugated to liposomes. The resulting immunoliposomes showed high levels of lung accumulation when injected intravenously into mice. Optimal target binding and retention were achieved if the lipid composition

  2. Cockpit management and Specific Behavioral Objectives (SBOs)

    Science.gov (United States)

    Mudge, R. W.

    1987-01-01

    One of the primary tools used to accomplish the task of effective training is the specific behavioral objective (SBO). An SBO is simply a statement which specifically identifies a small segment of the final behavior sought, and a little more. The key word is specific. The company pinpoints exactly what it is it wants the pilot to do after completing training, and what it should evaluate from the point of view of both the program and the pilot. It tells the junior crewmember exactly, specifically, what he should monitor and support insofar as the management function is concerned. It gives greater meaning to the term second in command. And finally, it tells the supervisory pilot exactly what he should observe, evaluate, and instruct, insofar as the management function is concerned.

  3. Specific detection of proteins using Nanomechanical resonators

    DEFF Research Database (Denmark)

    Fischer, Lee MacKenzie; Wright, V.A.; Guthy, C.

    2008-01-01

    of probes onto their surfaces in order to enable the specificity of the detection. Such nanoresonator-based specific detection of proteins is here reported using streptavidin as target system, and immobilized biotin as probe. Nanomechanical resonators resistant to stiction were first realized from silicon...... carbonitride using a novel fabrication method. Vapor-phase deposition of mercaptopropyl trimethoxysilane was performed, and an added mass of 2.22 +/- 0.07 fg/mu m(2) was measured. This linker molecule was used to attach biotin onto the devices, enabling the specific detection of streptavidin. A mass of 3.6 fg....../mu m(2) was attributed to the added streptavidin, corresponding to one molecule per 27 nm(2). The specificity of this recognition was confirmed by exposing the devices to a solution of streptavidin that was already saturated with biotin. An additional negative control was also performed by also...

  4. Chemical cleaning specification: few tube test model

    International Nuclear Information System (INIS)

    Hampton, L.V.; Simpson, J.L.

    1979-09-01

    The specification is for the waterside chemical cleaning of the 2 1/4 Cr - 1 Mo steel steam generator tubes. It describes the reagents and conditions for post-chemical cleaning passivation of the evaporator tubes

  5. Standard specification for silvered flat glass mirror

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2008-01-01

    1.1 This specification covers the requirements for silvered flat glass mirrors of rectangular shape supplied as cut sizes, stock sheets or as lehr ends and to which no further processing (such as edgework or other fabrication) has been done. 1.2 This specification covers the quality requirements of silvered annealed monolithic clear and tinted flat glass mirrors up to 6 mm (¼ in.) thick. The mirrors are intended to be used indoors for mirror glazing, for components of decorative accessories or for similar uses. 1.3 This specification does not address safety glazing materials nor requirements for mirror applications. Consult model building codes and other applicable standards for safety glazing applications. 1.4 Mirrors covered in this specification are not intended for use in environments where high humidity or airborne corrosion promoters, or both, are consistently present (such as swimming pool areas, ocean-going vessels, chemical laboratories and other corrosive environments). 1.5 The dimensional val...

  6. Standard Technical Specifications, Babcock and Wilcox Plants

    International Nuclear Information System (INIS)

    1992-09-01

    This NUREG contains improved Standard Technical Specifications (STS) for Babcock and Wilcox (B ampersand W) plants and documents the positions of the Nuclear Regulatory Commission (NRC) based on the B ampersand W Owners Group's proposed STS. This document is the result of extensive technical meetings and discussions among the NRC staff, the Nuclear Steam Supply System (NSSS) Owners Groups, the NSSS vendors, and the Nuclear Management and Resources Council. The improved STS were developed based on the criteria in the interim Commission Policy Statement on Technical Specification Improvements for Nuclear Power Reactors, dated February 6, 1987. The improved STS will be used as the basis for developing improved plant-specific technical specifications by individual nuclear power plant licensees. This volume contains sections 3.4--3.9 which cover: Reactor coolant systems, emergency core cooling systems, containment systems, plant systems, electrical power systems, refueling operations

  7. Technical specifications: Health Physics Research Reactor

    International Nuclear Information System (INIS)

    1986-03-01

    These technical specifications define the key limitations that must be observed for safe operation of the Health Physics Research Reactor (HPRR) and an envelope of operation within which there is assurance that these limits will not be exceeded

  8. Generic performance specification for printed boards

    CERN Document Server

    IPC - Association Connecting Electronics Industries. Northbrook, IL

    1996-01-01

    This specification establishes the general requirements and responsibilities for suppliers and users of printed boards. Describes quality and reliability assurance requirements that must be met. For use with IPC-6012 through IPC-6018.

  9. Specification for symbol for ionizing radiation

    International Nuclear Information System (INIS)

    1974-01-01

    This Malaysia Standard specification specifies a symbol recommended for use only to signify the actual or potential presence of ionizing radiation (#betta#, α, #betta# only) and to identify objects, devices, materials or combinations of materials which emit such radiation. (author)

  10. Technical specifications for the bulk shielding reactor

    International Nuclear Information System (INIS)

    1986-05-01

    This report provides information concerning the technical specifications for the Bulk Shielding Reactor. Areas covered include: safety limits and limiting safety settings; limiting conditions for operation; surveillance requirements; design features; administrative controls; and monitoring of airborne effluents. 10 refs

  11. NORMAL LOAD BEARING BY SITE SPECIFIC CANISTER

    Energy Technology Data Exchange (ETDEWEB)

    NA

    2005-03-23

    The overall purpose of this calculation is to perform a preliminary analysis of the Site Specific Canister/Basket, subject to static gravity loads that include the self weight of the Canister Shell, the Basket, the Spent Nuclear Fuel, the Shield Plug and the related hardware, so that the loads are approximately known for sizing purposes. Based on these loads the stress levels in various components of the Site Specific Canister/Basket are evaluated.

  12. Task-Specific Training and Job Design

    OpenAIRE

    Felipe Balmaceda

    2006-01-01

    This paper provides a simple theoretical framework based on a new type of human capital introduced by Gibbons and Waldman (2004), called task-specific training, to understand job design. Mainly, in the presence of task-specific training, promotions might result ex-post in the underutilization of human capital and thus firms at the time of designing jobs should attempt to diversify this risk.

  13. Germ cell specification and regeneration in planarians.

    Science.gov (United States)

    Newmark, P A; Wang, Y; Chong, T

    2008-01-01

    In metazoans, two apparently distinct mechanisms specify germ cell fate: Determinate specification (observed in animals including Drosophila, Caenorhabditis elegans, zebra fish, and Xenopus) uses cytoplasmic factors localized to specific regions of the egg, whereas epigenetic specification (observed in many basal metazoans, urodeles, and mammals) involves inductive interactions between cells. Much of our understanding of germ cell specification has emerged from studies of model organisms displaying determinate specification. In contrast, our understanding of epigenetic/inductive specification is less advanced and would benefit from studies of additional organisms. Freshwater planarians--widely known for their remarkable powers of regeneration--are well suited for studying the mechanisms by which germ cells can be induced. Classic experiments showed that planarians can regenerate germ cells from body fragments entirely lacking reproductive structures, suggesting that planarian germ cells could be specified by inductive signals. Furthermore, the availability of the genome sequence of the planarian Schmidtea mediterranea, coupled with the animal's susceptibility to systemic RNA interference (RNAi), facilitates functional genomic analyses of germ cell development and regeneration. Here, we describe recent progress in studies of planarian germ cells and frame some of the critical unresolved questions for future work.

  14. Autobiographical memory specificity in dissociative identity disorder.

    Science.gov (United States)

    Huntjens, Rafaële J C; Wessel, Ineke; Hermans, Dirk; van Minnen, Agnes

    2014-05-01

    A lack of adequate access to autobiographical knowledge has been related to psychopathology. More specifically, patients suffering from depression or a history of trauma have been found to be characterized by overgeneral memory, in other words, they show a relative difficulty in retrieving a specific event from memory located in time and place. Previous studies of overgeneral memory have not included patients with dissociative disorders. These patients are interesting to consider, as they are hypothesized to have the ability to selectively compartmentalize information linked to negative emotions. This study examined avoidance and overgeneral memory in patients with dissociative identity disorder (DID; n = 12). The patients completed the autobiographical memory test (AMT). Their performance was compared with control groups of posttraumatic stress disorder (PTSD) patients (n = 26), healthy controls (n = 29), and DID simulators (n = 26). Specifically, we compared the performance of separate identity states in DID hypothesized to diverge in the use of avoidance as a coping strategy to deal with negative affect. No significant differences in memory specificity were found between the separate identities in DID. Irrespective of identity state, DID patients were characterized by a lack of memory specificity, which was similar to the lack of memory specificity found in PTSD patients. The converging results for DID and PTSD patients add empirical evidence for the role of overgeneral memory involved in the maintenance of posttraumatic psychopathology.

  15. Specific discharge variability in a boreal landscape

    Science.gov (United States)

    Lyon, Steve W.; Nathanson, Marcus; Spans, André; Grabs, Thomas; Laudon, Hjalmar; Temnerud, Johan; Bishop, Kevin H.; Seibert, Jan

    2012-08-01

    Specific discharge variations within a mesoscale catchment were studied on the basis of three synoptic sampling campaigns. These were conducted during stable flow conditions within the Krycklan catchment study area in northern Sweden. During each campaign, about 80 individual locations were measured for discharge draining from catchment areas ranging between 0.12 and 67 km2. These discharge samplings allowed for the comparison between years within a given season (September 2005 versus September 2008) and between seasons within a given year (May 2008 versus September 2008) of specific discharge across this boreal landscape. There was considerable variability in specific discharge across this landscape. The ratio of the interquartile range (IQR) defined as the difference between the 75th and 25th percentiles of the specific discharges to the median of the specific discharges ranged from 37% to 43%. Factor analysis was used to explore potential relations between landscape characteristics and the specific discharge observed for 55 of the individual locations that were measured in all three synoptic sampling campaigns. Percentage wet area (i.e., wetlands, mires, and lakes) and elevation were found to be directly related to the specific discharge during the drier September 2008 sampling while potential annual evaporation was found to be inversely related. There was less of a relationship determined during the wetter post spring flood May 2008 sampling and the late summer rewetted September 2005 sampling. These results indicate the ability of forests to "dry out" parts of the catchment over the summer months while wetlands "keep wet" other parts. To demonstrate the biogeochemical implications of such spatiotemporal variations in specific discharge, we estimate dissolved organic carbon (DOC) exports with available data for the May 2008 and September 2008 samplings using both the spatially variable observed specific discharges and the spatially constant catchment average

  16. New primers for methylation-specific polymerase chain reaction enhance specificity of detecting STAT1 methylation

    Directory of Open Access Journals (Sweden)

    Ming-Cheng Chang

    2012-03-01

    Conclusion: Specific primers for methylation-specific PCR are mandatory for the accurate detection of STAT1 gene methylation. Besides, specific primers can generate correct interpretation of STAT1 gene methylation, and its correlation with the clinicopathological characteristics and outcome of cancer patients.

  17. Producing specific milks for speciality cheeses.

    Science.gov (United States)

    Bertoni, G; Calamari, L; Maianti, M G

    2001-05-01

    Protected denomination of origin (PDO) cheeses have distinctive sensorial characteristics. They can be made only from raw milk possessing specific features, which is processed through the 'art' of the cheesemaker. In general, the distinctive sensorial traits of PDO cheese cannot be achieved under different environmental-production conditions for two main reasons: (1) some milk features are linked to specific animal production systems; (2) cheese ripening is affected by the interaction between milk (specific) and the traditional technology applied to the transformation process (non-specific). Also, the environment for a good ripening stage can be quite specific and not reproducible. With reference to milk, factors of typicality are species and/or breed, pedoclimatic conditions, animal management system and feeding. Other factors that influence cheese quality are milk treatments, milk processing and the ripening procedures. The technology applied to most cheeses currently known as PDO utilizes only raw milk, rennet and natural lactic acid bacteria, so that milk must be, at its origin, suitable for processing. The specific milk characteristics that ensure a high success rate for PDO cheeses are high protein content and good renneting properties, appropriate fat content with appropriate fatty acid composition and the presence of chemical flavours originating from local feeds. Moreover, an appropriate microflora is also of major importance. The factors that contribute to achieving milk suitable for transformation into PDO cheese are genetics, age, lactation stage, season and climate, general management and health conditions, milking and particularly feeding, which affect nutrient availability, endocrine response and health status, and also the presence of microbes and chemical substances which enrich or reduce the milk-cheese quality. Many of these factors are regulated by the Producer Associations. However, the secret of the success of PDO cheeses is the combination of

  18. Eliminating Direction Specificity in Visuomotor Learning.

    Science.gov (United States)

    Yin, Cong; Bi, Yuqing; Yu, Cong; Wei, Kunlin

    2016-03-30

    The generalization of learning offers a unique window for investigating the nature of motor learning. Error-based motor learning reportedly cannot generalize to distant directions because the aftereffects are direction specific. This direction specificity is often regarded as evidence that motor adaptation is model-based learning, and is constrained by neuronal tuning characteristics in the primary motor cortices and the cerebellum. However, recent evidence indicates that motor adaptation also involves model-free learning and explicit strategy learning. Using rotation paradigms, here we demonstrate that savings (faster relearning), which is closely related to model-free learning and explicit strategy learning, is also direction specific. However, this new direction specificity can be abolished when the participants receive exposure to the generalization directions via an irrelevant visuomotor gain-learning task. Control evidence indicates that this exposure effect is weakened when direction error signals are absent during gain learning. Therefore, the direction specificity in visuomotor learning is not solely related to model-based learning; it may also result from the impeded expression of model-free learning and explicit strategy learning with untrained directions. Our findings provide new insights into the mechanisms underlying motor learning, and may have important implications for practical applications such as motor rehabilitation. Motor learning is more useful if it generalizes to untrained scenarios when needed, especially for sports training and motor rehabilitation. However, as a form of motor learning, motor adaptation is typically direction specific. Here we first show that savings with motor adaptation, an index for model-free learning and explicit strategy learning in motor learning, is also direction specific. However, the participants' additional exposure to untrained directions via an irrelevant gain-learning task can enable the complete

  19. Domain Specific Language Support for Exascale

    Energy Technology Data Exchange (ETDEWEB)

    Mellor-Crummey, John [Rice Univ., Houston, TX (United States)

    2017-10-20

    A multi-institutional project known as D-TEC (short for “Domain- specific Technology for Exascale Computing”) set out to explore technologies to support the construction of Domain Specific Languages (DSLs) to map application programs to exascale architectures. DSLs employ automated code transformation to shift the burden of delivering portable performance from application programmers to compilers. Two chief properties contribute: DSLs permit expression at a high level of abstraction so that a programmer’s intent is clear to a compiler and DSL implementations encapsulate human domain-specific optimization knowledge so that a compiler can be smart enough to achieve good results on specific hardware. Domain specificity is what makes these properties possible in a programming language. If leveraging domain specificity is the key to keep exascale software tractable, a corollary is that many different DSLs will be needed to encompass the full range of exascale computing applications; moreover, a single application may well need to use several different DSLs in conjunction. As a result, developing a general toolkit for building domain-specific languages was a key goal for the D-TEC project. Different aspects of the D-TEC research portfolio were the focus of work at each of the partner institutions in the multi-institutional project. D-TEC research and development work at Rice University focused on on three principal topics: understanding how to automate the tuning of code for complex architectures, research and development of the Rosebud DSL engine, and compiler technology to support complex execution platforms. This report provides a summary of the research and development work on the D-TEC project at Rice University.

  20. Chromosome-specific DNA Repeat Probes

    Energy Technology Data Exchange (ETDEWEB)

    Baumgartner, Adolf; Weier, Jingly Fung; Weier, Heinz-Ulrich G.

    2006-03-16

    In research as well as in clinical applications, fluorescence in situ hybridization (FISH) has gained increasing popularity as a highly sensitive technique to study cytogenetic changes. Today, hundreds of commercially available DNA probes serve the basic needs of the biomedical research community. Widespread applications, however, are often limited by the lack of appropriately labeled, specific nucleic acid probes. We describe two approaches for an expeditious preparation of chromosome-specific DNAs and the subsequent probe labeling with reporter molecules of choice. The described techniques allow the preparation of highly specific DNA repeat probes suitable for enumeration of chromosomes in interphase cell nuclei or tissue sections. In addition, there is no need for chromosome enrichment by flow cytometry and sorting or molecular cloning. Our PCR-based method uses either bacterial artificial chromosomes or human genomic DNA as templates with {alpha}-satellite-specific primers. Here we demonstrate the production of fluorochrome-labeled DNA repeat probes specific for human chromosomes 17 and 18 in just a few days without the need for highly specialized equipment and without the limitation to only a few fluorochrome labels.

  1. Face recognition: a model specific ability

    Directory of Open Access Journals (Sweden)

    Jeremy B Wilmer

    2014-10-01

    Full Text Available In our everyday lives, we view it as a matter of course that different people are good at different things. It can be surprising, in this context, to learn that most of what is known about cognitive ability variation across individuals concerns the broadest of all cognitive abilities, often labeled g. In contrast, our knowledge of specific abilities, those that correlate little with g, is severely constrained. Here, we draw upon our experience investigating an exceptionally specific ability, face recognition, to make the case that many specific abilities could easily have been missed. In making this case, we derive key insights from earlier false starts in the measurement of face recognition’s variation across individuals, and we highlight the convergence of factors that enabled the recent discovery that this variation is specific. We propose that the case of face recognition ability illustrates a set of tools and perspectives that could accelerate fruitful work on specific cognitive abilities. By revealing relatively independent dimensions of human ability, such work would enhance our capacity to understand the uniqueness of individual minds.

  2. Face recognition: a model specific ability.

    Science.gov (United States)

    Wilmer, Jeremy B; Germine, Laura T; Nakayama, Ken

    2014-01-01

    In our everyday lives, we view it as a matter of course that different people are good at different things. It can be surprising, in this context, to learn that most of what is known about cognitive ability variation across individuals concerns the broadest of all cognitive abilities; an ability referred to as general intelligence, general mental ability, or just g. In contrast, our knowledge of specific abilities, those that correlate little with g, is severely constrained. Here, we draw upon our experience investigating an exceptionally specific ability, face recognition, to make the case that many specific abilities could easily have been missed. In making this case, we derive key insights from earlier false starts in the measurement of face recognition's variation across individuals, and we highlight the convergence of factors that enabled the recent discovery that this variation is specific. We propose that the case of face recognition ability illustrates a set of tools and perspectives that could accelerate fruitful work on specific cognitive abilities. By revealing relatively independent dimensions of human ability, such work would enhance our capacity to understand the uniqueness of individual minds.

  3. Formal specification level concepts, methods, and algorithms

    CERN Document Server

    Soeken, Mathias

    2015-01-01

    This book introduces a new level of abstraction that closes the gap between the textual specification of embedded systems and the executable model at the Electronic System Level (ESL). Readers will be enabled to operate at this new, Formal Specification Level (FSL), using models which not only allow significant verification tasks in this early stage of the design flow, but also can be extracted semi-automatically from the textual specification in an interactive manner.  The authors explain how to use these verification tasks to check conceptual properties, e.g. whether requirements are in conflict, as well as dynamic behavior, in terms of execution traces. • Serves as a single-source reference to a new level of abstraction for embedded systems, known as the Formal Specification Level (FSL); • Provides a variety of use cases which can be adapted to readers’ specific design flows; • Includes a comprehensive illustration of Natural Language Processing (NLP) techniques, along with examples of how to i...

  4. Human ovarian carcinomas detected by specific odor.

    Science.gov (United States)

    Horvath, György; Järverud, Gunvor Af Klinteberg; Järverud, Sven; Horváth, István

    2008-06-01

    The high mortality rate associated with ovarian carcinoma is mainly owing to late diagnosis. It is thus essential to develop inexpensive and simple methods for early diagnosis. Papers on canine scent detection of malignancies such as melanoma and bladder, lung, and breast cancer have recently been published in peer-reviewed journals, indicating a new diagnostic tool for malignancies. However, in these studies the dogs may have responded to odors associated with cancer, such as inflammation or metabolic products, rather than specifically to cancer itself. Therefore, it is important to ascertain whether or not human cancers are characterized by specific odors. We hypothesized that if ovarian carcinoma emits a specific odor, dogs may be trained to detect it. Using our training method, we taught a dog to distinguish different histopathological types and grades of ovarian carcinomas, including borderline tumors, from healthy control samples. Double-blind tests showed 100% sensitivity and 97.5% specificity. Moreover, the odor of ovarian carcinomas seems to differ from those of other gynecological malignances such cervical, endometrial, and vulvar carcinomas. Our study strongly suggests that the most common ovarian carcinomas are characterized by a single specific odor.

  5. The Role of Non-specific and Specific Immune Systems in Poultry against Newcastle Disease

    Directory of Open Access Journals (Sweden)

    Dyah Ayu Hewajuli

    2015-09-01

    Full Text Available Newcastle disease (ND is caused by avian paramyxovirus-1 which belong to Avulavirus genus and Paramyxoviridae family. The birds have abnormalities in humoral (bursa fabricius and cellular (thymus and spleen lymphoid organs. Lesions decrease the immune system. Immune system consists of non-specific and specific immune systems. The main components of non-specific immunity are physical and chemical barrier (feather and skin or mucosa, phagocytic cells (macrophages and natural killer, protein complement and the mediator of inflammation and cytokines. Interferons (IFNs belong to a group of cytokines that play a major role in the nonspecific or innate (natural immunity. The virulent ND virus encodes protein of V gene can be suppressed IFN type I. This leads to non-specific immune system fail to respond to the virulent strains resulting in severe pathogenicity. The defense mechanism of the host is replaced by specific immunity (adaptive immunity when natural immunity fails to overcome the infection. The specific immune system consists of humoral mediated immunity (HMI and cell-mediated immunity (CMI. The cells of immune system that react specifically with the antigen are B lymphocytes producing the antibodies, T lymphocytes that regulate the synthesis of antibodies and T cells as effector or the direct cytotoxic cells. Both non-specific and specific immunities are complementary against the invasion of ND virus in the birds. The objective of this article is to discuss the role of non specific and specific immune system in ND.

  6. Emergency Medicine Gender-specific Education.

    Science.gov (United States)

    Ashurst, John V; McGregor, Alyson J; Safdar, Basmah; Weaver, Kevin R; Quinn, Shawn M; Rosenau, Alex M; Goyke, Terrence E; Roth, Kevin R; Greenberg, Marna R

    2014-12-01

    The 2014 Academic Emergency Medicine consensus conference has taken the first step in identifying gender-specific care as an area of importance to both emergency medicine (EM) and research. To improve patient care, we need to address educational gaps in this area concurrent with research gaps. In this article, the authors highlight the need for sex- and gender-specific education in EM and propose guidelines for medical student, resident, and faculty education. Specific examples of incorporating this content into grand rounds, simulation, bedside teaching, and journal club sessions are reviewed. Future challenges and strategies to fill the gaps in the current education model are also described. © 2014 by the Society for Academic Emergency Medicine.

  7. Specifications for human factors guiding documents

    International Nuclear Information System (INIS)

    Rhodes, W.; Szlapetis, I.; MacGregor, C.

    1995-04-01

    This report specifies the content, function and appearance of three proposed human factors guiding documents to be used by the Atomic Energy Control board and its licensees. These three guiding documents, to be developed at a later date, are: (a) Human Factors Process Guide; (b) Human Factors Activities Guide; and (c) Human Factors Design Integration Guide. The specifications were developed by examining the best documents as identified in a previous contract with the AECB (Review of Human Factors Guidelines and Methods by W. Rhodes, I. Szlapetis et al. 1992), and a brief literature review. The best features and content were selected from existing documents and used to develop specifications for the guiding documents. The developer of the actual guides would use these specifications to produce comprehensive and consolidated documents at a later date. (author). 128 ref., 7 figs

  8. Procedures for evaluating technical specifications (PETS)

    International Nuclear Information System (INIS)

    Samanta, P.K.; Boccio, J.L.; Vesely, W.E.

    1987-01-01

    In this paper, aspects of technical specifications relating to Generic Issues B-56 and B-61 are discussed from a risk-standpoint. These primarily deal with the risk issues associated with (1) adaptive diesel test requirements/surveillance test intervals, and (2) the effectiveness of cumulative outage time requirements for controlling downtime risk. Risk and reliability approaches are presented which (1) allow risk-acceptable test intervals to be determined for any diesel and (2) show the potential risk-control capability of prescribed allowed cumulative outage times. This work was conducted through NRC's Procedures for Evaluating Technical Specifications (PETS) Program. The overall objective of this program is to develop and demonstrate methodologies that utilize risk insights and reliability techniques for evaluating the scope, detailed requirements, and safety impact of plant technical specifications

  9. Testing Library Specifications by Verifying Conformance Tests

    DEFF Research Database (Denmark)

    Kiniry, Joseph Roland; Zimmerman, Daniel; Hyland, Ralph

    2012-01-01

    Formal specifications of standard libraries are necessary when statically verifying software that uses those libraries. Library specifications must be both correct, accurately reflecting library behavior, and useful, describing library behavior in sufficient detail to allow static verification...... of client programs. Specication and verification researchers regularly face the question of whether the library specications we use are correct and useful, and we have collectively provided no good answers. Over the past few years we have created and refined a software engineering process, which we call...... the Formal CTD Process (FCTD), to address this problem. Although FCTD is primarily targeted toward those who write Java libraries (or specifications for existing Java libraries) using the Java Modeling Language (JML), its techniques are broadly applicable. The key to FCTD is its novel usage of library...

  10. Mode specificity in unimolecular reaction dynamics

    International Nuclear Information System (INIS)

    Waite, B.A.

    1982-07-01

    Theoretical studies on mode specificity in unimolecular reaction dynamics are presented, based on essentially exact quantum mechanical methods, a semi-classical multichannel branching model, and classical trajectory methods. The principal aim is to discover the relevant factors governing whether a unimolecular system exhibits mode specificity in its individual state rate constants, i.e., whether quasi-degenerate metastable states decay with significantly different rates. Model studies of two nonlinearly coupled oscillators (one of which can dissociate) demonstrate the effects of various features of potential energy surfaces on the character of the rates (e.g., degeneracy of modes, reaction path curvature, frequency modulation, etc.). These results and those obtained for the Henon-Heiles potential energy surface indicate and apparent absence of correlation between the quasi-periodic/ergodic motion of classical mechanics and the mode specific/statistical behavior of the unimolecular rate constants

  11. Computational network design from functional specifications

    KAUST Repository

    Peng, Chi Han

    2016-07-11

    Connectivity and layout of underlying networks largely determine agent behavior and usage in many environments. For example, transportation networks determine the flow of traffic in a neighborhood, whereas building floorplans determine the flow of people in a workspace. Designing such networks from scratch is challenging as even local network changes can have large global effects. We investigate how to computationally create networks starting from only high-level functional specifications. Such specifications can be in the form of network density, travel time versus network length, traffic type, destination location, etc. We propose an integer programming-based approach that guarantees that the resultant networks are valid by fulfilling all the specified hard constraints and that they score favorably in terms of the objective function. We evaluate our algorithm in two different design settings, street layout and floorplans to demonstrate that diverse networks can emerge purely from high-level functional specifications.

  12. Transactions in domain-specific information systems

    Science.gov (United States)

    Zacek, Jaroslav

    2017-07-01

    Substantial number of the current information system (IS) implementations is based on transaction approach. In addition, most of the implementations are domain-specific (e.g. accounting IS, resource planning IS). Therefore, we have to have a generic transaction model to build and verify domain-specific IS. The paper proposes a new transaction model for domain-specific ontologies. This model is based on value oriented business process modelling technique. The transaction model is formalized by the Petri Net theory. First part of the paper presents common business processes and analyses related to business process modeling. Second part defines the transactional model delimited by REA enterprise ontology paradigm and introduces states of the generic transaction model. The generic model proposal is defined and visualized by the Petri Net modelling tool. Third part shows application of the generic transaction model. Last part of the paper concludes results and discusses a practical usability of the generic transaction model.

  13. Action-specific disruption of perceptual confidence.

    Science.gov (United States)

    Fleming, Stephen M; Maniscalco, Brian; Ko, Yoshiaki; Amendi, Namema; Ro, Tony; Lau, Hakwan

    2015-01-01

    Theoretical models of perception assume that confidence is related to the quality or strength of sensory processing. Counter to this intuitive view, we showed in the present research that the motor system also contributes to judgments of perceptual confidence. In two experiments, we used transcranial magnetic stimulation (TMS) to manipulate response-specific representations in the premotor cortex, selectively disrupting postresponse confidence in visual discrimination judgments. Specifically, stimulation of the motor representation associated with the unchosen response reduced confidence in correct responses, thereby reducing metacognitive capacity without changing visual discrimination performance. Effects of TMS on confidence were observed when stimulation was applied both before and after the response occurred, which suggests that confidence depends on late-stage metacognitive processes. These results place constraints on models of perceptual confidence and metacognition by revealing that action-specific information in the premotor cortex contributes to perceptual confidence. © The Author(s) 2014.

  14. Forum on specification and Design Languages

    CERN Document Server

    Maehne, Torsten

    2015-01-01

    This book brings together a selection of the best papers from the sixteenth edition of the Forum on specification and Design Languages Conference (FDL), which was held in September 2013 in Paris, France. FDL is a well-established international forum devoted to dissemination of research results, practical experiences and new ideas in the application of specification, design and verification languages to the design, modeling and verification of integrated circuits, complex hardware/software embedded systems, and mixed-technology systems. • Covers applications of formal methods for specification, verification and debug; • Includes embedded analog and mixed-signal system design; • Enables model-driven engineering for embedded systems design and development.

  15. Analysis on judo specific and unspecific test

    Directory of Open Access Journals (Sweden)

    Luis Santos Rodríguez

    2012-07-01

    Full Text Available In specialized literature it is not easy to find test which give us information about judokas developing their specific kinetic habits. Although judo is included in sociomotor sports (Parlebas, 2001, judokas physical fitness is normally evaluated through test which come from other type of sports, mainly from phychomotor sports. At the same time, batteries as the battery Eurofit (Conseil de L´Europe, 1989, are use to evaluate perceptive-motors aspects. In this article, we describe some of the tests found in specific western bibliography. Once finished this analysis, we mention the need of creating test which value the reality of competition confrontation more specifically, and which can be reliable, objective and reproductive (López and cols. 2004 being easy and useful to the trainer as well.

  16. Spent nuclear fuel project product specification

    International Nuclear Information System (INIS)

    Pajunen, A.L.

    1998-01-01

    Product specifications are limits and controls established for each significant parameter that potentially affects safety and/or quality of the Spent Nuclear Fuel (SNF) packaged for transport to dry storage. The product specifications in this document cover the spent fuel packaged in MultiCanister Overpacks (MCOs) to be transported throughout the SNF Project. The SNF includes N Reactor fuel and single-pass reactor fuel. The FRS removes the SNF from the storage canisters, cleans it, and places it into baskets. The MCO loading system places the baskets into MCO/Cask assembly packages. These packages are then transferred to the Cold Vacuum Drying (CVD) Facility. After drying at the CVD Facility, the MCO cask packages are transferred to the Canister Storage Building (CSB), where the MCOs are removed from the casks, staged, inspected, sealed (by welding), and stored until a suitable permanent disposal option is implemented. The key criteria necessary to achieve these goals are documented in this specification

  17. Property Specification Patterns for intelligence building software

    Science.gov (United States)

    Chun, Seungsu

    2018-03-01

    In this paper, through the property specification pattern research for Modal MU(μ) logical aspects present a single framework based on the pattern of intelligence building software. In this study, broken down by state property specification pattern classification of Dwyer (S) and action (A) and was subdivided into it again strong (A) and weaknesses (E). Through these means based on a hierarchical pattern classification of the property specification pattern analysis of logical aspects Mu(μ) was applied to the pattern classification of the examples used in the actual model checker. As a result, not only can a more accurate classification than the existing classification systems were easy to create and understand the attributes specified.

  18. Specific and non-specific immunity of piglets from sows fed diets containing specific fatty acids in field conditions.

    Science.gov (United States)

    Benzoni, G; Foresti, F; Archetti, I L; Coceva, G; Guyonvarch, A; Alborali, L

    2013-10-01

    The transfer of passive immunity from sows to piglets is important and it is the first immune protection of the new born piglet. Improving sows immunity by adding immuno-stimulating product in sows diet can positively affect colostrum composition and transfer of immune molecules to piglets. The aim of the current study is to evaluate the benefit of a different solution, made of specific fatty acids from marine origin that have been used in human medicine for decades, for sows and piglets. Two trials were conducted in commercial farm, involving 240 sows at different periods of the year. Sows were divided in a control group, without supplementation, and a test group, supplemented with the feed additive from the 90th day of gestation to weaning. Sows body condition, piglets viability and growth were recorded. Milk immunoglobulin content was measured, as well as Aujeszky antibodies in sows and piglets blood as marker of specific immunity, and blood bactericidal activity, complement activity and lysozyme as markers of non specific immunity. No effect of the product was observed on piglets zootechnical criteria and specific immunity parameters but significant improvement of piglet non specific immunity, was observed. No difference was observed neither in the piglets blood PRRSV and PCV2 antibodies and viruses nor in Aujeszky antibodies. Blood complement activity seems to be an accurate indicator of immuno-stimulating additive efficiency. Giving alkyl-glycerol fatty acids to sows in late gestation and lactation can improve the passive immunity transfer to piglets. © 2012 Blackwell Verlag GmbH.

  19. An Approach to Greater Specificity for Glucocorticoids

    Directory of Open Access Journals (Sweden)

    Carson C. Chow

    2018-03-01

    Full Text Available Glucocorticoid steroids are among the most prescribed drugs each year. Nonetheless, the many undesirable side effects, and lack of selectivity, restrict their greater usage. Research to increase glucocorticoid specificity has spanned many years. These efforts have been hampered by the ability of glucocorticoids to both induce and repress gene transcription and also by the lack of success in defining any predictable properties that control glucocorticoid specificity. Correlations of transcriptional specificity have been observed with changes in steroid structure, receptor and chromatin conformation, DNA sequence for receptor binding, and associated cofactors. However, none of these studies have progressed to the point of being able to offer guidance for increased specificity. We summarize here a mathematical theory that allows a novel and quantifiable approach to increase selectivity. The theory applies to all three major actions of glucocorticoid receptors: induction by agonists, induction by antagonists, and repression by agonists. Simple graphical analysis of competition assays involving any two factors (steroid, chemical, peptide, protein, DNA, etc. yields information (1 about the kinetically described mechanism of action for each factor at that step where the factor acts in the overall reaction sequence and (2 about the relative position of that step where each factor acts. These two pieces of information uniquely provide direction for increasing the specificity of glucocorticoid action. Consideration of all three modes of action indicate that the most promising approach for increased specificity is to vary the concentrations of those cofactors/pharmaceuticals that act closest to the observed end point. The potential for selectivity is even greater when varying cofactors/pharmaceuticals in conjunction with a select class of antagonists.

  20. From UML Specification into FPGA Implementation

    Directory of Open Access Journals (Sweden)

    Grzegorz Bazydlo

    2014-01-01

    Full Text Available In the paper a method of using the Unified Modeling Language for specification of digital systems, especially logic controllers, is presented. The proposed method is based mainly on the UML state machine diagrams and uses Hierarchical Concurrent Finite State Machines (HCFSMs as a temporary model. The paper shows a way to transform the UML diagrams, expressed in XML language, to the form that is acceptable by reconfigurable FPGAs (Field Programmable Gate Arrays. The UML specification is used to generate an effective program in Hardware Description Languages (HDLs, especially Verilog.

  1. Automated effect-specific mammographic pattern measures

    DEFF Research Database (Denmark)

    Raundahl, Jakob; Loog, Marco; Pettersen, Paola

    2008-01-01

    We investigate the possibility to develop methodologies for assessing effect specific structural changes of the breast tissue using a general statistical machine learning framework. We present an approach of obtaining objective mammographic pattern measures quantifying a specific biological effect......, such as hormone replacement therapy (HRT). We compare results using this approach to using standard density measures. We show that the proposed method can quantify both age related effects and effects caused by HRT. Age effects are significantly detected by our method where standard methodologies fail...

  2. DOE site-specific threat assessment

    International Nuclear Information System (INIS)

    West, D.J.; Al-Ayat, R.A.; Judd, B.R.

    1985-01-01

    A facility manager faced with the challenges of protecting a nuclear facility against potential threats must consider the likelihood and consequences of such threats, know the capabilities of the facility safeguards and security systems, and make informed decisions about the cost-effectivness of safeguards and security upgrades. To help meet these challenges, the San Francisco Operations Office of the Department of Energy, in conjunction with the Lawrence Livermore Laboratory, has developed a site-specific threat assessment approach and a quantitative model to improve the quality and consistency of site-specific threat assessment and resultant security upgrade decisions at sensitive Department of Energy facilities. 5 figs

  3. A Class-Specific Optimizing Compiler

    Directory of Open Access Journals (Sweden)

    Michael D. Sharp

    1993-01-01

    Full Text Available Class-specific optimizations are compiler optimizations specified by the class implementor to the compiler. They allow the compiler to take advantage of the semantics of the particular class so as to produce better code. Optimizations of interest include the strength reduction of class:: array address calculations, elimination of large temporaries, and the placement of asynchronous send/recv calls so as to achieve computation/communication overlap. We will outline our progress towards the implementation of a C++ compiler capable of incorporating class-specific optimizations.

  4. Engineered waste-package-system design specification

    Energy Technology Data Exchange (ETDEWEB)

    1983-05-01

    This report documents the waste package performance requirements and geologic and waste form data bases used in developing the conceptual designs for waste packages for salt, tuff, and basalt geologies. The data base reflects the latest geotechnical information on the geologic media of interest. The parameters or characteristics specified primarily cover spent fuel, defense high-level waste, and commercial high-level waste forms. The specification documents the direction taken during the conceptual design activity. A separate design specification will be developed prior to the start of the preliminary design activity.

  5. Technical specifications for PWR secondary water chemistry

    International Nuclear Information System (INIS)

    Weeks, J.R.; van Rooyen, D.

    1977-08-01

    The bases for establishing Technical Specifications for PWR secondary water chemistry are reviewed. Whereas extremely stringent control of secondary water needs to be maintained to prevent denting in some units, sound bases for establishing limits that will prevent stress corrosion, wastage, and denting do not exist at the present time. This area is being examined very thoroughly by industry-sponsored research programs. Based on the evidence available to date, short term control limits are suggested; establishment of these or other limits as Technical Specifications is not recommended until the results of the research programs have been obtained and evaluated

  6. Engineered waste-package-system design specification

    International Nuclear Information System (INIS)

    1983-05-01

    This report documents the waste package performance requirements and geologic and waste form data bases used in developing the conceptual designs for waste packages for salt, tuff, and basalt geologies. The data base reflects the latest geotechnical information on the geologic media of interest. The parameters or characteristics specified primarily cover spent fuel, defense high-level waste, and commercial high-level waste forms. The specification documents the direction taken during the conceptual design activity. A separate design specification will be developed prior to the start of the preliminary design activity

  7. Domain Specific Language Support for Exascale

    Energy Technology Data Exchange (ETDEWEB)

    Sadayappan, Ponnuswamy [The Ohio State Univ., Columbus, OH (United States)

    2017-02-24

    Domain-Specific Languages (DSLs) offer an attractive path to Exascale software since they provide expressive power through appropriate abstractions and enable domain-specific optimizations. But the advantages of a DSL compete with the difficulties of implementing a DSL, even for a narrowly defined domain. The DTEC project addresses how a variety of DSLs can be easily implemented to leverage existing compiler analysis and transformation capabilities within the ROSE open source compiler as part of a research program focusing on Exascale challenges. The OSU contributions to the DTEC project are in the area of code generation from high-level DSL descriptions, as well as verification of the automatically-generated code.

  8. System specifications for the NDS Dictionary System

    International Nuclear Information System (INIS)

    Attree, P.M.; Smith, P.M.

    1979-09-01

    The NDS Dictionary System is a computerized system for maintaining and distributing the EXFOR dictionaries and for preparing internal versions of these dictionaries for use in the NDS EXFOR System and other NDS systems. This document is an internal manual for the system specifications of the NDS Dictionary System. It includes flow charts, system and program summaries, input and output specifications and file and record descriptions. This manual is updated from time to time when system modifications are made; this is the version of January 1979

  9. Site-Specific Infrared Probes of Proteins

    Science.gov (United States)

    Ma, Jianqiang; Pazos, Ileana M.; Zhang, Wenkai; Culik, Robert M.; Gai, Feng

    2015-04-01

    Infrared spectroscopy has played an instrumental role in the study of a wide variety of biological questions. However, in many cases, it is impossible or difficult to rely on the intrinsic vibrational modes of biological molecules of interest, such as proteins, to reveal structural and environmental information in a site-specific manner. To overcome this limitation, investigators have dedicated many recent efforts to the development and application of various extrinsic vibrational probes that can be incorporated into biological molecules and used to site-specifically interrogate their structural or environmental properties. In this review, we highlight recent advancements in this rapidly growing research area.

  10. Site-Specific Infrared Probes of Proteins

    Science.gov (United States)

    Ma, Jianqiang; Pazos, Ileana M.; Zhang, Wenkai; Culik, Robert M.; Gai, Feng

    2015-01-01

    Infrared spectroscopy has played an instrumental role in studying a wide variety of biological questions. However, in many cases it is impossible or difficult to rely on the intrinsic vibrational modes of biological molecules of interest, such as proteins, to reveal structural and/or environmental information in a site-specific manner. To overcome this limitation, many recent efforts have been dedicated to the development and application of various extrinsic vibrational probes that can be incorporated into biological molecules and used to site-specifically interrogate their structural and/or environmental properties. In this Review, we highlight some recent advancements of this rapidly growing research area. PMID:25580624

  11. Immunotherapy with GD2 specific monoclonal antibodies

    International Nuclear Information System (INIS)

    Cheung, N.K.V.; Medof, E.M.; Munn, D.

    1988-01-01

    Targeted immunotherapy focuses anti-tumor activity of antibodies and effector cells, which are actively developed by the host or adoptively transferred, onto tumor cells and into tumor sites. Such tumor selective therapy can be more specific and efficient. The value of such an approach is evident in the classical interaction of antibodies. This paper reports that the ganglioside G D2 is an ideal antigen for specific tumor targeting because of its relative lack of heterogeneity among human neuroblastoma, its high density on tumor cells, its lack of antigen modulation upon binding to antibody, and its restricted distribution in normal tissues

  12. Clojure for domain-specific languages

    CERN Document Server

    Kelker, Ryan D

    2013-01-01

    An example-oriented approach to develop custom domain-specific languages.If you've already developed a few Clojure applications and wish to expand your knowledge on Clojure or domain-specific languages in general, then this book is for you. If you're an absolute Clojure beginner, then you may only find the detailed examples of the core Clojure components of value. If you've developed DSLs in other languages, this Lisp and Java-based book might surprise you with the power of Clojure.

  13. Spent Nuclear Fuel (SNF) Project Product Specification

    International Nuclear Information System (INIS)

    PAJUNEN, A.L.

    2000-01-01

    The process for removal of Spent Nuclear Fuel (SNF) from the K Basins has been divided into major sub-systems. The Fuel Retrieval System (FRS) removes fuel from the existing storage canisters, cleans it, and places it into baskets. The multi-canister overpack (MCO) loading system places the baskets into an MCO that has been pre-loaded in a cask. The cask, containing a loaded MCO, is then transferred to the Cold Vacuum Drying (CVD) Facility. After drying at the CVD Facility, the cask, and MCO, are transferred to the Canister Storage Building (CSB), where the MCO is removed from the cask, staged, inspected, sealed (by welding), and stored until a suitable permanent disposal option is implemented. The purpose of this document is to specify the process related characteristics of an MCO at the interface between major process systems. The characteristics are derived from the primary technical documents that form the basis for safety analysis and design calculations. This document translates the calculation assumptions into implementation requirements and describes the method of verifying that the requirement is achieved. These requirements are used to define validation test requirements and describe requirements that influence multiple sub-project safety analysis reports. This product specification establishes limits and controls for each significant process parameter at interfaces between major sub-systems that potentially affect the overall safety and/or quality of the SNF packaged for processing, transport, and interim dry storage. The product specifications in this document cover the SNF packaged in MCOs to be transported throughout the SNF Project. The description of the product specifications are organized in the document as follows: Section 2.0--Summary listing of product specifications at each major sub-system interface. Section 3.0--Summary description providing guidance as to how specifications are complied with by equipment design or processing within a major

  14. Specifications in early conceptual design work

    DEFF Research Database (Denmark)

    Hansen, Claus Thorp; Andreasen, Mogens Myrup

    2007-01-01

    In early conceptual design the design team is working in an uncertain situation, where the understanding of a need is limited and not much is known about the solution space. In this situation the design team has to both analyse need and explore solution space. Thus, the team has to formulate design...... specifications, which express attractive product goals, and has to synthesise the product idea. The authors of this paper see a challenge to enhance and improve our understanding of the nature of design specifications as a means to support the synthesis of a product idea. In this empirical study we analyse...

  15. Formal Specification of Real-Time Systems

    Energy Technology Data Exchange (ETDEWEB)

    Groven, Arne-Kristian

    1996-07-01

    This report presents the results of a study on formal specification of real-time distributed control systems. Emphasis has been but on the ability to describe both system architecture, system functionality and timed system behaviour inside the same formal framework. A timed extension of the ISO standardized formal description language LOTOS (ISO 8807), called TE-LOTOS, has been used for describing the timed behaviour. The functionality can be described in LOTOS, which is a subset of the timed extension. A graphical notation has been used for describing system architecture, transformable to a subset of LOTOS. This methodology has been used to specify a test example, a steam-boiler control system. Modularization of the specification is an important issue. This is achieved by isolating the time-dependent aspect in one part of the specification, and the system functionality in another. This modularization facilitates the separation of general aspect from the more specific aspects. This is demonstrated by comparison with another type of control systems, the APRM system (HWR-397). (author)

  16. Canine specific ELISA for coagulation factor VII

    DEFF Research Database (Denmark)

    Knudsen, Tom; Kjelgaard-Hansen, Mads; Tranholm, Mikael

    2011-01-01

    available to date. In this study, a canine specific ELISA for measurement of FVII:Ag in plasma was developed and validated. The FVII:Ag ELISA correctly diagnosed homozygous and heterozygous hereditary FVII deficiency. Together with activity based assays, such as FVII:C, the FVII:Ag ELISA should be valuable...

  17. COMPARATIVE STUDY ON SPECIFIC AND EARLY DETECTION ...

    African Journals Online (AJOL)

    The objective of this study was to compare the sensitivity and specificity of smear and culture methods with rapid serological EIA myco kits manufactured by Omega diagnostics, for the early detection of Mycobacterium tuberculosis (MTB) complex. Sera from various categories of smear and culture results were compared ...

  18. PHYSICOCHEMICAL PROPERTIES OF A LACTOSE SPECIFIC ...

    African Journals Online (AJOL)

    The lectin agglutinated human and rabbit erythrocytes, with a slight preference for the human O blood group. The hemagglutinating activity ..... Table 1: Blood Group Specificity of Erythrina senegalensis Seed Lectin. Each experiment consisted of ... fractionation of the seed extract when subjected to gel filtration on Sephadex ...

  19. Iron addition to soil specifically stabilized lignin

    Science.gov (United States)

    Steven J. Hall; Whendee L. Silver; Vitaliy I. Timokhin; Kenneth E. Hammel

    2016-01-01

    The importance of lignin as a recalcitrant constituent of soil organic matter (SOM) remains contested. Associations with iron (Fe) oxides have been proposed to specifically protect lignin from decomposition, but impacts of Fe-lignin interactions on mineralization rates remain unclear. Oxygen (O2) fluctuations characteristic of humid tropical...

  20. DETERMINATION OF THE SPECIFIC GROWTH RATE ON ...

    African Journals Online (AJOL)

    Sewage generation is one of the dense problems Nigerians encounter on daily bases, mostly at the urbanized area where factories and industries are located. This paper is aimed at determining the specific growth rate “K” of biological activities on cassava wastewater during degradation using Michaelis-Menten Equation.

  1. Specific Ion Effects in Cholesterol Monolayers

    Directory of Open Access Journals (Sweden)

    Teresa Del Castillo-Santaella

    2016-05-01

    Full Text Available The interaction of ions with interfaces and, in particular, the high specificity of these interactions to the particular ions considered, are central questions in the field of surface forces. Here we study the effect of different salts (NaI, NaCl, CaCl2 and MgCl2 on monolayers made of cholesterol molecules, both experimentally (surface area vs. lateral pressure isotherms measured by a Langmuir Film Balance and theoretically (molecular dynamics (MD all-atomic simulations. We found that surface isotherms depend, both quantitatively and qualitatively, on the nature of the ions by altering the shape and features of the isotherm. In line with the experiments, MD simulations show clear evidences of specific ionic effects and also provide molecular level details on ion specific interactions with cholesterol. More importantly, MD simulations show that the interaction of a particular ion with the surface depends strongly on its counterion, a feature ignored so far in most theories of specific ionic effects in surface forces.

  2. Designing specificity of protein-substrate interactions

    NARCIS (Netherlands)

    Coluzza, I.; Frenkel, D.

    2004-01-01

    One of the key properties of biological molecules is that they can bind strongly to certain substrates yet interact only weakly with the very large number of other molecules that they encounter. Using a simple lattice model, we test several methods to design molecule-substrate binding specificity.

  3. Materials and Process Specifications and Standards

    Science.gov (United States)

    1977-11-01

    factors involved in setting standards of this type are social (which usually predominates), legal, political, and then, to a lesser extent, economic, and...regulatory agencies. Material and process specifications are obviously affected by these relatively new social forces and, in turn, may...Welding Society Basic Standardization Agreement Conference Internationale des Grands Reseaux Internationale (International Conference on Large High

  4. Isotope specific arbitrary material flow meter

    Science.gov (United States)

    Barty, Christopher P. J.; Post, John C.; Jones, Edwin

    2016-10-25

    A laser-based mono-energetic gamma-ray source is used to provide non-destructive and non-intrusive, quantitative determination of the absolute amount of a specific isotope contained within pipe as part of a moving fluid or quasi-fluid material stream.

  5. 21 CFR 107.100 - Nutrient specifications.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Nutrient specifications. 107.100 Section 107.100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Vitamin K Micrograms 4 Thiamine (vitamin B1) do 40 Riboflavin (vitamin B2) do 60 Vitamin B6 do 35 Vitamin...

  6. Community-Specific Strategies of Intergenerational Language ...

    African Journals Online (AJOL)

    This study concerns minority language maintenance, specifically it explores local practices that make it possible for a community to sustain its traditional language. Two variables were the focus of the research; speakers' attitudes and language use patterns. These were examined to determine their influence in facilitating ...

  7. Brayton Isotope Power System (BIPS) facility specification

    International Nuclear Information System (INIS)

    1976-01-01

    General requirements for the Brayton Isotope Power System (BIPS)/Ground Demonstration System (GDS) assembly and test facility are defined. The facility will include provisions for a complete test laboratory for GDS checkout, performance, and endurance testing, and a contamination-controlled area for assembly, fabrication, storage, and storage preparation of GDS components. Specifications, schedules, and drawings are included

  8. Specificity of Structural Assessment of Knowledge

    Science.gov (United States)

    Trumpower, David L.; Sharara, Harold; Goldsmith, Timothy E.

    2010-01-01

    This study examines the specificity of information provided by structural assessment of knowledge (SAK). SAK is a technique which uses the Pathfinder scaling algorithm to transform ratings of concept relatedness into network representations (PFnets) of individuals' knowledge. Inferences about individuals' overall domain knowledge based on the…

  9. Organ-specific responses during brain death

    DEFF Research Database (Denmark)

    Van Erp, A C; Rebolledo, R A; Hoeksma, D

    2018-01-01

    Hepatic and renal energy status prior to transplantation correlates with graft survival. However, effects of brain death (BD) on organ-specific energy status are largely unknown. We studied metabolism, perfusion, oxygen consumption, and mitochondrial function in the liver and kidneys following BD...

  10. Patient-specific models of cardiac biomechanics

    Science.gov (United States)

    Krishnamurthy, Adarsh; Villongco, Christopher T.; Chuang, Joyce; Frank, Lawrence R.; Nigam, Vishal; Belezzuoli, Ernest; Stark, Paul; Krummen, David E.; Narayan, Sanjiv; Omens, Jeffrey H.; McCulloch, Andrew D.; Kerckhoffs, Roy C. P.

    2013-07-01

    Patient-specific models of cardiac function have the potential to improve diagnosis and management of heart disease by integrating medical images with heterogeneous clinical measurements subject to constraints imposed by physical first principles and prior experimental knowledge. We describe new methods for creating three-dimensional patient-specific models of ventricular biomechanics in the failing heart. Three-dimensional bi-ventricular geometry is segmented from cardiac CT images at end-diastole from patients with heart failure. Human myofiber and sheet architecture is modeled using eigenvectors computed from diffusion tensor MR images from an isolated, fixed human organ-donor heart and transformed to the patient-specific geometric model using large deformation diffeomorphic mapping. Semi-automated methods were developed for optimizing the passive material properties while simultaneously computing the unloaded reference geometry of the ventricles for stress analysis. Material properties of active cardiac muscle contraction were optimized to match ventricular pressures measured by cardiac catheterization, and parameters of a lumped-parameter closed-loop model of the circulation were estimated with a circulatory adaptation algorithm making use of information derived from echocardiography. These components were then integrated to create a multi-scale model of the patient-specific heart. These methods were tested in five heart failure patients from the San Diego Veteran's Affairs Medical Center who gave informed consent. The simulation results showed good agreement with measured echocardiographic and global functional parameters such as ejection fraction and peak cavity pressures.

  11. Measuring Language-Specific Phonetic Settings

    Science.gov (United States)

    Mennen, Ineke; Scobbie, James M.; de Leeuw, Esther; Schaeffler, Sonja; Schaeffler, Felix

    2010-01-01

    While it is well known that languages have different phonemes and phonologies, there is growing interest in the idea that languages may also differ in their "phonetic setting". The term "phonetic setting" refers to a tendency to make the vocal apparatus employ a language-specific habitual configuration. For example, languages may differ in their…

  12. Methodes for identification of specific language impairment

    Directory of Open Access Journals (Sweden)

    Toktam Maleki Shahmahmood

    2014-06-01

    Full Text Available Background and Aim: Specific language impiarment (SLI is one of the most prevalent developmental language disorders its diagnosis is a problematic issue among researchers and clinicians because of the heterogeneity of language profiles in the affected population and overlapping with other developmental language disorders. The aim of this study was to review the suggested diagnostic criteria for this disorder, controversies about these criteria and identify the most accurate diagnostic methods.Methods: Published article from 1980 to 2012 in bibliographic and publisher databases including Pubmed, Google scholar, Cochran library, Web of Science, ProQuest, Springer, Oxford, Science direct, Ovid, Iran Medex and Magiran about the diagnostic methods for discriminating preschoool children with specific language impiarment from normal developing children were reviewd in this article. These keywords were used for research: “specific language impairment”, “SLI”, “diagnosis or identification”, “standardized tests”, and “tests for language development”.Conclusion: The results of this study show inspite of agreement of researchers and clinicians about exclusionary criteria as one basic part of the diagnosis of specific language impiarment , there is no consensus about the other part, inclusionary criteria. Different studies used different inclusionary criteria which can be divided to categories of clincal judgment, discrepancy-based criteria, standardized testing, clinical markers and markers from spontaneous speech samples. Advantages, disadvantages, and clinical applicability of each diagnostic method are discussed in this article.

  13. ESP: Teaching English for Specific Purposes.

    Science.gov (United States)

    Schleppegrell, Mary; Bowman, Brenda

    This manual is a guide to the development of an instructional program in English for Specific Purposes (ESP). Step-by-step procedures for assessing student needs, setting achievable goals, designing a program, and selecting appropriate materials and activities for the classroom are outlined. The four language skills (listening, reading, speaking,…

  14. IPv6-specific misconfigurations in the DNS

    NARCIS (Netherlands)

    Hendriks, Luuk; de Boer, Pieter-Tjerk; Pras, Aiko

    2017-01-01

    With the Internet transitioning from IPv4 to IPv6, the number of IPv6-specific DNS records (AAAA) increases. Misconfigurations in these records often go unnoticed, as most systems are provided with connectivity over both IPv4 and IPv6, and automatically fall back to IPv4 in case of connection

  15. TAL effectors specificity stems from negative discrimination.

    Directory of Open Access Journals (Sweden)

    Basile I M Wicky

    Full Text Available Transcription Activator-Like (TAL effectors are DNA-binding proteins secreted by phytopathogenic bacteria that interfere with native cellular functions by binding to plant DNA promoters. The key element of their architecture is a domain of tandem-repeats with almost identical sequences. Most of the polymorphism is located at two consecutive amino acids termed Repeat Variable Diresidue (RVD. The discovery of a direct link between the RVD composition and the targeted nucleotide allowed the design of TAL-derived DNA-binding tools with programmable specificities that revolutionized the field of genome engineering. Despite structural data, the molecular origins of this specificity as well as the recognition mechanism have remained unclear. Molecular simulations of the recent crystal structures suggest that most of the protein-DNA binding energy originates from non-specific interactions between the DNA backbone and non-variable residues, while RVDs contributions are negligible. Based on dynamical and energetic considerations we postulate that, while the first RVD residue promotes helix breaks--allowing folding of TAL as a DNA-wrapping super-helix--the second provides specificity through a negative discrimination of matches. Furthermore, we propose a simple pharmacophore-like model for the rationalization of RVD-DNA interactions and the interpretation of experimental findings concerning shared affinities and binding efficiencies. The explanatory paradigm presented herein provides a better comprehension of this elegant architecture and we hope will allow for improved designs of TAL-derived biotechnological tools.

  16. 31 CFR 595.312 - Specific license.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Specific license. 595.312 Section 595.312 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TERRORISM SANCTIONS REGULATIONS General Definitions...

  17. MODEL OF TEACHING PROFESSION SPECIFIC BILATERAL TRANSLATION

    Directory of Open Access Journals (Sweden)

    Yana Fabrychna

    2017-03-01

    Full Text Available The article deals with the author’s interpretation of the process of teaching profession specific bilateral translation to student teacher of English in the Master’s program. The goal of the model of teaching profession specific bilateral translation development is to determine the logical sequence of educational activities of the teacher as the organizer of the educational process and students as its members. English and Ukrainian texts on methods of foreign languages and cultures teaching are defined as the object of study. Learning activities aimed at the development of student teachers of English profession specific competence in bilateral translation and Translation Proficiency Language Portfolio for Student Teachers of English are suggested as teaching tools. The realization of the model of teaching profession specific bilateral translation to student teachers of English in the Master’s program is suggested within the module topics of the academic discipline «Practice of English as the first foreign language»: Globalization; Localization; Education; Work; The role of new communication technologies in personal and professional development. We believe that the amount of time needed for efficient functioning of the model is 48 academic hours, which was determined by calculating the total number of academic hours allotted for the academic discipline «Practice of English as the first foreign language» in Ukrainian universities. Peculiarities of the model realization as well as learning goals and content of class activities and home self-study work of students are outlined.

  18. Teaching Case: Enterprise Architecture Specification Case Study

    Science.gov (United States)

    Steenkamp, Annette Lerine; Alawdah, Amal; Almasri, Osama; Gai, Keke; Khattab, Nidal; Swaby, Carval; Abaas, Ramy

    2013-01-01

    A graduate course in enterprise architecture had a team project component in which a real-world business case, provided by an industry sponsor, formed the basis of the project charter and the architecture statement of work. The paper aims to share the team project experience on developing the architecture specifications based on the business case…

  19. 32 CFR 292.4 - Specific policy.

    Science.gov (United States)

    2010-07-01

    ... INFORMATION ACT PROGRAM DEFENSE INTELLIGENCE AGENCY (DIA) FREEDOM OF INFORMATION ACT § 292.4 Specific policy... of source and object codes, regardless of medium are not agency records. (This does not include the... existing computer program or printout for retrieval of the requested information. (c) The prior application...

  20. VSAT networks in India - Specifications and applications

    Science.gov (United States)

    Ghose, A. K.

    1993-08-01

    This paper describes briefly the evolution of VSATs in India, including the existing and proposed networks and their applications. The salient specifications of the various types of VSATs are described. Some of the VSATs under advanced stages of development as well as those to be used in proposed networks due for implementation soon are also covered.

  1. XML Based Markup Languages for Specific Domains

    Science.gov (United States)

    Varde, Aparna; Rundensteiner, Elke; Fahrenholz, Sally

    A challenging area in web based support systems is the study of human activities in connection with the web, especially with reference to certain domains. This includes capturing human reasoning in information retrieval, facilitating the exchange of domain-specific knowledge through a common platform and developing tools for the analysis of data on the web from a domain expert's angle. Among the techniques and standards related to such work, we have XML, the eXtensible Markup Language. This serves as a medium of communication for storing and publishing textual, numeric and other forms of data seamlessly. XML tag sets are such that they preserve semantics and simplify the understanding of stored information by users. Often domain-specific markup languages are designed using XML, with a user-centric perspective. Standardization bodies and research communities may extend these to include additional semantics of areas within and related to the domain. This chapter outlines the issues to be considered in developing domain-specific markup languages: the motivation for development, the semantic considerations, the syntactic constraints and other relevant aspects, especially taking into account human factors. Illustrating examples are provided from domains such as Medicine, Finance and Materials Science. Particular emphasis in these examples is on the Materials Markup Language MatML and the semantics of one of its areas, namely, the Heat Treating of Materials. The focus of this chapter, however, is not the design of one particular language but rather the generic issues concerning the development of domain-specific markup languages.

  2. Interventions in individuals with specific needs.

    Science.gov (United States)

    Mandal, Piyali; Dhawan, Anju

    2018-02-01

    With the growing understanding of substance use problems among special populations like women, gender minority groups, as well as in the geriatric population, there is a drive to develop sensitive interventions catering to their unique needs. This chapter is a short review of psycho-social interventions targeted towards these individuals with specific needs.

  3. Language specific bootstraps for UG categories

    NARCIS (Netherlands)

    van Kampen, N.J.

    2005-01-01

    This paper argues that the universal categories N/V are not applied to content words before the grammatical markings for reference D(eterminers) and predication I(nflection) have been acquired (van Kampen, 1997, contra Pinker, 1984). Child grammar starts as proto-grammar with language-specific

  4. Side-Specific Reward Memories in Honeybees

    Science.gov (United States)

    Gil, Mariana; Menzel, Randolf; De Marco, Rodrigo J.

    2009-01-01

    We report a hitherto unknown form of side-specific learning in honeybees. We trained bees individually by coupling gustatory and mechanical stimulation of each antenna with either increasing or decreasing volumes of sucrose solution offered to the animal's proboscis along successive learning trials. Next, we examined their proboscis extension…

  5. Specificity in liquid metal induced embrittlement

    CSIR Research Space (South Africa)

    Fernandes, PJL

    1996-12-01

    Full Text Available One of the most intriguing features of liquid metal induced embrittlement (LMIE) is the observation that some liquid metal-solid metal couples are susceptible to embrittlement, while others appear to be immune. This is referred to as the specificity...

  6. 10 CFR 71.12 - Specific exemptions.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Specific exemptions. 71.12 Section 71.12 Energy NUCLEAR... grant any exemption from the requirements of the regulations in this part that it determines is authorized by law and will not endanger life or property nor the common defense and security. ...

  7. 10 CFR 62.5 - Specific exemptions.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Specific exemptions. 62.5 Section 62.5 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CRITERIA AND PROCEDURES FOR EMERGENCY ACCESS TO NON-FEDERAL AND REGIONAL... requirements of the regulations in this part that it determines is authorized by law and will not endanger life...

  8. 10 CFR 25.11 - Specific exemptions.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Specific exemptions. 25.11 Section 25.11 Energy NUCLEAR... regulations of this part, that are— (a) Authorized by law, will not present an undue risk to the public health... more of the following: (1) An application of the regulation in the particular circumstances conflicts...

  9. 10 CFR 73.5 - Specific exemptions.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Specific exemptions. 73.5 Section 73.5 Energy NUCLEAR... initiative, grant such exemptions from the requirements of the regulations in this part as it determines are authorized by law and will not endanger life or property or the common defense and security, and are...

  10. 10 CFR 95.11 - Specific exemptions.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Specific exemptions. 95.11 Section 95.11 Energy NUCLEAR... regulations of this part, that are— (a) Authorized by law, will not present an undue risk to the public health... more of the following: (1) An application of the regulation in the particular circumstances conflicts...

  11. 10 CFR 140.8 - Specific exemptions.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Specific exemptions. 140.8 Section 140.8 Energy NUCLEAR... its own initiative, grant such exemptions from the requirements of the regulations in this part as it determines are authorized by law and are otherwise in the public interest. [34 FR 19546, Dec. 11, 1969] ...

  12. 10 CFR 40.14 - Specific exemptions.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Specific exemptions. 40.14 Section 40.14 Energy NUCLEAR... from the requirements of the regulation in this part as it determines are authorized by law and will... interest. (b) [Reserved] (c) The Department of Energy is exempt from the requirements of this part to the...

  13. 10 CFR 76.23 - Specific exemptions.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Specific exemptions. 76.23 Section 76.23 Energy NUCLEAR..., grant such exemptions from the requirements of the certification regulations as it determines are authorized by law and will not endanger life, or property, or the common defense and security, and are...

  14. Removing the Barriers: Accessibility Guidelines and Specifications.

    Science.gov (United States)

    Cotler, Stephen R.

    This guide provides guidelines for meeting the accessibility requirements of the Americans with Disabilities (ADA) Act in college and university buildings. The publication is divided into 10 chapters, the first 7 of which present construction drawings, evaluation criteria, and specifications for: (1) site accessibility (external path of travel,…

  15. Body-Specific Representations of Spatial Location

    Science.gov (United States)

    Brunye, Tad T.; Gardony, Aaron; Mahoney, Caroline R.; Taylor, Holly A.

    2012-01-01

    The body specificity hypothesis (Casasanto, 2009) posits that the way in which people interact with the world affects their mental representation of information. For instance, right- versus left-handedness affects the mental representation of affective valence, with right-handers categorically associating good with rightward areas and bad with…

  16. FRENCH FOR SPECIFIC PURPOSES: THE GATEWAY TO ...

    African Journals Online (AJOL)

    JONATHAN

    2016-07-01

    Jul 1, 2016 ... FRENCH FOR SPECIFIC PURPOSES: THE GATEWAY TO EMPLOYMENT. OPPORTUNITIES FOR NIGERIAN GRADUATES. Nwabueze Joe Obinaju. &. Chukwunonso Hyacinth Muotoo. Abstract. For some years now, accessing jobs after graduation has become a serious issue for Nigerian graduates, their ...

  17. 49 CFR 172.407 - Label specifications.

    Science.gov (United States)

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HAZARDOUS MATERIALS REGULATIONS HAZARDOUS MATERIALS TABLE, SPECIAL... each side having a solid line inner border 5.0 to 6.3 mm (0.2 to 0.25 inches) from the edge. (2) The...) Displayed on color charts conforming to the technical specifications for charts set forth in table 1 or 2 in...

  18. [The "specific" liability regime for blood products].

    Science.gov (United States)

    Byk, Christian

    2017-10-13

    Based on the system of liability for defective products as organized by the European Directive of 25 July 1985, responsibility for blood products does not therefore constitute a genuine specific regime. However, European law leaves States a margin of discretion in the implementation of the Directive with regard to health products. This is the case in particular with the exemption for development risk.

  19. Towards a typology of specific language impairment.

    Science.gov (United States)

    van Weerdenburg, Marjolijn; Verhoeven, Ludo; van Balkom, Hans

    2006-02-01

    The population of children with specific language impairments (SLI) is heterogeneous. The present study was conducted to examine this heterogeneity more closely, by identifying and describing subgroups within the population of children with SLI in the Netherlands. A broad battery of language tests and language-related cognitive tests were administered to 147 six-year-old and 136 eight-year-old children with SLI. Factor analyses revealed 4 factors indicating 4 distinctive linguistic domains for both age samples: 1) lexical-semantic abilities, 2) auditory conceptualization, 3) verbal sequential memory and 4) speech production. These empirical findings were further validated by the positive correlations found between the language factors and the judgments of teachers and speech therapists. Finally, a cluster analysis revealed 4 distinct clusters of SLI children for each sample with specific language profiles based on the 4 factors. Results were nearly the same for both age samples. The language problems that emerged from the two samples of children with SLI could be described as falling into four types. Based on these language types, four subgroups of children with SLI could be distinguished, each with a specific profile. Some subgroups had severe problems on one specific type of language problem; others had severe problems in more than one type of language problem when compared to the other subgroups of the same age sample. The different profiles may indicate that a more dynamic approach is needed in intervention, considering the presence of both compensating and restricting factors within each child with SLI.

  20. Towards a typology of specific language impairment

    NARCIS (Netherlands)

    Weerdenburg, M.W.C. van; Verhoeven, L.T.W.; Balkom, L.J.M. van

    2006-01-01

    Background - The population of children with specific language impairments (SLI) is heterogeneous. The present study was conducted to examine this heterogeneity more closely, by identifying and describing subgroups within the population of children with SLI in the Netherlands. Method - A broad

  1. Primary Auditory Cortex Regulates Threat Memory Specificity

    Science.gov (United States)

    Wigestrand, Mattis B.; Schiff, Hillary C.; Fyhn, Marianne; LeDoux, Joseph E.; Sears, Robert M.

    2017-01-01

    Distinguishing threatening from nonthreatening stimuli is essential for survival and stimulus generalization is a hallmark of anxiety disorders. While auditory threat learning produces long-lasting plasticity in primary auditory cortex (Au1), it is not clear whether such Au1 plasticity regulates memory specificity or generalization. We used…

  2. Volatiles in inter-specific bacterial interactions

    NARCIS (Netherlands)

    Tyc, Olaf; Zweers, H.; Boer, de W.; Garbeva, P.

    2015-01-01

    The importance of volatile organic compounds for functioning of microbes is receiving increased research attention. However, to date very little is known on how inter-specific bacterial interactions effect volatiles production as most studies have been focused on volatiles produced by monocultures

  3. Specification of the somatic musculature in Drosophila†

    Science.gov (United States)

    Dobi, Krista C.; Schulman, Victoria K.; Baylies, Mary K.

    2015-01-01

    The somatic muscle system formed during Drosophila embryogenesis is required for larvae to hatch, feed, and crawl. This system is replaced in the pupa by a new adult muscle set, responsible for activities such as feeding, walking, and flight. Both the larval and adult muscle systems are comprised of distinct muscle fibers to serve these specific motor functions. In this way, the Drosophila musculature is a valuable model for patterning within a single tissue: while all muscle cells share properties such as the contractile apparatus, properties such as size, position, and number of nuclei are unique for a particular muscle. In the embryo, diversification of muscle fibers relies first on signaling cascades that pattern the mesoderm. Subsequently, the combinatorial expression of specific transcription factors leads muscle fibers to adopt particular sizes, shapes, and orientations. Adult muscle precursors (AMPs), set aside during embryonic development, proliferate during the larval phases and seed the formation of the abdominal, leg, and flight muscles in the adult fly. Adult muscle fibers may either be formed de novo from the fusion of the AMPs, or are created by the binding of AMPs to an existing larval muscle. While less is known about adult muscle specification compared to the larva, expression of specific transcription factors is also important for its diversification. Increasingly, the mechanisms required for the diversification of fly muscle have found parallels in vertebrate systems and mark Drosophila as a robust model system to examine questions about how diverse cell types are generated within an organism. PMID:25728002

  4. Chapter 9: Questions from CNEN specific exams

    International Nuclear Information System (INIS)

    2018-01-01

    The following are real questions from CNEN specific exams for obtaining the certification of RSO for gamma irradiators. These are questions that require essay answers, that are interpretative ones and therefore that may accept more than one interpretation, therefore more than one answer. For this reason, suggestions of answers will be presented in the second part of this chapter

  5. Specification and Construction of Control Flow Semantics

    NARCIS (Netherlands)

    Smelik, R.; Rensink, Arend; Kastenberg, H.; Grundy, J; Howse, J.

    In this paper we propose a visual language CFSL for specifying control flow semantics of programming languages. We also present a translation from CFSL to graph production systems (GPS) for flow graph construction; that is, any CFSL specification, say for a language L, gives rise to a GPS that

  6. Specificity of cognitive distortions to antisocial behaviours.

    Science.gov (United States)

    Barriga, Alvaro Q; Hawkins, Mark A; Camelia, Carl R T

    2008-01-01

    Cognitive distortions have long been posited to facilitate antisocial behaviours, but the specificity of such distortions has rarely been studied. To replicate findings of specificity between particular cognitions and externalizing or internalizing behaviours; to test for specificity of relationship between particular cognitions and different types of externalizing behaviours. The participants were 239 male youths aged 10 to 19 years (mean (M) = 14.22, standard deviation (SD) = 1.64) from schools on the island of Curaçao. Their cognitive distortions and problem behaviours were investigated through self-report. Results In controlled analyses, self-serving cognitive distortions were associated with externalizing behaviours whereas self-debasing cognitive distortions were associated with internalizing behaviours. Within the externalizing domain, self-serving distortions with overt behavioural referents were linked to aggressive behaviour while self-serving distortions with covert behavioural referents were linked to delinquent behaviour. Within the aggression domain, distortions with opposition-defiance referents related to verbal aggression whereas distortions with physical aggression referents related to physically aggressive behaviour. The degree of cognitive-behavioural specificity documented by this study was remarkable. The observed pattern suggests that cognitive interventions designed for externalizing versus internalizing behaviours should differ in therapeutic approach.

  7. Analyzing Languages for Specific Purposes Discourse

    Science.gov (United States)

    Bowles, Hugo

    2012-01-01

    In the last 20 years, technological advancement and increased multidisciplinarity has expanded the range of data regarded as within the scope of languages for specific purposes (LSP) research and the means by which they can be analyzed. As a result, the analytical work of LSP researchers has developed from a narrow focus on specialist terminology…

  8. Ultrahigh Specific Impulse Nuclear Thermal Propulsion

    Energy Technology Data Exchange (ETDEWEB)

    Anne Charmeau; Brandon Cunningham; Samim Anghaie

    2009-02-09

    Research on nuclear thermal propulsion systems (NTP) have been in forefront of the space nuclear power and propulsion due to their design simplicity and their promise for providing very high thrust at reasonably high specific impulse. During NERVA-ROVER program in late 1950's till early 1970's, the United States developed and ground tested about 18 NTP systems without ever deploying them into space. The NERVA-ROVER program included development and testing of NTP systems with very high thrust (~250,000 lbf) and relatively high specific impulse (~850 s). High thrust to weight ratio in NTP systems is an indicator of high acceleration that could be achieved with these systems. The specific impulse in the lowest mass propellant, hydrogen, is a function of square root of absolute temperature in the NTP thrust chamber. Therefor optimizing design performance of NTP systems would require achieving the highest possible hydrogen temperature at reasonably high thrust to weight ratio. High hydrogen exit temperature produces high specific impulse that is a diret measure of propellant usage efficiency.

  9. A Specification Language for Organisational Performance Indicators

    NARCIS (Netherlands)

    Popova, V.N.; Treur, J.

    2007-01-01

    A specification language for performance indicators and their relations and requirements is presented and illustrated for a case study in logistics. The language can be used in different forms, varying from informal, semiformal, graphical to formal. A software environment has been developed that

  10. A specification language for organisational performance indicators

    NARCIS (Netherlands)

    Popova, Viara; Treur, Jan

    2007-01-01

    A specification language for performance indicators and their relations and requirements is presented and illustrated for a case study in logistics. The language can be used in different forms, varying from informal, semiformal, graphical to formal. A software environment has been developed that

  11. Investment specific technological progress and structural change

    Directory of Open Access Journals (Sweden)

    Ricardo Silva Azevedo Araujo

    2010-12-01

    Full Text Available In this paper we introduce investment specific technical progress into Pasinetti's model of structural change. Our aim is to assess the effects of embodied technical progress on economic growth and macroeconomic variables. Our findings suggest that despite the fact that this type of technical progress increases the productivity of capital, it has negative effects on conditions that promote full employment.

  12. A camera specification for tendering purposes

    International Nuclear Information System (INIS)

    Lunt, M.J.; Davies, M.D.; Kenyon, N.G.

    1985-01-01

    A standardized document is described which is suitable for sending to companies which are being invited to tender for the supply of a gamma camera. The document refers to various features of the camera, the performance specification of the camera, maintenance details, price quotations for various options and delivery, installation and warranty details. (U.K.)

  13. Beneficiary Perceptions of Gender Specific Extension Delivery ...

    African Journals Online (AJOL)

    Women play major roles in agricultural production although only an estimated 5 percent actually benefit from mainstream extension activities. The Gender Specific Extension Delivery Service was instituted to remedy this trend. This study was an attempt to document women beneficiaries' perceptions on the effectiveness of ...

  14. Towards a typology of specific language impairment

    NARCIS (Netherlands)

    Weerdenburg, M.W.C. van; Verhoeven, L.T.W.; Balkom, L.J.M. van

    2006-01-01

    BACKGROUND: The population of children with specific language impairments (SLI) is heterogeneous. The present study was conducted to examine this heterogeneity more closely, by identifying and describing subgroups within the population of children with SLI in the Netherlands. METHOD: A broad battery

  15. Spent nuclear fuel project product specification

    International Nuclear Information System (INIS)

    PAJUNEN, A.L.

    1999-01-01

    This document establishes the limits and controls for the significant parameters that could potentially affect the safety and/or quality of the Spent Nuclear Fuel (SNF) packaged for processing, transport, and storage. The product specifications in this document cover the SNF packaged in Multi-Canister Overpacks to be transported throughout the SNF Project

  16. NIF small optics laser damage test specifications

    International Nuclear Information System (INIS)

    Sheehan, L

    1999-01-01

    The Laser Damage Group is currently conducting tests on small optics samples supplied for initial evaluation of potential NIF suppliers. This document is meant to define the specification of laser-induced damage for small optics and the test methods used to collect the data. A rating system which will be applied for vendor selection is presented

  17. Prospects for site specific weed management

    DEFF Research Database (Denmark)

    Christensen, Svend; Rasmussen, Jesper; Pedersen, Søren Marcus

    2014-01-01

    Research on Site Specific Weed Management (SSWM) started in the late 80's. Since that moment, considerable research has been conducted on different aspects of SSWM, from fundamental studies on the spatial ecology of weeds to the applied development and testing of new technologies for weed detection...

  18. Accounting valuation development of specific assets

    Directory of Open Access Journals (Sweden)

    I.V. Zhigley

    2017-12-01

    Full Text Available The current issues of accounting estimate development are considered. The necessity of the development of accounting estimate in the context of the non-institutional theory principles based on the selection of a number of reasons is grounded. The reasons for deterioration of accounting reputation as a separate socio-economic institute in the context of developing the methodology for specific assets accounting are discovered. The system of normative regulation of accounting estimate of enterprise non-current assets in the case of diminishing their usefulness is analyzed. The procedure for determining and accounting for the depreciation of assets in accordance with IFRS 36 «Depreciation of Assets» is developed. The features of the joint use of the concept of «value in use» and «fair value» in the accounting system are disclosed. The procedure for determining the value of compensation depending on the degree of specificity of assets is developed. The necessity to clarify the features that indicate the possibility of diminishing the usefulness of specific assets (termination or pre-term termination of the contract for the use of a specific asset is grounded.

  19. Essential Specification Elements for Heat Exchanger Replacement

    Energy Technology Data Exchange (ETDEWEB)

    Bower, L.

    2015-07-01

    Performance upgrade and equipment degradation are the primary impetuses for a nuclear power plant to engage in the large capital cost project of heat exchanger replacement. Along with attention to these issues, consideration of heat exchanger Codes and Standards, material improvements, thermal redesign, and configuration are essential for developing User’s Design Specifications for successful replacement projects. The User’s Design Specification is the central document in procuring ASME heat exchangers. Properly stated objectives for the heat exchanger replacement are essential for obtaining the materials, configurations and thermal designs best suited for the nuclear power plant. Additionally, the code of construction required and the applied manufacturing standard (TEMA or HEI) affects how the heat exchanger may be designed or configured to meet the replacement goals. Knowledge of how Codes and Standards affect design and configuration details will aid in writing the User’s Design Specification. Joseph Oat Corporation has designed and fabricated many replacement heat exchangers for the nuclear power industry. These heat exchangers have been constructed per ASME Section III to various Code-Years or ASME Section VIII-1 to the current Code-Year also in accordance with TEMA and HEI. These heat exchangers have been a range of like-for-like replacement to complete thermal, material and configuration redesigns. Several examples of these heat exchangers with their Code, Standard and specification implications are presented. (Author.

  20. Specific IgE to colophony?

    Science.gov (United States)

    Elms, Joanne; Fishwick, David; Robinson, Edward; Burge, Sherwood; Huggins, Vicky; Barber, Chris; Williams, Nerys; Curran, Andrew

    2005-05-01

    Colophony (rosin) is a natural product obtained from coniferous trees. It is used in a diverse range of products such as adhesives, ink, paints and soldering fluxes. Some workers exposed to colophony during soldering can develop occupational asthma; at present, no specific IgE test is available to assess sensitization to colophony. Serum samples were obtained from exposed symptomatic individuals (n = 7), some with a likely diagnosis of occupational asthma, exposed asymptomatic individuals (n = 10) and unexposed individuals (n = 11). Serum was tested for specific IgE antibodies against a protein extract produced following in vitro challenge of mono-mac-6 cells with colophony extract. Serum from exposed symptomatic individuals showed increased binding of specific IgE antibodies to a range of colophony-cell protein conjugates [29% (2/7) of samples tested when cut-off > 0.1 or 86% (6/7) of samples tested when cut-off > 0%] compared with both the exposed asymptomatic [0% when cut-off > 0.1, or 20% when cut-off > 0% (2/10)] and the non-exposed control populations [0% when cut-off > 0.1, or 27% when cut-off > 0% (3/11)]. This novel approach for the production of conjugates to assess sensitization to colophony was able to detect specific IgE in colophony-exposed workers with a likely diagnosis of occupational asthma.

  1. EFFECTS OF MACRONUTRIENT COMPOSITION ON SPECIFIC ...

    African Journals Online (AJOL)

    Admin

    Open-flow respirometry was used to measure the magnitude of specific dynamic action (SDA), the maximum rate of oxygen consumption ..... Table 2: Body mass of female mice and respiratory quotient of macronutrient diets. Diets. Body mass before SDA (g). Body mass after SDA (g). VO2. (ml/min. VCO2. (ml/min). RQ. HP.

  2. Molecular and cellular limits to somatosensory specificity

    Directory of Open Access Journals (Sweden)

    Viana Félix

    2008-04-01

    Full Text Available Abstract Animals detect environmental changes through sensory neural mechanisms that enable them to differentiate the quality, intensity and temporal characteristics of stimuli. The 'doctrine of specific nervous energies' postulates that the different sensory modalities experienced by humans result of the activation of specific nervous pathways. Identification of functional classes of sensory receptors provided scientific support to the concept that somatosensory modalities (touch, pain, temperature, kinesthesis are subserved by separate populations of sensory receptor neurons specialized in detecting innocuous and injurious stimuli of different quality (mechanical forces, temperature, chemical compounds. The identification of receptor proteins activated by different physicochemical stimuli, in particular ion channels of the Transient Receptor Potential (TRP superfamily, has put forward the concept that specificity of peripheral sensory receptor neurons is determined by their expression of a particular "molecular sensor" that confers to each functional type its selectivity to respond with a discharge of nerve impulses to stimuli of a given quality. Nonetheless, recent experimental data suggest that the various molecular sensors proposed as specific transducer molecules for stimuli of different quality are not as neatly associated with the distinct functional types of sensory receptors as originally proposed. First, many ion channel molecules initially associated to the transduction of only one particular form of energy are also activated by stimuli of different quality, implying a limited degree of specificity in their transducing capacities. Second, molecular sensors associated with a stimulus quality and hence to a sensory receptor type and ultimately to a sensory modality may be concomitantly expressed in sensory receptor neurons functionally defined as specific for another stimulus quality. Finally, activation of voltage gated channels

  3. URPD: a specific product primer design tool

    Directory of Open Access Journals (Sweden)

    Chuang Li-Yeh

    2012-06-01

    Full Text Available Abstract Background Polymerase chain reaction (PCR plays an important role in molecular biology. Primer design fundamentally determines its results. Here, we present a currently available software that is not located in analyzing large sequence but used for a rather straight-forward way of visualizing the primer design process for infrequent users. Findings URPD (yoUR Primer Design, a web-based specific product primer design tool, combines the NCBI Reference Sequences (RefSeq, UCSC In-Silico PCR, memetic algorithm (MA and genetic algorithm (GA primer design methods to obtain specific primer sets. A friendly user interface is accomplished by built-in parameter settings. The incorporated smooth pipeline operations effectively guide both occasional and advanced users. URPD contains an automated process, which produces feasible primer pairs that satisfy the specific needs of the experimental design with practical PCR amplifications. Visual virtual gel electrophoresis and in silico PCR provide a simulated PCR environment. The comparison of Practical gel electrophoresis comparison to virtual gel electrophoresis facilitates and verifies the PCR experiment. Wet-laboratory validation proved that the system provides feasible primers. Conclusions URPD is a user-friendly tool that provides specific primer design results. The pipeline design path makes it easy to operate for beginners. URPD also provides a high throughput primer design function. Moreover, the advanced parameter settings assist sophisticated researchers in performing experiential PCR. Several novel functions, such as a nucleotide accession number template sequence input, local and global specificity estimation, primer pair redesign, user-interactive sequence scale selection, and virtual and practical PCR gel electrophoresis discrepancies have been developed and integrated into URPD. The URPD program is implemented in JAVA and freely available at http://bio.kuas.edu.tw/urpd/.

  4. Are videogame training gains specific or general?

    Science.gov (United States)

    Oei, Adam C; Patterson, Michael D

    2014-01-01

    Many recent studies using healthy adults document enhancements in perception and cognition from playing commercial action videogames (AVGs). Playing action games (e.g., Call of Duty, Medal of Honor) is associated with improved bottom-up lower-level information processing skills like visual-perceptual and attentional processes. One proposal states a general improvement in the ability to interpret and gather statistical information to predict future actions which then leads to better performance across different perceptual/attentional tasks. Another proposal claims all the tasks are separately trained in the AVGs because the AVGs and laboratory tasks contain similar demands. We review studies of action and non-AVGs to show support for the latter proposal. To explain transfer in AVGs, we argue that the perceptual and attention tasks share common demands with the trained videogames (e.g., multiple object tracking (MOT), rapid attentional switches, and peripheral vision). In non-AVGs, several studies also demonstrate specific, limited transfer. One instance of specific transfer is the specific enhancement to mental rotation after training in games with a spatial emphasis (e.g., Tetris). In contrast, the evidence for transfer is equivocal where the game and task do not share common demands (e.g., executive functioning). Thus, the "common demands" hypothesis of transfer not only characterizes transfer effects in AVGs, but also non-action games. Furthermore, such a theory provides specific predictions, which can help in the selection of games to train human cognition as well as in the design of videogames purposed for human cognitive and perceptual enhancement. Finally this hypothesis is consistent with the cognitive training literature where most post-training gains are for tasks similar to the training rather than general, non-specific improvements.

  5. Hand Specific Representations in Language Comprehension

    Directory of Open Access Journals (Sweden)

    Claire eMoody-Triantis

    2014-06-01

    Full Text Available Theories of embodied cognition argue that language comprehension involves sensory-motor re-enactments of the actions described. However, the degree of specificity of these re-enactments as well as the relationship between action and language remains a matter of debate. Here we investigate these issues by examining how hand-specific information (left or right hand is recruited in language comprehension and action execution. An fMRI study tested right-handed participants in two separate tasks that were designed to be as similar as possible to increase sensitivity of the comparison across task: an action execution go/no-go task where participants performed right or left hand actions, and a language task where participants read sentences describing the same left or right handed actions as in the execution task. We found that language-induced activity did not match the hand-specific patterns of activity found for action execution in primary somatosensory and motor cortex, but it overlapped with pre-motor and parietal regions associated with action planning. Within these pre-motor regions, both right hand actions and sentences elicited stronger activity than left hand actions and sentences - a dominant hand effect -. Importantly, both dorsal and ventral sections of the left pre-central gyrus were recruited by both tasks, suggesting different action features being recruited. These results suggest that (a language comprehension elicits motor representations that are hand-specific and akin to multimodal action plans, rather than full action re-enactments; and (b language comprehension and action execution share schematic hand-specific representations that are richer for the dominant hand, and thus linked to previous motor experience.

  6. Are videogame training gains specific or general?

    Directory of Open Access Journals (Sweden)

    Adam C. Oei

    2014-04-01

    Full Text Available Many recent studies using healthy adults document enhancements in perception and cognition from playing commercial action videogames. Playing action games (e.g., Call of Duty, Medal of Honor is associated with improved bottom-up lower-level information processing skills like visual-perceptual and attentional processes. One proposal states a general improvement in the ability to interpret and gather statistical information to predict future actions which then leads to better performance across different perceptual/attentional tasks. Another proposal claims all the tasks are separately trained in the action videogames because the action videogames and laboratory tasks contain similar demands. We review studies of action and non-action videogames to show support for the latter proposal. To explain transfer in action videogames, we argue that the perceptual and attention tasks share common demands with the trained videogames (e.g., multiple object tracking, rapid attentional switches, and peripheral vision. In non-action videogames, several studies also demonstrate specific, limited transfer. One instance of specific transfer is the specific enhancement to mental rotation after training in games with a spatial emphasis (e.g, Tetris. In contrast, the evidence for transfer is equivocal where the game and task do not share common demands (e.g., executive functioning. Thus, the common demands hypothesis of transfer not only characterizes transfer effects in action videogames, but also non-action games. Furthermore, such a theory provides specific predictions, which can help in the selection of games to train human cognition as well as in the design of videogames purposed for human cognitive and perceptual enhancement. Finally this hypothesis is consistent with the cognitive training literature where most post-training gains are for tasks similar to the training rather than general, non-specific improvements.

  7. The field theory of specific heat

    Science.gov (United States)

    Gusev, Yu. V.

    2016-01-01

    Finite temperature quantum field theory in the heat kernel method is used to study the heat capacity of condensed matter. The lattice heat is treated à la P. Debye as energy of the elastic (sound) waves. The dimensionless functional of free energy is re-derived with a cut-off parameter and used to obtain the specific heat of crystal lattices. The new dimensionless thermodynamical variable is formed as Planck's inverse temperature divided by the lattice constant. The dimensionless constant, universal for the class of crystal lattices, which determines the low temperature region of molar specific heat, is introduced and tested with the data for diamond lattice crystals. The low temperature asymptotics of specific heat is found to be the fourth power in temperature instead of the cubic power law of the Debye theory. Experimental data for the carbon group elements (silicon, germanium) and other materials decisively confirm the quartic law. The true low temperature regime of specific heat is defined by the surface heat, therefore, it depends on the geometrical characteristics of the body, while the absolute zero temperature limit is geometrically forbidden. The limit on the growth of specific heat at temperatures close to critical points, known as the Dulong-Petit law, appears from the lattice constant cut-off. Its value depends on the lattice type and it is the same for materials with the same crystal lattice. The Dulong-Petit values of compounds are equal to those of elements with the same crystal lattice type, if one mole of solid state matter were taken as the Avogadro number of the composing atoms. Thus, the Neumann-Kopp law is valid only in some special cases.

  8. Adolescents with specific learning disabilities - perceptions of specific learning disabilities in the environment of secondary schools

    OpenAIRE

    Pospíšilová, Zuzana

    2012-01-01

    The thesis focuses on adolescents with specific learning disabilities in the milieu of secondary schools. It is divided into a theoretical part and an empirical part. The first part introduces a topic of specific learning disabilities in the developmental stage of adolescence. It first describes the most relevant aspects of adolescent development. The attention is then paid to typical manifestations of specific learning disabilities in adolescence, and also to secondary symptoms usually conne...

  9. The Role of Non-specific and Specific Immune Systems in Poultry against Newcastle Disease

    OpenAIRE

    Dyah Ayu Hewajuli; NLPI Dharmayanti

    2015-01-01

    Newcastle disease (ND) is caused by avian paramyxovirus-1 which belong to Avulavirus genus and Paramyxoviridae family. The birds have abnormalities in humoral (bursa fabricius) and cellular (thymus and spleen) lymphoid organs. Lesions decrease the immune system. Immune system consists of non-specific and specific immune systems. The main components of non-specific immunity are physical and chemical barrier (feather and skin or mucosa), phagocytic cells (macrophages and natural killer), protei...

  10. Specific developmental pathways underlie host specificity in the parasitic plant Orobanche

    Science.gov (United States)

    Hiscock, Simon

    2010-01-01

    Parasitic angiosperms are an ecologically and economically important group of plants. However our understanding of the basis for host specificity in these plants is embryonic. Recently we investigated host specificity in the parasitic angiosperm Orobanche minor, and demonstrated that this host generalist parasite comprises genetically defined races that are physiologically adapted to specific hosts. Populations occurring naturally on red clover (Trifolium pratense) and sea carrot (Daucus carota subsp. gummifer) respectively, showed distinct patterns of host specificity at various developmental stages, and a higher fitness on their natural hosts, suggesting these races are locally adapted. Here we discuss the implications of our findings from a broader perspective. We suggest that differences in signal responsiveness and perception by the parasite, as well as qualitative differences in signal production by the host, may elicit host specificity in this parasitic plant. Together with our earlier demonstration that these O. minor races are genetically distinct based on molecular markers, our recent data provide a snapshot of speciation in action, driven by host specificity. Indeed, host specificity may be an underestimated catalyst for speciation in parasitic plants generally. We propose that identifying host specific races using physiological techniques will complement conventional molecular marker-based approaches to provide a framework for delineating evolutionary relationships among cryptic host-specific parasitic plants. PMID:20081361

  11. Simplicity and Specificity in Language: Domain general biases have domain specific effects

    Directory of Open Access Journals (Sweden)

    Jennifer eCulbertson

    2016-01-01

    Full Text Available The extent to which the linguistic system—its architecture, the representations it operates on, the constraints it is subject to—is specific to language has broad implications for cognitive science and its relation to evolutionary biology. Importantly, a given property of the linguistic system can be specific to the domain of language in several ways. For example, if the property evolved by natural selection under the pressure of the linguistic function it serves then the property is domain­-specific in the sense that its design is tailored for language. Equally though, if that property evolved to serve a different function or if that property is domain-general, it may nevertheless interact with the linguistic system in a way that is unique. This gives a second sense in which a property can be thought of as specific to language. An evolutionary approach to the language faculty might at first blush appear to favor domain­-specificity in the first sense, with individual properties of the language faculty being specifically linguistic adaptations. However, we argue that interactions between learning, culture and biological evolution mean any domain-specific adaptations that evolve will take the form of weak biases rather than hard constraints. Turning to the latter sense of domain-specificity, we highlight a very general bias, simplicity, which operates widely in cognition and yet interacts with linguistic representations in a domain-­specific way.

  12. Specific and non-specific upper extremity musculoskeletal disorder syndromes in automobile manufacturing workers

    Science.gov (United States)

    d'Errico, Angelo; Katz, Jeffrey N.; Gore, Rebecca; Punnett, Laura

    2009-01-01

    Objective A longitudinal cohort of automobile manufacturing workers (n = 1214) was examined for: 1) prevalence and persistence of specific upper extremity musculoskeletal disorders (UEMSDs) such as lateral epicondylitis and de Quervain's disease, and non-specific disorders (NSDs) defined in symptomatic individuals without any specific disorder, and 2) disorder prognoses based on symptom characteristics and other factors. Methods Eight specific disorders were identified through case definitions based on upper extremity physical examinations and symptom surveys administered on three occasions over six years. Results At baseline, 41% of the cohort reported upper extremity symptoms; 18% (n = 214) of these had NSDs. In each survey, tendon-related conditions accounted for over half of the specific morbidity. Twenty-five percent had UEMSDs in multiple anatomical sites, and most with hand/wrist disorders had two or more hand/wrist UEMSDs. Persistence for all specific disorders decreased with length of follow-up. Specific UEMSDs were characterized by greater pain severity and functional impairment, and more lost work days than NSDs. Conclusions Upper extremity symptoms and diagnoses vary over time. NSDs may be the early stages of conditions that will eventually become more specific. NSDs and overlapping specific UEMSDs should be taken into account in UEMSD classification. PMID:19016265

  13. Nanoparticles for Site Specific Genome Editing

    Science.gov (United States)

    McNeer, Nicole Ali

    Triplex-forming peptide nucleic acids (PNAs) can be used to coordinate the recombination of short 50-60 by "donor DNA" fragments into genomic DNA, resulting in site-specific correction of genetic mutations or the introduction of advantageous genetic modifications. Site-specific gene editing in hematopoietic stem and progenitor cells (HSPCs) could result in treatment or cure of inherited disorders of the blood such as beta-thalassemia. Gene editing in HSPCs and differentiated T cells could help combat HIV/AIDs by modifying receptors, such as CCR5, necessary for R5-tropic HIV entry. However, translation of genome modification technologies to clinical practice is limited by challenges in intracellular delivery, especially in difficult-to-transfect hematolymphoid cells. In vivo gene editing could also provide novel treatment for systemic monogenic disorders such as cystic fibrosis, an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane receptor. Here, we have engineered biodegradable nanoparticles to deliver oligonucleotides for site-specific genome editing of disease-relevant genes in human cells, with high efficiency, low toxicity, and editing of clinically relevant cell types. We designed nanoparticles to edit the human beta-globin and CCR5 genes in hematopoietic cells. We show that poly(lactic-co-glycolic acid) (PLGA) nanoparticles can delivery PNA and donor DNA for site-specific gene modification in human hematopoietic cells in vitro and in vivo in NOD-scid IL2rgammanull mice. Nanoparticles delivered by tail vein localized to hematopoietic compartments in the spleen and bone marrow of humanized mice, resulting in modification of the beta-globin and CCR5 genes. Modification frequencies ranged from 0.005 to 20% of cells depending on the organ and cell type, without detectable toxicity. This project developed highly versatile methods for delivery of therapeutics to hematolymphoid cells and hematopoietic stem cells, and will help to

  14. Risk management through dynamic technical specifications

    International Nuclear Information System (INIS)

    Klopp, George T.; Petersen, Thomas A.

    2004-01-01

    The wide deployment of plant specific probabilistic risk assessments for nuclear power plants has provided the means to effect a fresh risk management perspective and a fresh, risk based, regulatory outlook on nuclear power. There has been a great deal of conversation on risk based regulation within the U. S. nuclear power industry but, curiously, very little on effective risk management. This paper proposes a means to link the two subjects through the plant Technical Specifications. A revised concept for Technical Specifications is suggested which is based on deterministic analyses and probabilistic risk assessments for each plant. The revised Technical Specifications would consider, on a real-time basis, the exact state of the plant in terms of the status of key components and systems. It would depict current plant risk levels and compare those levels to the desired and limiting (alert/action) levels. It would advise the plant operator on the risk impact of proposed actions through a simple query system and illustrate the impact of such actions on plant status relative to designated risk values. The basis for the proposed approach lies in realistic deterministic plant analyses and probabilistic risk assessment (PRA) deployment tools being developed, in parallel, by a number of parties in the U.S. today. These PRAs are based primarily on the existing plant responses to Generic Letter 88-20, 'Individual Plant Examinations' (IPEs). Each of these tools allows the plant operator to input, on a real-time basis, the status of key equipment and systems. The tools then provide explicit illustrations of dependency effects; updated, 'real-time' risk status indications such as core damage frequency; and, in some cases, allow the operator to assess the risk impact of removing from service selected components for maintenance or testing. These systems generally operate on personal computers and provide nearly instantaneous responses to plant queries. Moving from these tools to

  15. Beta-endorphin radioimmunoassay: specificity studies

    Energy Technology Data Exchange (ETDEWEB)

    Colas-Linhart, N.; Perdrisot, R.; Petiet, A.; Bok, B.

    1986-01-01

    This note describes the technical details of a cerebrospinal fluid (CSF) B-Endorphin (B-End) radioimmunoassay (RIA). We used an antiserum raised in rabbits against human B-End which cross-reacs 100% with B-Lipotrophin (B-Lph). Thus, filtration chromatography is used to separate both peptides. The assay is sensitive (limit detection=14 pmoles/l), reproducible (the intra and inter assay coefficients of variation are 5 and 6% respectively). Specificity studies are performed to verify the cross-reactions with other opioid peptides and the non specific reactions with the biological fluid (CSF). In order to evaluate the effects of iodine-containing contrast media on the RIA, additional standard curves were analyzed in the presence of varying concentrations of two contrast materials.

  16. XRLSim model specifications and user interfaces

    Energy Technology Data Exchange (ETDEWEB)

    Young, K.D.; Breitfeller, E.; Woodruff, J.P.

    1989-12-01

    The two chapters in this manual document the engineering development leading to modification of XRLSim -- an Ada-based computer program developed to provide a realistic simulation of an x-ray laser weapon platform. Complete documentation of the FY88 effort to develop XRLSim was published in April 1989, as UCID-21736:XRLSIM Model Specifications and User Interfaces, by L. C. Ng, D. T. Gavel, R. M. Shectman. P. L. Sholl, and J. P. Woodruff. The FY89 effort has been primarily to enhance the x-ray laser weapon-platform model fidelity. Chapter 1 of this manual details enhancements made to XRLSim model specifications during FY89. Chapter 2 provides the user with changes in user interfaces brought about by these enhancements. This chapter is offered as a series of deletions, replacements, and insertions to the original document to enable XRLSim users to implement enhancements developed during FY89.

  17. Duration and specificity of olfactory nonassociative memory.

    Science.gov (United States)

    Freedman, Kaitlin G; Radhakrishna, Sreya; Escanilla, Olga; Linster, Christiane

    2013-05-01

    Olfactory habituation is a simple form of nonassociative memory in which responsiveness to stable but behaviorally nonsignificant stimuli is decreased. Olfactory habituation has recently become a paradigm widely used to probe the neural substrate underlying olfactory perception and memory. This simple behavioral paradigm has been used successfully used to probe many aspects of olfactory processing, and it has recently become clear that the neural processes underlying olfactory habituation can depend on the task parameters used. We here further investigate memory specificity and duration using 2 variations in task parameters: the number of habituation trials and the time delay between habituation and cross-habituation testing. We find that memory specificity increases with the number of habituation trials but decreases with time after the last habituation trial.

  18. Shape configuration and category-specificity

    DEFF Research Database (Denmark)

    Gerlach, Christian; Law, I; Paulson, Olaf B.

    2006-01-01

    a recent account of category-specificity and lends support to the notion that category-specific impairments can occur for both natural objects and artefacts following damage to pre-semantic stages in visual object recognition. The implications of the present findings are discussed in relation to theories......We examined the neural correlates of visual shape configuration, the binding of local shape characteristics into wholistic object descriptions, by comparing the regional cerebral blood flow associated with recognition of outline drawings and fragmented drawings. We found no areas that responded...... more to fragmented drawings than to outline drawings even though fragmentation had a clear impact on recognition performance. Instead, a region extending from the inferior occipital gyri to the middle parts of the fusiform gyri was activated during shape configuration of both outline drawings...

  19. Morphing patient-specific musculoskeletal models

    DEFF Research Database (Denmark)

    Rasmussen, John; Galibarov, Pavel E.; Al-Munajjed, Amir

    or surface scans. Furthermore, we assume that a set of corresponding anatomical landmarks can be identified in the medical imaging data and on the generic musculoskeletal model. A nonlinear transformation, i.e. a morphing, is created by means of radial basis functions that maps points set (i) to point set...... (ii). The morphing is subsequently used to transform parts of the generic musculoskeletal model to a patient-specific version, thus changing bone shapes, muscle insertion points, joint locations and other geometrical properties. Research questions include how to select point sets and whether...... other conditions may require CT or MRI data. The method and its theoretical assumptions, advantages and limitations are presented, and several examples will illustrate morphing to patient-specific models. [1] Carbes S; Tørholm S; Rasmussen, J. A Detailed Twenty-six Segments Kinematic Foot model...

  20. The Econometric Procedures of Specific Transaction Identification

    Directory of Open Access Journals (Sweden)

    Doszyń Mariusz

    2017-06-01

    Full Text Available The paper presents the econometric procedures of identifying specific transactions, in which atypical conditions or attributes may occur. These procedures are based on studentized and predictive residuals of the accordingly specified econometric models. The dependent variable is a unit transactional price, and explanatory variables are both the real properties’ attributes and accordingly defined artificial binary variables. The utility of the proposed method has been verified by means of a real market data base. The proposed procedures can be helpful during the property valuation process, making it possible to reject real properties that are specific (both from the point of view of the transaction conditions and the properties’ attributes and, consequently, to select an appropriate set of similar attributes that are essential for the valuation process.

  1. Photoreceptor cell fate specification in vertebrates

    Science.gov (United States)

    Brzezinski, Joseph A.; Reh, Thomas A.

    2015-01-01

    Photoreceptors – the light-sensitive cells in the vertebrate retina – have been extremely well-characterized with regards to their biochemistry, cell biology and physiology. They therefore provide an excellent model for exploring the factors and mechanisms that drive neural progenitors into a differentiated cell fate in the nervous system. As a result, great progress in understanding the transcriptional network that controls photoreceptor specification and differentiation has been made over the last 20 years. This progress has also enabled the production of photoreceptors from pluripotent stem cells, thereby aiding the development of regenerative medical approaches to eye disease. In this Review, we outline the signaling and transcription factors that drive vertebrate photoreceptor development and discuss how these function together in gene regulatory networks to control photoreceptor cell fate specification. PMID:26443631

  2. Specific xerostomia during Urbach-Wiethe disease.

    Science.gov (United States)

    Disdier, P; Harlé, J R; Andrac, L; Swiader, L; Weiller, P J

    1994-01-01

    We describe the case of a 59-year-old woman who had suffered from a typical Urbach-Wiethe disease since childhood and who complains of progressive mouth and ocular dryness since the age of 54 years. Xerostomia was severe with very poor salivation and was associated with a slight keratoconjunctivitis sicca. A specific lipoid proteinosis was evidenced in salivary glands (lower lip biopsy) with a PAS-positive hyalin-like deposit around vessels, capillaries and salivary gland canaliculi. An ultrastructural study showed the typical aspect of multilamination of the basal lamina of capillary vessels. Dysphonia and hoarseness are commonly found in Urbach-Wiethe disease, but, to our knowledge, a specific xerostomia has never been reported.

  3. Reversal of target-specific oral anticoagulants

    Science.gov (United States)

    Siegal, D.M.; Cuker, Adam

    2014-01-01

    Target-specific oral anticoagulants (TSOACs) provide safe and effective anticoagulation for the prevention and treatment of thrombosis in a variety of clinical settings by interfering with the activity of thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban, edoxaban, betrixaban). Although TSOACs have practical advantages over vitamin K antagonists (VKAs), there are currently no antidotes to reverse their anticoagulant effect. Herein we summarize the available evidence for TSOAC reversal using nonspecific and specific reversal agents. We discuss important limitations of existing evidence, which is derived from studies in human volunteers, animal models and in vitro experiments. Studies evaluating the safety and efficacy of reversal agents on clinical outcomes such as bleeding and mortality in patients with TSOAC-associated bleeding are needed. PMID:24880102

  4. Drug delivery by organ-specific immunoliposomes

    Energy Technology Data Exchange (ETDEWEB)

    Maruyama, Kazuo; Mori, Atsuhide; Hunag, Leaf (Tennessee Univ., Knoxville, TN (USA). Dept. of Biochemistry); Kennel, S.J. (Oak Ridge National Lab., TN (USA))

    1990-01-01

    Monoclonal antibodies highly specific to the mouse pulmonary endothelial cells were conjugated to liposomes. The resulting immunoliposomes showed high levels of lung accumulation when injected intravenously into mice. Optimal target binding and retention were achieved if the lipid composition included ganglioside GM{sub 1} to reduce the uptake of immunoliposomes by the reticuloendothelial system. Details of the construction and optimization of these organ-specific immunoliposomes are reviewed. The drug delivery potential of this novel liposome system was demonstrated in an experimental pulmonary metastasis model. Immunoliposomes containing a lipophilic prodrug of deoxyfluorouridine effectively prolonged the survival time of the tumor-bearing mice. This and other therapeutic applications of the immunoliposomes are discussed. 25 refs., 5 figs.

  5. Specification and thermodynamical properties of semigroup actions

    Science.gov (United States)

    Rodrigues, Fagner B.; Varandas, Paulo

    2016-05-01

    In the present paper, we study the thermodynamical properties of finitely generated continuous subgroup actions. We propose a notion of topological entropy and pressure functions that do not depend on the growth rate of the semigroup and introduce strong and orbital specification properties, under which the semigroup actions have positive topological entropy and all points are entropy points. Moreover, we study the convergence and Lipschitz regularity of the pressure function and obtain relations between topological entropy and exponential growth rate of periodic points in the context of semigroups of expanding maps, obtaining a partial extension of the results obtained by Ruelle for ℤd-actions [D. Ruelle, Trans. Am. Math. Soc., 187, 237-251 (1973)]. The specification properties for semigroup actions and the corresponding one for its generators and the action of push-forward maps are also discussed.

  6. A beta-endorphin radioimmunoassay: specificity studies

    International Nuclear Information System (INIS)

    Colas-Linhart, N.; Perdrisot, R.; Petiet, A.; Bok, B.

    1986-01-01

    This note describes the technical details of a cerebrospinal fluid (CSF) B-Endorphin (B-End) radioimmunoassay (RIA). We used an antiserum raised in rabbits against human B-End which cross-reacs 100% with B-Lipotrophin (B-Lph). Thus, filtration chromatography is used to separate both peptides. The assay is sensitive (limit detection=14 pmoles/l), reproducible (the intra and inter assay coefficients of variation are 5 and 6% respectively). Specificity studies are performed to verify the cross-reactions with other opioid peptides and the non specific reactions with the biological fluid (CSF). In order to evaluate the effects of iodine-containing contrast media on the RIA, additional standard curves were analyzed in the presence of varying concentrations of two contrast materials [fr

  7. Specificity of economic and social nature tourism

    Directory of Open Access Journals (Sweden)

    Chabanjuk Oleg Vasil'evich

    2015-11-01

    Full Text Available The article considers a number of factors specific to the tourism industry: a multiplier effect, a kind of method of generating working capital, specific "invisible exports", the factor most risky activities, the principle of direct and inverse transformation, and others. The data of experts of the World Tourism Organization (UNWTO on tourism as an indicator of welfare. It is emphasized along with the economic function of tourism on the social dimension of tourism in its mass phenomenon. The paper highlights the main problems and shortcomings of tourism as a complex socio-economic system; analysis of theoretical approaches to periodization of tourism that reflects the genesis of approaches regarding the nature of tourism; The factors of external and internal tourism development, made their ranking to measure the relationship between the measurement periods allocated for tourism development using the Spearman rank correlation coefficient.

  8. Specificity and robustness in transcription control networks.

    Science.gov (United States)

    Sengupta, Anirvan M; Djordjevic, Marko; Shraiman, Boris I

    2002-02-19

    Recognition by transcription factors of the regulatory DNA elements upstream of genes is the fundamental step in controlling gene expression. How does the necessity to provide stability with respect to mutation constrain the organization of transcription control networks? We examine the mutation load of a transcription factor interacting with a set of n regulatory response elements as a function of the factor/DNA binding specificity and conclude on theoretical grounds that the optimal specificity decreases with n. The predicted correlation between variability of binding sites (for a given transcription factor) and their number is supported by the genomic data for Escherichia coli. The analysis of E. coli genomic data was carried out using an algorithm suggested by the biophysical model of transcription factor/DNA binding. Complete results of the search for candidate transcription factor binding sites are available at http://www.physics.rockefeller.edu/~boris/public/search_ecoli.

  9. The specific targeting of immune regulation

    DEFF Research Database (Denmark)

    Andersen, Mads Hald

    2012-01-01

    -inflammatory signals, and IDO-based immunotherapy may consequently be synergistic with additional immunotherapy. In this regard, we have shown that the presence of IDO-specific T cells boosted immunity against CMV and tumor antigens by eliminating IDO(+) suppressive cells and changing the regulatory microenvironment......Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme that is implicated in suppressing T-cell immunity in many settings including cancer. In recent years, we have described spontaneous CD8(+) as well as CD4(+) T-cell reactivity against IDO in the tumor microenvironment of different...... cancer patients as well as in the peripheral blood of both cancer patients and to a lesser extent in healthy donors. We have demonstrated that IDO-reactive CD8(+) T cells were peptide-specific, cytotoxic effector cells, which are able to recognize and kill IDO-expressing cells including tumor cells...

  10. Site-specific weed control technologies

    DEFF Research Database (Denmark)

    Christensen, Svend; Søgaard, Henning Tangen; Kudsk, Per

    2009-01-01

    Site-specific weed control technologies are defined as machinery or equipment embedded with technologies that detect weeds growing in a crop and, taking into account predefined factors such as economics, takes action to maximise the chances of successfully controlling them. In the article, we...... describe the basic parts of site specific weed control technologies, comprising of weed sensing systems, weed management models and precision weed control implements. A review of state-of-the-art technologies shows that several weed sensing systems and precision implements have been developed over the last...... two decades, though barriers prevent their breakthrough. Most important among these is the lack of a truly robust weed recognition method, owing to mutual shading among plants and limitations in the capacity of highly accurate spraying and weeding apparatuses.   Another barrier is the lack...

  11. Fatigue behavior of ADI: Some specific features

    Energy Technology Data Exchange (ETDEWEB)

    Svejcar, J.; Vechet, S.; Pokluda, J. [Technical Univ. of Brno (Czech Republic). Faculty of Mechanical Engineering

    1997-12-31

    The paper summarizes the results of fatigue tests on austempered ductile iron. Attention is mainly focused on the effect of graphite on crack propagation and on some irregularities exhibited by ADI and other ductile irons, e.g., some specific features of fatigue fracture (especially the occurrence of fatigue striations on intergranular facets), decrease of fatigue limit with increasing UTS, and anomalous dependence of loading cycle amplitude on mean cycle stress.

  12. Specific heat of praseodymium and neodymium

    International Nuclear Information System (INIS)

    Narayana Murthy, J.V.S.S.; Ramji Rao, R.

    1983-01-01

    The elements of the dynamical matrix of an ideal deep lattice, with nearest neighbour central interactions, have been obtained in a homogeneously strained state. The dispersion relations along the [0001] direction, on this model, have been presented for Pr and Nd. The frequency distribution function g(ω) is obtained and the lattice specific heat is calculated for Pr and Nd and the temperature variation of the equivalent Debye temperature is presented. (author)

  13. Performance specifications for proton medical facility

    Energy Technology Data Exchange (ETDEWEB)

    Chu, W.T.; Staples, J.W.; Ludewigt, B.A.; Renner, T.R.; Singh, R.P.; Nyman, M.A.; Collier, J.M.; Daftari, I.K.; Petti, P.L.; Alonso, J.R. [Lawrence Berkeley Lab., CA (United States); Kubo, H.; Verhey, L.J. [University of California Davis Medical Center, Sacramento, CA (United States). Cancer Center]|[California Univ., San Francisco, CA (United States). School of Medicine; Castro, J.R. [Lawrence Berkeley Lab., CA (United States)]|[University of California Davis Medical Center, Sacramento, CA (United States). Cancer Center]|[California Univ., San Francisco, CA (United States). School of Medicine

    1993-03-01

    Performance specifications of technical components of a modern proton radiotherapy facility are presented. The technical items specified include: the accelerator; the beam transport system including rotating gantry; the treatment beamline systems including beam scattering, beam scanning, and dosimetric instrumentation; and an integrated treatment and accelerator control system. Also included are treatment ancillary facilities such as diagnostic tools, patient positioning and alignment devices, and treatment planning systems. The facility specified will accommodate beam scanning enabling the three-dimensional conformal therapy deliver .

  14. Extinction Generates Outcome-Specific Conditioned Inhibition.

    Science.gov (United States)

    Laurent, Vincent; Chieng, Billy; Balleine, Bernard W

    2016-12-05

    Extinction involves altering a previously established predictive relationship between a cue and its outcome by repeatedly presenting that cue alone. Although it is widely accepted that extinction generates some form of inhibitory learning [1-4], direct evidence for this claim has been lacking, and the nature of the associative changes induced by extinction have, therefore, remained a matter of debate [5-8]. In the current experiments, we used a novel behavioral approach that we recently developed and that provides a direct measure of conditioned inhibition [9] to compare the influence of extinguished and non-extinguished cues on choice between goal-directed actions. Using this approach, we provide direct evidence that extinction generates outcome-specific conditioned inhibition. Furthermore, we demonstrate that this inhibitory learning is controlled by the infralimbic cortex (IL); inactivation of the IL using M4 DREADDs abolished outcome-specific inhibition and rendered the cue excitatory. Importantly, we found that context modulated this inhibition. Outside its extinction context, the cue was excitatory and functioned as a specific predictor of its previously associated outcome, biasing choice toward actions earning the same outcome. In its extinction context, however, the cue acted as a specific inhibitor and biased choice toward actions earning different outcomes. Context modulation of these excitatory and inhibitory memories was mediated by the dorsal hippocampus (HPC), suggesting that the HPC and IL act in concert to control the influence of conditioned inhibitors on choice. These findings demonstrate for the first time that extinction turns a cue into a net inhibitor that can influence choice via counterfactual action-outcome associations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Domain Specific Languages for Interactive Web Services

    DEFF Research Database (Denmark)

    Brabrand, Claus

    This dissertation shows how domain specific languages may be applied to the domain of interactive Web services to obtain flexible, safe, and efficient solutions. We show how each of four key aspects of interactive Web services involving sessions, dynamic creation of HTML/XML documents, form field......, , that supports virtually all aspects of the development of interactive Web services and provides flexible, safe, and efficient solutions....

  16. Specific methods on in-pile gammametry

    International Nuclear Information System (INIS)

    Pointud, M.-L.; Michel, Francois.

    1979-01-01

    The gammametry technique in nuclear research reactors has evolved by the adequation of its means and the quality of its results since its beginnings in 1972. We do not propose here to make a detailed presentation, nor describe the kinds of well known results that can henceforth be attained with it in a conventional manner; our intention, on the other hand, is to describe a few specific methods developed for using it in the SILOE reactor of the CEN/G [fr

  17. Sedentary behavior and residual-specific mortality

    OpenAIRE

    Paul D. Loprinzi; Meghan K. Edwards; Eveleen Sng; Ovuokerie Addoh

    2016-01-01

    Background: The purpose of this study was to examine the association of accelerometer-assessed sedentary behavior and residual-specific mortality. Methods: Data from the 2003-2006 National Health and Nutrition Examination Survey (NHANES) were used (N = 5536), with follow-up through 2011. Sedentary behavior was objectively measured over 7 days via accelerometry. Results: When expressing sedentary behavior as a 60 min/day increase, the hazard ratio across the models ranged from 1.07-1.40 (P < 0...

  18. Cultural Specifics of Management in Multinational Companies

    OpenAIRE

    Křečková Kroupová, Zuzana

    2002-01-01

    Nowadays the world is becoming increasingly economically connected, and cultural diversity of employees is gaining importance as a crucial competitive advantage. Cross-cultural communication ability is becoming a key management skill in multinational firms and is equally important for other employees who are exposed to other cultures in the workplace. This work mainly focuses on cultural specifics of management in multinational firms. The goal of this thesis is to discover how different natio...

  19. Specificity in ROS Signaling and Transcript Signatures

    OpenAIRE

    Vaahtera, Lauri; Brosché, Mikael; Wrzaczek, Michael; Kangasjärvi, Jaakko

    2014-01-01

    Significance: Reactive oxygen species (ROS), important signaling molecules in plants, are involved in developmental control and stress adaptation. ROS production can trigger broad transcriptional changes; however, it is not clear how specificity in transcriptional regulation is achieved. Recent Advances: A large collection of public transcriptome data from the model plant Arabidopsis thaliana is available for analysis. These data can be used for the analysis of biological processes that are a...

  20. Characterization and carbohydrate specificity of pradimicin S

    OpenAIRE

    Shahzad-ul-Hussan, Syed; Ghirlando, Rodolfo; Dogo-Isonagie, Cajetan I.; Igarashi, Yasuhiro; Balzarini, Jan; Bewley, Carole A.

    2012-01-01

    The pradimicin family of antibiotics is attracting attention due to its anti-infective properties and as a model for understanding the requirements for carbohydrate recognition by small molecules. Members of the pradimicin family are unique among natural products in their ability to bind sugars in a Ca2+-dependent manner, but the oligomerization to insoluble aggregates that occurs upon Ca2+ binding has prevented detailed characterization of their carbohydrate specificity and biologically rele...

  1. [Constipation in the elderly, which specificities? ].

    Science.gov (United States)

    Jacques, M-C

    2014-11-05

    Although constipation is very common in the geriatric population of both sexes, its importance is often underestimated as older people complain less frequently of rare stools compared to younger adults. The diagnostic approach includes an assessment of risk factors and associated pathologies specific to old age. The initial treatment is conservative, behavioral and pharmacological, in the absence of signs of severity. In case of initial treatment failure, investigations or specialized treatment will depend on individual situations.

  2. HAL/S-FC compiler system specifications

    Science.gov (United States)

    1976-01-01

    This document specifies the informational interfaces within the HAL/S-FC compiler, and between the compiler and the external environment. This Compiler System Specification is for the HAL/S-FC compiler and its associated run time facilities which implement the full HAL/S language. The HAL/S-FC compiler is designed to operate stand-alone on any compatible IBM 360/370 computer and within the Software Development Laboratory (SDL) at NASA/JSC, Houston, Texas.

  3. Volatiles in Inter-Specific Bacterial Interactions.

    Science.gov (United States)

    Tyc, Olaf; Zweers, Hans; de Boer, Wietse; Garbeva, Paolina

    2015-01-01

    The importance of volatile organic compounds for functioning of microbes is receiving increased research attention. However, to date very little is known on how inter-specific bacterial interactions effect volatiles production as most studies have been focused on volatiles produced by monocultures of well-described bacterial genera. In this study we aimed to understand how inter-specific bacterial interactions affect the composition, production and activity of volatiles. Four phylogenetically different bacterial species namely: Chryseobacterium, Dyella, Janthinobacterium, and Tsukamurella were selected. Earlier results had shown that pairwise combinations of these bacteria induced antimicrobial activity in agar media whereas this was not the case for monocultures. In the current study, we examined if these observations were also reflected by the production of antimicrobial volatiles. Thus, the identity and antimicrobial activity of volatiles produced by the bacteria were determined in monoculture as well in pairwise combinations. Antimicrobial activity of the volatiles was assessed against fungal, oomycetal, and bacterial model organisms. Our results revealed that inter-specific bacterial interactions affected volatiles blend composition. Fungi and oomycetes showed high sensitivity to bacterial volatiles whereas the effect of volatiles on bacteria varied between no effects, growth inhibition to growth promotion depending on the volatile blend composition. In total 35 volatile compounds were detected most of which were sulfur-containing compounds. Two commonly produced sulfur-containing volatile compounds (dimethyl disulfide and dimethyl trisulfide) were tested for their effect on three target bacteria. Here, we display the importance of inter-specific interactions on bacterial volatiles production and their antimicrobial activities.

  4. Volatiles in inter-specific bacterial interactions

    Directory of Open Access Journals (Sweden)

    Olaf eTyc

    2015-12-01

    Full Text Available The importance of volatile organic compounds for functioning of microbes is receiving increased research attention. However, to date very little is known on how inter-specific bacterial interactions effect volatiles production as most studies have been focused on volatiles produced by monocultures of well described bacterial genera. In this study we aimed to understand how inter-specific bacterial interactions affect the composition, production and activity of volatiles. Four phylogenetically different bacterial species namely: Chryseobacterium, Dyella, Janthinobacterium and Tsukamurella were selected. Earlier results had shown that pairwise combinations of these bacteria induced antimicrobial activity in agar media whereas this was not the case for monocultures. In the current study, we examined if these observations were also reflected by the production of antimicrobial volatiles. Thus, the identity and antimicrobial activity of volatiles produced by the bacteria were determined in monoculture as well in pairwise combinations. Antimicrobial activity of the volatiles was assessed against fungal, oomycetal and bacterial model organisms. Our results revealed that inter-specific bacterial interactions affected volatiles blend composition. Fungi and oomycetes showed high sensitivity to bacterial volatiles whereas the effect of volatiles on bacteria varied between no effects, growth inhibition to growth promotion depending on the volatile blend composition. In total 35 volatile compounds were detected most of which were sulfur-containing compounds. Two commonly produced sulfur-containing volatile compounds (dimethyl disulfide and dimethyl trisulfide were tested for their effect on three target bacteria. Here we display the importance of inter-specific interactions on bacterial volatiles production and their antimicrobial activities.

  5. Salt Bridges: Geometrically Specific, Designable Interactions

    OpenAIRE

    Donald, Jason E.; Kulp, Daniel W.; DeGrado, William F.

    2011-01-01

    Salt bridges occur frequently in proteins, providing conformational specificity and contributing to molecular recognition and catalysis. We present a comprehensive analysis of these interactions in protein structures by surveying a large database of protein structures. Salt bridges between Asp or Glu and His, Arg, or Lys display extremely well-defined geometric preferences. Several previously observed preferences are confirmed and others that were previously unrecognized are discovered. Salt ...

  6. Group specific component in serum and otosclerosis

    DEFF Research Database (Denmark)

    Kjeldsen, A D; Vase, P; Thymann, M

    1994-01-01

    An earlier Swedish study suggested a positive association between otosclerosis and the group-specific component GC*1F marker. We investigated the distribution of GC subtypes in 101 Danish patients with otosclerosis who all had surgery performed in the county of Funen. Compared to 1674 Danish...... controls we found no evidence of any association between markers from the GC serum protein system and otosclerosis....

  7. A Requirement Specification Language for AADL

    Science.gov (United States)

    2016-06-01

    Group. OMG Systems Modeling Language . OMG. 2015. http://www.omgsysml.org [OSATE 2016] Open Source AADL Tool Environment (OSATE), Version 2. Computer ...A Requirement Specification Language for AADL Peter H. Feiler Julien Delange Lutz Wrage June 2016 TECHNICAL REPORT CMU/SEI-2016-TR-008...reproduced in its entirety, without modification, and freely distrib- uted in written or electronic form without requesting formal permission. Permission

  8. Behavioural effects of caffeine: the specificity hypothesis

    OpenAIRE

    Snowden, Wendy

    2012-01-01

    This thesis argues that caffeine use offered a survival advantage to our ancestors and that moderate use continues to offer modern humans benefits. Caffeine ingestion, through the blocking of adenosine receptors, elicits broad elements of the mammalian threat response, specifically from the ‘flight or fight’ and ‘tend and befriend’ repertoires of behaviour: in effect, caffeine hijacks elements of the stress response. If the effects of caffeine had been discovered recently, rather than being a...

  9. Element specific X-ray fluorescene microtomography

    OpenAIRE

    Günzler, Til Florian

    2003-01-01

    X-ray fluorescence is widely known as an element-specific scanning analytic tool. It is used in many fields of science and technology and has given major new insights into different problems. The relatively large penetration depth of x rays into matter makes them ideally suited for tomography. The combination of x-ray fluorescence analysis and scanning microtomography, hereafter called x-ray fluorescence microtomography, has been further developed and improved in this work. Employing the newl...

  10. Specifications development for "Karbatril" codenamed tablets

    Directory of Open Access Journals (Sweden)

    L. I. Kucherenko

    2017-08-01

    Full Text Available Introduction. According to current legislation of Ukraine the specifications of tablets include the following indicators: description, identification, average weight, disintegration and assay. The aim of the study. The development of specifications and project of quality control methods for "Karbatril" codenamed tablets. Materials and methods. During the study we analyzed 6 series of tablets "Karbatril." For the description, identification, determination of the average mass, disintegration, active ingredients quantify of "Karbatril" codenamed tablets we used appropriate methods and instruments. Results and discussion. Tablets "Karbatril" were analyzed for the following parameters: - Overview - Tablets white or nearly white; - Average weight - during the study the average weight of 6 series of obtained tablets ranged from 339,0 mg to 369,9 mg according to SPU from 337,0 mg to 373,0 mg; - Disintegration – according to SPU the disintegration for tablet without shell shall not exceed 15 min. Analyzed tablets disintegrated in the period from 5 to 10 minutes; - Identification and quantification of the active ingredients of tablets were conducted using modified HPLC methods. During the identification obtained chromatograms show compliance with SPU. In quantitative determination of the active ingredients content in "Karbatril" codenamed tablets we found carbamazepine from 148.18 mg to 150.19 mg, thiotriazoline - from 98.93 mg to 99.71 mg. This data is consistent to SPU which regulates content of carbamazepine - 150 mg ± 7,5%, thiotriazoline - 100 mg ± 10%. Conclusions. This study has developed specification for "Karbatril" codenamed tablets and also methods of HPLC qualitative and quantitative determination of active ingredients. In the specification the following parameters are included: description, identification, average weight, disintegration and assay. The study drafted quality control methods which are planned to be later offered to the

  11. Learning LM Specificity for Ganglion Cells

    Science.gov (United States)

    Ahumada, Albert J.

    2015-01-01

    Unsupervised learning models have been proposed based on experience (Ahumada and Mulligan, 1990;Wachtler, Doi, Lee and Sejnowski, 2007) that allow the cortex to develop units with LM specific color opponent receptive fields like the blob cells reported by Hubel and Wiesel on the basis of visual experience. These models used ganglion cells with LM indiscriminate wiring as inputs to the learning mechanism, which was presumed to occur at the cortical level.

  12. Salt bridges: geometrically specific, designable interactions.

    Science.gov (United States)

    Donald, Jason E; Kulp, Daniel W; DeGrado, William F

    2011-03-01

    Salt bridges occur frequently in proteins, providing conformational specificity and contributing to molecular recognition and catalysis. We present a comprehensive analysis of these interactions in protein structures by surveying a large database of protein structures. Salt bridges between Asp or Glu and His, Arg, or Lys display extremely well-defined geometric preferences. Several previously observed preferences are confirmed, and others that were previously unrecognized are discovered. Salt bridges are explored for their preferences for different separations in sequence and in space, geometric preferences within proteins and at protein-protein interfaces, co-operativity in networked salt bridges, inclusion within metal-binding sites, preference for acidic electrons, apparent conformational side chain entropy reduction on formation, and degree of burial. Salt bridges occur far more frequently between residues at close than distant sequence separations, but, at close distances, there remain strong preferences for salt bridges at specific separations. Specific types of complex salt bridges, involving three or more members, are also discovered. As we observe a strong relationship between the propensity to form a salt bridge and the placement of salt-bridging residues in protein sequences, we discuss the role that salt bridges might play in kinetically influencing protein folding and thermodynamically stabilizing the native conformation. We also develop a quantitative method to select appropriate crystal structure resolution and B-factor cutoffs. Detailed knowledge of these geometric and sequence dependences should aid de novo design and prediction algorithms. Copyright © 2010 Wiley-Liss, Inc.

  13. Reflections about therapeutic internments and his specificity

    Directory of Open Access Journals (Sweden)

    Ángel Estalayo Hernández

    2014-10-01

    Full Text Available There are cases treated in detention centers that present some specificities with respect to other affordable educational strategies from social component. This we refer to the need to address situations in which the same symptom of transgression resulting in an offense that carries a legal measure has other bases that generate and / or maintain, or etiology marking its expression and so much attention. The approach to interventions with children and young people is a seriously disruptive content submitted to numerous debates, discussions and disagreements. In this regard, therapeutic placements would be for those cases in which the intervention on symptom requires a specific and specialized perspective. Beyond clinical approaches, therapeutic placements should from the intervention on self-regulation problems (emotional, behavioral, and cognitive and behavioral expression and as a key defining element. To this we add that we have observed in our practice in recent years an increase in problems related to the field of mental health and / or drug and alcohol consumption on children and young people entering the judicial context. This requires expertise and implement a therapeutic approach in centers for juvenile justice. It is particularly important in these cases performed from the beginning of internment clinical and social diagnostics to guide and design the specific educational and therapeutic intervention required for each particular case, in the interest of optimizing the operation and achieve higher levels of efficiency

  14. Site-Specific PEGylation of Therapeutic Proteins

    Directory of Open Access Journals (Sweden)

    Jonathan K. Dozier

    2015-10-01

    Full Text Available The use of proteins as therapeutics has a long history and is becoming ever more common in modern medicine. While the number of protein-based drugs is growing every year, significant problems still remain with their use. Among these problems are rapid degradation and excretion from patients, thus requiring frequent dosing, which in turn increases the chances for an immunological response as well as increasing the cost of therapy. One of the main strategies to alleviate these problems is to link a polyethylene glycol (PEG group to the protein of interest. This process, called PEGylation, has grown dramatically in recent years resulting in several approved drugs. Installing a single PEG chain at a defined site in a protein is challenging. Recently, there is has been considerable research into various methods for the site-specific PEGylation of proteins. This review seeks to summarize that work and provide background and context for how site-specific PEGylation is performed. After introducing the topic of site-specific PEGylation, recent developments using chemical methods are described. That is followed by a more extensive discussion of bioorthogonal reactions and enzymatic labeling.

  15. One step processing for future diesel specifications

    International Nuclear Information System (INIS)

    Brierley, G.R.

    1997-01-01

    The trend in diesel fuel specifications is to limit the sulfur level to less than 0.05 wt- per cent. Many regions have also specified that diesel fuels must have lower aromatic levels, higher cetane numbers, and lower distillation end points. These changes will require significant refinery investment to meet the new diesel fuel specifications. The changes may also significantly affect the value of synthetic crude stocks. UOP has developed a new hydroprocessing catalyst which makes it possible to meet the new diesel specifications in one single processing step and at minimal cost. The catalyst saturates aromatics while opening ring structures at the same time. By selectively cracking heavy components into the diesel range with minimal cracking to gas or naphtha, heavier feedstocks can be upgraded to diesel, and refinery diesel yield can be augmented. Synthetic crude distillate is often high in aromatics and low in cetane number. This new UOP hydroprocessing system will allow synthetic crude producers and refiners to produce diesel fuels with higher cetane numbers, high-quality distillate blendstocks and distillate fuels. 26 figs

  16. New visions in specific immunotherapy in children

    DEFF Research Database (Denmark)

    Halken, Susanne; Lau, Susanne; Valovirta, Erkka

    2008-01-01

    Specific immunotherapy is indicated for confirmed immunoglobulin E-mediated airway diseases using standardized allergen products with documented clinical efficacy and safety. For decades the subcutaneous route of administration (SCIT) has been the gold standard. Recently, the sublingual immunothe......Specific immunotherapy is indicated for confirmed immunoglobulin E-mediated airway diseases using standardized allergen products with documented clinical efficacy and safety. For decades the subcutaneous route of administration (SCIT) has been the gold standard. Recently, the sublingual...... immunotherapy (SLIT) has also been investigated in children. SCIT, especially with grass and birch pollens but also house dust mites, is an effective treatment in children with allergic rhinitis and asthma when a significant part of their symptoms are caused by these allergens. A long-term effect up to 12 yr...... both with SCIT and SLIT. This review was initiated by iPAC (international Pediatric Allergy and Asthma Consortium) and aims to review current knowledge related to specific immunotherapy in childhood, and to identify needs for future research in this field....

  17. Trait-specific dependence in romantic relationships.

    Science.gov (United States)

    Ellis, Bruce J; Simpson, Jeffry A; Campbell, Lorne

    2002-10-01

    Informed by three theoretical frameworks--trait psychology, evolutionary psychology, and interdependence theory--we report four investigations designed to develop and test the reliability and validity of a new construct and accompanying multiscale inventory, the Trait-Specific Dependence Inventory (TSDI). The TSDI assesses comparisons between present and alternative romantic partners on major dimensions of mate value. In Study 1, principal components analyses revealed that the provisional pool of theory-generated TSDI items were represented by six factors: Agreeable/Committed, Resource Accruing Potential, Physical Prowess, Emotional Stability, Surgency, and Physical Attractiveness. In Study 2, confirmatory factor analysis replicated these results on a different sample and tested how well different structural models fit the data. Study 3 provided evidence for the convergent and discriminant validity of the six TSDI scales by correlating each one with a matched personality trait scale that did not explicitly incorporate comparisons between partners. Study 4 provided further validation evidence, revealing that the six TSDI scales successfully predicted three relationship outcome measures--love, time investment, and anger/upset--above and beyond matched sets of traditional personality trait measures. These results suggest that the TSDI is a reliable, valid, and unique construct that represents a new trait-specific method of assessing dependence in romantic relationships. The construct of trait-specific dependence is introduced and linked with other theories of mate value.

  18. Species-specific beaked whale echolocation signals.

    Science.gov (United States)

    Baumann-Pickering, Simone; McDonald, Mark A; Simonis, Anne E; Solsona Berga, Alba; Merkens, Karlina P B; Oleson, Erin M; Roch, Marie A; Wiggins, Sean M; Rankin, Shannon; Yack, Tina M; Hildebrand, John A

    2013-09-01

    Beaked whale echolocation signals are mostly frequency-modulated (FM) upsweep pulses and appear to be species specific. Evolutionary processes of niche separation may have driven differentiation of beaked whale signals used for spatial orientation and foraging. FM pulses of eight species of beaked whales were identified, as well as five distinct pulse types of unknown species, but presumed to be from beaked whales. Current evidence suggests these five distinct but unidentified FM pulse types are also species-specific and are each produced by a separate species. There may be a relationship between adult body length and center frequency with smaller whales producing higher frequency signals. This could be due to anatomical and physiological restraints or it could be an evolutionary adaption for detection of smaller prey for smaller whales with higher resolution using higher frequencies. The disadvantage of higher frequencies is a shorter detection range. Whales echolocating with the highest frequencies, or broadband, likely lower source level signals also use a higher repetition rate, which might compensate for the shorter detection range. Habitat modeling with acoustic detections should give further insights into how niches and prey may have shaped species-specific FM pulse types.

  19. Recent advances in dermatomyositis-specific autoantibodies.

    Science.gov (United States)

    Fujimoto, Manabu; Watanabe, Rei; Ishitsuka, Yosuke; Okiyama, Naoko

    2016-11-01

    In dermatomyositis, disease-specific autoantibodies now cover more than 70% of patients. These autoantibodies closely correlate with distinct clinical manifestations. In the past few years, extensive evidence has been accumulated on clinical significance of dermatomyositis-specific autoantibodies including autoantibodies against melanoma differentiation antigen 5 (MDA5), transcriptional intermediary factor 1 (TIF1), nuclear matrix protein 2 (NXP2), and small ubiquitin-like modifier activating enzyme (SAE). Anti-MDA5 antibodies are found with high specificity in clinically amyopathic dermatomyositis presenting rapidly progressive interstitial lung disease (ILD) especially in Asian population. Similar tendency has been reported in the US/Europe, although the frequency of positivity and the type of ILD may differ. Anti-TIF1 antibodies are present in juvenile and adult dermatomyositis patients with close correlation with malignancy in adult population. Anti-NXP2 antibodies share similar phenotype with anti-TIF1 antibodies, except that anti-NXP2 antibodies are associated with calcinosis and severe muscle disease. Although numbers are still small, patients with anti-SAE antibodies tend to present skin disease first and then progress to muscle weakness with systematic symptoms including dysphagia. Moreover, distinct cutaneous manifestations and muscle histopathology findings for each autoantibody have been reported. 'Autoantibody-based classification' of dermatomyositis subsets is now a useful strategy for comprehending the heterogeneous spectrum of dermatomyositis.

  20. Specificity of dyspraxia in children with autism.

    Science.gov (United States)

    MacNeil, Lindsey K; Mostofsky, Stewart H

    2012-03-01

    To explore the specificity of impaired praxis and postural knowledge to autism by examining three samples of children, including those with autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and typically developing (TD) children. Twenty-four children with ASD, 24 children with ADHD, and 24 TD children, ages 8-13, completed measures assessing basic motor control (the Physical and Neurological Exam for Subtle Signs; PANESS), praxis (performance of skilled gestures to command, with imitation, and tool use) and the ability to recognize correct hand postures necessary to perform skilled gestures (the Postural Knowledge Test; PKT). Children with ASD performed significantly worse than TD children on all three assessments. In contrast, children with ADHD performed significantly worse than TD controls on PANESS but not on the praxis examination or PKT. Furthermore, children with ASD performed significantly worse than children with ADHD on both the praxis examination and PKT, but not on the PANESS. Whereas both children with ADHD and children with ASD show impairments in basic motor control, impairments in performance and recognition of skilled motor gestures, consistent with dyspraxia, appear to be specific to autism. The findings suggest that impaired formation of perceptual-motor action models necessary to development of skilled gestures and other goal directed behavior is specific to autism; whereas, impaired basic motor control may be a more generalized finding.