Generation of anti-idiotype scFv for pharmacokinetic measurement in lymphoma patients treated with chimera anti-CD22 antibody SM03.

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Qi Zhao

Full Text Available Pre-clinical and clinical studies of therapeutic antibodies require highly specific reagents to examine their immune responses, bio-distributions, immunogenicity, and pharmacodynamics in patients. Selective antigen-mimicking anti-idiotype antibody facilitates the assessment of therapeutic antibody in the detection, quantitation and characterization of antibody immune responses. Using mouse specific degenerate primer pairs and splenocytic RNA, we generated an idiotype antibody-immunized phage-displayed scFv library in which an anti-idiotype antibody against the therapeutic chimera anti-CD22 antibody SM03 was isolated. The anti-idiotype scFv recognized the idiotype of anti-CD22 antibody and inhibited binding of SM03 to CD22 on Raji cell surface. The anti-idiotype scFv was subsequently classified as Ab2γ type. Moreover, our results also demonstrated firstly that the anti-idiotype scFv could be used for pharmacokinetic measurement of circulating residual antibody in lymphoma patients treated with chimera anti-CD22 monoclonal antibody SM03. Of important, the present approach could be easily adopted to generate anti-idiotype antibodies for therapeutic antibodies targeting membrane proteins, saving the cost and time for producing a soluble antigen.

PET imaging of 64Cu-DOTA-scFv-anti-PSMA lipid nanoparticles (LNPs): Enhanced tumor targeting over anti-PSMA scFv or untargeted LNPs

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Wong, Patty; Li, Lin; Chea, Junie; Delgado, Melissa K.; Crow, Desiree; Poku, Erasmus; Szpikowska, Barbara; Bowles, Nicole; Channappa, Divya; Colcher, David; Wong, Jeffrey Y.C.; Shively, John E.; Yazaki, Paul J.

2017-01-01

Introduction: Single chain (scFv) antibodies are ideal targeting ligands due to their modular structure, high antigen specificity and affinity. These monovalent ligands display rapid tumor targeting but have limitations due to their fast urinary clearance. Methods: An anti-prostate membrane antigen (PSMA) scFv with a site-specific cysteine was expressed and evaluated in a prostate cancer xenograft model by Cu-64 PET imaging. To enhance tumor accumulation, the scFv-cys was conjugated to the co-polymer DSPE-PEG-maleimide that spontaneously assembled into a homogeneous multivalent lipid nanoparticle (LNP). Results: The targeted LNP exhibited a 2-fold increase in tumor uptake compared to the scFv alone using two different thiol ester chemistries. The anti-PSMA scFv-LNP exhibited a 1.6 fold increase in tumor targeting over the untargeted LNP. Conclusions: The targeted anti-PSMA scFv-LNP showed enhanced tumor accumulation over the scFv alone or the untargeted DOTA-micelle providing evidence for the development of this system for drug delivery. Advances in knowledge and implications for patient care: Anti-tumor scFv antibody fragments have not achieved their therapeutic potential due to their fast blood clearance. Conjugation to an LNP enables multivalency to the tumor antigen as well as increased molecular size for chemotherapy drug delivery.

PET Imaging of 64Cu-DOTA-scFv-Anti-PSMA Lipid Nanoparticles (LNPs): Enhanced Tumor Targeting over Anti-PSMA scFv or Untargeted LNPs

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Wong, Patty; Li, Lin; Chea, Junie; Delgado, Melissa K.; Crow, Desiree; Poku, Erasmus; Szpikowska, Barbara; Bowles, Nicole; Channappa, Divya; Colcher, David; Wong, Jeffrey Y.C.; Shively, John E.; Yazaki, Paul J.

2017-01-01

Introduction Single chain (scFv) antibodies are ideal targeting ligands due to their modular structure, high antigen specificity and affinity. These monovalent ligands display rapid tumor targeting but have limitations due to their fast urinary clearance. Methods An anti-prostate membrane antigen (PSMA) scFv with a site-specific cysteine was expressed and evaluated in a prostate cancer xenograft model by Cu-64 PET imaging. To enhance tumor accumulation, the scFv-cys was conjugated to the co-polymer DSPE-PEG-maleimide that spontaneously assembled into a homogeneous multivalent lipid nanoparticle (LNP). Results The targeted LNP exhibited a 2-fold increase in tumor uptake compared to the scFv alone using two different thiol ester chemistries. The anti-PSMA scFv-LNP exhibited a 1.6 fold increase in tumor targeting over the untargeted LNP. Conclusions The targeted anti-PSMA scFv-LNP showed enhanced tumor accumulation over the scFv alone or the untargeted DOTA-micelle providing evidence for the development of this system for drug delivery. Advances in Knowledge and implications for patient care Anti-tumor scFv antibody fragments have not achieved their therapeutic potential due to their fast blood clearance. Conjugation to a LNP enables multivalency to the tumor antigen as well as increased molecular size for chemotherapy drug delivery. PMID:28126683

Affinity Purification of Tumor Necrosis Factor-α Expressed in Raji Cells by Produced scFv Antibody Coupled CNBr-Activated Sepharose

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Abdolalizadeh, Jalal; Majidi Zolbanin, Jafar; Nouri, Mohammad; Baradaran, Behzad; Movassaghpour, AliAkbar; Farajnia, Safar; Omidi, Yadollah

2013-01-01

Purpose: Recombinant tumor necrosis factor-alpha (TNF-α) has been utilized as an antineoplastic agent for the treatment of patients with melanoma and sarcoma. It targets tumor cell antigens by impressing tumor-associated vessels. Protein purification with affinity chromatography has been widely used in the downstream processing of pharmaceutical-grade proteins. Methods:In this study, we examined the potential of our produced anti-TNF-α scFv fragments for purification of TNF-α produced by Raji cells. The Raji cells were induced by lipopolysaccharides (LPS) to express TNF-α. Western blotting and Fluorescence-activated cell sorting (FACS) flow cytometry analyses were used to evaluate the TNF-α expression. The anti-TNF-α scFv selected from antibody phage display library was coupled to CNBr-activated sepharose 4B beads used for affinity purification of expressed TNF-α and the purity of the protein was assessed by SDS-PAGE. Results: Western blot and FACS flow cytometry analyses showed the successful expression of TNF-α with Raji cells. SDS-PAGE analysis showed the performance of scFv for purification of TNF-α protein with purity over 95%. Conclusion: These findings confirm not only the potential of the produced scFv antibody fragments but also this highly pure recombinant TNF-α protein can be applied for various in vitro and in vivo applications. PMID:24312807

Generation of human scFv antibody libraries: PCR amplification and assembly of light- and heavy-chain coding sequences.

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Andris-Widhopf, Jennifer; Steinberger, Peter; Fuller, Roberta; Rader, Christoph; Barbas, Carlos F

2011-09-01

The development of therapeutic antibodies for use in the treatment of human diseases has long been a goal for many researchers in the antibody field. One way to obtain these antibodies is through phage-display libraries constructed from human lymphocytes. This protocol describes the construction of human scFv (single chain antibody fragment) libraries using a short linker (GGSSRSS) or a long linker (GGSSRSSSSGGGGSGGGG). In this method, the individual rearranged heavy- and light-chain variable regions are amplified separately and are linked through a series of overlap polymerase chain reaction (PCR) steps to give the final scFv products that are used for cloning.

A cancer specific cell-penetrating peptide, BR2, for the efficient delivery of an scFv into cancer cells.

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Ki Jung Lim

Full Text Available Cell-penetrating peptides (CPPs have proven very effective as intracellular delivery vehicles for various therapeutics. However, there are some concerns about non-specific penetration and cytotoxicity of CPPs for effective cancer treatments. Herein, based on the cell-penetrating motif of an anticancer peptide, buforin IIb, we designed several CPP derivatives with cancer cell specificity. Among the derivatives, a 17-amino acid peptide (BR2 was found to have cancer-specificity without toxicity to normal cells. After specifically targeting cancer cells through interaction with gangliosides, BR2 entered cells via lipid-mediated macropinocytosis. Moreover, BR2 showed higher membrane translocation efficiency than the well-known CPP Tat (49-57. The capability of BR2 as a cancer-specific drug carrier was demonstrated by fusion of BR2 to a single-chain variable fragment (scFv directed toward a mutated K-ras (G12V. BR2-fused scFv induced a higher degree of apoptosis than Tat-fused scFv in K-ras mutated HCT116 cells. These results suggest that the novel cell-penetrating peptide BR2 has great potential as a useful drug delivery carrier with cancer cell specificity.

A cancer specific cell-penetrating peptide, BR2, for the efficient delivery of an scFv into cancer cells.

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Lim, Ki Jung; Sung, Bong Hyun; Shin, Ju Ri; Lee, Young Woong; Kim, Da Jung; Yang, Kyung Seok; Kim, Sun Chang

2013-01-01

Cell-penetrating peptides (CPPs) have proven very effective as intracellular delivery vehicles for various therapeutics. However, there are some concerns about non-specific penetration and cytotoxicity of CPPs for effective cancer treatments. Herein, based on the cell-penetrating motif of an anticancer peptide, buforin IIb, we designed several CPP derivatives with cancer cell specificity. Among the derivatives, a 17-amino acid peptide (BR2) was found to have cancer-specificity without toxicity to normal cells. After specifically targeting cancer cells through interaction with gangliosides, BR2 entered cells via lipid-mediated macropinocytosis. Moreover, BR2 showed higher membrane translocation efficiency than the well-known CPP Tat (49-57). The capability of BR2 as a cancer-specific drug carrier was demonstrated by fusion of BR2 to a single-chain variable fragment (scFv) directed toward a mutated K-ras (G12V). BR2-fused scFv induced a higher degree of apoptosis than Tat-fused scFv in K-ras mutated HCT116 cells. These results suggest that the novel cell-penetrating peptide BR2 has great potential as a useful drug delivery carrier with cancer cell specificity.

Isolation of scFv antibody fragments against HER2 and CEA tumor antigens from combinatorial antibody libraries derived from cancer patients.

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Ayat, Hoda; Burrone, Oscar R; Sadghizadeh, Majid; Jahanzad, Eissa; Rastgou, Nasrin; Moghadasi, Sarrira; Arbabi, Mehdi

2013-11-01

Tumor cells expressing HER-2/neu and CEA antigens are potentially ideal targets for antibody-targeted therapy. In this study, two large human combinatorial libraries have been generated from the lymph nodes of breast cancer patients that express HER2 and CEA antigens in their tumors. These 'immune' libraries have been constructed in two different formats of scFv, differing in the length of the peptide linker connecting the two variable VH and VL domains. Libraries derived from these patients may contain a larger pool of anti-tumor antigen antibodies and are useful repertoire for isolating scFvs against any tumor markers. The results of this study showed that we were successful in obtaining human scFvs against HER-2/neu and CEA. For HER-2, cell-panning strategy was performed and resulted in two scFv binders that detected the complete HER-2 receptor on the cell membrane and internalized to the cells. Also, preliminary ELISA data showed that several anti-CEA scFv binders were isolated by panning. Copyright © 2013 The International Alliance for Biological Standardization. All rights reserved.

IG and TR single chain fragment variable (scFv) sequence analysis: a new advanced functionality of IMGT/V-QUEST and IMGT/HighV-QUEST.

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Giudicelli, Véronique; Duroux, Patrice; Kossida, Sofia; Lefranc, Marie-Paule

2017-06-26

IMGT®, the international ImMunoGeneTics information system® ( http://www.imgt.org ), was created in 1989 in Montpellier, France (CNRS and Montpellier University) to manage the huge and complex diversity of the antigen receptors, and is at the origin of immunoinformatics, a science at the interface between immunogenetics and bioinformatics. Immunoglobulins (IG) or antibodies and T cell receptors (TR) are managed and described in the IMGT® databases and tools at the level of receptor, chain and domain. The analysis of the IG and TR variable (V) domain rearranged nucleotide sequences is performed by IMGT/V-QUEST (online since 1997, 50 sequences per batch) and, for next generation sequencing (NGS), by IMGT/HighV-QUEST, the high throughput version of IMGT/V-QUEST (portal begun in 2010, 500,000 sequences per batch). In vitro combinatorial libraries of engineered antibody single chain Fragment variable (scFv) which mimic the in vivo natural diversity of the immune adaptive responses are extensively screened for the discovery of novel antigen binding specificities. However the analysis of NGS full length scFv (~850 bp) represents a challenge as they contain two V domains connected by a linker and there is no tool for the analysis of two V domains in a single chain. The functionality "Analyis of single chain Fragment variable (scFv)" has been implemented in IMGT/V-QUEST and, for NGS, in IMGT/HighV-QUEST for the analysis of the two V domains of IG and TR scFv. It proceeds in five steps: search for a first closest V-REGION, full characterization of the first V-(D)-J-REGION, then search for a second V-REGION and full characterization of the second V-(D)-J-REGION, and finally linker delimitation. For each sequence or NGS read, positions of the 5'V-DOMAIN, linker and 3'V-DOMAIN in the scFv are provided in the 'V-orientated' sense. Each V-DOMAIN is fully characterized (gene identification, sequence description, junction analysis, characterization of mutations and amino

Stability engineering of anti-EGFR scFv antibodies by rational design of a lambda-to-kappa swap of the VL framework using a structure-guided approach.

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Lehmann, Andreas; Wixted, Josephine H F; Shapovalov, Maxim V; Roder, Heinrich; Dunbrack, Roland L; Robinson, Matthew K

2015-01-01

Phage-display technology facilitates rapid selection of antigen-specific single-chain variable fragment (scFv) antibodies from large recombinant libraries. ScFv antibodies, composed of a VH and VL domain, are readily engineered into multimeric formats for the development of diagnostics and targeted therapies. However, the recombinant nature of the selection strategy can result in VH and VL domains with sub-optimal biophysical properties, such as reduced thermodynamic stability and enhanced aggregation propensity, which lead to poor production and limited application. We found that the C10 anti-epidermal growth factor receptor (EGFR) scFv, and its affinity mutant, P2224, exhibit weak production from E. coli. Interestingly, these scFv contain a fusion of lambda3 and lambda1 V-region (LV3 and LV1) genes, most likely the result of a PCR aberration during library construction. To enhance the biophysical properties of these scFvs, we utilized a structure-based approach to replace and redesign the pre-existing framework of the VL domain to one that best pairs with the existing VH. We describe a method to exchange lambda sequences with a more stable kappa3 framework (KV3) within the VL domain that incorporates the original lambda DE-loop. The resulting scFvs, C10KV3_LV1DE and P2224KV3_LV1DE, are more thermodynamically stable and easier to produce from bacterial culture. Additionally, C10KV3_LV1DE and P2224KV3_LV1DE retain binding affinity to EGFR, suggesting that such a dramatic framework swap does not significantly affect scFv binding. We provide here a novel strategy for redesigning the light chain of problematic scFvs to enhance their stability and therapeutic applicability.

Affinity Purification of Tumor Necrosis Factor-α Expressed in Raji Cells by Produced scFv Antibody Coupled CNBr-Activated Sepharose

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Safar Farajnia

2013-02-01

Full Text Available Purpose: Recombinant tumor necrosis factor-alpha (TNF-α has been utilized as an antineoplastic agent for the treatment of patients with melanoma and sarcoma. It targets tumor cell antigens by impressing tumor-associated vessels. Protein purification with affinity chromatography has been widely used in the downstream processing of pharmaceutical-grade proteins. Methods: In this study, we examined the potential of our produced anti-TNF-scFv fragments for purification of TNF-α produced by Raji cells. he Raji cells were induced by lipopolysaccharides (LPS to express TNF-α. Western blotting and Fluorescence-activated cell sorting (FACS flow cytometry analyses were used to evaluate the TNF-α expression. The anti-TNF-α scFv selected from antibody phage display library was coupled to CNBr-activated sepharose 4B beads used for affinity purification of expressed TNF-α and the purity of the protein was assessed by SDS-PAGE. Results: Western blot and FACS flow cytometry analyses showed the successful expression of TNF-α with Raji cells. SDS-PAGE analysis showed the performance of scFv for purification of TNF-α protein with purity over 95%. Conclusion: These findings confirm not only the potential of the produced scFv antibody fragments but also this highly pure recombinant TNF-α protein can be applied for various in vitro and in vivo applications.

Production of recombinant single chain antibodies (scFv) in vegetatively reproductive Kalanchoe pinnata by in planta transformation.

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Jung, Yuchul; Rhee, Yong; Auh, Chung-Kyoon; Shim, Hyekyung; Choi, Jung-Jin; Kwon, Suk-Tae; Yang, Joo-Sung; Kim, Donggiun; Kwon, Myung-Hee; Kim, Yong-Sung; Lee, Sukchan

2009-10-01

We developed an asexual reproductive plant, Kalanchoe pinnata, as a new bioreactor for plant-based molecular farming using a newly developed transformation method. Leaf crenate margins were pin-pricked to infect the plant with the Agrobacterium strain LBA4404 and vacuum infiltration was also applied to introduce the target gene into the plants. Subsequently, the young mother leaf produced new clones at the leaf crenate margins without the need for time- and labor-consuming tissue culture procedures. The average transformation rates were approximately 77 and 84% for pin-prickling and vacuum-infiltration methods, respectively. To functionally characterize an introduced target protein, a nucleic acid hydrolyzing recombinant 3D8 scFv was selected and the plant based 3D8 scFv proteins were purified and analyzed. Based on abzyme analysis, the purified protein expressed with this system had catalytic activity and exhibited all of properties of the protein produced in an E. coli system. This result suggested that vegetatively reproductive K. pinnata can be a novel and potent bioreactor for bio-pharmaceutical proteins.

Improved scFv Anti-HIV-1 p17 Binding Affinity Guided from the Theoretical Calculation of Pairwise Decomposition Energies and Computational Alanine Scanning

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Panthip Tue-ngeun

2013-01-01

Full Text Available Computational approaches have been used to evaluate and define important residues for protein-protein interactions, especially antigen-antibody complexes. In our previous study, pairwise decomposition of residue interaction energies of single chain Fv with HIV-1 p17 epitope variants has indicated the key specific residues in the complementary determining regions (CDRs of scFv anti-p17. In this present investigation in order to determine whether a specific side chain group of residue in CDRs plays an important role in bioactivity, computational alanine scanning has been applied. Molecular dynamics simulations were done with several complexes of original scFv anti-p17 and scFv anti-p17mutants with HIV-1 p17 epitope variants with a production run up to 10 ns. With the combination of pairwise decomposition residue interaction and alanine scanning calculations, the point mutation has been initially selected at the position MET100 to improve the residue binding affinity. The calculated docking interaction energy between a single mutation from methionine to either arginine or glycine has shown the improved binding affinity, contributed from the electrostatic interaction with the negative favorably interaction energy, compared to the wild type. Theoretical calculations agreed well with the results from the peptide ELISA results.

Generation of functional scFv intrabody to abate the expression of CD147 surface molecule of 293A cells

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Mai Sabine

2008-01-01

Full Text Available Abstract Background Expression of intracellular antibodies (intrabodies has become a broadly applicable technology for generation of phenotypic knockouts in vivo. The method uses surface depletion of cellular membrane proteins to examine their biological function. In this study, we used this strategy to block the transport of cell surface molecule CD147 to the cell membrane. Phage display technology was introduced to generate the functional antibody fragment to CD147, and we subsequently constructed a CD147-specific scFv that was expressed intracellularly and retained in the endoplasmic reticulum by adenoviral gene transfer. Results The recombinant antibody fragments, Fab and scFv, of the murine monoclonal antibody (clone M6-1B9 reacted specifically to CD147 by indirect enzyme-linked immunosorbent assays (ELISA using a recombinant CD147-BCCP as a target. This indicated that the Fab- and scFv-M6-1B9 displaying on phage surfaces were correctly folded and functionally active. We subsequently constructed a CD147-specific scFv, scFv-M6-1B9-intrabody, in 293A cells. The expression of CD147 on 293A cell surface was monitored at 36 h after transduction by flow cytometry and demonstrated remarkable reduction. Colocalization of scFv-M6-1B9 intrabody with CD147 in the ER network was depicted using a 3D deconvolution microscopy system. Conclusion The results suggest that our approach can generate antibody fragments suitable for decreasing the expression of CD147 on 293A cells. This study represents a step toward understanding the role of the cell surface protein, CD147.

Development of a Targeted anti-HER2 scFv Chimeric Peptide for Gene Delivery into HER2-Positive Breast Cancer Cells.

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Cheraghi, Roya; Nazari, Mahboobeh; Alipour, Mohsen; Majidi, Asia; Hosseinkhani, Saman

2016-12-30

Chimeric polymers are known as suitable carriers for gene delivery. Certain properties are critical for a polymer to be used as a gene delivery vector. A new polymer was designed for the targeted delivery of genes into breast cancer cell lines, based on MPG peptide. It is composed of different functional domains, including HIV gp41, nuclear localization sequence of SV40 T-antigen, two C-terminus repeats of histone H1, and the scFv of anti-HER2 antibody. The results demonstrated that the vector can effectively condense plasmid DNA into nanoparticles with an average size of 250nm. Moreover, fusion of the scFv portion to the carrier brought about the specific recognition of HER2. Overall, the transfection efficiency of the vector demonstrated that it could deliver the desired gene into BT-474 HER2-positive breast cancer cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Identification of a GTP-bound Rho specific scFv molecular sensor by phage display selection

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Chinestra Patrick

2008-03-01

Full Text Available Abstract Background The Rho GTPases A, B and C proteins, members of the Rho family whose activity is regulated by GDP/GTP cycling, function in many cellular pathways controlling proliferation and have recently been implicated in tumorigenesis. Although overexpression of Rho GTPases has been correlated with tumorigenesis, only their GTP-bound forms are able to activate the signalling pathways implicated in tumorigenesis. Thus, the focus of much recent research has been to identify biological tools capable of quantifying the level of cellular GTP-bound Rho, or determining the subcellular location of activation. However useful, these tools used to study the mechanism of Rho activation still have limitations. The aim of the present work was to employ phage display to identify a conformationally-specific single chain fragment variable (scFv that recognizes the active, GTP-bound, form of Rho GTPases and is able to discriminate it from the inactive, GDP-bound, Rho in endogenous settings. Results After five rounds of phage selection using a constitutively activated mutant of RhoB (RhoBQ63L, three scFvs (A8, C1 and D11 were selected for subsequent analysis. Further biochemical characterization was pursued for the single clone, C1, exhibiting an scFv structure. C1 was selective for the GTP-bound form of RhoA, RhoB, as well as RhoC, and failed to recognize GTP-loaded Rac1 or Cdc42, two other members of the Rho family. To enhance its production, soluble C1 was expressed in fusion with the N-terminal domain of phage protein pIII (scFv C1-N1N2, it appeared specifically associated with GTP-loaded recombinant RhoA and RhoB via immunoprecipitation, and endogenous activated Rho in HeLa cells as determined by immunofluorescence. Conclusion We identified an antibody, C1-N1N2, specific for the GTP-bound form of RhoB from a phage library, and confirmed its specificity towards GTP-bound RhoA and RhoC, as well as RhoB. The success of C1-N1N2 in discriminating activated

A humanized anti-M2 scFv shows protective in vitro activity against influenza

Energy Technology Data Exchange (ETDEWEB)

Bradbury, Andrew M [Los Alamos National Laboratory; Velappan, Nileena [Los Alamos National Laboratory; Schmidt, Jurgen G [Los Alamos National Laboratory

2008-01-01

M2 is one of the most conserved influenza proteins, and has been widely prospected as a potential universal vaccine target, with protection predominantly mediated by antibodies. In this paper we describe the creation of a humanized single chain Fv from 14C2, a potent monoclonal antibody against M2. We show that the humanized scFv demonstrates similar activity to the parental mAb: it is able to recognize M2 in its native context on cell surfaces and is able to show protective in vitro activity against influenza, and so represents a potential lead antibody candidate for universal prophylactic or therapeutic intervention in influenza.

Aptamers, antibody scFv, and antibody Fab' fragments: An overview and comparison of three of the most versatile biosensor biorecognition elements.

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Crivianu-Gaita, Victor; Thompson, Michael

2016-11-15

The choice of biosensing elements is crucial for the development of the optimal biosensor. Three of the most versatile biosensing elements are antibody single-chain Fv fragments (scFv), antibody fragment-antigen binding (Fab') units, and aptamers. This article provides an overview of these three biorecognition elements with respects to their synthesis/engineering, various immobilization techniques, and examples of their use in biosensors. Furthermore, the final section of the review compares and contrasts their characteristics (time/cost of development, ease and variability of immobilization, affinity, stability) illustrating their advantages and disadvantages. Overall, scFv fragments are found to display the highest customizability (i.e. addition of functional groups, immobilizing peptides, etc.) due to recombinant synthesis techniques. If time and cost are an issue in the development of the biosensor, Fab' fragments should be chosen as they are relatively cheap and can be developed quickly from whole antibodies (several days). However, if there are sufficient funds and time is not a factor, aptamers should be utilized as they display the greatest affinity towards their target analytes and are extremely stable (excellent biosensor regenerability). Copyright © 2016 Elsevier B.V. All rights reserved.

Generation of a rabbit single-chain fragment variable (scFv) antibody for specific detection of Bradyrhizobium sp. DOA9 in both free-living and bacteroid forms.

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Vu, Nguyen Xuan; Pruksametanan, Natcha; Srila, Witsanu; Yuttavanichakul, Watcharin; Teamtisong, Kamonluck; Teaumroong, Neung; Boonkerd, Nantakorn; Tittabutr, Panlada; Yamabhai, Montarop

2017-01-01

A simple and reliable method for the detection of specific nitrogen-fixing bacteria in both free-living and bacteroid forms is essential for the development and application of biofertilizer. Traditionally, a polyclonal antibody generated from an immunized rabbit was used for detection. However, the disadvantages of using a polyclonal antibody include limited supply and cross-reactivity to related bacterial strains. This is the first report on the application of phage display technology for the generation of a rabbit recombinant monoclonal antibody for specific detection and monitoring of nitrogen-fixing bacteria in both free-living form and in plant nodules. Bradyrhizobium sp. DOA9, a broad host range soil bacteria, originally isolated from the root nodules of Aeschynomene americana in Thailand was used as a model in this study. A recombinant single-chain fragment variable (scFv) antibody library was constructed from the spleen of a rabbit immunized with DOA9. After three rounds of biopanning, one specific phage-displayed scFv antibody, designated bDOA9rb8, was identified. Specific binding of this antibody was confirmed by phage enzyme-linked immunosorbent assay (phage ELISA). The phage antibody could bind specifically to DOA9 in both free-living cells (pure culture) and bacteroids inside plant nodules. In addition to phage ELISA, specific and robust immunofluorescence staining of both free-living and bacteroid forms could also be observed by confocal-immunofluorescence imaging, without cross-reactivity with other tested bradyrhizobial strains. Moreover, specific binding of free scFv to DOA9 was also demonstrated by ELISA. This recombinant antibody can also be used for the study of the molecular mechanism of plant-microbe interactions in the future.

Radiation curing - twenty five years on

International Nuclear Information System (INIS)

Garnett, J.L.

1995-01-01

Progress in UV/EB curing during the past twenty five years is briefly reviewed. During this time developments in unique polymer chemistry, novel equipment design and the introduction of relevant educational programmes has enabled radiation curing to become an established technology with specific strengths in certain industries. Possible reasons for the emergence of the technology in these niche markets are discussed. Despite the worldwide recession, radiation curing is shown to be expanding at 5% per annum with the prospect of higher growth with improving economic conditions. (Author)

Identification and characterisation of the proteins bound by specific phage-displayed recombinant antibodies (scFv) obtained against Brazil nut and almond extracts.

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de la Cruz, Silvia; Madrid, Raquel; García-García, Aina; Alcocer, Marcos; Martín, Rosario; González, Isabel; García, Teresa

2018-03-01

Almonds and Brazil nuts are widely consumed allergenic nuts whose presence must be declared according to food labelling regulations. Their detection in food products has been recently achieved by ELISA methods with recombinant antibodies (scFv) isolated against complete Brazil nut and almond protein extracts. The screening of phage-scFv libraries against complete protein extracts confers a series of advantages over the use of purified proteins, as recombinant proteins might alter their native folding. However, using this strategy, the nature of the target detected by phage-displayed antibodies remains unknown, and requires further research to identify whether they are nut allergens or other molecules present in the extract, but not related to their allergenic potential. Electrophoretic, chromatographic, immunological and spectrometric techniques revealed that the Brazil nut (BE95) and almond (PD1F6 and PD2C9) specific phage-scFvs detected conformational epitopes of the Brazil nut and almond 11S globulins, recognised by WHO/IUIS as Ber e 2 and Pru du 6 major allergens. Circular dichroism data indicated that severe heat treatment would entail loss of epitope structure, disabling scFv for target detection. The presence of important Brazil nut and almond allergens (Ber e 2 and Pru du 6) in foodstuffs can be determined by using phage-display antibodies BE95, PD1F6 and PD2C9 as affinity probes in ELISA. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Targeting the active site of the placental isozyme of alkaline phosphatase by phage-displayed scFv antibodies selected by a specific uncompetitive inhibitor

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Kala Mrinalini

2005-12-01

Full Text Available Abstract Background The isozymes of alkaline phosphatase, the tissue non-specific, intestinal and placental, have similar properties and a high degree of identity. The placental isozyme (PLAP is an oncofetal antigen expressed in several malignancies including choriocarcinoma, seminoma and ovarian carcinoma. We had earlier attempted to isolate PLAP-specific scFv from a synthetic human immunoglobulin library but were unable to do so, presumably because of the similarity between the isozymes. In this work, we have employed a PLAP-specific uncompetitive inhibitor, L-Phe-Gly-Gly, to select isozyme specific scFvs. An uncompetitive inhibitor binds to the enzyme in the presence of substrate and stabilizes the enzyme-substrate complex. Several uncompetitive inhibitors have varying degrees of isozyme specificity for human alkaline phosphatase isozymes. A specific uncompetitive inhibitor would be able to unmask conformational differences between the otherwise very similar molecules. Also, such inhibitors would be directed to regions at/close to the active site of the enzyme. In this work, the library was first incubated with PLAP and the bound clones then eluted by incubation with L-Phe-Gly-Gly along with the substrate, para-nitro phenyl phosphate (pNPP. The scFvs were then studied with regard to the biochemical modulation of their binding, isozyme specificity and effect on enzyme activity. Results Of 13 clones studied initially, the binding of 9 was inhibited by L-Phe-Gly-Gly (with pNPP and 2 clones were inhibited by pNPP alone. Two clones had absolute and 2 clones had partial specificity to PLAP. Two clones were cross-reactive with only one other isozyme. Three scFv clones, having an accessible His6-tag, were purified and studied for their modulation of enzyme activity. All the three scFvs inhibited PLAP activity with the kinetics of competitive inhibition. Cell ELISA could demonstrate binding of the specific scFvs to the cell surface expressed PLAP

Antiproliferative and apoptotic effects of a specific anti-insulin-like growth factor I receptor single chain antibody on breast cancer cells.

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Motallebnezhad, Morteza; Younesi, Vahid; Aghebati-Maleki, Leili; Nickho, Hamid; Safarzadeh, Elham; Ahmadi, Majid; Movassaghpour, Ali Akbar; Hosseini, Ahmad; Yousefi, Mehdi

2016-11-01

Insulin-like growth factor I receptor (IGF-IR) is expressed on breast cancer cells and involves in metastasis, survival, and proliferation. Currently, application of IGF-IR-targeting monoclonal antibodies (mAbs), alone or in combination with other drugs, is a promising strategy for breast cancer therapy. Single-chain fragment variable (scFv) antibodies have been introduced as appropriate tools for tumor-targeting purposes because of their advantages over whole antibodies. In the present study, we employed a naïve phage library and isolated scFvs against a specific epitope from extracellular domain of IGF-IR by panning process. The selected scFvs were further characterized using polyclonal and monoclonal phage ELISA, soluble monoclonal ELISA, and colony PCR and sequencing. Antiproliferative and apoptotic effects of selected scFv antibodies on breast cancer cell lines were also evaluated by MTT and Annexin V/PI assays. The results of ELISA indicated specific reactions of the isolated scFvs against the IGF-IR peptide, and analyses of PCR product and sequencing confirmed the presence of full length V H and Vκ inserts. Treatment of MCF7 and SKBR3 cells with anti-IGF-IR scFv led to a significant growth inhibition. The results also showed that scFv treatment significantly augmented trastuzumab growth inhibitory effects on SKBR3 cells. The percentage of the apoptotic MCF7 and SKBR3 cells after 24-h treatment with scFv was 39 and 30.70 %, respectively. Twenty-four-hour treatment with scFv in combination with trastuzumab resulted in 44.75 % apoptosis of SKBR3 cells. Taken together, our results demonstrate that the targeting of IGF-IR by scFv can be an effective strategy in the treatment of breast cancer and provide further evidence for effectiveness of dual targeting of HER2 and IGF-IR in breast cancer therapy.

Screening of synthetic phage display scFv libraries yields competitive ligands of human leptin receptor.

Science.gov (United States)

Molek, Peter; Vodnik, Miha; Strukelj, Borut; Bratkovič, Tomaž

2014-09-26

Initially considered the main endogenous anorexigenic factor, fat-derived leptin turned out to be a markedly pleiotropic hormone, influencing diverse physiological processes. Moreover, hyperleptinemia in obese individuals has been linked to the onset or progression of serious disorders, such as cancer, autoimmune diseases, and atherosclerosis, and antagonizing peripheral leptin's signalization has been shown to improve these conditions. To develop an antibody-based leptin antagonist we have devised a tailored panning procedure and screened two phage display libraries of single chain variable antibody fragments (scFvs) against recombinant leptin receptor. One of the scFvs was expressed in Escherichia coli and its interaction with leptin receptor was characterized in more detail. It was found to recognize a discontinuous epitope and to compete with leptin for receptor binding with IC50 and Kd values in the nanomolar range. The reported scFv represents a lead for development of leptin antagonists that may ultimately find use in therapy of various hyperleptinemia-related disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

Construção de uma biblioteca de fragmentos de anticorpos monoclonais de galinhas com cadeia única (scFv por phage display com reatividade cruzada para estirpes heterólogas do vírus da bronquite infecciosa aviária Construction of an avian single chain monoclonal antibodies (scFv library by phage display that cross-reacted with heterologous avian infectious bronchitis virus strains

Directory of Open Access Journals (Sweden)

Camila Cesário Fernandes

2010-06-01

Full Text Available Anticorpos monoclonais constituem a base de vários testes usados na detecção e na identificação de antígenos. Nesse contexto, tais imuno-reagentes têm sido extensivamente empregados na identificação de estirpes virais envolvidas na etiologia de surtos de bronquite infecciosa a campo, permitindo o aperfeiçoamento das técnicas de detecção e caracterização antigênica do vírus da bronquite infecciosa das galinhas (VBI. No presente estudo, uma biblioteca de fragmentos de anticorpos de galinha originalmente preparada por phage display contra a estirpe vacinal (H120 do VBI foi usada para a seleção de fragmentos de anticorpos recombinantes com reatividade cruzada para as estirpes heterólogas IBVPR01 e IBVPR05, isoladas de surtos a campo no Brasil e a estirpe SE-17, isolada nos Estados Unidos. Após três ciclos de panning, foi identificado, pelo ELISA, um conjunto de 15 anticorpos scFv expressos em fagos e com reatividade cruzada para essas mesmas estirpes do VBI. A análise por Western-blotting revelou que dois desses clones apresentavam fagos expressando fragmentos de anticorpos monoclonais com reatividade cruzada para a nucleoproteína N das três estirpes do VBI e também para a forma recombinante dessa nucleoproteína derivada da estirpe M41. Concluindo, os fragmentos de anticorpos monoclonais recombinantes scFv-N produzidos em fagos interagem com um epítopo mais conservado da proteína N do VBI e apresentam um grande potencial para utilização na detecção e no diagnóstico direto desse vírus.Monoclonal antibodies are the basis of various techniques used for antigen detection or characterization, and their use is specially recommended for the identification of viral strains involved in the etiology of infectious bronchitis outbreaks. These antibodies are homogeneous, highly specific and fully characterizable, allowing the improvement of immunological techniques detection and antigenic characterization of avian infectious

Comparison of the efficiency of antibody selection from semi-synthetic scFv and non-immune Fab phage display libraries against protein targets for rapid development of diagnostic immunoassays.

Science.gov (United States)

Chan, Conrad E Z; Chan, Annie H Y; Lim, Angeline P C; Hanson, Brendon J

2011-10-28

Rapid development of diagnostic immunoassays against novel emerging or genetically modified pathogens in an emergency situation is dependent on the timely isolation of specific antibodies. Non-immune antibody phage display libraries are an efficient in vitro method for selecting monoclonal antibodies and hence ideal in these circumstances. Such libraries can be constructed from a variety of sources e.g. B cell cDNA or synthetically generated, and use a variety of antibody formats, typically scFv or Fab. However, antibody source and format can impact on the quality of antibodies generated and hence the effectiveness of this methodology for the timely production of antibodies. We have carried out a comparative screening of two antibody libraries, a semi-synthetic scFv library and a human-derived Fab library against the protective antigen toxin component of Bacillus anthracis and the epsilon toxin of Clostridium botulinum. We have shown that while the synthetic library produced a diverse collection of specific scFv-phage, these contained a high frequency of unnatural amber stops and glycosylation sites which limited their conversion to IgG, and also a high number which lost specificity when expressed as IgG. In contrast, these limitations were overcome by the use of a natural human library. Antibodies from both libraries could be used to develop sandwich ELISA assays with similar sensitivity. However, the ease and speed with which full-length IgG could be generated from the human-derived Fab library makes screening this type of library the preferable method for rapid antibody generation for diagnostic assay development. Copyright © 2011 Elsevier B.V. All rights reserved.

Human scFv antibodies (Afribumabs) against Africanized bee venom: Advances in melittin recognition.

Science.gov (United States)

Pessenda, Gabriela; Silva, Luciano C; Campos, Lucas B; Pacello, Elenice M; Pucca, Manuela B; Martinez, Edson Z; Barbosa, José E

2016-03-15

Africanized Apis mellifera bees, also known as killer bees, have an exceptional defensive instinct, characterized by mass attacks that may cause envenomation or death. From the years 2000-2013, 77,066 bee accidents occurred in Brazil. Bee venom comprises several substances, including melittin and phospholipase A2 (PLA2). Due to the lack of antivenom for bee envenomation, this study aimed to produce human monoclonal antibody fragments (single chain fragment variable; scFv), by using phage display technology. These fragments targeted melittin and PLA2, the two major components of bee venom, to minimize their toxic effects in cases of mass envenomation. Two phage antibody selections were performed using purified melittin. As the commercial melittin is contaminated with PLA2, phages specific to PLA2 were also obtained during one of the selections. Specific clones for melittin and PLA2 were selected for the production of soluble scFvs, named here Afribumabs: prefix: afrib- (from Africanized bee); stem/suffix: -umab (fully human antibody). Afribumabs 1 and 2 were tested in in vitro and in vivo assays to assess their ability to inhibit the toxic actions of purified melittin, PLA2, and crude bee venom. Afribumabs reduced hemolysis caused by purified melittin and PLA2 and by crude venom in vitro and reduced edema formation in the paws of mice and prolonged the survival of venom-injected animals in vivo. These results demonstrate that Afribumabs may contribute to the production of the first non-heterologous antivenom treatment against bee envenomation. Such a treatment may overcome some of the difficulties associated with conventional immunotherapy techniques. Copyright © 2016 Elsevier Ltd. All rights reserved.

Overcoming the Constraints of Anti-HIV/CD89 Bispecific Antibodies That Limit Viral Inhibition

Directory of Open Access Journals (Sweden)

Xiaocong Yu

2016-01-01

Full Text Available Innovative strategies are necessary to maximize the clinical application of HIV neutralizing antibodies. To this end, bispecific constructs of human antibody F240, reactive with well-conserved gp41 epitope and antibody 14A8, reactive with the IgA receptor (CD89 on effector cells, were constructed. A F240 × 14A8 bispecific single chain variable region (scFv molecule was constructed by linking two scFvs using a conventional GGGGS linker. Despite immunoreactivity with HIV gp41 and neutrophils, this bispecific scFv failed to inhibit HIV infection. This is in sharp contrast to viral inhibition using a chemical conjugate of the Fab of these two antibodies. Therefore, we constructed two novel Fab-like bispecific antibody molecules centered on fusion of the IgG1 CH1 domain or CH1-hinge domain to the C-terminus of F240scFv and fusion of the kappa chain CL domain to the C-terminus of 14A8scFv. Both Bi-Fab antibodies showed significant ADCVI activity for multiple clade B and clade C isolates by arming the neutrophils to inhibit HIV infection. The approach presented in this study is unique for HIV immunotherapy in that the impetus of neutralization is to arm and mobilize PMN to destroy HIV and HIV infected cells.

The in vivo characteristics of genetically engineered divalent and tetravalent single-chain antibody constructs

International Nuclear Information System (INIS)

Wittel, Uwe A.; Jain, Maneesh; Goel, Apollina; Chauhan, Subhash C.; Colcher, David; Batra, Surinder K.

2005-01-01

Engineered multivalent single-chain Fv (scFv) constructs have been demonstrated to exhibit rapid blood clearance and better tumor penetration. To understand the short plasma half-life of multivalent single-chain antibody fragments, the pharmacokinetic properties of covalent dimeric scFv [sc(Fv) 2 ], noncovalent tetrameric scFv {[sc(Fv) 2 ] 2 } and IgG of MAb CC49 were examined. The scFvs displayed an ability to form higher molecular aggregates in vivo. A specific proteolytic cleavage of the linker sequence of the covalent dimeric or a deterioration of the noncovalent association of the dimeric scFv into tetravalent scFv constructs was not observed. In conclusion, sc(Fv) 2 and [sc(Fv) 2 ] 2 are stable in vivo and have significant potential for diagnostic and therapeutic applications

A human scFv antibody that targets and neutralizes high molecular weight pathogenic amyloid-β oligomers.

Science.gov (United States)

Sebollela, Adriano; Cline, Erika N; Popova, Izolda; Luo, Kevin; Sun, Xiaoxia; Ahn, Jay; Barcelos, Milena A; Bezerra, Vanessa N; Lyra E Silva, Natalia M; Patel, Jason; Pinheiro, Nathalia R; Qin, Lei A; Kamel, Josette M; Weng, Anthea; DiNunno, Nadia; Bebenek, Adrian M; Velasco, Pauline T; Viola, Kirsten L; Lacor, Pascale N; Ferreira, Sergio T; Klein, William L

2017-07-03

Brain accumulation of soluble oligomers of the amyloid-β peptide (AβOs) is increasingly considered a key early event in the pathogenesis of Alzheimer's disease (AD). A variety of AβO species have been identified, both in vitro and in vivo, ranging from dimers to 24mers and higher order oligomers. However, there is no consensus in the literature regarding which AβO species are most germane to AD pathogenesis. Antibodies capable of specifically recognizing defined subpopulations of AβOs would be a valuable asset in the identification, isolation, and characterization of AD-relevant AβO species. Here, we report the characterization of a human single chain antibody fragment (scFv) denoted NUsc1, one of a number of scFvs we have identified that stringently distinguish AβOs from both monomeric and fibrillar Aβ. NUsc1 readily detected AβOs previously bound to dendrites in cultured hippocampal neurons. In addition, NUsc1 blocked AβO binding and reduced AβO-induced neuronal oxidative stress and tau hyperphosphorylation in cultured neurons. NUsc1 further distinguished brain extracts from AD-transgenic mice from wild type (WT) mice, and detected endogenous AβOs in fixed AD brain tissue and AD brain extracts. Biochemical analyses indicated that NUsc1 targets a subpopulation of AβOs with apparent molecular mass greater than 50 kDa. Results indicate that NUsc1 targets a particular AβO species relevant to AD pathogenesis, and suggest that NUsc1 may constitute an effective tool for AD diagnostics and therapeutics. © 2017 International Society for Neurochemistry.

Outlook: The Next Twenty Years

Energy Technology Data Exchange (ETDEWEB)

Murayama, Hitoshi

2003-12-07

I present an outlook for the next twenty years in particle physics. I start with the big questions in our field, broken down into four categories: horizontal, vertical, heaven, and hell. Then I discuss how we attack the bigquestions in each category during the next twenty years. I argue for a synergy between many different approaches taken in our field.

Vectorization in an oncolytic vaccinia virus of an antibody, a Fab and a scFv against programmed cell death -1 (PD-1) allows their intratumoral delivery and an improved tumor-growth inhibition.

Science.gov (United States)

Kleinpeter, Patricia; Fend, Laetitia; Thioudellet, Christine; Geist, Michel; Sfrontato, Nathalie; Koerper, Véronique; Fahrner, Catherine; Schmitt, Doris; Gantzer, Murielle; Remy-Ziller, Christelle; Brandely, Renée; Villeval, Dominique; Rittner, Karola; Silvestre, Nathalie; Erbs, Philippe; Zitvogel, Laurence; Quéméneur, Eric; Préville, Xavier; Marchand, Jean-Baptiste

2016-01-01

We report here the successful vectorization of a hamster monoclonal IgG (namely J43) recognizing the murine Programmed cell death-1 (mPD-1) in Western Reserve (WR) oncolytic vaccinia virus. Three forms of mPD-1 binders have been inserted into the virus: whole antibody (mAb), Fragment antigen-binding (Fab) or single-chain variable fragment (scFv). MAb, Fab and scFv were produced and assembled with the expected patterns in supernatants of cells infected by the recombinant viruses. The three purified mPD-1 binders were able to block the binding of mPD-1 ligand to mPD-1 in vitro . Moreover, mAb was detected in tumor and in serum of C57BL/6 mice when the recombinant WR-mAb was injected intratumorally (IT) in B16F10 and MCA 205 tumors. The concentration of circulating mAb detected after IT injection was up to 1,900-fold higher than the level obtained after a subcutaneous (SC) injection (i.e., without tumor) confirming the virus tropism for tumoral cells and/or microenvironment. Moreover, the overall tumoral accumulation of the mAb was higher and lasted longer after IT injection of WR-mAb1, than after IT administration of 10 µg of J43. The IT injection of viruses induced a massive infiltration of immune cells including activated lymphocytes (CD8 + and CD4 + ). Interestingly, in the MCA 205 tumor model, WR-mAb1 and WR-scFv induced a therapeutic control of tumor growth similar to unarmed WR combined to systemically administered J43 and superior to that obtained with an unarmed WR. These results pave the way for next generation of oncolytic vaccinia armed with immunomodulatory therapeutic proteins such as mAbs.

Twenty Practices of an Entrepreneurial University

DEFF Research Database (Denmark)

Gjerding, Allan Næs; Wilderom, Celeste P.M.; Cameron, Shona P.B.

2006-01-01

studies twenty organisational practices against which a University's entrepreneurship can be measured. These twenty practices or factors in effect formed the basis for an entrepreneurship audit. During a series of interviews, the extent to which the universities are seen as entrepreneurial...

Enzymatic single-chain antibody tagging: a universal approach to targeted molecular imaging and cell homing in cardiovascular disease.

Science.gov (United States)

Ta, H T; Prabhu, S; Leitner, E; Jia, F; von Elverfeldt, D; Jackson, Katherine E; Heidt, T; Nair, A K N; Pearce, H; von Zur Muhlen, C; Wang, X; Peter, K; Hagemeyer, C E

2011-08-05

Antibody-targeted delivery of imaging agents can enhance the sensitivity and accuracy of current imaging techniques. Similarly, homing of effector cells to disease sites increases the efficacy of regenerative cell therapy while reducing the number of cells required. Currently, targeting can be achieved via chemical conjugation to specific antibodies, which typically results in the loss of antibody functionality and in severe cell damage. An ideal conjugation technique should ensure retention of antigen-binding activity and functionality of the targeted biological component. To develop a biochemically robust, highly reproducible, and site-specific coupling method using the Staphylococcus aureus sortase A enzyme for the conjugation of a single-chain antibody (scFv) to nanoparticles and cells for molecular imaging and cell homing in cardiovascular diseases. This scFv specifically binds to activated platelets, which play a pivotal role in thrombosis, atherosclerosis, and inflammation. The conjugation procedure involves chemical and enzyme-mediated coupling steps. The scFv was successfully conjugated to iron oxide particles (contrast agents for magnetic resonance imaging) and to model cells. Conjugation efficiency ranged between 50% and 70%, and bioactivity of the scFv after coupling was preserved. The targeting of scFv-coupled cells and nanoparticles to activated platelets was strong and specific as demonstrated in in vitro static adhesion assays, in a flow chamber system, in mouse intravital microscopy, and in in vivo magnetic resonance imaging of mouse carotid arteries. This unique biotechnological approach provides a versatile and broadly applicable tool for procuring targeted regenerative cell therapy and targeted molecular imaging in cardiovascular and inflammatory diseases and beyond.

Unique biological properties of catalytic domain directed human anti-CAIX antibodies discovered through phage-display technology.

Directory of Open Access Journals (Sweden)

Chen Xu

2010-03-01

Full Text Available Carbonic anhydrase IX (CAIX, gene G250/MN-encoded transmembrane protein is highly expressed in various human epithelial tumors such as renal clear cell carcinoma (RCC, but absent from the corresponding normal tissues. Besides the CA signal transduction activity, CAIX may serve as a biomarker in early stages of oncogenesis and also as a reliable marker of hypoxia, which is associated with tumor resistance to chemotherapy and radiotherapy. Although results from preclinical and clinical studies have shown CAIX as a promising target for detection and therapy for RCC, only a limited number of murine monoclonal antibodies (mAbs and one humanized mAb are available for clinical testing and development. In this study, paramagnetic proteoliposomes of CAIX (CAIX-PMPLs were constructed and used for anti-CAIX antibody selection from our 27 billion human single-chain antibody (scFv phage display libraries. A panel of thirteen human scFvs that specifically recognize CAIX expressed on cell surface was identified, epitope mapped primarily to the CA domain, and affinity-binding constants (KD determined. These human anti-CAIX mAbs are diverse in their functions including induction of surface CAIX internalization into endosomes and inhibition of the carbonic anhydrase activity, the latter being a unique feature that has not been previously reported for anti-CAIX antibodies. These human anti-CAIX antibodies are important reagents for development of new immunotherapies and diagnostic tools for RCC treatment as well as extending our knowledge on the basic structure-function relationships of the CAIX molecule.

[Construction of a phage antibody library and screening of anti-epidermal growth factor receptor variant III single chain antibody].

Science.gov (United States)

Han, Dong-gang; Duan, Xiao-yi; Guo, You-min; Zhou, Qi; Wang, Quan-ying; Yang, Guang-xiao

2010-01-01

To obtain specific anti-epidermal growth factor receptor variant III (EGFRvIII) single chain antibody (ScFv) by phage antibody library display system. The total RNA was extracted from the spleen B cells of BALB/c mice immunized with pep-3-OVA protein, and the first-strand cDNA was synthesized by reverse transcription. Antibody VH and VL gene fragments were amplified and joined to a ScFv gene with the linker. The ScFv gene was ligated into the phagemid vector pCANTAB5E, which was transformed into competent E. coli TG1. The transformed cells were then infected with M13KO7 helper phage to yield the recombinant phage to construct the phage ScFv library. Pep-3-BSA protein was used to screen the phage antibody library and ELISA carried out to characterize the activity of the antibody. The VH and VL gene fragments of the antibody were about 350 bp and 320 bp in length as analyzed by agarose gel electrophoresis. The ScFv gene was 780 bp, consistent with the expected length. The recombinant phagemid with ScFv gene insert was rescued, and an immune phage ScFv library with the content of 5.0x10(6) was constructed. The recombinant ScFv phage had a titer of 3.0x10(4) cfu/ml, and the fourth phage harvest yielded 56 times as much as that of the first one. SDS-PAGE demonstrated a molecular mass of the soluble ScFv of about 28 kD. ELISA results indicated good specificity of the ScFv to bind EGFRvIII. An immune phage ScFv library is successfully constructed, and the ScFv antibody fragment is capable of specific binding to EGFRvIII.

Plutonium uniqueness

International Nuclear Information System (INIS)

Silver, G.L.

1984-01-01

A standard is suggested against which the putative uniqueness of plutonium may be tested. It is common folklore that plutonium is unique among the chemical elements because its four common oxidation states can coexist in the same solution. Whether this putative uniqueness appears only during transit to equilibrium, or only at equilibrium, or all of the time, is not generally made clear. But while the folklore may contain some truth, it cannot be put to test until some measure of 'uniqueness' is agreed upon so that quantitative comparisons are possible. One way of measuring uniqueness is as the magnitude of the product of the mole fractions of the element at equilibrium. A 'coexistence index' is defined and discussed. (author)

Generation and analyses of human synthetic antibody libraries and their application for protein microarrays

DEFF Research Database (Denmark)

Säll, Anna; Walle, Maria; Wingren, Christer

2016-01-01

in a high-throughput manner. To address this we designed and constructed two human synthetic antibody fragment (scFv) libraries denoted HelL-11 and HelL-13. By the use of phage display technology, in total 466 unique scFv antibodies specific for 114 different antigens were generated. The specificities......Antibody-based proteomics offers distinct advantages in the analysis of complex samples for discovery and validation of biomarkers associated with disease. However, its large-scale implementation requires tools and technologies that allow development of suitable antibody or antibody fragments...... for diagnostics and therapeutics. In addition, this work provides a great example on how a synthetic approach can be used to optimize library designs. By having precise control of the diversity introduced into the antigen-binding sites, synthetic libraries offer increased understanding of how different diversity...

Capital in the Twenty-First Century

DEFF Research Database (Denmark)

Hansen, Per H.

2014-01-01

Review essay on: Capital in the Twenty-First Century. By Thomas Piketty . Translated by Arthur Goldhammer . Cambridge, Mass.: The Belknap Press of Harvard University Press, 2014. viii + 685 pp......Review essay on: Capital in the Twenty-First Century. By Thomas Piketty . Translated by Arthur Goldhammer . Cambridge, Mass.: The Belknap Press of Harvard University Press, 2014. viii + 685 pp...

Secretion of an immunoreactive single-chain variable fragment antibody against mouse interleukin 6 by Lactococcus lactis.

Science.gov (United States)

Shigemori, Suguru; Ihara, Masaki; Sato, Takashi; Yamamoto, Yoshinari; Nigar, Shireen; Ogita, Tasuku; Shimosato, Takeshi

2017-01-01

Interleukin 6 (IL-6) is an important pathogenic factor in development of various inflammatory and autoimmune diseases and cancer. Blocking antibodies against molecules associated with IL-6/IL-6 receptor signaling are an attractive candidate for the prevention or therapy of these diseases. In this study, we developed a genetically modified strain of Lactococcus lactis secreting a single-chain variable fragment antibody against mouse IL-6 (IL6scFv). An IL6scFv-secretion vector was constructed by cloning an IL6scFv gene fragment into a lactococcal secretion plasmid and was electroporated into L. lactis NZ9000 (NZ-IL6scFv). Secretion of recombinant IL6scFv (rIL6scFv) by nisin-induced NZ-IL6scFv was confirmed by western blotting and was optimized by tuning culture conditions. We found that rIL6scFv could bind to commercial recombinant mouse IL-6. This result clearly demonstrated the immunoreactivity of rIL6scFv. This is the first study to engineer a genetically modified strain of lactic acid bacteria (gmLAB) that produces a functional anti-cytokine scFv. Numerous previous studies suggested that mucosal delivery of biomedical proteins using gmLAB is an effective and low-cost way to treat various disorders. Therefore, NZ-IL6scFv may be an attractive tool for the research and development of new IL-6 targeting agents for various inflammatory and autoimmune diseases as well as for cancer.

Targeted delivery of CD44s-siRNA by ScFv overcomes de novo resistance to cetuximab in triple negative breast cancer.

Science.gov (United States)

Fu, Wenyan; Sun, Hefen; Zhao, Yang; Chen, Mengting; Yang, Lipeng; Yang, Xueli; Jin, Wei

2018-05-16

The overexpression of EGFR often occurs in TNBC, and the anti-EGFR receptor antibody cetuximab is used widely to treat metastatic cancer in the clinic. However, EGFR-targeted therapies have been developed for TNBC without clinical success. In this study, we show that impaired EGFR degradation is crucial for resistance to cetuximab, which depends on the cell surface molecule CD44. To further investigate the role of CD44 in EGFR signaling and its treatment potential, we developed a targeting fusion protein composed of an anti-EGFR scFv generated from cetuximab and truncated protamine, called Ce-tP. CD44 siRNA can be specifically delivered into EGFR-positive TNBC cells by Ce-tP. Efficient knockdown of CD44 and suppression of both EGFR and downstream signaling by the Ce-tP/siRNA complex were observed in EGFR-positive TNBC cells. More importantly, our results also showed that targeted delivery of siRNA specific for CD44 can efficiently overcome resistance to EGFR targeting in TNBC cells both in vitro and in vivo. Overall, our results establish a new principle to achieve EGFR inhibition in TNBC and limit drug resistance. Copyright © 2018 Elsevier Ltd. All rights reserved.

Diagnostic potential of recombinant scFv antibodies generated against hemagglutinin protein of influenza A virus

Directory of Open Access Journals (Sweden)

Roopali eRajput

2015-09-01

Full Text Available Human influenza A viruses have been the cause of enormous socio-economic losses worldwide. In order to combat such a notorious pathogen, hemagglutinin protein (HA has been a preferred target for generation of neutralizing-antibodies, as potent therapeutic/ diagnostic agents. In the present study, recombinant anti-HA single chain variable fragment (scFv antibodies were constructed using the phage display technology to aid in diagnosis and treatment of human influenza A virus infections. Spleen cells of mice hyper-immunized with A/New Caledonia/20/99 (H1N1 virus were used as the source for recombinant antibody (rAb production. The antigen-binding phages were quantified after 6 rounds of bio-panning against A/New Caledonia/20/99 (H1N1, A/California/07/2009 (H1N1-like, or A/Udorn/307/72(H3N2 viruses. The phage yield was maximum for the A/New Caledonia/20/99 (H1N1, however, considerable cross-reactivity was observed for the other virus strains as well. The HA-specific polyclonal rAb preparation was subjected to selection of single clones for identification of high reactive relatively conserved epitopes. The high affinity rAbs were tested against certain known conserved HA epitopes by peptide ELISA. Three recombinant mAbs showed reactivity with both the H1N1 strains and one (C5 showed binding with all the three viral strains. The C5 antibody was thus used for development of an ELISA test for diagnosis of influenza virus infection. Based on the sample size in the current analysis, the ELISA test demonstrated 83.9% sensitivity and 100% specificity. Thus, the ELISA, developed in our study, may prove as a cheaper alternative to the presently used real time RT-PCR test for detection of human influenza A viruses in clinical specimens, which will be beneficial, especially in the developing countries. Since, the two antibodies identified in this study are reactive to conserved HA epitopes; these may prove as potential therapeutic agents as well.

INCREASING OF THE EXPRESSION OF RECOMBINANT scFv-ANTIBODIES EFFICIENCY

Directory of Open Access Journals (Sweden)

O.V. Galkin

2017-10-01

Full Text Available Obtaining single-chain variable fragments (scFv of recombinant antibodies in E. coli cells is often associated with numerous problems causing low yields or inactive conformation of the product. The aim of this work was to study the influence of staphylococcal protein A fragment fused with scFv antibodies (SpA-tag on the efficiency of expression of final product. Examination of scFv antibodies of different origin and specificity has shown that in similar expression systems fused scFv is synthesized in much higher quantities than free scFv. Furthermore, the scFv antibodies in fused form retained their antigen-binding properties and the SpA fragment the ability to bind other immunoglobulins. Thus, the proposed strategy can be considered effective in improving the efficiency of scFv-antibodies production in E. coli cells.

Construction of bifunctional molecules specific to antigen and antibody’s Fc-fragment by fusion of scFv-antibodies with staphylococcal protein A

Directory of Open Access Journals (Sweden)

Kolibo D. V.

2009-06-01

Full Text Available Aim. To develop approach for detection of scFv and their complexes with antigens. Methods. The fusion proteins, which include sequences of scFv and staphylococcal protein A, were constructed and the obtained bifunctional molecules were immunochemically analysed. Results. It was shown, that scFv fused with protein A and their complexes with antigens are effectively recognized by labelled immunoglobulins with unrestricted antigenic specificity. Conclusions. The fusion of scFv with protein A fragment is a perspective approach to increase the efficiency of application in ELISA. The obtained scFv, fused with protein A, could be used for development of test-systems for the detection of diphtheria toxin.

Niels Bohr and the philosophy of physics twenty-first century perspectives

CERN Document Server

Folse, Henry

2017-01-01

Niels Bohr and Philosophy of Physics: Twenty-First Century Perspectives examines the philosophical views, influences and legacy of the Nobel Prize physicist and philosophical spokesman of the quantum revolution, Niels Bohr. The sixteen contributions in this collection by some of the best contemporary philosophers and physicists writing on Bohr's philosophy today all carefully distinguish his subtle and unique interpretation of quantum mechanics from views often imputed to him under the banner of the “Copenhagen Interpretation.” With respect to philosophical influences on Bohr's outlook, the contributors analyse prominent similarities between his viewpoint and Kantian ways of thinking, the views of the Danish philosopher Harald Høffding, and themes characteristic of American pragmatism. In recognizing the importance of Bohr's epistemological naturalism they examine his defence of the indispensability of classical concepts from a variety of different perspectives. This collection shows us that Bohr's int...

Identification and production of mouse scFv to specific epitope of enterovirus-71 virion protein-2 (VP2).

Science.gov (United States)

Thanongsaksrikul, Jeeraphong; Srimanote, Potjanee; Tongtawe, Pongsri; Glab-Ampai, Kittirat; Malik, Aijaz Ahmad; Supasorn, Oratai; Chiawwit, Phatcharaporn; Poovorawan, Yong; Chaicumpa, Wanpen

2018-05-01

Enterovirus-71 (EV71) and coxsackievirus-A16 (CA16) frequently cause hand-foot-mouth disease (HFMD) epidemics among infants and young children. CA16 infections are usually mild, while EV71 disease may be fatal due to neurologic complications. As such, the ability to rapidly and specifically recognize EV71 is needed to facilitate proper case management and epidemic control. Accordingly, the aim of this study was to generate antibodies to EV71-virion protein-2 (VP2) by phage display technology for further use in specific detection of EV71. A recombinant peptide sequence of EV71-VP2, carrying a predicted conserved B cell epitope fused to glutathione-S-transferase (GST) (designated GST-EV71-VP2/131-160), was produced. The fusion protein was used as bait in in-solution biopanning to separate protein-bound phages from a murine scFv (MuscFv) phage display library constructed from an immunoglobulin gene repertoire from naïve ICR mice. Three phage-transformed E. coli clones (clones 63, 82, and 83) produced MuscFvs that bound to the GST-EV71-VP2/131-160 peptide. The MuscFv of clone 83 (MuscFv83), which produced the highest ELISA signal to the target antigen, was further tested. MuscFv83 also bound to full-length EV71-VP2 and EV71 particles, but did not bind to GST, full-length EV71-VP1, or the antigenically related CA16. MuscFv83 could be a suitable reagent for rapid antigen-based immunoassay, such as immunochromatography (ICT), for the specific detection and/or diagnosis of EV71 infection as well as epidemic surveillance.

Anti-CTGF single-chain variable fragment dimers inhibit human airway smooth muscle (ASM) cell proliferation by down-regulating p-Akt and p-mTOR levels.

Science.gov (United States)

Gao, Wei; Cai, Liting; Xu, Xudong; Fan, Juxiang; Xue, Xiulei; Yan, Xuejiao; Qu, Qinrong; Wang, Xihua; Zhang, Chen; Wu, Guoqiu

2014-01-01

Connective tissue growth factor (CTGF) contributes to airway smooth muscle (ASM) cell hyperplasia in asthma. Humanized single-chain variable fragment antibody (scFv) was well characterized as a CTGF antagonist in the differentiation of fibroblast into myofibroblast and pulmonary fibrosis in our previous studies. To further improve the bioactivity of scFv, we constructed a plasmid to express scFv-linker-matrilin-6×His fusion proteins that could self-assemble into the scFv dimers by disulfide bonds in matrilin under non-reducing conditions. An immunoreactivity assay demonstrated that the scFv dimer could highly bind to CTGF in a concentration-dependent manner. The MTT and EdU assay results revealed that CTGF (≥10 ng/mL) promoted the proliferation of ASM cells, and this effect was inhibited when the cells were treated with anti-CTGF scFv dimer. The western blot analysis results showed that increased phosphorylation of Akt and mTOR induced by CTGF could be suppressed by this scFv dimer. Based on these findings, anti-CTGF scFv dimer may be a potential agent for the prevention of airway remodeling in asthma.

Production of a phage-displayed single chain variable fragment ...

African Journals Online (AJOL)

Purpose: To develop specific single chain variable fragments (scFv) against infectious bursal disease virus (IBDV) via phage display technology. Methods: Purified viruses were initially applied for iterative panning rounds of scFv phage display libraries. The binding ability of the selected scFv antibody fragments against the ...

Preventive Activity against Influenza (H1N1 Virus by Intranasally Delivered RNA-Hydrolyzing Antibody in Respiratory Epithelial Cells of Mice

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Seungchan Cho

2015-09-01

Full Text Available The antiviral effect of a catalytic RNA-hydrolyzing antibody, 3D8 scFv, for intranasal administration against avian influenza virus (H1N1 was described. The recombinant 3D8 scFv protein prevented BALB/c mice against H1N1 influenza virus infection by degradation of the viral RNA genome through its intrinsic RNA-hydrolyzing activity. Intranasal administration of 3D8 scFv (50 μg/day for five days prior to infection demonstrated an antiviral activity (70% survival against H1N1 infection. The antiviral ability of 3D8 scFv to penetrate into epithelial cells from bronchial cavity via the respiratory mucosal layer was confirmed by immunohistochemistry, qRT-PCR, and histopathological examination. The antiviral activity of 3D8 scFv against H1N1 virus infection was not due to host immune cytokines or chemokines, but rather to direct antiviral RNA-hydrolyzing activity of 3D8 scFv against the viral RNA genome. Taken together, our results suggest that the RNase activity of 3D8 scFv, coupled with its ability to penetrate epithelial cells through the respiratory mucosal layer, directly prevents H1N1 virus infection in a mouse model system.

A compact phage display human scFv library for selection of antibodies to a wide variety of antigens

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Kristensen Peter

2009-01-01

Full Text Available Abstract Background Phage display technology is a powerful new tool for making antibodies outside the immune system, thus avoiding the use of experimental animals. In the early days, it was postulated that this technique would eventually replace hybridoma technology and animal immunisations. However, since this technology emerged more than 20 years ago, there have only been a handful reports on the construction and application of phage display antibody libraries world-wide. Results Here we report the simplest and highly efficient method for the construction of a highly useful human single chain variable fragment (scFv library. The least number of oligonucleotide primers, electroporations and ligation reactions were used to generate a library of 1.5 × 108 individual clones, without generation of sub-libraries. All possible combinations of heavy and light chains, among all immunoglobulin isotypes, were included by using a mixture of primers and overlapping extension PCR. The key difference from other similar libraries was the highest diversity of variable gene repertoires, which was derived from 140 non-immunized human donors. A wide variety of antigens were successfully used to affinity select specific binders. These included pure recombinant proteins, a hapten and complex antigens such as viral coat proteins, crude snake venom and cancer cell surface antigens. In particular, we were able to use standard bio-panning method to isolate antibody that can bind to soluble Aflatoxin B1, when using BSA-conjugated toxin as a target, as demonstrated by inhibition ELISA. Conclusion These results suggested that by using an optimized protocol and very high repertoire diversity, a compact and efficient phage antibody library can be generated. This advanced method could be adopted by any molecular biology laboratory to generate both naïve or immunized libraries for particular targets as well as for high-throughput applications.

Purification and refolding of anti-T-antigen single chain antibodies (scFvs) expressed in Escherichia coli as inclusion bodies.

Science.gov (United States)

Yuasa, Noriyuki; Koyama, Tsubasa; Fujita-Yamaguchi, Yoko

2014-02-01

T-antigen (Galβ1-3GalNAcα-1-Ser/Thr) is an oncofetal antigen that is commonly expressed as a carbohydrate determinant in many adenocarcinomas. Since it is associated with tumor progression and metastasis, production of recombinant antibodies specific for T-antigen could lead to the development of cancer diagnostics and therapeutics. Previously, we isolated and characterized 11 anti-T-antigen phage clones from a phage library displaying human single-chain antibodies (scFvs) and purified one scFv protein, 1G11. More recently, we purified and characterized 1E8 scFv protein using a Drosophila S2 expression system. In the current study, four anti-T-antigen scFv genes belonging to Groups 1-4 were purified from inclusion bodies expressed in Escherichia coli cells. Inclusion bodies isolated from E. coli cells were denatured in 3.5 M Gdn-HCl. Solubilized His-tagged scFv proteins were purified using Ni(2+)-Sepharose column chromatography in the presence of 3.5 M Gdn-HCl. Purified scFv proteins were refolded according to a previously published method of step-wise dialysis. Two anti-T-antigen scFv proteins, 1E6 and 1E8 that belong to Groups 1 and 2, respectively, were produced in sufficient amounts, thus allowing further characterization of their binding activity with T-antigen. Specificity and affinity constants determined using enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR), respectively, provided evidence that both 1E8 and 1E6 scFv proteins are T-antigen specific and suggested that 1E8 scFv protein has a higher affinity for T-antigen than 1E6 scFv protein.

A simple and robust approach to immobilization of antibody fragments.

Science.gov (United States)

Ikonomova, Svetlana P; He, Ziming; Karlsson, Amy J

2016-08-01

Antibody fragments, such as the single-chain variable fragment (scFv), have much potential in research and diagnostics because of their antigen-binding ability similar to a full-sized antibody and their ease of production in microorganisms. Some applications of antibody fragments require immobilization on a surface, and we have established a simple immobilization method that is based on the biotin-streptavidin interaction and does not require a separate purification step. We genetically fused two biotinylation tags-the biotin carboxyl carrier protein (BCCP) or the AviTag minimal sequence-to six different scFvs (scFv13R4, scFvD10, scFv26-10, scFv3, scFv5, and scFv12) for site-specific biotinylation in vivo by endogenous biotin ligases produced by Escherichia coli. The biotinylated scFvs were immobilized onto streptavidin-coated plates directly from cell lysates, and immobilization was detected through enzyme-linked immunosorbent assays. All scFvs fusions were successfully immobilized, and scFvs biotinylated via the BCCP tag tended to immobilize better than those biotinylated via the AviTag, even when biotinylation efficiency was improved with the biotin ligase BirA. The ability of immobilized scFvs to bind antigens was confirmed using scFv13R4 and scFvD10 with their respective targets β-galactosidase and bacteriophage lambda head protein D (gpD). The immobilized scFv13R4 bound to β-galactosidase at the same level for both biotinylation tags when the surface was saturated with the scFv, and immobilized scFvs retained their functionality for at least 100days after immobilization. The simplicity and robustness of our method make it a promising approach for future applications that require antibody fragment immobilization. Copyright © 2016 Elsevier B.V. All rights reserved.

Exploring the Unique Features of a First Nations Graduate-Level Social Work Program

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Ralph C. Bodor

2015-03-01

Full Text Available Recently, a one-time cohort of graduate-level social work students completed a unique MSW program. The program was delivered in partnership between the Faculty of Social Work, University of Calgary and Blue Quills First Nations College and, of the twenty four graduates; twenty-one were of First Nations or Me´tis ancestry. The program honored traditional knowledge and ways of learning combined with a critical analysis of Western perspectives of social work knowledge. Strong fiscal resources enabled the program to establish a formal support network for the students and to support the development of Indigenous curriculum and programming that encouraged success for the students. The program was fundamentally different than urban on-campus programs while still maintaining graduate level accreditation requirements. This analysis of the program required the use of Indigenous Research Methodology to collect and create an understanding of the program. Instructors commented on the centered, empowered, balanced, and congruent students. The formal and informal, concrete and invisible supports to the students ensured the success of this program and this cohort of students. As one student commented, the program started in ceremony, ended in ceremony, and could not fail within the context ceremony.

[Construction and screening of phage antibody libraries against epidermal growth factor receptor and soluble expression of single chain Fv].

Science.gov (United States)

Sheng, Wei-Jin; Miao, Qing-Fang; Zhen, Yong-Su

2009-06-01

Recent studies have shown that epidermal growth factor receptor (EGFR) is an important target for cancer therapy. The present study prepared single chain Fv (scFv) directed against EGFR. Balb/c mice were immunized by human carcinoma A431 cells, and total RNA of the splenic cells was extracted. VH and VL gene fragments were amplified by RT-PCR and further joined into scFv gene with a linker, then scFv gene fragments were ligated into the phagemid vector pCANTAB 5E. The phagemid containing scFv were transformed into electro-competent E. coli TG1 cells. The recombinant phage antibody library was constructed through rescuing the transformed cells with help phage M13K07. The specified recombinant phages were enriched through 5 rounds of affinity panning and the anti-EGFR phage scFv clones were screened and identified with ELISA. A total of 48 clones from the library were selected randomly and 45 clones were identified positive. After infecting E. coli HB2151 cells with one positive clone, soluble recombinant antibodies about 27 kD were produced and located in the periplasm and the supernatant. The result of sequencing showed that the scFv gene was 768 bp, which encoded 256 amino acid residues. VH and VL including 3 CDRs and 4 FRs, respectively, were all homologous to mouse Ig. The soluble scFv showed the specific binding activity to purified EGFR and EGFR located in carcinoma cell membrane. The successful preparation of anti-EGFR scFv will provide an EGFR targeted molecule for the development of antibody-based drugs and biological therapy of cancer.

Unique Path Partitions

DEFF Research Database (Denmark)

Bessenrodt, Christine; Olsson, Jørn Børling; Sellers, James A.

2013-01-01

We give a complete classification of the unique path partitions and study congruence properties of the function which enumerates such partitions.......We give a complete classification of the unique path partitions and study congruence properties of the function which enumerates such partitions....

Isolation and characterisation of a human-like antibody fragment (scFv that inactivates VEEV in vitro and in vivo.

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Torsten Rülker

Full Text Available Venezuelan equine encephalitis virus (VEEV belongs to the Alphavirus genus and several species of this family are pathogenic to humans. The viruses are classified as potential agents of biological warfare and terrorism and sensitive detection as well as effective prophylaxis and antiviral therapies are required.In this work, we describe the isolation of the anti-VEEV single chain Fragment variable (scFv, ToR67-3B4, from a non-human primate (NHP antibody gene library. We report its recloning into the bivalent scFv-Fc format and further immunological and biochemical characterisation.The scFv-Fc ToR67-3B4 recognised viable as well as formalin and ß-propionolactone (ß-Pl inactivated virus particles and could be applied for immunoblot analysis of VEEV proteins and immuno-histochemistry of VEEV infected cells. It detected specifically the viral E1 envelope protein of VEEV but did not react with reduced viral glycoprotein preparations suggesting that recognition depends upon conformational epitopes. The recombinant antibody was able to detect multiple VEEV subtypes and displayed only marginal cross-reactivity to other Alphavirus species except for EEEV. In addition, the scFv-Fc fusion described here might be of therapeutic use since it successfully inactivated VEEV in a murine disease model. When the recombinant antibody was administered 6 hours post challenge, 80% to 100% of mice survived lethal VEEV IA/B or IE infection. Forty to sixty percent of mice survived when scFv-Fc ToR67-3B4 was applied 6 hours post challenge with VEEV subtypes II and former IIIA. In combination with E2-neutralising antibodies the NHP antibody isolated here could significantly improve passive protection as well as generic therapy of VEE.

Ophiophagus hannah Venom: Proteome, Components Bound by Naja kaouthia Antivenin and Neutralization by N. kaouthia Neurotoxin-Specific Human ScFv

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Witchuda Danpaiboon

2014-05-01

Full Text Available Venomous snakebites are an important health problem in tropical and subtropical countries. King cobra (Ophiophagus hannah is the largest venomous snake found in South and Southeast Asia. In this study, the O. hannah venom proteome and the venom components cross-reactive to N. kaouthia monospecific antivenin were studied. O. hannah venom consisted of 14 different protein families, including three finger toxins, phospholipases, cysteine-rich secretory proteins, cobra venom factor, muscarinic toxin, L-amino acid oxidase, hypothetical proteins, low cysteine protein, phosphodiesterase, proteases, vespryn toxin, Kunitz, growth factor activators and others (coagulation factor, endonuclease, 5’-nucleotidase. N. kaouthia antivenin recognized several functionally different O. hannah venom proteins and mediated paratherapeutic efficacy by rescuing the O. hannah envenomed mice from lethality. An engineered human ScFv specific to N. kaouthia long neurotoxin (NkLN-HuScFv cross-neutralized the O. hannah venom and extricated the O. hannah envenomed mice from death in a dose escalation manner. Homology modeling and molecular docking revealed that NkLN-HuScFv interacted with residues in loops 2 and 3 of the neurotoxins of both snake species, which are important for neuronal acetylcholine receptor binding. The data of this study are useful for snakebite treatment when and where the polyspecific antivenin is not available. Because the supply of horse-derived antivenin is limited and the preparation may cause some adverse effects in recipients, a cocktail of recombinant human ScFvs for various toxic venom components shared by different venomous snakes, exemplified by the in vitro produced NkLN-HuScFv in this study, should contribute to a possible future route for an improved alternative to the antivenins.

Ophiophagus hannah venom: proteome, components bound by Naja kaouthia antivenin and neutralization by N. kaouthia neurotoxin-specific human ScFv.

Science.gov (United States)

Danpaiboon, Witchuda; Reamtong, Onrapak; Sookrung, Nitat; Seesuay, Watee; Sakolvaree, Yuwaporn; Thanongsaksrikul, Jeeraphong; Dong-din-on, Fonthip; Srimanote, Potjanee; Thueng-in, Kanyarat; Chaicumpa, Wanpen

2014-05-13

Venomous snakebites are an important health problem in tropical and subtropical countries. King cobra (Ophiophagus hannah) is the largest venomous snake found in South and Southeast Asia. In this study, the O. hannah venom proteome and the venom components cross-reactive to N. kaouthia monospecific antivenin were studied. O. hannah venom consisted of 14 different protein families, including three finger toxins, phospholipases, cysteine-rich secretory proteins, cobra venom factor, muscarinic toxin, L-amino acid oxidase, hypothetical proteins, low cysteine protein, phosphodiesterase, proteases, vespryn toxin, Kunitz, growth factor activators and others (coagulation factor, endonuclease, 5'-nucleotidase). N. kaouthia antivenin recognized several functionally different O. hannah venom proteins and mediated paratherapeutic efficacy by rescuing the O. hannah envenomed mice from lethality. An engineered human ScFv specific to N. kaouthia long neurotoxin (NkLN-HuScFv) cross-neutralized the O. hannah venom and extricated the O. hannah envenomed mice from death in a dose escalation manner. Homology modeling and molecular docking revealed that NkLN-HuScFv interacted with residues in loops 2 and 3 of the neurotoxins of both snake species, which are important for neuronal acetylcholine receptor binding. The data of this study are useful for snakebite treatment when and where the polyspecific antivenin is not available. Because the supply of horse-derived antivenin is limited and the preparation may cause some adverse effects in recipients, a cocktail of recombinant human ScFvs for various toxic venom components shared by different venomous snakes, exemplified by the in vitro produced NkLN-HuScFv in this study, should contribute to a possible future route for an improved alternative to the antivenins.

Suppression of Aggrus/podoplanin-induced platelet aggregation and pulmonary metastasis by a single-chain antibody variable region fragment

International Nuclear Information System (INIS)

Miyata, Kenichi; Takagi, Satoshi; Sato, Shigeo; Morioka, Hiroshi; Shiba, Kiyotaka; Minamisawa, Tamiko; Takami, Miho; Fujita, Naoya

2014-01-01

Almost all highly metastatic tumor cells possess high platelet aggregating abilities, thereby form large tumor cell-platelet aggregates in the microvasculature. Embolization of tumor cells in the microvasculature is considered to be the first step in metastasis to distant organs. We previously identified the platelet aggregation-inducing factor expressed on the surfaces of highly metastatic tumor cells and named as Aggrus. Aggrus was observed to be identical to the marker protein podoplanin (alternative names, T1α, OTS-8, and others). Aggrus is frequently overexpressed in several types of tumors and enhances platelet aggregation by interacting with the platelet receptor C-type lectin-like receptor 2 (CLEC-2). Here, we generated a novel single-chain antibody variable region fragment (scFv) by linking the variable regions of heavy and light chains of the neutralizing anti-human Aggrus monoclonal antibody MS-1 with a flexible peptide linker. Unfortunately, the generated KM10 scFv failed to suppress Aggrus-induced platelet aggregation in vitro. Therefore, we performed phage display screening and finally obtained a high-affinity scFv, K-11. K-11 scFv was able to suppress Aggrus-induced platelet aggregation in vitro. Moreover, K-11 scFv prevented the formation of pulmonary metastasis in vivo. These results suggest that K-11 scFv may be useful as metastasis inhibitory scFv and is expected to aid in the development of preclinical and clinical examinations of Aggrus-targeted cancer therapies

Uniqueness and non-uniqueness of semigroups generated by singular diffusion operators

CERN Document Server

Eberle, Andreas

1999-01-01

This book addresses both probabilists working on diffusion processes and analysts interested in linear parabolic partial differential equations with singular coefficients. The central question discussed is whether a given diffusion operator, i.e., a second order linear differential operator without zeroth order term, which is a priori defined on test functions over some (finite or infinite dimensional) state space only, uniquely determines a strongly continuous semigroup on a corresponding weighted Lp space. Particular emphasis is placed on phenomena causing non-uniqueness, as well as on the relation between different notions of uniqueness appearing in analytic and probabilistic contexts.

Expression and purification of a novel therapeutic single-chain variable fragment antibody against BNP from inclusion bodies of Escherichia coli.

Science.gov (United States)

Bu, Dawei; Zhou, Yuwei; Tang, Jian; Jing, Fang; Zhang, Wei

2013-12-01

Abnormal brain natriuretic peptide (BNP) secretion is regarded as the dominating mechanism of cerebral salt wasting syndrome (CSW), which results from a renal loss of sodium and water during intracranial disease leading to hyponatremia. Scale preparation of therapeutic single-chain variable fragment (scFv) that can neutralize elevated circulating BNP may have potential value for clinical use. In this report, we used a recently isolated humanized anti-BNP scFv fragment (3C1) as model antibody (Ab) to evaluate the potential of scale production of this therapeutic protein. The truncated gene encoding for scFv fragment cloned in pET22b (+) was mainly overexpressed as inclusion bodies in Escherichia coli (E. coli) Rosetta (DE3) pLysS cells. The insoluble fragment was solubilized and purified by Ni-NTA agarose resin under denaturation conditions, and recovered via an effective refolding buffer containing 50 mM Tris-HCl, pH 8.0, 0.15 M NaCl, 1 mM EDTA, 0.5 M arginine, 2 mM GSH, 1 mM GSSG, and 5% glycerol. The refolded scFv fragment was concentrated by PEG20000, and dialyzed in PBS (containing 5% glycerol, pH 7.4). The final yield was approximately 10.2 mg active scFv fragment per liter of culture (3.4 g wet weight cells). The scFv fragment was more than 95% pure assessed by SDS-PAGE assay. Recombinant scFv fragment with His tag displayed its immunoreactivity with anti-His tag Ab by western blotting. ELISA showed the scFv fragment specifically bound to BNP, and it displayed similar activity as the traditional anti-BNP monoclonal Ab (mAb). Thus, the current strategy allows convenient small-scale production of this therapeutic protein. Copyright © 2013 Elsevier Inc. All rights reserved.

[Uniqueness seeking behavior as a self-verification: an alternative approach to the study of uniqueness].

Science.gov (United States)

Yamaoka, S

1995-06-01

Uniqueness theory explains that extremely high perceived similarity between self and others evokes negative emotional reactions and causes uniqueness seeking behavior. However, the theory conceptualizes similarity so ambiguously that it appears to suffer from low predictive validity. The purpose of the current article is to propose an alternative explanation of uniqueness seeking behavior. It posits that perceived uniqueness deprivation is a threat to self-concepts, and therefore causes self-verification behavior. Two levels of self verification are conceived: one based on personal categorization and the other on social categorization. The present approach regards uniqueness seeking behavior as the personal-level self verification. To test these propositions, a 2 (very high or moderate similarity information) x 2 (with or without outgroup information) x 2 (high or low need for uniqueness) between-subject factorial-design experiment was conducted with 95 university students. Results supported the self-verification approach, and were discussed in terms of effects of uniqueness deprivation, levels of self-categorization, and individual differences in need for uniqueness.

Light-chain residue 95 is critical for antigen binding and multispecificity of monoclonal antibody G2.

Science.gov (United States)

Usui, Daiki; Inaba, Satomi; Kamatari, Yuji O; Ishiguro, Naotaka; Oda, Masayuki

2017-09-02

The monoclonal antibody, G2, specifically binds to the immunogen peptide derived from the chicken prion protein, Pep18mer, and two chicken proteins derived peptides, Pep8 and Pep395; G2 binds with equal affinity to Pep18mer. The amino acid sequences of the three peptides are completely different, and so the recognition mechanism of G2 is unique and interesting. We generated a single-chain Fv (scFv) antibody of G2, and demonstrated its correct folding with an antigen binding function similar to intact G2 antibody. We also generated a Pro containing mutant of G2 scFv at residue 95 of the light chain, and analyzed its antigen binding using a surface plasmon biosensor. The mutant lost its binding ability to Pep18mer, but remained those to Pep8 and Pep395. The results clearly indicate residue 95 as being critical for multispecific antigen binding of G2 at the site generated from the junctional diversity introduced at the joints between the V and J gene segments. Copyright © 2017 Elsevier Inc. All rights reserved.

Antibody phage display applications for nuclear medicine imaging and therapy

International Nuclear Information System (INIS)

Winthrop, M.D.; Denardo, G.L.; Denardo, S.J.

2000-01-01

Antibody-based constructs genetically engineered from genes of diverse origin provide a remarkable opportunity to develop functional molecular imaging techniques and specific molecular targeted radionuclide therapies. Phage display libraries of antibody fragment genes can be used to select antibody-based constructs that bind any chosen epitope. A large naive human antibody-based library was used to illustrate binding of antibody constructs to a variety of common and unique antigens. Antibody-based libraries from hybridoma cells, lymphocytes from immunized humans or from mice and human antibody repertoires produced in transgenic mice have also been described. Several orders of magnitude of affinity enhancement can be achieved by random or site specific mutations of the selected binding peptide domains of the scFv. Affinities (K d ) as high as 10 - 11 M (10 pM) for affinity-matured scFv have been documented. Such gene libraries thus offer an almost limitless variety of antibody-based molecular binding peptide modules that can be used in creative ways for the construction of new targeting agents for functional or molecular imaging and therapy

Identification of tumor associated single-chain Fv by panning and screening antibody phage library using tumor cells

Science.gov (United States)

Nie, Yong-Zhan; He, Feng-Tian; Li, Zhi-Kui; Wu, Kai-Chun; Cao, Yun-Xin; Chen, Bao-Jun; Fan, Dai-Ming

2002-01-01

AIM: To study the feasibility of panning and screening phage-displaying recombinant single-chain variable fragment (ScFv) of anti-tumor monoclonal antibodies for fixed whole cells as the carriers of mAb-binding antigens. METHODS: The recombinant phage displaying libraries for anti-colorectal tumor mAb MC3Ab, MC5Ab and anti-gastric tumor mAb MGD1 was constructed. Panning and screening were carried out by means of modified fixation of colorectal and gastric tumor cells expressed the mAb-binding antigens. Concordance of binding specificity to tumor cells between phage clones and parent antibodies was analyzed. The phage of positive clones was identified with competitive ELISA, and infected by E. coli HB2151 to express soluble ScFv. RESULTS: The ratio of positive clones to MC3-ScF-MC5-ScFv and MGD1-ScFv were 60%, 24% and 30%. MC3-ScFv had Mr 32000 confirmed by Western blot. The specificity to antigen had no difference between 4 positive recombinant phage antibodies and MC3Ab. CONCLUSION: The modified process of fixing whole tumor cells is efficient, convenient and feasible to pan and screen the phage-displaying ScFv of anti-tumor monoclonal antibodies. PMID:12174367

The twenty-eight lodges (xiu 宿)

OpenAIRE

Morgan, Daniel Patrick

2018-01-01

The twenty-eight lodges (xiu 宿). Named and numbered in the central circle, the twenty-eight lodges, represent uneven orange-segment-like divisions of the celestial sphere running from pole to pole through the ‘guide stars’ (juxing 距星) at/near the western extremity of the constellations after which they are named. In the inner circle are the modern identifications of those guide stars. In the outer circle are the equatorial lodge widths in contemporary use in du 度 / days, where the number of d...

Proceedings: Twenty years of energy policy: Looking toward the twenty-first century

International Nuclear Information System (INIS)

1992-01-01

In 1973, immediately following the Arab Oil Embargo, the Energy Resources Center, University of Illinois at Chicago initiated an innovative annual public service program called the Illinois Energy Conference. The objective was to provide a public forum each year to address an energy or environmental issue critical to the state, region and nation. Twenty years have passed since that inaugural program, and during that period we have covered a broad spectrum of issues including energy conservation nuclear power, Illinois coal, energy policy options, natural gas, alternative fuels, new energy technologies, utility deregulation and the National Energy Strategy

Proceedings: Twenty years of energy policy: Looking toward the twenty-first century

Energy Technology Data Exchange (ETDEWEB)

1992-12-31

In 1973, immediately following the Arab Oil Embargo, the Energy Resources Center, University of Illinois at Chicago initiated an innovative annual public service program called the Illinois Energy Conference. The objective was to provide a public forum each year to address an energy or environmental issue critical to the state, region and nation. Twenty years have passed since that inaugural program, and during that period we have covered a broad spectrum of issues including energy conservation nuclear power, Illinois coal, energy policy options, natural gas, alternative fuels, new energy technologies, utility deregulation and the National Energy Strategy.

Why the American public supports twenty-first century learning.

Science.gov (United States)

Sacconaghi, Michele

2006-01-01

Aware that constituent support is essential to any educational endeavor, the AOL Time Warner Foundation (now the Time Warner Foundation), in conjunction with two respected national research firms, measured Americans' attitudes toward the implementation of twenty-first century skills. The foundation's national research survey was intended to explore public perceptions of the need for changes in the educational system, in school and after school, with respect to the teaching of twenty-first century skills. The author summarizes the findings of the survey, which were released by the foundation in June 2003. One thousand adults were surveyed by telephone, including African Americans, Latinos, teachers, and business executives. In general, the survey found that Americans believe today's students need a "basics-plus" education, meaning communication, technology, and critical thinking skills in addition to the traditional basics of reading, writing, and math. In fact, 92 percent of respondents stated that students today need different skills from those of ten to twenty years ago. Also, after-school programs were found to be an appropriate vehicle to teach these skills. Furthermore, the survey explored how well the public perceives schools to be preparing youth for the workforce and postsecondary education, which twenty-first century skills are seen as being taught effectively, and the level of need for after-school and summer programs. The survey results provide conclusive evidence of national support for basics-plus education. Thus, a clear opportunity exists to build momentum for a new model of education for the twenty-first century.

Twenty lectures on thermodynamics

CERN Document Server

Buchdahl, H A

2013-01-01

Twenty Lectures on Thermodynamics is a course of lectures, parts of which the author has given various times over the last few years. The book gives the readers a bird's eye view of phenomenological and statistical thermodynamics. The book covers many areas in thermodynamics such as states and transition; adiabatic isolation; irreversibility; the first, second, third and Zeroth laws of thermodynamics; entropy and entropy law; the idea of the application of thermodynamics; pseudo-states; the quantum-static al canonical and grand canonical ensembles; and semi-classical gaseous systems. The text

The Twenty Statement Test in Teacher Development

Directory of Open Access Journals (Sweden)

Ahmet Aypay

2011-10-01

Full Text Available The purpose of this study is to describe teacher characteristics using Twenty Statements Test (TST. Study group includes a total of thirty-five individuals, including teachers, guidance and counselors and research assistants. The study used a qualitative approach on teacher identity. TST is one of the qualitative methods that were used to determine individual self-conceptualization. Study group were requested to write twenty statements that describe themselves responding to the question “Who I am?” in a free format. The findings indicated that teachers were overwhelmingly in group c (reflective. No differences were found in terms of gender and profession. Only few significant differences have been found based on marital status. The utility of TST in teacher training and development was discussed.

The Twenty Statement Test in Teacher Development

Directory of Open Access Journals (Sweden)

Ahmet Aypay

2011-04-01

Full Text Available The purpose of this study is to describe teacher characteristics using Twenty Statements Test (TST. Study group includes a total of thirty-five individuals, including teachers, guidance and counselors and research assistants. The study used a qualitative approach on teacher identity. TST is one of the qualitative methods that were used to determine individual self-conceptualization. Study group were requested to write twenty statements that describe themselves responding to the question “Who I am?” in a free format. The findings indicated that teachers were overwhelmingly in group c (reflective. No differences were found in terms of gender and profession. Only few significant differences have been found based on marital status. The utility of TST in teacher training and development was discussed

Uniquely Strongly Clean Group Rings

Institute of Scientific and Technical Information of China (English)

WANG XIU-LAN

2012-01-01

A ring R is called clean if every element is the sum of an idempotent and a unit,and R is called uniquely strongly clean (USC for short) if every element is uniquely the sum of an idempotent and a unit that commute.In this article,some conditions on a ring R and a group G such that RG is clean are given.It is also shown that if G is a locally finite group,then the group ring RG is USC if and only if R is USC,and G is a 2-group.The left uniquely exchange group ring,as a middle ring of the uniquely clean ring and the USC ring,does not possess this property,and so does the uniquely exchange group ring.

Developing twenty-first century skills: insights from an intensive interdisciplinary workshop Mosaic of Life

Directory of Open Access Journals (Sweden)

Tamara Milosevic

2013-11-01

Full Text Available The Baltic Sea, one of the world’s largest semi-enclosed seas, which, with its very low salinity and quasi-isolation from the big oceans cannot decide whether it is a sea or a large lake. This geologically-unique environment supports an even more surprising and delicate marine ecosystem, where a complex community of fishes, marine mammals and important microscopic organisms creates a magical mosaic of life. Humans have enjoyed the abundance of life in the Baltic Sea for thousands of years, and major Scandinavian and Baltic cities have oriented themselves towards this geo-ecosystem in order to develop and seek ecological, economical and cultural inspiration and wealth. The ‘Mosaic of Life’ workshop aimed at going beyond the obvious in examining the meaning of the Baltic Sea by gathering together a selection of young, creative minds from different backgrounds ranging from the arts and economics to geology and life sciences. This intensive workshop was designed as a unique training opportunity to develop essential twenty-first century skills – to introduce and develop creative, critical and interdisciplinary thinking and collaborative teamwork, as well as to foster a visual and scientific literacy, using project-based learning and hands-on activities. Our final goal has been to be inspired by the resulting connections, differences and unifying concepts, creating innovative, interdisciplinary projects which would look further than the sea – further than the eye can see and further into the future.

Production of a phage-displayed single chain variable fragment ...

African Journals Online (AJOL)

Abstract. Purpose: To develop specific single chain variable fragments (scFv) against ... libraries. The binding ability of the selected scFv antibody fragments against the IBDV particles was ..... Hermelink H, Koscielniak E. A human recombinant.

How Has Elderly Migration Changed in the Twenty-First Century? What the Data Can-and Cannot-Tell Us.

Science.gov (United States)

Conway, Karen Smith; Rork, Jonathan C

2016-08-01

Interstate elderly migration has strong implications for state tax policies and health care systems, yet little is known about how it has changed in the twenty-first century. Its relative rarity requires a large data set with which to construct reliable measures, and the replacement of the U.S. Census long form (CLF) with the American Community Survey (ACS) has made such updates difficult. Two commonly used alternative migration data sources-the Current Population Survey (CPS) and the Statistics of Income (SOI) program of the Internal Revenue Service (IRS)-suffer serious limitations in studying the migration of any subpopulation, including the elderly. Our study informs migration research in the post-2000 era by identifying methodological differences between data sources and devising strategies for reconciling the CLF and ACS. Our investigation focusing on the elderly suggests that the ACS can generate comparable migration data that reveal a continuation of previously identified geographic patterns as well as changes unique to the 2000s. However, its changed definition of residence and survey timing leaves us unable to construct a comparable national migration rate, suggesting that one must use national trends in the smaller CPS to investigate whether elderly migration has increased or decreased in the twenty-first century.

Establishing the R&D Agenda for Twenty-First Century Learning

Science.gov (United States)

Kay, Ken; Honey, Margaret

2006-01-01

Much ink has flowed over the past few years describing the need to incorporate twenty-first century skills into K-12 education. Preparing students to succeed as citizens, thinkers, and workers--the bedrock of any educational system--in this environment means arming them with more than a list of facts and important dates. Infusing twenty-first…

The next twenty years - IAEA's role

International Nuclear Information System (INIS)

Tape, G.F.

1977-01-01

The twentieth anniversary of an institution is an appropriate time to look back and to ask what has been achieved. It is also an appropriate time to look ahead and to ask what should be the mission for the future. How can the strengths of the International Atomic Energy Agency (IAEA) be best utilized, what new opportunities should be seized upon, and what challenges should the IAEA be prepared to meet in the next twenty years? Forward planning is a very necessary activity in today's world. There are so many demands on national or institutional resources that careful analysis of options is necessary to establish priorities and ultimately to provide for implementation. But such planning must be done carefully with full appreciation for the validity and sensitivity of the input assumptions and data. Furthermore, today's plan, while setting goals and directions, cannot be so inflexible that it cannot be responsive to ever-changing political, economic and technical constraints or opportunities. Thus in looking ahead, the plan must contain provisions for flexibility to provide for further modifications in the light of ever-changing knowledge, attitudes, and world conditions. The experience of the past five years in the energy field, and especially in nuclear energy, underscores this need. In looking ahead for the next twenty years, we are attempting to describe the International Atomic Energy Agency and its role through the twentieth century. In doing so, we are automatically laying the base for the Agency's work going into the twenty-first century. In short, we are trying to visualize a programme that can serve the coming generation and, in doing so, creating a base from which the needs of the succeeding generation can be met. This is a large order and the crystal ball is less than clear. (author)

A natively paired antibody library yields drug leads with higher sensitivity and specificity than a randomly paired antibody library.

Science.gov (United States)

Adler, Adam S; Bedinger, Daniel; Adams, Matthew S; Asensio, Michael A; Edgar, Robert C; Leong, Renee; Leong, Jackson; Mizrahi, Rena A; Spindler, Matthew J; Bandi, Srinivasa Rao; Huang, Haichun; Tawde, Pallavi; Brams, Peter; Johnson, David S

2018-04-01

Deep sequencing and single-chain variable fragment (scFv) yeast display methods are becoming more popular for discovery of therapeutic antibody candidates in mouse B cell repertoires. In this study, we compare a deep sequencing and scFv display method that retains native heavy and light chain pairing with a related method that randomly pairs heavy and light chain. We performed the studies in a humanized mouse, using interleukin 21 receptor (IL-21R) as a test immunogen. We identified 44 high-affinity binder scFv with the native pairing method and 100 high-affinity binder scFv with the random pairing method. 30% of the natively paired scFv binders were also discovered with the randomly paired method, and 13% of the randomly paired binders were also discovered with the natively paired method. Additionally, 33% of the scFv binders discovered only in the randomly paired library were initially present in the natively paired pre-sort library. Thus, a significant proportion of "randomly paired" scFv were actually natively paired. We synthesized and produced 46 of the candidates as full-length antibodies and subjected them to a panel of binding assays to characterize their therapeutic potential. 87% of the antibodies were verified as binding IL-21R by at least one assay. We found that antibodies with native light chains were more likely to bind IL-21R than antibodies with non-native light chains, suggesting a higher false positive rate for antibodies from the randomly paired library. Additionally, the randomly paired method failed to identify nearly half of the true natively paired binders, suggesting a higher false negative rate. We conclude that natively paired libraries have critical advantages in sensitivity and specificity for antibody discovery programs.

A conjugate of an anti-midkine single-chain variable fragment to doxorubicin inhibits tumor growth

Energy Technology Data Exchange (ETDEWEB)

Zhao, Shuli [Immunology and Reproductive Biology Laboratory, Medical School & State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing (China); Nanjing Affiliated First Hospital, Nanjing Medical University, Nanjing (China); Zhao, Guangfeng; Xie, Hao; Huang, Yahong [Immunology and Reproductive Biology Laboratory, Medical School & State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing (China); Hou, Yayi [Immunology and Reproductive Biology Laboratory, Medical School & State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing (China); Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing (China)

2012-01-27

Doxorubicin (DOX) was conjugated to a single-chain variable fragment (scFv) against human midkine (MK), and the conjugate (scFv-DOX) was used to target the chemotherapeutic agent to a mouse solid tumor model in which the tumor cells expressed high levels of human MK. The His-tagged recombinant scFv was expressed in bacteria, purified by metal affinity chromatography, and then conjugated to DOX using oxidative dextran (Dex) as a linker. The molecular formula of this immunoconjugate was scFv(Dex){sub 1.3}(DOX){sub 20}. In vitro apoptosis assays showed that the scFv-DOX conjugate was more cytotoxic against MK-transfected human adenocarcinoma cells (BGC823-MK) than untransfected cells (55.3 ± 2.4 vs 22.4 ± 3.8%) for three independent experiments. Nude mice bearing BGC823-MK solid tumors received scFv-DOX or equivalent doses of scFv + DOX for 2 weeks and tumor growth was more effectively inhibited by the scFv-DOX conjugate than by scFv + DOX (51.83% inhibition vs 40.81%). Histological analysis of the tumor tissues revealed that the highest levels of DOX accumulated in tumors from mice treated with scFv-DOX and this resulted in more extensive tumor cell death than in animals treated with the equivalent dose of scFv + DOX. These results show that the scFv-DOX conjugate effectively inhibited tumor growth in vivo and suggest that antigen-specific scFv may be competent drug-carriers.

A conjugate of an anti-midkine single-chain variable fragment to doxorubicin inhibits tumor growth

International Nuclear Information System (INIS)

Zhao, Shuli; Zhao, Guangfeng; Xie, Hao; Huang, Yahong; Hou, Yayi

2012-01-01

Doxorubicin (DOX) was conjugated to a single-chain variable fragment (scFv) against human midkine (MK), and the conjugate (scFv-DOX) was used to target the chemotherapeutic agent to a mouse solid tumor model in which the tumor cells expressed high levels of human MK. The His-tagged recombinant scFv was expressed in bacteria, purified by metal affinity chromatography, and then conjugated to DOX using oxidative dextran (Dex) as a linker. The molecular formula of this immunoconjugate was scFv(Dex) 1.3 (DOX) 20 . In vitro apoptosis assays showed that the scFv-DOX conjugate was more cytotoxic against MK-transfected human adenocarcinoma cells (BGC823-MK) than untransfected cells (55.3 ± 2.4 vs 22.4 ± 3.8%) for three independent experiments. Nude mice bearing BGC823-MK solid tumors received scFv-DOX or equivalent doses of scFv + DOX for 2 weeks and tumor growth was more effectively inhibited by the scFv-DOX conjugate than by scFv + DOX (51.83% inhibition vs 40.81%). Histological analysis of the tumor tissues revealed that the highest levels of DOX accumulated in tumors from mice treated with scFv-DOX and this resulted in more extensive tumor cell death than in animals treated with the equivalent dose of scFv + DOX. These results show that the scFv-DOX conjugate effectively inhibited tumor growth in vivo and suggest that antigen-specific scFv may be competent drug-carriers

Development of anti-bovine IgA single chain variable fragment and its application in diagnosis of foot-and-mouth disease

Science.gov (United States)

Sridevi, N. V.; Shukra, A. M.; Neelakantam, B.; Anilkumar, J.; Madhanmohan, M.; Rajan, S.; Dev Chandran

2014-01-01

Recombinant antibody fragments like single chain variable fragments (scFvs) represent an attractive yet powerful alternative to immunoglobulins and hold great potential in the development of clinical diagnostic/therapeutic reagents. Structurally, scFvs are the smallest antibody fragments capable of retaining the antigen-binding capacity of whole antibodies and are composed of an immunoglobulin (Ig) variable light (VL) and variable heavy (VH) chain joined by a flexible polypeptide linker. In the present study, we constructed a scFv against bovine IgA from a hybridoma cell line IL-A71 that secretes a monoclonal antibody against bovine IgA using recombinant DNA technology. The scFv was expressed in Escherichia coli and purified using immobilized metal affinity chromatography (IMAC). The binding activity and specificity of the scFv was established by its non-reactivity toward other classes of immunoglobulins as determined by enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis. Kinetic measurement of the scFv indicated that the recombinant antibody fragment had an affinity in picomolar range toward purified IgA. Furthermore, the scFv was used to develop a sensitive ELISA for the detection of foot and mouth disease virus (FMDV) carrier animals. PMID:24678404

SINGLE CHAIN VARIABLE FRAGMENTS OF ANTIBODIES AGAINST DIPHTHERIA TOXIN B-SUBUNIT ISOLATED FROM PHAGE DISPLAY HUMAN ANTIBODY LIBRARY

Directory of Open Access Journals (Sweden)

Oliinyk O. S.

2014-02-01

Full Text Available Diphtheria toxin is an exoantigen of Corynebacterium diphtheriae that inhibits protein synthesis and kills sensitive cells. The aim of this study was to obtain human recombinant single-chain variable fragment (scFv antibodies against receptor-binding B subunit of diphtheria toxin. 12 specific clones were selected after three rounds of a phage display naїve (unimmunized human antibody library against recombinant B-subunit. scFv DNA inserts from these 12 clones were digested with MvaI, and 6 unique restriction patterns were found. Single-chain antibodies were expressed in Escherichia coli XL1-blue. The recombinant proteins were characterized by immunoblotting of bacterial extracts and detection with an anti-E-tag antibody. The toxin B-subunit-binding function of the single-chain antibody was shown by ELISA. The affinity constants for different clones were found to be from 106 to 108 М–1. Due to the fact, that these antibody fragments recognized epitopes in the receptor-binding Bsubunit of diphtheria toxin, further studies are interesting to evaluate their toxin neutralization properties and potential for therapeutic applications. Obtained scFv-antibodies can also be used for detection and investigation of biological properties of diphtheria toxin.

Twenty-One at TREC-8: using Language Technology for Information Retrieval

NARCIS (Netherlands)

Kraaij, Wessel; Pohlmann, Renée; Hiemstra, Djoerd; Voorhees, E.M; Harman, D.K.

2000-01-01

This paper describes the official runs of the Twenty-One group for TREC-8. The Twenty-One group participated in the Ad-hoc, CLIR, Adaptive Filtering and SDR tracks. The main focus of our experiments is the development and evaluation of retrieval methods that are motivated by natural language

Strategic Leader Competencies for the Twenty-First Century

National Research Council Canada - National Science Library

Becker, Bradley A

2007-01-01

...: interpersonal skills, conceptual skills, and technical skills. From these three primary strategic leadership skills, there is a list of twenty-one competencies that a strategic leader should posses...

Twenty-One at TREC-7: ad-hoc and cross-language track

NARCIS (Netherlands)

Hiemstra, Djoerd; Kraaij, Wessel; Voorhees, E.M; Harman, D.K.

1999-01-01

This paper describes the official runs of the Twenty-One group for TREC-7. The Twenty-One group participated in the ad-hoc and the cross-language track and made the following accomplishments: We developed a new weighting algorithm, which outperforms the popular Cornell version of BM25 on the ad-hoc

Cancer: Unique to Older Adults

Science.gov (United States)

... A to Z › Cancer › Unique to Older Adults Font size A A A Print Share Glossary Unique ... group with other older people with the same type of cancer. Researchers have found that support groups ...

Uniqueness in time measurement

International Nuclear Information System (INIS)

Lorenzen, P.

1981-01-01

According to P. Janich a clock is defined as an apparatus in which a point ( hand ) is moving uniformly on a straight line ( path ). For the definition of uniformly first the scaling (as a constant ratio of velocities) is defined without clocks. Thereafter the uniqueness of the time measurement can be proved using the prove of scaling of all clocks. But the uniqueness can be defined without scaling, as it is pointed out here. (orig.) [de

Twenty-First Century Literacy: A Matter of Scale from Micro to Mega

Science.gov (United States)

Brown, Abbie; Slagter van Tryon, Patricia J.

2010-01-01

Twenty-first century technologies require educators to look for new ways to teach literacy skills. Current communication methods are combinations of traditional and newer, network-driven forms. This article describes the changes twenty-first century technologies cause in the perception of time, size, distance, audience, and available data, and…

Modularity, comparative cognition and human uniqueness.

Science.gov (United States)

Shettleworth, Sara J

2012-10-05

Darwin's claim 'that the difference in mind between man and the higher animals … is certainly one of degree and not of kind' is at the core of the comparative study of cognition. Recent research provides unprecedented support for Darwin's claim as well as new reasons to question it, stimulating new theories of human cognitive uniqueness. This article compares and evaluates approaches to such theories. Some prominent theories propose sweeping domain-general characterizations of the difference in cognitive capabilities and/or mechanisms between adult humans and other animals. Dual-process theories for some cognitive domains propose that adult human cognition shares simple basic processes with that of other animals while additionally including slower-developing and more explicit uniquely human processes. These theories are consistent with a modular account of cognition and the 'core knowledge' account of children's cognitive development. A complementary proposal is that human infants have unique social and/or cognitive adaptations for uniquely human learning. A view of human cognitive architecture as a mosaic of unique and species-general modular and domain-general processes together with a focus on uniquely human developmental mechanisms is consistent with modern evolutionary-developmental biology and suggests new questions for comparative research.

Expression, production and renaturation of a functional single-chain ...

African Journals Online (AJOL)

The single-chain variable antibody fragment (scFv) against human intercellular adhesion molecule-1 (ICAM-1) was expressed at a high level in Escherichia coli as inclusion bodies. We attempted to refold the scFv by ion-exchange chromatography (IEC), dialysis and dilution. The results show that the column ...

Afterword: Victorian Sculpture for the Twenty-First Century

Directory of Open Access Journals (Sweden)

David J. Getsy

2016-06-01

Full Text Available Commenting on the directions proposed by this issue of '19', the afterword discusses the broad trends in twenty-first century studies of Victorian sculpture and the opportunity for debate arising from the first attempt at a comprehensive exhibition.

Open Adoption Placement by Birth Mothers in Their Twenties.

Science.gov (United States)

Clutter, Lynn B

The purpose of this study was to summarize birth mothers' descriptions of unplanned pregnancy experienced in their twenties and how open adoption influenced their lives. Naturalistic inquiry was used with purposive sampling from one agency and telephone interviews of women who experienced unplanned pregnancy in their twenties and relinquishment through open adoption. Recorded, transcribed, and deidentified interviews were analyzed for qualitative themes. Fifteen participants judiciously weighed the open adoption decision. Over half parented other children prior to placement. Most knew they could not have parented this child due to life stressors. Placement was a hard decision, but ongoing contact with birth child and adoptive family was valued. Open adoption processes made them stronger by being happy that their child experienced family life with greater opportunities than birth mothers could offer at the time. Summarized themes used the acronym COMMITTED: C-care deeply about what is best for the child, O-ongoing open adoption: good and hard, M-meeting together regularly, M-moving on in personal growth, accomplishments, and milestones, I-independence from previous stressors or crises, T-transitions, T-therapeutic support, E-emotions, D-depression giving way to deepened strength and personal direction. Open adoption is reinforced as a positive resolution of unintended pregnancy for birth mothers in their twenties.

Nuclear power in the twenty-first century - An assessment (Part 1)

OpenAIRE

von Hirschhausen, Christian

2017-01-01

Nuclear power was one of the most important discoveries of the twentieth century, and it continues to play an important role in twenty-first century discussions about the future energy mix, climate change, innovation, proliferation, geopolitics, and many other crucial policy topics. This paper addresses some key issues around the emergence of nuclear power in the twentieth century and perspectives going forward in the twenty-first, including questions of economics and competitiveness, the str...

Twenty-first workshop on geothermal reservoir engineering: Proceedings

Energy Technology Data Exchange (ETDEWEB)

None

1996-01-26

PREFACE The Twenty-First Workshop on Geothermal Reservoir Engineering was held at the Holiday Inn, Palo Alto on January 22-24, 1996. There were one-hundred fifty-five registered participants. Participants came from twenty foreign countries: Argentina, Austria, Canada, Costa Rica, El Salvador, France, Iceland, Indonesia, Italy, Japan, Mexico, The Netherlands, New Zealand, Nicaragua, the Philippines, Romania, Russia, Switzerland, Turkey and the UK. The performance of many geothermal reservoirs outside the United States was described in several of the papers. Professor Roland N. Horne opened the meeting and welcomed visitors. The key note speaker was Marshall Reed, who gave a brief overview of the Department of Energy's current plan. Sixty-six papers were presented in the technical sessions of the workshop. Technical papers were organized into twenty sessions concerning: reservoir assessment, modeling, geology/geochemistry, fracture modeling hot dry rock, geoscience, low enthalpy, injection, well testing, drilling, adsorption and stimulation. Session chairmen were major contributors to the workshop, and we thank: Ben Barker, Bobbie Bishop-Gollan, Tom Box, Jim Combs, John Counsil, Sabodh Garg, Malcolm Grant, Marcel0 Lippmann, Jim Lovekin, John Pritchett, Marshall Reed, Joel Renner, Subir Sanyal, Mike Shook, Alfred Truesdell and Ken Williamson. Jim Lovekin gave the post-dinner speech at the banquet and highlighted the exciting developments in the geothermal field which are taking place worldwide. The Workshop was organized by the Stanford Geothermal Program faculty, staff, and graduate students. We wish to thank our students who operated the audiovisual equipment. Shaun D. Fitzgerald Program Manager.

Summary record of the twenty-seventh meeting

International Nuclear Information System (INIS)

Young, P.

1990-01-01

The topics presented and discussed at the twenty-seventh international meeting of the Nuclear Data Committee of the Nuclear Energy Agency are summarized. Relations with other committees and reports of data centers are analyzed. Problems concerning nuclear model codes are underlined. National evaluation efforts on data library and data file are reported. Reports from several laboratories and subcommittees are summarized

Computational topology and the Unique Games Conjecture

OpenAIRE

Grochow, Joshua A.; Tucker-Foltz, Jamie

2018-01-01

Covering spaces of graphs have long been useful for studying expanders (as "graph lifts") and unique games (as the "label-extended graph"). In this paper we advocate for the thesis that there is a much deeper relationship between computational topology and the Unique Games Conjecture. Our starting point is Linial's 2005 observation that the only known problems whose inapproximability is equivalent to the Unique Games Conjecture - Unique Games and Max-2Lin - are instances of Maximum Section of...

Barnase as a new therapeutic agent triggering apoptosis in human cancer cells.

Directory of Open Access Journals (Sweden)

Evelina Edelweiss

Full Text Available BACKGROUND: RNases are currently studied as non-mutagenic alternatives to the harmful DNA-damaging anticancer drugs commonly used in clinical practice. Many mammalian RNases are not potent toxins due to the strong inhibition by ribonuclease inhibitor (RI presented in the cytoplasm of mammalian cells. METHODOLOGY/PRINCIPAL FINDINGS: In search of new effective anticancer RNases we studied the effects of barnase, a ribonuclease from Bacillus amyloliquefaciens, on human cancer cells. We found that barnase is resistant to RI. In MTT cell viability assay, barnase was cytotoxic to human carcinoma cell lines with half-inhibitory concentrations (IC(50 ranging from 0.2 to 13 microM and to leukemia cell lines with IC(50 values ranging from 2.4 to 82 microM. Also, we characterized the cytotoxic effects of barnase-based immunoRNase scFv 4D5-dibarnase, which consists of two barnase molecules serially fused to the single-chain variable fragment (scFv of humanized antibody 4D5 that recognizes the extracellular domain of cancer marker HER2. The scFv 4D5-dibarnase specifically bound to HER2-positive cells and was internalized via receptor-mediated endocytosis. The intracellular localization of internalized scFv 4D5-dibarnase was determined by electronic microscopy. The cytotoxic effect of scFv 4D5-dibarnase on HER2-positive human ovarian carcinoma SKOV-3 cells (IC(50 = 1.8 nM was three orders of magnitude greater than that of barnase alone. Both barnase and scFv 4D5-dibarnase induced apoptosis in SKOV-3 cells accompanied by internucleosomal chromatin fragmentation, membrane blebbing, the appearance of phosphatidylserine on the outer leaflet of the plasma membrane, and the activation of caspase-3. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that barnase is a potent toxic agent for targeting to cancer cells.

Digital earth applications in the twenty-first century

NARCIS (Netherlands)

de By, R.A.; Georgiadou, P.Y.

2014-01-01

In these early years of the twenty-first century, we must look at how the truly cross-cutting information technology supports other innovations, and how it will fundamentally change the information positions of government, private sector and the scientific domain as well as the citizen. In those

ESCRT-mediated uptake and degradation of brain-targeted α-synuclein single chain antibody attenuates neuronal degeneration in vivo.

Science.gov (United States)

Spencer, Brian; Emadi, Sharareh; Desplats, Paula; Eleuteri, Simona; Michael, Sarah; Kosberg, Kori; Shen, Jay; Rockenstein, Edward; Patrick, Christina; Adame, Anthony; Gonzalez, Tania; Sierks, Michael; Masliah, Eliezer

2014-10-01

Parkinson's disease and dementia with Lewy bodies are neurodegenerative disorders characterized by accumulation of α-synuclein (α-syn). Recently, single-chain fragment variables (scFVs) have been developed against individual conformational species of α-syn. Unlike more traditional monoclonal antibodies, these scFVs will not activate or be endocytosed by Fc receptors. For this study, we investigated an scFV directed against oligomeric α-syn fused to the LDL receptor-binding domain from apolipoprotein B (apoB). The modified scFV showed enhanced brain penetration and was imported into neuronal cells through the endosomal sorting complex required for transport (ESCRT) pathway, leading to lysosomal degradation of α-syn aggregates. Further analysis showed that the scFV was effective at ameliorating neurodegenerative pathology and behavioral deficits observed in the mouse model of dementia with Lewy bodies/Parkinson's disease. Thus, the apoB modification had the effect of both increasing accumulation of the scFV in the brain and directing scFV/α-syn complexes for degradation through the ESCRT pathway, leading to improved therapeutic potential of immunotherapy.

Early twenty-first-century droughts during the warmest climate

Directory of Open Access Journals (Sweden)

Felix Kogan

2016-01-01

Full Text Available The first 13 years of the twenty-first century have begun with a series of widespread, long and intensive droughts around the world. Extreme and severe-to-extreme intensity droughts covered 2%–6% and 7%–16% of the world land, respectively, affecting environment, economies and humans. These droughts reduced agricultural production, leading to food shortages, human health deterioration, poverty, regional disturbances, population migration and death. This feature article is a travelogue of the twenty-first-century global and regional droughts during the warmest years of the past 100 years. These droughts were identified and monitored with the National Oceanic and Atmospheric Administration operational space technology, called vegetation health (VH, which has the longest period of observation and provides good data quality. The VH method was used for assessment of vegetation condition or health, including drought early detection and monitoring. The VH method is based on operational satellites data estimating both land surface greenness (NDVI and thermal conditions. The twenty-first-century droughts in the USA, Russia, Australia and Horn of Africa were intensive, long, covered large areas and caused huge losses in agricultural production, which affected food security and led to food riots in some countries. This research also investigates drought dynamics presenting no definite conclusion about drought intensification or/and expansion during the time of the warmest globe.

Safety regulation - twenty years after Chernobyl accident

International Nuclear Information System (INIS)

Aleksashin, P.P.; Bukrinskij, A.M.; Gordon, B.G.

2006-01-01

Main stages of development, successes, achievements and shortcomings of activity of supervision body after the Chernobyl NPP accident are analysed. The estimation of the realized variations of the functions of the state supervision department is carried out. Results of the twenty year period of improvement of the supervision body are summed up. The measures for increasing the efficiency of the supervision body operation are outlined [ru

Journal of Biosciences | Indian Academy of Sciences

Indian Academy of Sciences (India)

... of scFv and BsFv were approximately 30 kDa and 60 kDa, respectively. Flow cytometry revealed that SLH10 BsFv bound the selected cell lines with greater signal intensity than the parental scFv. The improved antigen binding of SLH10 BsFv may be useful for immunodiagnostics or targeted gene therapy for liver cancer.

A simple vector system to improve performance and utilisation of recombinant antibodies

Directory of Open Access Journals (Sweden)

Vincent Karen J

2006-12-01

Full Text Available Abstract Background Isolation of recombinant antibody fragments from antibody libraries is well established using technologies such as phage display. Phage display vectors are ideal for efficient display of antibody fragments on the surface of bacteriophage particles. However, they are often inefficient for expression of soluble antibody fragments, and sub-cloning of selected antibody populations into dedicated soluble antibody fragment expression vectors can enhance expression. Results We have developed a simple vector system for expression, dimerisation and detection of recombinant antibody fragments in the form of single chain Fvs (scFvs. Expression is driven by the T7 RNA polymerase promoter in conjunction with the inducible lysogen strain BL21 (DE3. The system is compatible with a simple auto-induction culture system for scFv production. As an alternative to periplasmic expression, expression directly in the cytoplasm of a mutant strain with a more oxidising cytoplasmic environment (Origami 2™ (DE3 was investigated and found to be inferior to periplasmic expression in BL21 (DE3 cells. The effect on yield and binding activity of fusing scFvs to the N terminus of maltose binding protein (a solubility enhancing partner, bacterial alkaline phosphatase (a naturally dimeric enzymatic reporter molecule, or the addition of a free C-terminal cysteine was determined. Fusion of scFvs to the N-terminus of maltose binding protein increased scFv yield but binding activity of the scFv was compromised. In contrast, fusion to the N-terminus of bacterial alkaline phosphatase led to an improved performance. Alkaline phosphatase provides a convenient tag allowing direct enzymatic detection of scFv fusions within crude extracts without the need for secondary reagents. Alkaline phosphatase also drives dimerisation of the scFv leading to an improvement in performance compared to monovalent constructs. This is illustrated by ELISA, western blot and

Heart Failure: Unique to Older Adults

Science.gov (United States)

... to Z › Heart Failure › Unique to Older Adults Font size A A A Print Share Glossary Unique ... will suffer from depression at some point. This type of severe depression is more serious than the ...

A Tat-grafted anti-nucleic acid antibody acquires nuclear-localization property and a preference for TAR RNA

International Nuclear Information System (INIS)

Jeong, Jong-Geun; Kim, Dong-Sik; Kim, Yong-Sung; Kwon, Myung-Hee

2011-01-01

Highlights: → We generate ' H3 Tat-3D8' by grafting Tat 48-60 peptide to VH CDR of 3D8 scFv antibody. → H3 Tat-3D8 antibody retains nucleic acid binding and hydrolyzing activities. → H3 Tat-3D8 acquires a preference for TAR RNA structure. → Properties of Tat 48-60 is transferred to an antibody via Tat-grafting into a CDR. -- Abstract: The 3D8 single chain variable fragment (3D8 scFv) is an anti-nucleic acid antibody that can hydrolyze nucleic acids and enter the cytosol of cells without reaching the nucleus. The Tat peptide, derived from the basic region of the HIV-1 Tat protein, translocates to cell nuclei and has TAR RNA binding activity. In this study, we generated a Tat-grafted antibody ( H3 Tat-3D8) by replacing complementarity-determining region 3 (CDR3) within the VH domain of the 3D8 scFv with a Tat 48-60 peptide (GRKKRRQRRRPPQ). H3 Tat-3D8 retained the DNA-binding and DNA-hydrolyzing activity of the scFv, and translocated to the nuclei of HeLa cells and preferentially recognized TAR RNA. Thus, the properties associated with the Tat peptide were transferred to the antibody via Tat-grafting without loss of the intrinsic DNA-binding and hydrolyzing activities of the 3D8 scFv antibody.

Fusion Peptide Improves Stability and Bioactivity of Single Chain Antibody against Rabies Virus.

Science.gov (United States)

Xi, Hualong; Zhang, Kaixin; Yin, Yanchun; Gu, Tiejun; Sun, Qing; Shi, Linqing; Zhang, Renxia; Jiang, Chunlai; Kong, Wei; Wu, Yongge

2017-04-28

The combination of rabies immunoglobulin (RIG) with a vaccine is currently effective against rabies infections, but improvements are needed. Genetic engineering antibody technology is an attractive approach for developing novel antibodies to replace RIG. In our previous study, a single-chain variable fragment, scFv57R, against rabies virus glycoprotein was constructed. However, its inherent weak stability and short half-life compared with the parent RIG may limit its diagnostic and therapeutic application. Therefore, an acidic tail of synuclein (ATS) derived from the C-terminal acidic tail of human alpha-synuclein protein was fused to the C-terminus of scFv57R in order to help it resist adverse stress and improve the stability and halflife. The tail showed no apparent effect on the preparation procedure and affinity of the protein, nor did it change the neutralizing potency in vitro. In the ELISA test of molecular stability, the ATS fusion form of the protein, scFv57R-ATS, showed an increase in thermal stability and longer half-life in serum than scFv57R. The protection against fatal rabies virus challenge improved after fusing the tail to the scFv, which may be attributed to the improved stability. Thus, the ATS fusion approach presented here is easily implemented and can be used as a new strategy to improve the stability and half-life of engineered antibody proteins for practical applications.

SEAPOWER: A GUIDE FOR THE TWENTY- FIRST CENTURY

African Journals Online (AJOL)

Abel

$154,37 (amazon.com hardback). With the publication of Seapower: A Guide for the Twenty-First Century. Geoffrey Till has set the standard for publications on all things maritime. The updated and expanded new edition of the book is an essential guide for students of naval history and maritime strategy and provides ...

Twenty-first century vaccines

Science.gov (United States)

Rappuoli, Rino

2011-01-01

In the twentieth century, vaccination has been possibly the greatest revolution in health. Together with hygiene and antibiotics, vaccination led to the elimination of many childhood infectious diseases and contributed to the increase in disability-free life expectancy that in Western societies rose from 50 to 78–85 years (Crimmins, E. M. & Finch, C. E. 2006 Proc. Natl Acad. Sci. USA 103, 498–503; Kirkwood, T. B. 2008 Nat. Med 10, 1177–1185). In the twenty-first century, vaccination will be expected to eliminate the remaining childhood infectious diseases, such as meningococcal meningitis, respiratory syncytial virus, group A streptococcus, and will address the health challenges of this century such as those associated with ageing, antibiotic resistance, emerging infectious diseases and poverty. However, for this to happen, we need to increase the public trust in vaccination so that vaccines can be perceived as the best insurance against most diseases across all ages. PMID:21893537

Vesico-vaginal fistula repair: experience with first twenty-three ...

African Journals Online (AJOL)

Vesico-vaginal fistula repair: experience with first twenty-three patients seen at a tertiary hospital in north-central Nigeria. Stephen D. Ngwan, Bassey E. Edem, Ajen S. Anzaku, Barnabas A. Eke, Mohammed A. Shittu, Solomon A. Obekpa ...

Unique specification of Yang-Mills solutions

International Nuclear Information System (INIS)

Campbell, W.B.; Joseph, D.W.; Morgan, T.A.

1980-01-01

Screened time-independent cylindrically-symmetric solutions of Yang-Mills equations are given which show that the source does not uniquely determine the field. However, these particular solutions suggest a natural way of uniquely specifying solutions in terms of a physical realization of a symmetry group. (orig.)

Deformation quantization: Twenty years after

International Nuclear Information System (INIS)

Sternheimer, Daniel

1998-01-01

We first review the historical developments, both in physics and in mathematics, that preceded (and in some sense provided the background of) deformation quantization. Then we describe the birth of the latter theory and its evolution in the past twenty years, insisting on the main conceptual developments and keeping here as much as possible on the physical side. For the physical part the accent is put on its relations to, and relevance for, 'conventional' physics. For the mathematical part we concentrate on the questions of existence and equivalence, including most recent developments for general Poisson manifolds; we touch also noncommutative geometry and index theorems, and relations with group theory, including quantum groups. An extensive (though very incomplete) bibliography is appended and includes background mathematical literature

Irrigation quality of ground water of twenty villages in Lahore district

Directory of Open Access Journals (Sweden)

M.S. Ali

2009-05-01

Full Text Available study was conducted in twenty villages of Lahore district to assess the suitability of ground water for irrigation. Three water samples were collected from each of twenty villages and were analyzed for electrical conductivity (EC, sodium adsorption ratio (SAR, residual sodium carbonate (RSC and chloride concentration. Out of total 60 water samples, 7 (11.7% were fit, 7 (11.7% were marginally fit, and remaining 46 (76.6% were unfit for irrigation. Twenty eight samples (46.6% had electrical conductivity higher than permissible limit (i.e. >1250 µS cm-1, 19 samples (31.6% were found with high SAR (i.e. >10 (m mol L-10. 5, 44 samples (73.3% had high RSC (i.e. >2.5 me L-1 and 10 samples (16.6% were found unfit for irrigation due to high concentration of chloride (i.e. >3.9 me L-1. It can be inferred from data that quality of available ground water in most ofthe villages is not suitable for sustainable crop production and soil health.

Uniqueness of time-independent electromagnetic fields

DEFF Research Database (Denmark)

Karlsson, Per W.

1974-01-01

As a comment on a recent paper by Steele, a more general uniqueness theorem for time-independent fields is mentioned. ©1974 American Institute of Physics......As a comment on a recent paper by Steele, a more general uniqueness theorem for time-independent fields is mentioned. ©1974 American Institute of Physics...

Twenty years of diffraction at the Tevatron

International Nuclear Information System (INIS)

Goulianos, K.; Rockefeller U.

2005-01-01

Results on diffractive particle interactions from the Fermilab Tevatron (bar p)p collider are placed in perspective through a QCD inspired phenomenological approach, which exploits scaling and factorization properties observed in data. The results discussed are those obtained by the CDF Collaboration from a comprehensive set of single, double, and multigap soft and hard diffraction processes studied during the twenty year period since 1985, when the CDF diffractive program was proposed and the first Blois Workshop was held

Changes in unique hues induced by chromatic surrounds.

Science.gov (United States)

Klauke, Susanne; Wachtler, Thomas

2016-03-01

A chromatic surround can have a strong influence on the perceived hue of a stimulus. We investigated whether chromatic induction has similar effects on the perception of colors that appear pure and unmixed (unique red, green, blue, and yellow) as on other colors. Subjects performed unique hue settings of stimuli in isoluminant surrounds of different chromaticities. Compared with the settings in a neutral gray surround, unique hue settings altered systematically with chromatic surrounds. The amount of induced hue shift depended on the difference between stimulus and surround hues, and was similar for unique hue settings as for settings of nonunique hues. Intraindividual variability in unique hue settings was roughly twice as high as for settings obtained in asymmetric matching experiments, which may reflect the presence of a reference stimulus in the matching task. Variabilities were also larger with chromatic surrounds than with neutral gray surrounds, for both unique hue settings and matching of nonunique hues. The results suggest that the neural representations underlying unique hue percepts are influenced by the same neural processing mechanisms as the percepts of other colors.

Is Life Unique?

Science.gov (United States)

Abel, David L.

2011-01-01

Is life physicochemically unique? No. Is life unique? Yes. Life manifests innumerable formalisms that cannot be generated or explained by physicodynamics alone. Life pursues thousands of biofunctional goals, not the least of which is staying alive. Neither physicodynamics, nor evolution, pursue goals. Life is largely directed by linear digital programming and by the Prescriptive Information (PI) instantiated particularly into physicodynamically indeterminate nucleotide sequencing. Epigenomic controls only compound the sophistication of these formalisms. Life employs representationalism through the use of symbol systems. Life manifests autonomy, homeostasis far from equilibrium in the harshest of environments, positive and negative feedback mechanisms, prevention and correction of its own errors, and organization of its components into Sustained Functional Systems (SFS). Chance and necessity—heat agitation and the cause-and-effect determinism of nature’s orderliness—cannot spawn formalisms such as mathematics, language, symbol systems, coding, decoding, logic, organization (not to be confused with mere self-ordering), integration of circuits, computational success, and the pursuit of functionality. All of these characteristics of life are formal, not physical. PMID:25382119

The liberal illusion of uniqueness.

Science.gov (United States)

Stern, Chadly; West, Tessa V; Schmitt, Peter G

2014-01-01

In two studies, we demonstrated that liberals underestimate their similarity to other liberals (i.e., display truly false uniqueness), whereas moderates and conservatives overestimate their similarity to other moderates and conservatives (i.e., display truly false consensus; Studies 1 and 2). We further demonstrated that a fundamental difference between liberals and conservatives in the motivation to feel unique explains this ideological distinction in the accuracy of estimating similarity (Study 2). Implications of the accuracy of consensus estimates for mobilizing liberal and conservative political movements are discussed.

A single-chain variable fragment intrabody prevents intracellular polymerization of Z α1-antitrypsin while allowing its antiproteinase activity.

Science.gov (United States)

Ordóñez, Adriana; Pérez, Juan; Tan, Lu; Dickens, Jennifer A; Motamedi-Shad, Neda; Irving, James A; Haq, Imran; Ekeowa, Ugo; Marciniak, Stefan J; Miranda, Elena; Lomas, David A

2015-06-01

Mutant Z α1-antitrypsin (E342K) accumulates as polymers within the endoplasmic reticulum (ER) of hepatocytes predisposing to liver disease, whereas low levels of circulating Z α1-antitrypsin lead to emphysema by loss of inhibition of neutrophil elastase. The ideal therapy should prevent polymer formation while preserving inhibitory activity. Here we used mAb technology to identify interactors with Z α1-antitrypsin that comply with both requirements. We report the generation of an mAb (4B12) that blocked α1-antitrypsin polymerization in vitro at a 1:1 molar ratio, causing a small increase of the stoichiometry of inhibition for neutrophil elastase. A single-chain variable fragment (scFv) intrabody was generated based on the sequence of mAb4B12. The expression of scFv4B12 within the ER (scFv4B12KDEL) and along the secretory pathway (scFv4B12) reduced the intracellular polymerization of Z α1-antitrypsin by 60%. The scFv4B12 intrabody also increased the secretion of Z α1-antitrypsin that retained inhibitory activity against neutrophil elastase. MAb4B12 recognized a discontinuous epitope probably located in the region of helices A/C/G/H/I and seems to act by altering protein dynamics rather than binding preferentially to the native state. This novel approach could reveal new target sites for small-molecule intervention that may block the transition to aberrant polymers without compromising the inhibitory activity of Z α1-antitrypsin. © FASEB.

Mapping the epitopes of a neutralizing antibody fragment directed against the lethal factor of Bacillus anthracis and cross-reacting with the homologous edema factor.

Directory of Open Access Journals (Sweden)

Philippe Thullier

Full Text Available The lethal toxin (LT of Bacillus anthracis, composed of the protective antigen (PA and the lethal factor (LF, plays an essential role in anthrax pathogenesis. PA also interacts with the edema factor (EF, 20% identity with LF to form the edema toxin (ET, which has a lesser role in anthrax pathogenesis. The first recombinant antibody fragment directed against LF was scFv 2LF; it neutralizes LT by blocking the interaction between PA and LF. Here, we report that scFv 2LF cross-reacts with EF and cross-neutralizes ET, and we present an in silico method taking advantage of this cross-reactivity to map the epitope of scFv 2LF on both LF and EF. This method identified five epitope candidates on LF, constituted of a total of 32 residues, which were tested experimentally by mutating the residues to alanine. This combined approach precisely identified the epitope of scFv 2LF on LF as five residues (H229, R230, Q234, L235 and Y236, of which three were missed by the consensus epitope candidate identified by pre-existing in silico methods. The homolog of this epitope on EF (H253, R254, E258, L259 and Y260 was experimentally confirmed to constitute the epitope of scFv 2LF on EF. Other inhibitors, including synthetic molecules, could be used to target these epitopes for therapeutic purposes. The in silico method presented here may be of more general interest.

ScFv anti-heparan sulfate antibodies unexpectedly activate endothelial and cancer cells through p38 MAPK: implications for antibody-based targeting of heparan sulfate proteoglycans in cancer.

Directory of Open Access Journals (Sweden)

Helena C Christianson

Full Text Available Tumor development requires angiogenesis and anti-angiogenic therapies have been introduced in the treatment of cancer. In this context, heparan sulfate proteoglycans (HSPGs emerge as interesting targets, owing to their function as co-receptors of major, pro-angiogenic factors. Accordingly, previous studies have suggested anti-tumor effects of heparin, i.e. over-sulfated HS, and various heparin mimetics; however, a significant drawback is their unspecific mechanism of action and potentially serious side-effects related to their anticoagulant properties. Here, we have explored the use of human ScFv anti-HS antibodies (αHS as a more rational approach to target HSPG function in endothelial cells (ECs. αHS were initially selected for their recognition of HS epitopes localized preferentially to the vasculature of patient glioblastoma tumors, i.e. highly angiogenic brain tumors. Unexpectedly, we found that these αHS exhibited potent pro-angiogenic effects in primary human ECs. αHS were shown to stimulate EC differentiation, which was associated with increased EC tube formation and proliferation. Moreover, αHS supported EC survival under hypoxia and starvation, i.e. conditions typical of the tumor microenvironment. Importantly, αHS-mediated proliferation was efficiently counter-acted by heparin and was absent in HSPG-deficient mutant cells, confirming HS-specific effects. On a mechanistic level, binding of αHS to HSPGs of ECs as well as glioblastoma cells was found to trigger p38 MAPK-dependent signaling resulting in increased proliferation. We conclude that several αHS that recognize HS epitopes abundant in the tumor vasculature may elicit a pro-angiogenic response, which has implications for the development of antibody-based targeting of HSPGs in cancer.

Twenty-five years of simulator training

International Nuclear Information System (INIS)

Anon.

2002-01-01

The first training simulator for nuclear power plant personnel in Germany was commissioned twenty-five years ago. The strategy of training by simulators was developed and pursued consistently and continuously in order to ensure sound training of nuclear power plant personnel. The present thirteen simulators cover a broad range of plants. A systematic training concept also helps to ensure a high level of competence and permanent qualification of plant personnel. The anniversary was marked by a festive event at which Erich K. Steiner read a paper on 'The Importance of Simulator Training', and Professor Dr. Adolf Birkhofer spoke about 'Nuclear Technology Education and Training'. (orig.)

A phage-displayed chicken single-chain antibody fused to alkaline phosphatase detects Fusarium pathogens and their presence in cereal grains

International Nuclear Information System (INIS)

Hu, Zu-Quan; Li, He-Ping; Zhang, Jing-Bo; Huang, Tao; Liu, Jin-Long; Xue, Sheng; Wu, Ai-Bo; Liao, Yu-Cai

2013-01-01

Graphical abstract: A phage-displayed chicken scFv antibody, FvSG7, binds on the surface antigen of conidiospores and the mycelia of F. verticillioides. Its fusion with alkaline phosphatase (AP) through a 218 linker displayed a 4-fold higher affinity compared with the parent scFv antibody and efficiently detected toxigenic Fusarium pathogens in cereal grains. Highlights: ► Generation of a highly reactive scFv antibody against F. verticillioides. ► Localization of the antibody binding to the surface target of F. verticillioides. ► Expression of the antibody–alkaline phosphatase (AP) fusion linked by a 218 linker. ► The antibody–AP fusion has a higher affinity than the parental antibody. ► The antibody–AP fusion detects toxigenic Fusarium pathogens in cereal grains. -- Abstract: Fusarium and its poisonous mycotoxins are distributed worldwide and are of particular interest in agriculture and food safety. A simple analytical method to detect pathogens is essential for forecasting diseases and controlling mycotoxins. This article describes a proposed method for convenient and sensitive detection of Fusarium pathogens that uses the fusion of single-chain variable fragment (scFv) and alkaline phosphatase (AP). A highly reactive scFv antibody specific to soluble cell wall-bound proteins (SCWPs) of F. verticillioides was selected from an immunized chicken phagemid library by phage display. The antibody was verified to bind on the surface of ungerminated conidiospores and mycelia of F. verticillioides. The scFv–AP fusion was constructed, and soluble expression in bacteria was confirmed. Both the antibody properties and enzymatic activity were retained, and the antigen-binding capacity of the fusion was enhanced by the addition of a linker. Surface plasmon resonance measurements confirmed that the fusion displayed 4-fold higher affinity compared with the fusion's parental scFv antibody. Immunoblot analyses showed that the fusion had good binding capacity to

A phage-displayed chicken single-chain antibody fused to alkaline phosphatase detects Fusarium pathogens and their presence in cereal grains

Energy Technology Data Exchange (ETDEWEB)

Hu, Zu-Quan [Molecular Biotechnology Laboratory of Triticeae Crops, Huazhong Agricultural University, Wuhan 430070 (China); Li, He-Ping [Molecular Biotechnology Laboratory of Triticeae Crops, Huazhong Agricultural University, Wuhan 430070 (China); College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Zhang, Jing-Bo [Molecular Biotechnology Laboratory of Triticeae Crops, Huazhong Agricultural University, Wuhan 430070 (China); College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Huang, Tao [Molecular Biotechnology Laboratory of Triticeae Crops, Huazhong Agricultural University, Wuhan 430070 (China); College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Liu, Jin-Long; Xue, Sheng [Molecular Biotechnology Laboratory of Triticeae Crops, Huazhong Agricultural University, Wuhan 430070 (China); Wu, Ai-Bo [Institute for Agri-food Standards and Testing Technology, Laboratory of Quality and Safety Risk Assessment for Agro-products, Ministry of Agriculture, Shanghai Academy of Agricultural Sciences, 1000 Jinqi Road, Shanghai 201403 (China); Liao, Yu-Cai, E-mail: ycliao06@yahoo.com.cn [Molecular Biotechnology Laboratory of Triticeae Crops, Huazhong Agricultural University, Wuhan 430070 (China); College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); National Center of Plant Gene Research, Wuhan 430070 (China)

2013-02-18

Graphical abstract: A phage-displayed chicken scFv antibody, FvSG7, binds on the surface antigen of conidiospores and the mycelia of F. verticillioides. Its fusion with alkaline phosphatase (AP) through a 218 linker displayed a 4-fold higher affinity compared with the parent scFv antibody and efficiently detected toxigenic Fusarium pathogens in cereal grains. Highlights: ► Generation of a highly reactive scFv antibody against F. verticillioides. ► Localization of the antibody binding to the surface target of F. verticillioides. ► Expression of the antibody–alkaline phosphatase (AP) fusion linked by a 218 linker. ► The antibody–AP fusion has a higher affinity than the parental antibody. ► The antibody–AP fusion detects toxigenic Fusarium pathogens in cereal grains. -- Abstract: Fusarium and its poisonous mycotoxins are distributed worldwide and are of particular interest in agriculture and food safety. A simple analytical method to detect pathogens is essential for forecasting diseases and controlling mycotoxins. This article describes a proposed method for convenient and sensitive detection of Fusarium pathogens that uses the fusion of single-chain variable fragment (scFv) and alkaline phosphatase (AP). A highly reactive scFv antibody specific to soluble cell wall-bound proteins (SCWPs) of F. verticillioides was selected from an immunized chicken phagemid library by phage display. The antibody was verified to bind on the surface of ungerminated conidiospores and mycelia of F. verticillioides. The scFv–AP fusion was constructed, and soluble expression in bacteria was confirmed. Both the antibody properties and enzymatic activity were retained, and the antigen-binding capacity of the fusion was enhanced by the addition of a linker. Surface plasmon resonance measurements confirmed that the fusion displayed 4-fold higher affinity compared with the fusion's parental scFv antibody. Immunoblot analyses showed that the fusion had good binding

Coexistence of uniquely ergodic subsystems of interval mapping

International Nuclear Information System (INIS)

Ye Xiangdong.

1991-10-01

The purpose of this paper is to show that uniquely ergodic subsystems of interval mapping also coexist in the same way as minimal sets do. To do this we give some notations in section 2. In section 3 we define D-function of a uniquely ergodic system and show its basic properties. We prove the coexistence of uniquely ergodic subsystems of interval mapping in section 4. Lastly we give the examples of uniquely ergodic systems with given D-functions in section 5. 27 refs

Technological sciences society of the twenty-first century

International Nuclear Information System (INIS)

1999-04-01

This book introduces information-oriented society of the twenty-first century connected to computer network for example memory of dream : F-ram, information-oriented society : New media, communications network for next generation ; ISDN on what is IDSN?, development of information service industry, from office automation to an intelligent building in the future, home shopping and home banking and rock that hinders information-oriented society.

Non-unique Product Groups on Two Generators

OpenAIRE

Carter, William Paul

2007-01-01

The main purpose of this paper is to better understand groups that do not have the unique product property. In particular, the goal is to better understand Promislow's example, G, of such a group. In doing so, we will develop methods for generating examples of other sets that do not have the unique product property. With these methods we can show that there exists other distinct 14 element, square, non-unique product sets in G that are not inversions or translations. Also, this paper answers ...

Book Review: Africa and Europe in the Twenty-First Century ...

African Journals Online (AJOL)

Abstract. Title: Africa and Europe in the Twenty-First Century. Author: Osita C. Eze and Amadu Sesay. Publisher: Nigerian Institute of International Affairs, 2010, xvi + 397pp, Tables, Index. ISBN: 978-002-102-7 ...

China's iGeneration - Cinema and Moving Image Culture for the Twenty-First Century

OpenAIRE

Johnson, Matthew D.; Wagner, Keith B.; Yu, Tianqui; Vulpiani, Luke

2014-01-01

Collection of essays on twenty-first century Chinese cinema and moving image culture. This innovative collection of essays on twenty-first century Chinese cinema and moving image culture features contributions from an international community of scholars, critics, and practitioners. Taken together, their perspectives make a compelling case that the past decade has witnessed a radical transformation of conventional notions of cinema. Following China's accession to the WTO in 2001, personal ...

Guidelines to design engineering education in the twenty-first century for supporting innovative product development

Science.gov (United States)

Violante, Maria Grazia; Vezzetti, Enrico

2017-11-01

In the twenty-first century, meeting our technological challenges demands educational excellence, a skilled populace that is ready for the critical challenges society faces. There is widespread consensus, however, that education systems are failing to adequately prepare all students with the essential twenty-first century knowledge and skills necessary to succeed in life, career, and citizenship. The purpose of this paper is to understand how twenty-first century knowledge and skills can be appropriately embedded in engineering education finalised to innovative product development by using additive manufacturing (AM). The study designs a learning model by which to achieve effective AM education to address the requirements of twenty-first century and to offer students the occasion to experiment with STEM (Science, technology, engineering, and mathematics) concepts. The study is conducted using the quality function deployment (QFD) methodology.

Twenty years of operation of Ljubljana's TRIGA Mark II reactor

International Nuclear Information System (INIS)

Dimic, V.

1986-01-01

Twenty years have now passed since the start of the TRIGA Mark II reactor in Ljubljana. The reactor was critical on May 31, 1966. The total energy produced until the end of May 1986 was 14.048 MWh or 585 MWd. For the first 14 years (until 1981) the yearly energy produced was about 600 MWh, since 1981 the yearly energy produced was 1000 MWh when a routine radioactive isotopes production started for medical use as well as other industrial applications, such as doping and irradiation with fast neutrons of silicon monocrystals, production of level indicators (irradiated cobalt wire), production of radioactive iridium for gamma-radiography, leak detection in pipes by sodium, etc. Besides these, applied research around the reactor is being conducted in the following main fields, where- many unique methods have been developed or have found their way into the local industry or hospitals: neutron radiography, neutron induced auto-radiography using solid state nuclear track detectors, nondestructive methods for assessment of nuclear burn-up, neutron dosimetry, calculation of core burn-up for the optimal in-core fuel management strategy. The solvent extraction method was developed for the everyday production of 99m Tc, which is the most widely used radionuclide in diagnostic nuclear medicine. The methods were developed for the production of the following isotopes: 18 F, 85m Kr, 24 Na, 82 Br, 64 Zn, 125 I. Neutron activation analysis represents one of the major usages for the TRIGA reactor. Basic research is being conducted in the following main fields: solid state physics (elastic and inelastic scattering of the neutrons), neutron dosimetry, neutron radiography, reactor physics and neutron activation analysis. The reactor is used very extensively as a main instrument in the Reactor Training Centre in Ljubljana where manpower training for our nuclear power plant and other organisations has been performed. Although the reactor was designed very carefully in order to be used for

Tattoos and piercings: bodily expressions of uniqueness?

Science.gov (United States)

Tiggemann, Marika; Hopkins, Louise A

2011-06-01

The study aimed to investigate the motivations underlying the body modification practices of tattooing and piercing. There were 80 participants recruited from an Australian music store, who provided descriptions of their tattoos and piercings and completed measures of need for uniqueness, appearance investment and distinctive appearance investment. It was found that tattooed individuals scored significantly higher on need for uniqueness than non-tattooed individuals. Further, individuals with conventional ear piercings scored significantly lower on need for uniqueness than individuals with no piercings or with facial and body piercings. Neither appearance investment nor distinctive appearance investment differed significantly among tattoo or piercing status groups. Strength of identification with music was significantly correlated with number of tattoos, but not number of piercings. It was concluded that tattooing, but not body piercing, represents a bodily expression of uniqueness. Copyright © 2011 Elsevier Ltd. All rights reserved.

Generation and analyses of human synthetic antibody libraries and their application for protein microarrays.

Science.gov (United States)

Säll, Anna; Walle, Maria; Wingren, Christer; Müller, Susanne; Nyman, Tomas; Vala, Andrea; Ohlin, Mats; Borrebaeck, Carl A K; Persson, Helena

2016-10-01

Antibody-based proteomics offers distinct advantages in the analysis of complex samples for discovery and validation of biomarkers associated with disease. However, its large-scale implementation requires tools and technologies that allow development of suitable antibody or antibody fragments in a high-throughput manner. To address this we designed and constructed two human synthetic antibody fragment (scFv) libraries denoted HelL-11 and HelL-13. By the use of phage display technology, in total 466 unique scFv antibodies specific for 114 different antigens were generated. The specificities of these antibodies were analyzed in a variety of immunochemical assays and a subset was further evaluated for functionality in protein microarray applications. This high-throughput approach demonstrates the ability to rapidly generate a wealth of reagents not only for proteome research, but potentially also for diagnostics and therapeutics. In addition, this work provides a great example on how a synthetic approach can be used to optimize library designs. By having precise control of the diversity introduced into the antigen-binding sites, synthetic libraries offer increased understanding of how different diversity contributes to antibody binding reactivity and stability, thereby providing the key to future library optimization. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Cone photoreceptor sensitivities and unique hue chromatic responses: correlation and causation imply the physiological basis of unique hues.

Science.gov (United States)

Pridmore, Ralph W

2013-01-01

This paper relates major functions at the start and end of the color vision process. The process starts with three cone photoreceptors transducing light into electrical responses. Cone sensitivities were once expected to be Red Green Blue color matching functions (to mix colors) but microspectrometry proved otherwise: they instead peak in yellowish, greenish, and blueish hues. These physiological functions are an enigma, unmatched with any set of psychophysical (behavioral) functions. The end-result of the visual process is color sensation, whose essential percepts are unique (or pure) hues red, yellow, green, blue. Unique hues cannot be described by other hues, but can describe all other hues, e.g., that hue is reddish-blue. They are carried by four opponent chromatic response curves but the literature does not specify whether each curve represents a range of hues or only one hue (a unique) over its wavelength range. Here the latter is demonstrated, confirming that opponent chromatic responses define, and may be termed, unique hue chromatic responses. These psychophysical functions also are an enigma, unmatched with any physiological functions or basis. Here both enigmas are solved by demonstrating the three cone sensitivity curves and the three spectral chromatic response curves are almost identical sets (Pearson correlation coefficients r from 0.95-1.0) in peak wavelengths, curve shapes, math functions, and curve crossover wavelengths, though previously unrecognized due to presentation of curves in different formats, e.g., log, linear. (Red chromatic response curve is largely nonspectral and thus derives from two cones.) Close correlation combined with deterministic causation implies cones are the physiological basis of unique hues. This match of three physiological and three psychophysical functions is unique in color vision.

Investigation of unique hue setting changes with ageing

Institute of Scientific and Technical Information of China (English)

Chenyang Fu; Kaida Xiao; Dimosthenis Karatzas; Sophie Wuerger

2011-01-01

Clromatic sensitivity along the protan, deutan, and tritan lines and the loci of the unique hues (red, green,yellow, blue) for a very large sample (n = 185) of colour-normal observers ranging from 18 to 75 years of age are assessed. Visual judgments are obtained under normal viewing conditions using colour patches on self-luminous display under controlled adaptation conditions. Trivector discrimination thresholds show an increase as a function of age along the protan, deutan, and tritan axes, with the largest increase present along the tritan line, less pronounced shifts in unique hue settings are also observed. Based on the chromatic (protan, deutan, tritan) thresholds and using scaled cone signals, we predict the unique hue changes with ageing. A dependency on age for unique red and unique yellow for predicted hue angle is found. We conclude that the chromatic sensitivity deteriorates significantly with age, whereas the appearance of unique hues is much less affected, remaining almost constant despite the known changes in the ocular media.%@@ Clromatic sensitivity along the protan, deutan, and tritan lines and the loci of the unique hues (red, green,yellow, blue) for a very large sample (n ＝ 185) of colour-normal observers ranging from 18 to 75 years of age are assessed.Visual judgments are obtained under normal viewing conditions using colour patches on self-luminous display under controlled adaptation conditions.Trivector discrimination thresholds show an increase as a function of age along the protan, deutan, and tritan axes, with the largest increase present along the tritan line, less pronounced shifts in unique hue settings are also observed.

Designing Vaccines for the Twenty-First Century Society

OpenAIRE

Finco, Oretta; Rappuoli, Rino

2014-01-01

The history of vaccination clearly demonstrates that vaccines have been highly successful in preventing infectious diseases, reducing significantly the incidence of childhood diseases and mortality. However, many infections are still not preventable with the currently available vaccines and they represent a major cause of mortality worldwide. In the twenty-first century, the innovation brought by novel technologies in antigen discovery and formulation together with a deeper knowledge of the h...

Proceedings of the Twenty-Eighth General Assembly Beijing 2012

Science.gov (United States)

Montmerle, Thierry

2015-09-01

Preface; 1. Inaugural ceremony; 2. Twenty-eighth General Assembly business sessions; 3. Closing ceremony; 4. Resolutions; 5. Report of Executive Committee, 2009-2012; 6. Reports on Division, Commission, and Working Group meetings; 7. Statutes, bye-laws, and working rules; 8. New members admitted at the General Assembly; 9. Divisions and their Commissions.

Application of SWAT99.2 to sensitivity analysis of water balance components in unique plots in a hilly region

Directory of Open Access Journals (Sweden)

Jun-feng Dai

2017-07-01

Full Text Available Although many sensitivity analyses using the soil and water assessment tool (SWAT in a complex watershed have been conducted, little attention has been paid to the application potential of the model in unique plots. In addition, sensitivity analysis of percolation and evapotranspiration with SWAT has seldom been undertaken. In this study, SWAT99.2 was calibrated to simulate water balance components for unique plots in Southern China from 2000 to 2001, which included surface runoff, percolation, and evapotranspiration. Twenty-one parameters classified into four categories, including meteorological conditions, topographical characteristics, soil properties, and vegetation attributes, were used for sensitivity analysis through one-at-a-time (OAT sampling to identify the factor that contributed most to the variance in water balance components. The results were shown to be different for different plots, with parameter sensitivity indices and ranks varying for different water balance components. Water balance components in the broad-leaved forest and natural grass plots were most sensitive to meteorological conditions, less sensitive to vegetation attributes and soil properties, and least sensitive to topographical characteristics. Compared to those in the natural grass plot, water balance components in the broad-leaved forest plot demonstrated higher sensitivity to the maximum stomatal conductance (GSI and maximum leaf area index (BLAI.

Uniqueness conditions for finitely dependent random fields

International Nuclear Information System (INIS)

Dobrushin, R.L.; Pecherski, E.A.

1981-01-01

The authors consider a random field for which uniqueness and some additional conditions guaranteeing that the correlations between the variables of the field decrease rapidly enough with the distance between the values of the parameter occur. The main result of the paper states that in such a case uniqueness is true for any other field with transition probabilities sufficiently close to those of the original field. Then they apply this result to some ''degenerate'' classes of random fields for which one can check this condition of correlation to decay, and thus obtain some new conditions of uniqueness. (Auth.)

Cone photoreceptor sensitivities and unique hue chromatic responses: correlation and causation imply the physiological basis of unique hues.

Directory of Open Access Journals (Sweden)

Ralph W Pridmore

Full Text Available This paper relates major functions at the start and end of the color vision process. The process starts with three cone photoreceptors transducing light into electrical responses. Cone sensitivities were once expected to be Red Green Blue color matching functions (to mix colors but microspectrometry proved otherwise: they instead peak in yellowish, greenish, and blueish hues. These physiological functions are an enigma, unmatched with any set of psychophysical (behavioral functions. The end-result of the visual process is color sensation, whose essential percepts are unique (or pure hues red, yellow, green, blue. Unique hues cannot be described by other hues, but can describe all other hues, e.g., that hue is reddish-blue. They are carried by four opponent chromatic response curves but the literature does not specify whether each curve represents a range of hues or only one hue (a unique over its wavelength range. Here the latter is demonstrated, confirming that opponent chromatic responses define, and may be termed, unique hue chromatic responses. These psychophysical functions also are an enigma, unmatched with any physiological functions or basis. Here both enigmas are solved by demonstrating the three cone sensitivity curves and the three spectral chromatic response curves are almost identical sets (Pearson correlation coefficients r from 0.95-1.0 in peak wavelengths, curve shapes, math functions, and curve crossover wavelengths, though previously unrecognized due to presentation of curves in different formats, e.g., log, linear. (Red chromatic response curve is largely nonspectral and thus derives from two cones. Close correlation combined with deterministic causation implies cones are the physiological basis of unique hues. This match of three physiological and three psychophysical functions is unique in color vision.

Practical relevance of pattern uniqueness in forensic science.

Science.gov (United States)

Jayaprakash, Paul T

2013-09-10

Uniqueness being unprovable, it has recently been argued that individualization in forensic science is irrelevant and, probability, as applied for DNA profiles, should be applied for all identifications. Critiques against uniqueness have omitted physical matching, a realistic and tangible individualization that supports uniqueness. Describing case examples illustrating pattern matches including physical matching, it is indicated that individualizations are practically relevant for forensic science as they establish facts on a definitive basis providing firm leads benefitting criminal investigation. As a tenet of forensic identification, uniqueness forms a fundamental paradigm relevant for individualization. Evidence on the indeterministic and stochastic causal pathways of characteristics in patterns available in the related fields of science sufficiently supports the proposition of uniqueness. Characteristics involved in physical matching and matching achieved in patterned evidence existing in the state of nature are not events amenable for counting; instead these are ensemble of visible units occupying the entire pattern area stretching the probability of re-occurrence of a verisimilitude pattern into infinity offering epistemic support to uniqueness. Observational methods are as respectable as instrumental or statistical methods since they are capable of generating results that are tangible and obviously valid as in physical matching. Applying the probabilistic interpretation used for DNA profiles to the other patterns would be unbefitting since these two are disparate, the causal pathways of the events, the loci, in the manipulated DNA profiles being determinable. While uniqueness enables individualizations, it does not vouch for eliminating errors. Instead of dismissing uniqueness and individualization, accepting errors as human or system failures and seeking remedial measures would benefit forensic science practice and criminal investigation. Copyright © 2013

Toward low-cost affinity reagents: lyophilized yeast-scFv probes specific for pathogen antigens.

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Sean A Gray

Full Text Available The generation of affinity reagents, usually monoclonal antibodies, remains a critical bottleneck in biomedical research and diagnostic test development. Recombinant antibody-like proteins such as scFv have yet to replace traditional monoclonal antibodies in antigen detection applications, in large part because of poor performance of scFv in solution. To address this limitation, we have developed assays that use whole yeast cells expressing scFv on their surfaces (yeast-scFv in place of soluble purified scFv or traditional monoclonal antibodies. In this study, a nonimmune library of human scFv displayed on the surfaces of yeast cells was screened for clones that bind to recombinant cyst proteins of Entamoeba histolytica, an enteric pathogen of humans. Selected yeast-scFv clones were stabilized by lyophilization and used in detection assay formats in which the yeast-scFv served as solid support-bound monoclonal antibodies. Specific binding of antigen to the yeast-scFv was detected by staining with rabbit polyclonal antibodies. In flow cytometry-based assays, lyophilized yeast-scFv reagents retained full binding activity and specificity for their cognate antigens after 4 weeks of storage at room temperature in the absence of desiccants or stabilizers. Because flow cytometry is not available to all potential assay users, an immunofluorescence assay was also developed that detects antigen with similar sensitivity and specificity. Antigen-specific whole-cell yeast-scFv reagents can be selected from nonimmune libraries in 2-3 weeks, produced in vast quantities, and packaged in lyophilized form for extended shelf life. Lyophilized yeast-scFv show promise as low cost, renewable alternatives to monoclonal antibodies for diagnosis and research.

Design and Generation of Humanized Single-chain Fv Derived from Mouse Hybridoma for Potential Targeting Application.

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Khantasup, Kannika; Chantima, Warangkana; Sangma, Chak; Poomputsa, Kanokwan; Dharakul, Tararaj

2015-12-01

Single-chain variable antibody fragments (scFvs) are attractive candidates for targeted immunotherapy in several human diseases. In this study, a concise humanization strategy combined with an optimized production method for humanizing scFvs was successfully employed. Two antibody clones, one directed against the hemagglutinin of H5N1 influenza virus, the other against EpCAM, a cancer biomarker, were used to demonstrate the validity of the method. Heavy chain (VH) and light chain (VL) variable regions of immunoglobulin genes from mouse hybridoma cells were sequenced and subjected to the construction of mouse scFv 3-D structure. Based on in silico modeling, the humanized version of the scFv was designed via complementarity-determining region (CDR) grafting with the retention of mouse framework region (FR) residues identified by primary sequence analysis. Root-mean-square deviation (RMSD) value between mouse and humanized scFv structures was calculated to evaluate the preservation of CDR conformation. Mouse and humanized scFv genes were then constructed and expressed in Escherichia coli. Using this method, we successfully generated humanized scFvs that retained the targeting activity of their respective mouse scFv counterparts. In addition, the humanized scFvs were engineered with a C-terminal cysteine residue (hscFv-C) for site-directed conjugation for use in future targeting applications. The hscFv-C expression was extensively optimized to improve protein production yield. The protocol yielded a 20-fold increase in production of hscFv-Cs in E. coli periplasm. The strategy described in this study may be applicable in the humanization of other antibodies derived from mouse hybridoma.

Critical Remarks on Piketty's 'Capital in the Twenty-first Century'

OpenAIRE

Homburg, Stefan

2014-01-01

This paper discusses the central macroeconomic claims that are made in Thomas Piketty's book 'Capital in the Twenty-first Century'. The paper aims to show that Piketty's contentions are not only logically flawed but also contradicted by his own data.

Structural Changes in Stx1 Engineering Monoclonal Antibody Improves Its Functionality as Diagnostic Tool for a Rapid Latex Agglutination Test

Directory of Open Access Journals (Sweden)

Daniela Luz

2018-02-01

Full Text Available Stx1 toxin is one of the AB5 toxins of Shiga toxin-producing Escherichia coli (STEC responsible for foodborne intoxication during outbreaks. The single-chain variable fragment (scFv is the most common recombinant antibody format; it consists of both variable chains connected by a peptide linker with conserved specificity and affinity for antigen. The drawbacks of scFv production in bacteria are the heterologous expression, conformation and stability of the molecule, which could change the affinity for the antigen. In this work, we obtained a stable and functional scFv-Stx1 in bacteria, starting from IgG produced by hybridoma cells. After structural modifications, i.e., change in protein orientation, vector and linker, its solubility for expression in bacteria was increased as well as the affinity for its antigen, demonstrated by a scFv dissociation constant (KD of 2.26 × 10−7 M. Also, it was able to recognize purified Stx1 and cross-reacted with Stx2 toxin by ELISA (Enzyme-Linked Immunosorbent Assay, and detected 88% of Stx1-producing strains using a rapid latex agglutination test. Thus, the scFv fragment obtained in the present work is a bacteria-produced tool for use in a rapid diagnosis test, providing an alternative for STEC diagnosis.

Hawadith Street Initiative: A unique Sudanese childhood charity experience.

Science.gov (United States)

Ahmed, Awad Mohamed; A-Rahman, Nada Hassan Ahmed

2015-01-01

Due to escalating conflicts and resultant economic constraints, different social services in low income and low-middle income countries have witnessed a decline in its standards, and increase in the costs. This situation has led to emergence of large numbers of patients and their families who cannot afford the costs of health services provided by public hospitals. On this background, and the old heritage of the Sudanese to help the needy, the Hawadith Street Initiative (HSI) was established. Named after the street on which it was founded - which translates indirectly to "Accidents Lane", HSI was established in 2012 by a group of youths, most of them in their twenties of age, and recently graduated. The main activity of the initiative is helping the needy hospital patients, especially with regards to their treatment costs, in Khartoum and other cities in Sudan. Starting with recreational programs for cancer patients, and public campaigns for donation of blood, the initiative's youths changed their activities. Using the social media, Facebook, they adopted the strategy of communication with potential donors, after sending posts containing brief anonymous presentations and call of help for needy cases. Currently HSI includes more than 2000 volunteers in Khartoum and 17 other cities. The most important achievement of HSI is the establishment of an intensive care unit at a children hospital in Omdurman city costing 435,880 US dollars. HSI demonstrates the possibility of delivering great services with minimum resources, and constitutes a unique organization, worldwide, in a new wave of Internet-based initiatives.

Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis.

Science.gov (United States)

Schmitt, Sarah E; Pargeon, Kimberly; Frechette, Eric S; Hirsch, Lawrence J; Dalmau, Josep; Friedman, Daniel

2012-09-11

To determine continuous EEG (cEEG) patterns that may be unique to anti-NMDA receptor (NMDAR) encephalitis in a series of adult patients with this disorder. We evaluated the clinical and EEG data of 23 hospitalized adult patients with anti-NMDAR encephalitis who underwent cEEG monitoring between January 2005 and February 2011 at 2 large academic medical centers. Twenty-three patients with anti-NMDAR encephalitis underwent a median of 7 (range 1-123) days of cEEG monitoring. The median length of hospitalization was 44 (range 2-200) days. Personality or behavioral changes (100%), movement disorders (82.6%), and seizures (78.3%) were the most common symptoms. Seven of 23 patients (30.4%) had a unique electrographic pattern, which we named "extreme delta brush" because of its resemblance to waveforms seen in premature infants. The presence of extreme delta brush was associated with a more prolonged hospitalization (mean 128.3 ± 47.5 vs 43.2 ± 39.0 days, p = 0.008) and increased days of cEEG monitoring (mean 27.6 ± 42.3 vs 6.2 ± 5.6 days, p = 0.012). The modified Rankin Scale score showed a trend toward worse scores in patients with the extreme delta brush pattern (mean 4.0 ± 0.8 vs 3.1 ± 1.1, p = 0.089). Extreme delta brush is a novel EEG finding seen in many patients with anti-NMDAR encephalitis. The presence of this pattern is associated with a more prolonged illness. Although the specificity of this pattern is unclear, its presence should raise consideration of this syndrome.

Construction of genetically engineered M13K07 helper phage for simultaneous phage display of gold binding peptide 1 and nuclear matrix protein 22 ScFv antibody.

Science.gov (United States)

Fatemi, Farnaz; Amini, Seyed Mohammad; Kharrazi, Sharmin; Rasaee, Mohammad Javad; Mazlomi, Mohammad Ali; Asadi-Ghalehni, Majid; Rajabibazl, Masoumeh; Sadroddiny, Esmaeil

2017-11-01

The most common techniques of antibody phage display are based on the use of M13 filamentous bacteriophages. This study introduces a new genetically engineered M13K07 helper phage displaying multiple copies of a known gold binding peptide on p8 coat proteins. The recombinant helper phages were used to rescue a phagemid vector encoding the p3 coat protein fused to the nuclear matrix protein 22 (NMP22) ScFv antibody. Transmission electron microscopy (TEM), UV-vis absorbance spectroscopy, and field emission scanning electron microscopy (FE-SEM) with energy dispersive X-ray spectroscopy (EDX) analysis revealed that the expression of gold binding peptide 1 (GBP1) on major coat protein p8 significantly enhances the gold-binding affinity of M13 phages. The recombinant bacteriophages at concentrations above 5×10 4 pfu/ml red-shifted the UV-vis absorbance spectra of gold nanoparticles (AuNPs); however, the surface plasmon resonance of gold nanoparticles was not changed by the wild type bacteriophages at concentrations up to 10 12 pfu/ml. The phage ELISA assay demonstrated the high affinity binding of bifunctional bacteriophages to NMP22 antigen at concentrations of 10 5 and 10 6 pfu/ml. Thus, the p3 end of the bifunctional bacteriophages would be able to bind to specific target antigen, while the AuNPs were assembled along the coat of virus for signal generation. Our results indicated that the complex of antigen-bacteriophages lead to UV-vis spectral changes of AuNPs and NMP22 antigen in concentration range of 10-80μg/ml can be detected by bifunctional bacteriophages at concentration of 10 4 pfu/ml. The ability of bifunctional bacteriophages to bind to antigen and generate signal at the same time, makes this approach applicable for identifying different antigens in immunoassay techniques. Copyright © 2017 Elsevier B.V. All rights reserved.

Guidelines to Design Engineering Education in the Twenty-First Century for Supporting Innovative Product Development

Science.gov (United States)

Violante, Maria Grazia; Vezzetti, Enrico

2017-01-01

In the twenty-first century, meeting our technological challenges demands educational excellence, a skilled populace that is ready for the critical challenges society faces. There is widespread consensus, however, that education systems are failing to adequately prepare all students with the essential twenty-first century knowledge and skills…

Human uniqueness-self-interest and social cooperation.

Science.gov (United States)

Okada, Daijiro; Bingham, Paul M

2008-07-21

Humans are unique among all species of terrestrial history in both ecological dominance and individual properties. Many, or perhaps all, of the unique elements of this nonpareil status can be plausibly interpreted as evolutionary and strategic elements and consequences of the unprecedented intensity and scale of our social cooperation. Convincing explanation of this unique human social adaptation remains a central, unmet challenge to the scientific enterprise. We develop a hypothesis for the ancestral origin of expanded cooperative social behavior. Specifically, we present a game theoretic analysis demonstrating that a specific pattern of expanded social cooperation between conspecific individuals with conflicts of interest (including non-kin) can be strategically viable, but only in animals that possess a highly unusual capacity for conspecific violence (credible threat) having very specific properties that dramatically reduce the costs of coercive violence. The resulting reduced costs allow preemptive or compensated coercion to be an instantaneously self-interested behavior under diverse circumstances rather than in rare, idiosyncratic circumstances as in actors (animals) who do not have access to inexpensive coercive threat. Humans are apparently unique among terrestrial organisms in having evolved conspecific coercive capabilities that fulfill these stringent requirements. Thus, our results support the proposal that access to a novel capacity for projection of coercive threat might represent the essential initiating event for the evolution of a human-like pattern of social cooperation and the subsequent evolution of the diverse features of human uniqueness. Empirical evidence indicates that these constraints were, in fact, met only in our evolutionary lineage. The logic for the emergence of uniquely human cooperation suggested by our analysis apparently accounts simply for the human fossil record.

Constructing Dense Graphs with Unique Hamiltonian Cycles

Science.gov (United States)

Lynch, Mark A. M.

2012-01-01

It is not difficult to construct dense graphs containing Hamiltonian cycles, but it is difficult to generate dense graphs that are guaranteed to contain a unique Hamiltonian cycle. This article presents an algorithm for generating arbitrarily large simple graphs containing "unique" Hamiltonian cycles. These graphs can be turned into dense graphs…

Proceedings of the Twenty-Third Annual Software Engineering Workshop

Science.gov (United States)

1999-01-01

The Twenty-third Annual Software Engineering Workshop (SEW) provided 20 presentations designed to further the goals of the Software Engineering Laboratory (SEL) of the NASA-GSFC. The presentations were selected on their creativity. The sessions which were held on 2-3 of December 1998, centered on the SEL, Experimentation, Inspections, Fault Prediction, Verification and Validation, and Embedded Systems and Safety-Critical Systems.

Using Quantum Confinement to Uniquely Identify Devices

Science.gov (United States)

Roberts, J.; Bagci, I. E.; Zawawi, M. A. M.; Sexton, J.; Hulbert, N.; Noori, Y. J.; Young, M. P.; Woodhead, C. S.; Missous, M.; Migliorato, M. A.; Roedig, U.; Young, R. J.

2015-11-01

Modern technology unintentionally provides resources that enable the trust of everyday interactions to be undermined. Some authentication schemes address this issue using devices that give a unique output in response to a challenge. These signatures are generated by hard-to-predict physical responses derived from structural characteristics, which lend themselves to two different architectures, known as unique objects (UNOs) and physically unclonable functions (PUFs). The classical design of UNOs and PUFs limits their size and, in some cases, their security. Here we show that quantum confinement lends itself to the provision of unique identities at the nanoscale, by using fluctuations in tunnelling measurements through quantum wells in resonant tunnelling diodes (RTDs). This provides an uncomplicated measurement of identity without conventional resource limitations whilst providing robust security. The confined energy levels are highly sensitive to the specific nanostructure within each RTD, resulting in a distinct tunnelling spectrum for every device, as they contain a unique and unpredictable structure that is presently impossible to clone. This new class of authentication device operates with minimal resources in simple electronic structures above room temperature.

Novel criteria of uniqueness for signal reconstruction from phase

NARCIS (Netherlands)

Ma, C.

1991-01-01

An approach for ascertaining whether a signal is uniquely determined by its Fourier transform phase is proposed. It is shown that uniqueness corresponds to the nonsingularity of a matrix which can be formed from the finite-length real sequence. The criterion of uniqueness for reconstructing a

Proceedings of the Twenty Second Nordic Seminar on Computational Mechanics

DEFF Research Database (Denmark)

This book contains the proceedings of the Twenty Second Nordic Seminar on Computational Mechanics (NSCM22), taking event 22-23 October 2009 at Aalborg University, Denmark. The papers presented at the Optimization Seminar in Honour of Niels Olhoff, held 21 October 2009 at Aalborg University, Denmark...

Management of twenty patients with neck trauma in Khartoum ENT ...

African Journals Online (AJOL)

Background: Neck trauma is a great surgical challenge, because there are multi organ and systems involved. Objective: To study the clinical presentation, management and outcome of twenty patients presented to Khartoum ENT Hospital with neck trauma. Methods: This is a prospective study conducted in Khartoum ENT ...

A Critical Feminist and Race Critique of Thomas Piketty's "Capital in the Twenty-First Century"

Science.gov (United States)

Moeller, Kathryn

2016-01-01

Thomas Piketty's "Capital in the Twenty-first Century" documents the foreboding nature of rising wealth inequality in the twenty-first century. In an effort to promote a more just and democratic global society and rein in the unfettered accumulation of wealth by the few, Piketty calls for a global progressive annual tax on corporate…

Twenty-first century learning for teachers: helping educators bring new skills into the classroom.

Science.gov (United States)

Wilson, John I

2006-01-01

The motivation behind every educator's dedication and hard work in the classroom is the knowledge that his or her teaching will result in students' success in life. Educators are committed to implementing twenty-first century skills; they have no question that students need such skills to be equipped for life beyond school. Members of the National Education Association are enthusiastic about the Partnership for 21st Century Skills framework, yet express frustration that many schools do not have adequate resources to make the necessary changes. Teaching these skills poses significant new responsibilities for schools and educators. To make it possible for teachers to build twenty-first century skills into the curriculum, physical and policy infrastructures must exist, professional development and curriculum materials must be offered, and meaningful assessments must be available. With an established understanding of what skills need to be infused into the classroom-problem solving, analysis, and com- munications-and educators' commitment to the new skill set, this chapter explores how to make such a dramatic reform happen. The author discusses existing strategies that will guide educators in infusing twenty-first century skills into traditional content areas such as math, English, geography, and science. Ultimately, public policy regarding educational standards, professional development, assessments, and physical school structures must exist to enable educators to employ twenty-first century skills, leading to student success in contemporary life. Any concern about the cost of bringing this nation's educational system up to par internationally should be offset by the price that not making twenty-first century skills a priority in the classroom will have on future economic well-being.

Mechanism of Action of Botulinum Neurotoxin and Overview of Medical Countermeasures for Intoxication

Science.gov (United States)

2008-01-01

techni-cally feasible. As a further refinement, a yeast display system was used as a technology platform for performingmolecular evolution by increasing...the affinity of those scFv antibodies that bind to BoNT/ A. Yeast -displayed scFv libraries have been constructed by selecting scFvs that bind with...hazelnut yoghurt. Epidemiol. Infect. 104:389-395. Oost, T., Sukonpan, C., Brewer , M., Goodnough, M., Tepp, W., Johnson, E.A, and Rich, D.H. 2003. Design

The conundrum of religious schools in twenty-first-century Europe

NARCIS (Netherlands)

Merry, M.S.

2015-01-01

In this paper Merry examines in detail the continued - and curious - popularity of religious schools in an otherwise ‘secular’ twenty-first century Europe. To do this he considers a number of motivations underwriting the decision to place one's child in a religious school and delineates what are

Foreign or Domestic CARs: Receptor Ligands as Antigen-Binding Domains

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Donald R. Shaffer

2014-01-01

Full Text Available Chimeric antigen receptors (CARs are increasingly being used in clinical trials to treat a variety of malignant conditions and recent results with CD19-specific CARs showing complete tumor regressions has sparked the interest of researchers and the public alike. Traditional CARs have been generated using single-chain variable fragments (scFv, often derived from murine monoclonal antibodies, for antigen specificity. As the clinical experience with CAR T cells grows, so does the potential for unwanted immune responses against the foreign transgene. Strategies that may reduce the immunogenicity of CAR T cells are humanization of the scFv and the use of naturally occurring receptor ligands as antigen-binding domains. Herein, we review the experience with alternatively designed CARs that contain receptor ligands rather than scFv. While most of the experiences have been in the pre-clinical setting, clinical data is also emerging.

Engineering an antibody with picomolar affinity to DOTA chelates of multiple radionuclides for pretargeted radioimmunotherapy and imaging

Energy Technology Data Exchange (ETDEWEB)

Orcutt, Kelly Davis; Slusarczyk, Adrian L. [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Cieslewicz, Maryelise [Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Ruiz-Yi, Benjamin [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Bhushan, Kumar R. [Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Frangioni, John V. [Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Wittrup, K. Dane, E-mail: wittrup@mit.ed [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States)

2011-02-15

Introduction: In pretargeted radioimmunotherapy (PRIT), a bifunctional antibody is administered and allowed to pre-localize to tumor cells. Subsequently, a chelated radionuclide is administered and captured by cell-bound antibody while unbound hapten clears rapidly from the body. We aim to engineer high-affinity binders to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelates for use in PRIT applications. Methods: We mathematically modeled antibody and hapten pharmacokinetics to analyze hapten tumor retention as a function of hapten binding affinity. Motivated by model predictions, we used directed evolution and yeast surface display to affinity mature the 2D12.5 antibody to DOTA, reformatted as a single chain variable fragment (scFv). Results: Modeling predicts that for high antigen density and saturating bsAb dose, a hapten-binding affinity of 100 pM is needed for near-maximal hapten retention. We affinity matured 2D12.5 with an initial binding constant of about 10 nM to DOTA-yttrium chelates. Affinity maturation resulted in a 1000-fold affinity improvement to biotinylated DOTA-yttrium, yielding an 8.2{+-}1.9 picomolar binder. The high-affinity scFv binds DOTA complexes of lutetium and gadolinium with similar picomolar affinity and indium chelates with low nanomolar affinity. When engineered into a bispecific antibody construct targeting carcinoembryonic antigen, pretargeted high-affinity scFv results in significantly higher tumor retention of a {sup 111}In-DOTA hapten compared to pretargeted wild-type scFv in a xenograft mouse model. Conclusions: We have engineered a versatile, high-affinity, DOTA-chelate-binding scFv. We anticipate it will prove useful in developing pretargeted imaging and therapy protocols to exploit the potential of a variety of radiometals.

Diabetes: Unique to Older Adults

Science.gov (United States)

... Stroke Urinary Incontinence Related Documents PDF Choosing Wisely: Diabetes Tests and Treatments Download Related Video Join our e-newsletter! Aging & Health A to Z Diabetes Unique to Older Adults This section provides information ...

Wicked Female Characters in Roddy Doyle’s “The Pram”: Revisiting Celtic and Polish Myths in the Context of Twenty-First Century Ireland

Directory of Open Access Journals (Sweden)

Burcu Gülüm Tekin

2015-07-01

Full Text Available “The Pram” is the only horror story in Roddy Doyle’s collection The Deportees and Other Stories (2007. It is also unique in terms of its approach to Ireland’s multicultural scene in the twenty-first century. Doyle turns the other side of the coin and introduces a migrant caretaker (Alina, who loses her mind due to her employees’ (the O’Reilly family ill-treatment. As a reaction to their scornful attitude, Alina becomes a murderer. Set in the context of twenty-first century Dublin, “The Pram” contains various references to Celtic and Polish mythological female figures (in particular, the Old Hag of Beara and Boginka, which strengthen the thrilling, mythical elements in the plot. This paper aims to examine the characters’ negative attitude towards migrants in Ireland in the light of the racist discourse present in the story. Also, I will focus on the story’s female characters and discuss the handicaps of being a female migrant in Ireland. The parallels between the mythical female figures and the protagonist Alina will be another point to be analyzed. The argument of this paper is that Doyle does not always portray the positive outcomes of a multicultural society. On the contrary, he conveys the perspective of the incoming migrant. “The Pram” stages the obstacles that a female outsider may experience in Ireland and her subsequent transformation as a result of the racism she encounters there.

Might "Unique" Factors Be "Common"? On the Possibility of Indeterminate Common-Unique Covariances

Science.gov (United States)

Grayson, Dave

2006-01-01

The present paper shows that the usual factor analytic structured data dispersion matrix lambda psi lambda' + delta can readily arise from a set of scores y = lambda eta + epsilon, shere the "common" (eta) and "unique" (epsilon) factors have nonzero covariance: gamma = Cov epsilon,eta) is not equal to 0. Implications of this finding are discussed…

Building On Builder: The Persistent Icarus Syndrome at Twenty Years

Science.gov (United States)

2013-06-01

mission of the United States Air Force is to "fly, fight, and win…in air, space and cyberspace"--as an intergral member of the Joint team that...Scenarios: A Military Futurist Explores War in the Twenty-First Century (New York: Bantam Books Trade Paperbacksl, 2009), 17. 33 Carl H. Builder

Improving the temporal transposability of lumped hydrological models on twenty diversified U.S. watersheds

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G. Seiller

2015-03-01

Full Text Available Study region: Twenty diversified U.S. watersheds. Study focus: Identifying optimal parameter sets for hydrological modeling on a specific catchment remains an important challenge for numerous applied and research projects. This is particularly the case when working under contrasted climate conditions that question the temporal transposability of the parameters. Methodologies exist, mainly based on Differential Split Sample Tests, to examine this concern. This work assesses the improved temporal transposability of a multimodel implementation, based on twenty dissimilar lumped conceptual structures and on twenty U.S. watersheds, over the performance of the individual models. New hydrological insights for the region: Individual and collective temporal transposabilities are analyzed and compared on the twenty studied watersheds. Results show that individual models performances on contrasted climate conditions are very dissimilar depending on test period and watershed, without the possibility to identify a best solution in all circumstances. They also confirm that performance and robustness are clearly enhanced using an ensemble of rainfall-runoff models instead of individual ones. The use of (calibrated weight averaged multimodels further improves temporal transposability over simple averaged ensemble, in most instances, confirming added-value of this approach but also the need to evaluate how individual models compensate each other errors. Keywords: Rainfall-runoff modeling, Multimodel approach, Differential Split Sample Test, Deterministic combination, Outputs averaging

The «Group of Twenty», IMF and EU and Reforming of Global Governance

Directory of Open Access Journals (Sweden)

Evgeniy J. Il'in

2014-01-01

Full Text Available This article is devoted to the process of reforming the global financial system and world economic organizations since the foundation of the International Monetary Fund at the Bretton Woods Conference in 1944 to present time. Special attention is given to results of cooperation of the IMF and the "Group of Twenty"in the context of the world financial crisis 2008-2009. This article mentions the key benchmarks of the historical development of world economy: foundation of the Bretton Woods financial system, rejection of the gold standard at the Jamaica Conference, transition to the floating exchange rates, the wave of crises in the 1990-s, the world financial crisis of 2008-2009. The process of evolution of the IMF within the framework of these global events is considered here. The cooperation of EU, IMF and "Group of Twenty" is considered. The reforms of the IMF and their results are analyzed. The policy of the IMF at different historical stages of its evolution is estimated. As well as it results, the article also deals with the formation and development of the "Group of Twenty". The increasing role of the "Group of Twenty" in the global economic governance and reforming the IMF is considered. Especially is marked the necessity of the further reforms of the IMF and increasing of participation of the "G-20" in the world economic and politic system.

Proceedings of the twenty-first LAMPF users group meeting

International Nuclear Information System (INIS)

1988-04-01

The Twenty-First Annual LAMPF Users Group Meeting was held November 9-10, 1987, at the Clinton P. Anderson Meson Physics Facility. The program included a number of invited talks on various aspects of nuclear and particle physics as well as status reports on LAMPF and discussions of upgrade options. The LAMPF working groups met and discussed plans for the secondary beam lines, experimental programs, and computing facilities

Proceedings of the twenty-second LAMPF users groupd meeting

International Nuclear Information System (INIS)

Marinuzzi, R.

1989-04-01

The Twenty-Second Annual LAMPF Users Group Meeting was held October 17--18, 1988, at the Clinton P. Anderson Meson Physics Facility. The program included a number of invited talks on various aspects of nuclear and particle physics as well as status reports on LAMPF and discussions of upgrade options. The LAMPF working groups met and discussed plans for the secondary beam lines, experimental programs, and computing facilities

NATO’s Relevance in the Twenty-First Century

Science.gov (United States)

2012-03-22

reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching...5d. PROJECT NUMBER Colonel John K. Jones 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES...Christopher Coker, Globalisation and Insecurity in the Twenty-first Century: NATO and the Management of Risk (The International Institute for Strategic

Customization: Ideal Varieties, Product Uniqueness and Price Competition

OpenAIRE

Oksana Loginova; X. Henry Wang

2009-01-01

We study customization in the Hotelling model with two firms. In addition to providing ideal varieties, the perceived uniqueness of a customized product contributes independently to consumer utility. We show that only when consumer preferences for uniqueness are high customization occurs in equilibrium.

Twenty-first century learning in schools: A case study of New Technology High School in Napa, California.

Science.gov (United States)

Pearlman, Bob

2006-01-01

The most pertinent question concerning teaching and learning in the twenty-first century is not what knowledge and skills students need--that laundry list was identified over a decade ago--but rather how to foster twenty-first century learning. What curricula, experiences, assessments, environments, and technology best support twenty-first century learning? New Technology High School (NTHS) in Napa, California, is one example of a successful twenty-first century school. In this chapter, the author describes the components of this exemplary high school, illustrating an environment that will cultivate twenty-first century student learning. New Technology High School began by defining eight learning outcomes, aligned with the standards of the Partnership for 21st Century Skills; to graduate, students demonstrate mastery of these outcomes through an online portfolio. To help students achieve the outcomes, NTHS employs project- and problem-based learning. Whereas in traditional classrooms students work alone on short-term assignments that do not lend themselves to deep understanding, the project-based learning approach has students working in teams on long-term, in-depth, rigorous projects. Students' work is supported by the school's workplace-like environment and effectiv use of technology. Meaningful assessment is essential to project-based learning; students receive continuous feedback, helping them become self-directed learners. In fact, NTHS uses outcome-based grading through which students constantly know how they are performing on the twenty-first century outcomes. Research has shown that NTHS graduates are better prepared for postsecondary education, careers, and citizenship than their peers from other schools. To facilitate twenty-first century learning, all schools need to rethink their approach to teaching and learning. New Technology High School is one way to do so.

Industries processing naturally occurring radioactive materials: twenty years of emission data in the Netherlands

International Nuclear Information System (INIS)

Tanzi, C.P.

2008-01-01

This paper provides a review of the dose assessment of discharges to air of two industries processing NORM (Naturally Occurring Radioactive Materials) in the Netherlands. An industrial plant producing elemental phosphorus (thermal process, unique within Europe) reports since 1987 its emission data to the Dutch Ministry of the Environment (VROM: Ministry of Housing, Spatial Planning and the Environment). This plant accounts for the highest release of Po-210 to air in the Netherlands, with a yearly average of approximately 500 GBq. Other significant NORM discharges to air arise from an industrial plant with blast-furnaces for steel production. Yearly discharges fall under permit, and are reported, since 1993. RIVM, the National Institute for Public Health and the Environment, is tasked by the Ministry to assess the dose to the general public arising from these discharges to air. Air transport modelling is used to determine both air concentration (for inhalation exposure) and deposition rate of the radionuclides. A (conservative) committed ingestion dose is determined by modelling the uptake of radionuclides from contaminated farmland, and assuming a food basket to be fairly representative for the population of the Netherlands. Discharges to water in the Netherlands have decreased in the past twenty years, due both to the closure of two phosphoric acid plants a decade ago and the improved treatment of waste fluids by other NORM industries. The collective dose assessed from discharges to air since 1987 is presented here. (author)

Humanities: The Unexpected Success Story of the Twenty-First Century

Science.gov (United States)

Davis, Virginia

2012-01-01

Humanities within universities faced challenges in the latter half of the twentieth century as their value in the modern world was questioned. This paper argues that there is strong potential for the humanities to thrive in the twenty-first century university sector. It outlines some of the managerial implications necessary to ensure that this…

Twenty Years of French "Didactique" Viewed from the United States

Science.gov (United States)

Kilpatrick, Jeremy

2003-01-01

One cannot begin considering the topic of this colloquium without asking, why twenty years? Why not two hundred? Two hundred years ago, Silvestre Franois Lacroix was about to be named chief officer of the Commission Executive de L'Instruction Publique. Out of that experience, together with his long career in instruction, especially as professor of…

Can facial uniqueness be inferred from impostor scores?

NARCIS (Netherlands)

Dutta, A.; Veldhuis, Raymond N.J.; Spreeuwers, Lieuwe Jan

2013-01-01

In Biometrics, facial uniqueness is commonly inferred from impostor similarity scores. In this paper, we show that such uniqueness measures are highly unstable in the presence of image quality variations like pose, noise and blur. We also experimentally demonstrate the instability of a recently

Accelerators for the twenty-first century a review

CERN Document Server

Wilson, Edmund J N

1990-01-01

The development of the synchrotron, and later the storage ring, was based upon the electrical technology at the turn of this century, aided by the microwave radar techniques of World War II. This method of acceleration seems to have reached its limit. Even superconductivity is not likely to lead to devices that will satisfy physics needs into the twenty-first century. Unless a new principle for accelerating elementary particles is discovered soon, it is difficult to imagine that high-energy physics will continue to reach out to higher energies and luminosities.

Kosovo case: A unique arbitrariness

Directory of Open Access Journals (Sweden)

Nakarada Radmila

2007-01-01

Full Text Available The end of Cold war, contrary to expectations has brought new conflicts and forms of violence, new divisions and new relativizations of the international legal order. Taking as an example the endeavors to resolve the Kosovo conflict, the author attempts to indicate the broader implications of the international efforts to constitute an independent state on part of the territory of an existing sovereign state. The arguments used to justify the redefinition of the borders of the Serbian state without its consent, the moral, democratic, peace arguments, are reviewed. Particular attention is paid to the argument that Kosovo is a unique case and therefore unique rules should be applied. The author seeks to understand the deeper significance of these efforts, concluding that dismantling the present international legal order is not only a potential danger but a possible aim.

Generation of recombinant monoclonal antibodies to study structure-function of envelope protein VP28 of white spot syndrome virus from shrimp

International Nuclear Information System (INIS)

Wang Yuzhen; Zhang Xiaohua; Yuan Li; Xu Tao; Rao Yu; Li Jia; Dai Heping

2008-01-01

White spot syndrome virus (WSSV) is a major pathogen in shrimp aquaculture. VP28 is one of the most important envelope proteins of WSSV. In this study, a recombinant antibody library, as single-chain fragment variable (scFv) format, displayed on phage was constructed using mRNA from spleen cells of mice immunized with full-length VP28 expressed in Escherichia coli. After several rounds of panning, six scFv antibodies specifically binding to the epitopes in the N-terminal, middle, and C-terminal regions of VP28, respectively, were isolated from the library. Using these scFv antibodies as tools, the epitopes in VP28 were located on the envelope of the virion by immuno-electron microscopy. Neutralization assay with these antibodies in vitro suggested that these epitopes may not be the attachment site of WSSV to host cell receptor. This study provides a new way to investigate the structure and function of the envelope proteins of WSSV

Ultra scaledown to predict filtering centrifugation of secreted antibody fragments from fungal broth.

Science.gov (United States)

Boulding, N; Yim, S S S; Keshavarz-Moore, E; Ayazi Shamlou, P; Berry, M

2002-08-20

Extracellularly expressed anti-hen egg lysozyme single-chain antibody fragments (scFv) produced by Aspergillus awamori were recovered using filtering centrifugation. Two filtering centrifuges with 0.5- and 30-L capacities were used to represent laboratory- and pilot-scale equipment, respectively. Critical regime analysis using the computational fluid dynamics (CFD) technique provided information about the local energy dissipation rates in both units. Experimental data indicated loss of scFv activity for energy dissipation rates above about 2.0 x 10(4) W kg(-1). This loss of activity increased in the presence of gas-liquid interfaces during filtering centrifugation. An ultra scaledown filtering centrifuge with a maximum working volume of 35 mL was designed to mimic the operating conditions identified by the critical regime analysis for the laboratory- and pilot-plant-scale units. The recovered scFv activity levels and the separation performance of the three units were comparable when operated at equal maximum energy dissipation rates. Copyright 2002 Wiley Periodicals, Inc.

Investigating the Twenty Year Lag in the Vocational Rehabilitation Process.

Science.gov (United States)

Lowitt, Julian

In the rehabilitation workshop there is insufficient attention to job development oriented to the current and future needs of industry. Many types of work which were done in vocational workshops in contract from industrial firms are now done by automation. Semiskilled labor is thus in diminished demand. There is a twenty year lag in the industrial…

Twenty five years of fundamental theory

International Nuclear Information System (INIS)

Bell, J.S.

1980-01-01

In reviewing the last twenty five years in fundamental physics theory it is stated that there has been no revolution in this field. In the absence of gravitation, Lorentz invariance remains a requirement on fundamental laws. Einstein's theory of gravitation inspires increasing conviction on the astronomical scale. Quantum theory remains the framework for all serious effort in microphysics, and quantum electrodynamics remains the model of a fully articulated microphysical theory, completely successful in its domain. However,a number of ideas have appeared, of great theoretical interest and some phenomenological success, which may well contribute to the next decisive step. Recent work on the following topics is mentioned; gravitational radiation, singularites, black body radiation from black holes, gauge and hidden symmetry in quantum electrodynamics, the renormalization of electromagnetic and weak interaction theory, non-Abelian gauge theories, magnetic monopoles as the most striking example of solitons, and supersymmetry. (UK)

An investigation of twenty-one cases of low-frequency noise complaints

DEFF Research Database (Denmark)

Pedersen, Christian Sejer; Møller, Henrik; Persson-Waye, Kerstin

2007-01-01

Twenty-one cases of low-frequency noise complaints were thoroughly investigated with the aim of answering the question whether it is real physical sound or low-frequency tinnitus that causes the annoyance. Noise recordings were made in the homes of the complainants taking the spatial variation...

HIV is Now a Manageable Long-Term Condition, But What Makes it Unique? A Qualitative Study Exploring Views About Distinguishing Features from Multi-Professional HIV Specialists in North West England.

Science.gov (United States)

Jelliman, Pauline; Porcellato, Lorna

HIV is evolving from a life-threatening infection to a long-term, manageable condition because of medical advances, radical changes in health and social care policy, and the impact of an aging population. However, HIV remains complex, presenting unique characteristics distinguishing it from other long-term conditions (LTCs). Our aim in this qualitative descriptive study was to identify and explore these features in the context of LTCs. A focus group (FG) method was used to gather the views and experiences of multi-professional HIV specialists who worked in North West England. Twenty-four staff participated in FGs (n = 3), which were audio recorded, manually transcribed, and thematically analyzed. We found four main themes: (a) stigma, (b) challenges faced by HIV specialists, (c) lack HIV-related knowledge, and (d) unique features, termed "stand alone." We concluded that these distinguishing features hindered full recognition and acceptance of HIV as an LTC. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Twenty five years of clusters -- from Bochum to Strasbourg

International Nuclear Information System (INIS)

Betts, R.R.; Chicago Univ., IL

1994-01-01

Developments in the area of clustering aspects of nuclear structure and reactions over the past twenty-five years are reviewed. The viewpoint is that the nucleus is an assembly of clusters. The question is whether clusters actually exist in the nucleus. Although there is abundant evidence for this in light nuclei, the situation for more complex clusters in heavier nuclei is much worse. Differential cross sections for scattering of alpha particles and heavy ions are shown

Twenty-fourth Semiannual Report of the Commission to the Congress, July 1958

Energy Technology Data Exchange (ETDEWEB)

Strauss, Lewis L.; McCone, John A.

1958-07-31

The document represents the twenty-fourth semiannual Atomic Energy Commission (AEC) report to Congress. The report sums up the major activities and developments in the national atomic energy program covering the period January - June 1958.

Twenty-second Semiannual Report of the Commission to the Congress, July 1957

Energy Technology Data Exchange (ETDEWEB)

Strauss, Lewis L.

1957-07-31

The document represents the twenty-second semiannual Atomic Energy Commission (AEC) report to Congress. The report sums up the major activities and developments in the national atomic energy program covering the period January - June 1957.

DECISIONS ET COMPETITIVITE SUR LE MARCHE UNIQUE EUROPEEN

Directory of Open Access Journals (Sweden)

Sirghi Nicoleta

2008-05-01

Full Text Available L’un des traits importants du marché unique européen, a comme source le męme énoncé du principal objectif de l’intégration européenne ainsi que: l’harmonisation des niveaux du développement des Etats Membres et l’augmentation du niveau de vie dans l’ensemble de la communauté. Pour le marché unique européen, cet aspect se traduit par une permanente et soutenue augmentation de la demande. Cet ouvrage présente au début une analyse des éléments spécifiques du marché européen. Ensuite on identifie les opportunités et les risques au niveau macroéconomique adjointes aux perspectives du marché unique européen. Comme fondement on présente des stratégies du développement réalisables au niveau microéconomique que puissent assurer l’augmentation du niveau sur la compétitivité des sociétés sur le marché unique européen.

Sufficient conditions for uniqueness of the weak value

International Nuclear Information System (INIS)

Dressel, J; Jordan, A N

2012-01-01

We review and clarify the sufficient conditions for uniquely defining the generalized weak value as the weak limit of a conditioned average using the contextual values formalism introduced in Dressel, Agarwal and Jordan (2010 Phys. Rev. Lett. http://dx.doi.org/10.1103/PhysRevLett.104.240401). We also respond to criticism of our work by Parrott (arXiv:1105.4188v1) concerning a proposed counter-example to the uniqueness of the definition of the generalized weak value. The counter-example does not satisfy our prescription in the case of an underspecified measurement context. We show that when the contextual values formalism is properly applied to this example, a natural interpretation of the measurement emerges and the unique definition in the weak limit holds. We also prove a theorem regarding the uniqueness of the definition under our sufficient conditions for the general case. Finally, a second proposed counter-example by Parrott (arXiv:1105.4188v6) is shown not to satisfy the sufficiency conditions for the provided theorem. (paper)

Twenty years of society of medical informatics of b&h and the journal acta informatica medica.

Science.gov (United States)

Masic, Izet

2012-03-01

In 2012, Health/Medical informatics profession celebrates five jubilees in Bosnia and Herzegovina: a) Thirty five years from the introduction of the first automatic manipulation of data; b) Twenty five years from establishing Society for Medical Informatics BiH; c) Twenty years from establishing scientific and professional journal of the Society for Medical Informatics of Bosnia and Herzegovina "Acta Informatica Medica"; d) Twenty years from establishing first Cathdra for Medical Informatics on biomedical faculties in Bosnia and Herzegovina and e) Ten years from the introduction of "Distance learning" in medical curriculum. All of the five mentioned activities in the area of Medical informatics had special importance and gave appropriate contribution in the development of Health/Medical informatics in Bosnia And Herzegovina.

After Twenty-Five Years: A Twenty-Five Year Follow-up Study of Middlesex County Vocational and Technical High School Graduates of the Class of June 1953.

Science.gov (United States)

Rogers, William; Zanzalari, J. Henry

A twenty-five-year follow-up study was conducted to determine the occupational, educational, marital and armed forces experiences of the graduating class of 1953 from the Middlesex County Vocational and Technical high schools located in New Brunswick, Perth, Amboy, and Woodbridge, New Jersey. Data, in the form of questionnaire responses, were…

Unique Physician Identification Number (UPIN) Directory

Data.gov (United States)

U.S. Department of Health & Human Services — The Unique Physician Identification Number (UPIN) Directory contains selected information on physicians, doctors of Osteopathy, limited licensed practitioners and...

Uniqueness theorems in linear elasticity

CERN Document Server

Knops, Robin John

1971-01-01

The classical result for uniqueness in elasticity theory is due to Kirchhoff. It states that the standard mixed boundary value problem for a homogeneous isotropic linear elastic material in equilibrium and occupying a bounded three-dimensional region of space possesses at most one solution in the classical sense, provided the Lame and shear moduli, A and J1 respectively, obey the inequalities (3 A + 2 J1) > 0 and J1>O. In linear elastodynamics the analogous result, due to Neumann, is that the initial-mixed boundary value problem possesses at most one solution provided the elastic moduli satisfy the same set of inequalities as in Kirchhoffs theorem. Most standard textbooks on the linear theory of elasticity mention only these two classical criteria for uniqueness and neglect altogether the abundant literature which has appeared since the original publications of Kirchhoff. To remedy this deficiency it seems appropriate to attempt a coherent description ofthe various contributions made to the study of uniquenes...

TPACK Updated to Measure Pre-Service Teachers' Twenty-First Century Skills

Science.gov (United States)

Valtonen, Teemu; Sointu, Erkko; Kukkonen, Jari; Kontkanen, Sini; Lambert, Matthew C.; Mäkitalo-Siegl, Kati

2017-01-01

Twenty-first century skills have attracted significant attention in recent years. Students of today and the future are expected to have the skills necessary for collaborating, problem solving, creative and innovative thinking, and the ability to take advantage of information and communication technology (ICT) applications. Teachers must be…

Why American business demands twenty-first century skills: an industry perspective.

Science.gov (United States)

Bruett, Karen

2006-01-01

Public education is the key to individual and business prosperity. With a vested stake in education, educators, employers, parents, policymakers, and the public should question how this nation's public education system is faring. Knowing that recent international assessments have shown little or no gains in American students' achievement, the author asserts the clear need for change. As both a large American corporate employer and a provider of technology for schools, Dell is concerned with ensuring that youth will thrive in their adult lives. Changing workplace expectations lead to a new list of skills students will need to acquire before completing their schooling. Through technology, Dell supports schools in meeting educational goals, striving to supply students with the necessary skills, referred to as twenty-first century skills. The Partnership for 21st Century Skills, of which Dell is a member, has led an initiative to define what twenty-first century learning should entail. Through extensive research, the partnership has built a framework outlining twenty-first century skills: analytical thinking, communication, collaboration, global awareness, and technological and economic literacy. Dell and the partnership are working state by state to promote the integration of these skills into curricula, professional development for teachers, and classroom environments. The authors describe two current initiatives, one in Virginia, the other in Texas, which both use technology to help student learning. All stakeholders can take part in preparing young people to compete in the global economy. Educators and administrators, legislators, parents, and employers must play their role in helping students be ready for what the workforce and the world has in store for them.

New Examples of Torsion-Free Non-unique Product Groups

OpenAIRE

Carter, William

2013-01-01

We give an infinite family of torsion-free groups that do not satisfy the unique product property. For these examples, we also show that each group contains arbitrarily large sets whose square has no uniquely represented element.

An IgE epitope of Bet v 1 and fagales PR10 proteins as defined by a human monoclonal IgE

DEFF Research Database (Denmark)

Hecker, J.; Diethers, A.; Schulz, D.

2012-01-01

-reactivities predicted by primary structure analyses of different isoforms and PR10 proteins were verified by allergen chip-based analyses. CONCLUSIONS: The obtained results demonstrate that hybrid IgE repertoires represent a source for human antibodies with genuine paratopes. The IgE-derived information about the Ig...... generation and epitope delineation of a human monoclonal IgE against the prototypic allergen Bet v 1. METHODS: Phage-display scFv hybrid libraries of allergic donor-derived VH epsilon and synthetic VL were established from 107 mononuclear cells. An obtained scFv was converted into human immunoglobulin...

Unique Perspectives on a Transforming Energy Economy: 2014 Annual Report (Brochure)

Energy Technology Data Exchange (ETDEWEB)

Gossett, S. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

2014-03-01

What makes JISEA unique? Unique perspectives. This brochure highlights the unique perspectives provided by the Joint Institute for Strategic Energy Analysis through JISEA's recent accomplishments and the people behind them.

Assessing twenty-first century skills through a teacher created video game for high school biology students

Science.gov (United States)

Annetta, Leonard A.; Cheng, Meng-Tzu; Holmes, Shawn

2010-07-01

As twenty-first century skills become a greater focus in K-12 education, an infusion of technology that meets the needs of today's students is paramount. This study looks at the design and creation of a Multiplayer Educational Gaming Application (MEGA) for high school biology students. The quasi-experimental, qualitative design assessed the twenty-first century skills of digital age literacy, inventive thinking, high productivity, and effective communication techniques of the students exposed to a MEGA. Three factors, as they pertained to these skills, emerged from classroom observations. Interaction with the teacher, discussion with peers, and engagement/time-on-task while playing the MEGA suggested that students playing an educational video game exhibited all of the projected twenty-first century skills while being engrossed in the embedded science content.

PET-CT in the typification of unique pulmonary injuries

International Nuclear Information System (INIS)

Cobos, P.; San Roman, Jose L.; Dalurzo, L.

2007-01-01

The objective of this document is to evaluate the usefulness of the PET-CT for the characterization of the unique pulmonary injuries. Retrospective analysis was made to patients with unique pulmonary injuries who carried out a PET-CT in the Italian Hospital between May of 2003 - March of 2005. Those patients with pulmonary outlying nodule, or unique pulmonary mass that had pathological anatomy of injury or follow-up through a computed tomography of thorax made with an interval of time not minor at 2 years of the PET-CT were included [es

Lattices with unique complements

CERN Document Server

Saliĭ, V N

1988-01-01

The class of uniquely complemented lattices properly contains all Boolean lattices. However, no explicit example of a non-Boolean lattice of this class has been found. In addition, the question of whether this class contains any complete non-Boolean lattices remains unanswered. This book focuses on these classical problems of lattice theory and the various attempts to solve them. Requiring no specialized knowledge, the book is directed at researchers and students interested in general algebra and mathematical logic.

Thomas Piketty – The Adam Smith of the Twenty-First Century?

Directory of Open Access Journals (Sweden)

Jacob Dahl Rendtorff

2014-11-01

Full Text Available Piketty’s book, Capital in the Twenty-First Century (2014 has become a bestseller in the world. Two month after its publication, it had sold more than 200.000 copies, and this success will surely continue for a long time. Piketty has established a new platform to discuss political economy.

Twenty-One Ways to Use Music in Teaching the Language Arts.

Science.gov (United States)

Cardarelli, Aldo F.

Twenty-one activities that integrate music and the language arts in order to capitalize on children's interests are described in this paper. Topics of the activities are as follows: alphabetical order, pantomime, vocabulary building from words of a favorite song, words that are "the most (whatever)" from songs, mood words, a configuration clue…

Twenty-First Water Reaction Safety Information Meeting

International Nuclear Information System (INIS)

Monteleone, S.

1994-04-01

This three-volume report contains 90 papers out of the 102 that were presented at the Twenty-First Water Reactor Safety Information Meeting held at the Bethesda Marriott Hotel, Bethesda, Maryland, during the week of October 25--27, 1993. The papers are printed in the order of their presentation in each session and describe progress and results of programs in nuclear safety research conducted in this country and abroad. Foreign participation in the meeting included papers presented by researchers from France, Germany, Japan, Russia, Switzerland, Taiwan, and United Kingdom. The titles of the papers and the names of the authors have been updated and may differ from those that appeared in the final program of the meeting. Individual papers have been cataloged separately. This document, Volume 2, presents papers on severe accident research

Twenty-First Water Reactor Safety Information Meeting

International Nuclear Information System (INIS)

Monteleone, S.

1994-04-01

This three-volume report contains 90 papers out of the 102 that were presented at the Twenty-First Water Reactor Safety Information Meeting held at the Bethesda Marriott Hotel, Bethesda, Maryland, during the week of October 25-27, 1993. The papers are printed in the order of their presentation in each session and describe progress and results of programs in nuclear safety research conducted in this country and abroad. Foreign participation in the meeting included papers presented by researchers from France, Germany, Japan, Russia, Switzerland, Taiwan, and United Kingdom. The titles of the papers and the names of the authors have been updated and may differ from those that appeared in the final program of the meeting. Selected papers were indexed separately for inclusion in the Energy Science and Technology Database

Twenty years of analysis of light elements at the LARN

International Nuclear Information System (INIS)

Demortier, G.

1992-01-01

We review the applications of ion beam analysis of light elements performed in the LARN during the last twenty years. The works mainly concern: helium bubbles in aluminum foils, Li in aluminum alloys, carbon in high purity MgO crystals and in olivines, nitrogen bubbles in glass and implanted nitrogen in iron and aluminum, oxygen in YBaCuO superconductors, fluorine in tooth enamel and implanted fluorine in metals. (orig.)

Father involvement: Identifying and predicting family members' shared and unique perceptions.

Science.gov (United States)

Dyer, W Justin; Day, Randal D; Harper, James M

2014-08-01

Father involvement research has typically not recognized that reports of involvement contain at least two components: 1 reflecting a view of father involvement that is broadly recognized in the family, and another reflecting each reporter's unique perceptions. Using a longitudinal sample of 302 families, this study provides a first examination of shared and unique views of father involvement (engagement and warmth) from the perspectives of fathers, children, and mothers. This study also identifies influences on these shared and unique perspectives. Father involvement reports were obtained when the child was 12 and 14 years old. Mother reports overlapped more with the shared view than father or child reports. This suggests the mother's view may be more in line with broadly recognized father involvement. Regarding antecedents, for fathers' unique view, a compensatory model partially explains results; that is, negative aspects of family life were positively associated with fathers' unique view. Children's unique view of engagement may partially reflect a sentiment override with father antisocial behaviors being predictive. Mothers' unique view of engagement was predicted by father and mother work hours and her unique view of warmth was predicted by depression and maternal gatekeeping. Taken, together finding suggests a far more nuanced view of father involvement should be considered.

Twenty First Century Education: Transformative Education for Sustainability and Responsible Citizenship

Science.gov (United States)

Bell, David V. J.

2016-01-01

Many ministries of education focus on twenty-first century education but unless they are looking at this topic through a sustainability lens, they will be missing some of its most important elements. The usual emphasis on developing skills for employability in the current global economy begs the question whether the global economy is itself…

How Do Students Value the Importance of Twenty-First Century Skills?

Science.gov (United States)

Ahonen, Arto Kalevi; Kinnunen, Päivi

2015-01-01

Frameworks of twenty-first century skills have attained a central role in school development and curriculum changes all over the world. There is a common understanding of the need for meta-skills such as problem solving, reasoning, collaboration, and self-regulation. This article presents results from a Finnish study, in which 718 school pupils…

Uniqueness of solutions for a mathematical model for magneto-viscoelastic flows

Science.gov (United States)

Schlömerkemper, A.; Žabenský, J.

2018-06-01

We investigate uniqueness of weak solutions for a system of partial differential equations capturing behavior of magnetoelastic materials. This system couples the Navier–Stokes equations with evolutionary equations for the deformation gradient and for the magnetization obtained from a special case of the micromagnetic energy. It turns out that the conditions on uniqueness coincide with those for the well-known Navier–Stokes equations in bounded domains: weak solutions are unique in two spatial dimensions, and weak solutions satisfying the Prodi–Serrin conditions are unique among all weak solutions in three dimensions. That is, we obtain the so-called weak-strong uniqueness result in three spatial dimensions.

Science Teacher Education in the Twenty-First Century: a Pedagogical Framework for Technology-Integrated Social Constructivism

Science.gov (United States)

Barak, Miri

2017-04-01

Changes in our global world have shifted the skill demands from acquisition of structured knowledge to mastery of skills, often referred to as twenty-first century competencies. Given these changes, a sequential explanatory mixed methods study was undertaken to (a) examine predominant instructional methods and technologies used by teacher educators, (b) identify attributes for learning and teaching in the twenty-first century, and (c) develop a pedagogical framework for promoting meaningful usage of advanced technologies. Quantitative and qualitative data were collected via an online survey, personal interviews, and written reflections with science teacher educators and student teachers. Findings indicated that teacher educators do not provide sufficient models for the promotion of reform-based practice via web 2.0 environments, such as Wikis, blogs, social networks, or other cloud technologies. Findings also indicated four attributes for teaching and learning in the twenty-first century: (a) adapting to frequent changes and uncertain situations, (b) collaborating and communicating in decentralized environments, (c) generating data and managing information, and (d) releasing control by encouraging exploration. Guided by social constructivist paradigms and twenty-first century teaching attributes, this study suggests a pedagogical framework for fostering meaningful usage of advanced technologies in science teacher education courses.

Over Twenty Years Of Experience In ITU TRIGA MARK-II Reactor

International Nuclear Information System (INIS)

Yavuz, Hasbi

2008-01-01

I.T.U. TRIGA MARK-II Training and Research Reactor, rated at 250 kW steady-state and 1200 MW pulsing power is the only research and training reactor owned and operated by a university in Turkey. Reactor has been operating since March 11, 1979; therefore the reactor has been operating successfully for more than twenty years. Over the twenty years of operation: - The tangential beam tube was equipped with a neutron radiography facility, which consists of a divergent collimator and exposure room; - A computerized data acquisition system was designed and installed such that all parameters of the reactor, which are observed from the console, could be monitored both in normal and pulse operations; - An electrical power calibration system was built for the thermal power calibration of the reactor; - Publications related with I.T.U. TRIGA MARK-II Training and Research Reactor are listed in Appendix; - Two majors undesired shutdown occurred; - The I.T.U. TRIGA MARK-II Training and Research Reactor is still in operation at the moment. (authors)

Uniqueness of the electrostatic solution in Schwarzschild space

International Nuclear Information System (INIS)

Molnar, Pal G.; Elsaesser, Klaus

2003-01-01

In this Brief Report we give the proof that the solution of any static test charge distribution in Schwarzschild space is unique. In order to give the proof we derive the first Green's identity written with p-forms on (pseudo) Riemannian manifolds. Moreover, the proof of uniqueness can be shown for either any purely electric or purely magnetic field configuration. The spacetime geometry is not crucial for the proof

Twenty Years of Australian Educational Computing: A Call for Modern Traditionalism

Science.gov (United States)

McDougall, Anne

2005-01-01

This article reflects on twenty or more years of development and research in educational computing. It argues that the emphasis on exploiting the technology in the service of contemporary ideas about learning held by many of the early workers has been lost to a focus on the technology itself and its capabilities. In schools this has led to an…

An analysis of players\\' performances in the first cricket Twenty20 ...

African Journals Online (AJOL)

The purpose of this paper is to show how batting and bowling performance measures for one-day internationals can be adapted for use in Twenty20 matches, specifically in the case of a very small number of matches played. These measures are then used to give rankings of the batsmen and bowlers who performed best in ...

Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-etiopathology considerations respecting jaw developmental biology-related unique features.

Science.gov (United States)

Wehrhan, Falk; Hyckel, Peter; Ries, Jutta; Stockmann, Phillip; Nkenke, Emeka; Schlegel, Karl A; Neukam, Friedrich W; Amann, Kerstin

2010-10-13

Bone-destructive disease treatments include bisphosphonates and antibodies against the osteoclast differentiator, RANKL (aRANKL); however, osteonecrosis of the jaw (ONJ) is a frequent side-effect. Current models fail to explain the restriction of bisphosphonate (BP)-related and denosumab (anti-RANKL antibody)-related ONJ to jaws. Msx-1 is exclusively expressed in craniofacial structures and pivotal to cranial neural crest (CNC)-derived periodontal tissue remodeling. We hypothesised that Msx-1 expression might be impaired in bisphosphonate-related ONJ. The study aim was to elucidate Msx-1 and RANKL-associated signal transduction (BMP-2/4, RANKL) in ONJ-altered and healthy periodontal tissue. Twenty ONJ and twenty non-BP exposed periodontal samples were processed for RT-PCR and immunohistochemistry. An automated staining-based alkaline phosphatase-anti-alkaline phosphatase method was used to measure the stained cells:total cell-number ratio (labelling index, Bonferroni adjustment). Real-time RT-PCR was performed on ONJ-affected and healthy jaw periodontal samples (n = 20 each) to quantitatively compare Msx-1, BMP-2, RANKL, and GAPDH mRNA levels. Semi-quantitative assessment of the ratio of stained cells showed decreased Msx-1 and RANKL and increased BMP-2/4 (all p Msx-1 (p Msx-1 suppression in ONJ-adjacent periodontal tissue suggested a bisphosphonate-related impairment in cellular differentiation that occurred exclusively jaw remodelling. Further research on developmental biology-related unique features of jaw bone structures will help to elucidate pathologies restricted to maxillofacial tissue.

Site-Specific Antibody Functionalization Using Tetrazine-Styrene Cycloaddition.

Science.gov (United States)

Umlauf, Benjamin J; Mix, Kalie A; Grosskopf, Vanessa A; Raines, Ronald T; Shusta, Eric V

2018-05-03

Biologics, such as antibody-drug conjugates, are becoming mainstream therapeutics. Consequently, methods to functionalize biologics without disrupting their native properties are essential for identifying, characterizing, and translating candidate biologics from the bench to clinical practice. Here, we present a method for site-specific, carboxy-terminal modification of single-chain antibody fragments (scFvs). ScFvs displayed on the surface of yeast were isolated and functionalized by combining intein-mediated expressed protein ligation (EPL) with inverse electron-demand Diels-Alder (IEDDA) cycloaddition using a styrene-tetrazine pair. The high thiol concentration required to trigger EPL can hinder the subsequent chemoselective ligation reactions; therefore, the EPL reaction was used to append styrene to the scFv, limiting tetrazine exposure to damaging thiols. Subsequently, the styrene-functionalized scFv was reacted with tetrazine-conjugated compounds in an IEDDA cycloaddition to generate functionalized scFvs that retain their native binding activity. Rapid functionalization of yeast surface-derived scFv in a site-directed manner could find utility in many downstream laboratory and preclinical applications.

The twenty-first century in space

CERN Document Server

Evans, Ben

2015-01-01

This final entry in the History of Human Space Exploration mini-series by Ben Evans continues with an in-depth look at the latter part of the 20th century and the start of the new millennium. Picking up where Partnership in Space left off, the story commemorating the evolution of manned space exploration unfolds in further detail. More than fifty years after Yuri Gagarin’s pioneering journey into space, Evans extends his overview of how that momentous voyage continued through the decades which followed. The Twenty-first Century in Space, the sixth book in the series, explores how the fledgling partnership between the United States and Russia in the 1990s gradually bore fruit and laid the groundwork for today’s International Space Station. The narrative follows the convergence of the Shuttle and Mir programs, together with standalone missions, including servicing the Hubble Space Telescope, many of whose technical and human lessons enabled the first efforts to build the ISS in orbit. The book also looks to...

Multiple floating metatarsals: a unique injury

Directory of Open Access Journals (Sweden)

Trikha Vivek

2013-04-01

Full Text Available 【Abstract】Concomitant dislocation of the tar-sometatarsal and metatarsophalangeal joints of foot is an extremely rare injury. Such injuries presenting in a single or adjacent dual rays have been described in few cases previously. We describe such an injury in adjacent three metatarsals of a polytrauma patient. These injuries are likely to be missed in the initial assessment of a polytrauma patient. These patients are at risk of an overlooked diagnosis but the consequences of missing this type of injury may be Vivek Trikha*, Tarun Goyal, Amit K Agarwal quite severe. This case is presented in view of its unique-ness along with possible mechanism of injury, the sequence of reduction and follow-up. Knowledge of such injury and its proper management may be useful to the trauma surgeons. Key words: Metatarsal bones; Metatarsophalangeal joint; Wounds and injuries

On the Non-Uniqueness of Sediment Yield

Science.gov (United States)

Kim, J.; Ivanov, V. Y.; Fatichi, S.

2014-12-01

There has been ample experimental evidence that soil erosion does not necessarily occur at the same rate, given the same amount of rainfall or runoff. Such a non-unique phenomenon has been often referred to in literature as due to 'natural variability'. Our recent study hypothesized that uncertainties in the distribution and properties of a sediment layer can be a potential clue to one of the reasons of the non-unique sediment yield. Specifically, numerical experimentation with a sophisticated two-dimensional model showed that a deposited layer plays two conflicting roles: it can both increase and decrease soil erosion, given the same magnitude of runoff. The difference in erodibilities of the "original, intact soil layer" and the "deposited, loose soil layer" and the composition of soil particles in the underlying layers give rise to the non-uniqueness of the amount of eroded materials. In continuing efforts, we attempt to investigate this phenomenon using a comprehensive the Universal Soil Loss Erosion (USLE) database, that contains data on paired hillslopes that show a high degree of non-uniqueness in the response, even though the hillslopes exhibit the same topography, soil type, rainfall and meteorological forcings, and landuse. An underlying hypothesis of this study is that uncertainties in the distribution of soil substrate prior to a rainfall event lead to low predictability skill, i.e., a stochastically-varying outcome. A large number of simulation cases demonstrating the proposed hypothesis are conducted using a coupled numerical model, tRIBS-VEGGIE-FEaST (Triangulated irregular network - based Real time Integrated Basin Simulator- VEGetation Generator for Interactive Evolution -Flow Erosion and Sediment Transport).

Fast-food consumption among 17-year-olds in the Birth to Twenty ...

African Journals Online (AJOL)

Objectives: Assessment of fast-food consumption in urban black adolescents. Design: The current research was a descriptive cross-sectional study. Setting: Subjects attending the Birth to Twenty (Bt20) research facility at the Chris Hani Baragwanath Hospital in Soweto, Johannesburg between September 2007 and May ...

Classical many-particle systems with unique disordered ground states

Science.gov (United States)

Zhang, G.; Stillinger, F. H.; Torquato, S.

2017-10-01

Classical ground states (global energy-minimizing configurations) of many-particle systems are typically unique crystalline structures, implying zero enumeration entropy of distinct patterns (aside from trivial symmetry operations). By contrast, the few previously known disordered classical ground states of many-particle systems are all high-entropy (highly degenerate) states. Here we show computationally that our recently proposed "perfect-glass" many-particle model [Sci. Rep. 6, 36963 (2016), 10.1038/srep36963] possesses disordered classical ground states with a zero entropy: a highly counterintuitive situation . For all of the system sizes, parameters, and space dimensions that we have numerically investigated, the disordered ground states are unique such that they can always be superposed onto each other or their mirror image. At low energies, the density of states obtained from simulations matches those calculated from the harmonic approximation near a single ground state, further confirming ground-state uniqueness. Our discovery provides singular examples in which entropy and disorder are at odds with one another. The zero-entropy ground states provide a unique perspective on the celebrated Kauzmann-entropy crisis in which the extrapolated entropy of a supercooled liquid drops below that of the crystal. We expect that our disordered unique patterns to be of value in fields beyond glass physics, including applications in cryptography as pseudorandom functions with tunable computational complexity.

A Three Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotype E Subtypes

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Consuelo Garcia-Rodriguez

2018-03-01

Full Text Available Human botulism is most commonly caused by botulinum neurotoxin (BoNT serotypes A, B, and E. For this work, we sought to develop a human monoclonal antibody (mAb-based antitoxin capable of binding and neutralizing multiple subtypes of BoNT/E. Libraries of yeast-displayed single chain Fv (scFv antibodies were created from the heavy and light chain variable region genes of humans immunized with pentavalent-toxoid- and BoNT/E-binding scFv isolated by Fluorescence-Activated Cell Sorting (FACS. A total of 10 scFv were isolated that bound one or more BoNT/E subtypes with nanomolar-level equilibrium dissociation constants (KD. By diversifying the V-regions of the lead mAbs and selecting for cross-reactivity, we generated three scFv that bound all four BoNT/E subtypes tested at three non-overlapping epitopes. The scFvs were converted to IgG that had KD values for the different BoNT/E subtypes ranging from 9.7 nM to 2.28 pM. An equimolar combination of the three mAbs was able to potently neutralize BoNT/E1, BoNT/E3, and BoNT/E4 in a mouse neutralization assay. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing multiple BoNT/E subtypes. A derivative of the three-antibody combination (NTM-1633 is in pre-clinical development with an investigational new drug (IND application filing expected in 2018.

A Three Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotype E Subtypes.

Science.gov (United States)

Garcia-Rodriguez, Consuelo; Razai, Ali; Geren, Isin N; Lou, Jianlong; Conrad, Fraser; Wen, Wei-Hua; Farr-Jones, Shauna; Smith, Theresa J; Brown, Jennifer L; Skerry, Janet C; Smith, Leonard A; Marks, James D

2018-03-01

Human botulism is most commonly caused by botulinum neurotoxin (BoNT) serotypes A, B, and E. For this work, we sought to develop a human monoclonal antibody (mAb)-based antitoxin capable of binding and neutralizing multiple subtypes of BoNT/E. Libraries of yeast-displayed single chain Fv (scFv) antibodies were created from the heavy and light chain variable region genes of humans immunized with pentavalent-toxoid- and BoNT/E-binding scFv isolated by Fluorescence-Activated Cell Sorting (FACS). A total of 10 scFv were isolated that bound one or more BoNT/E subtypes with nanomolar-level equilibrium dissociation constants (K D ). By diversifying the V-regions of the lead mAbs and selecting for cross-reactivity, we generated three scFv that bound all four BoNT/E subtypes tested at three non-overlapping epitopes. The scFvs were converted to IgG that had K D values for the different BoNT/E subtypes ranging from 9.7 nM to 2.28 pM. An equimolar combination of the three mAbs was able to potently neutralize BoNT/E1, BoNT/E3, and BoNT/E4 in a mouse neutralization assay. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing multiple BoNT/E subtypes. A derivative of the three-antibody combination (NTM-1633) is in pre-clinical development with an investigational new drug (IND) application filing expected in 2018.

Accessibility of physical states and non-uniqueness of entanglement measure

International Nuclear Information System (INIS)

Morikoshi, Fumiaki; Santos, Marcelo Franca; Vedral, Vlatko

2004-01-01

Ordering physical states is the key to quantifying some physical property of the states uniquely. Bipartite pure entangled states are totally ordered under local operations and classical communication (LOCC) in the asymptotic limit and uniquely quantified by the well-known entropy of entanglement. However, we show that mixed entangled states are partially ordered under LOCC even in the asymptotic limit. Therefore, non-uniqueness of entanglement measure is understood on the basis of an operational notion of asymptotic convertibility

Fab-based bispecific antibody formats with robust biophysical properties and biological activity.

Science.gov (United States)

Wu, Xiufeng; Sereno, Arlene J; Huang, Flora; Lewis, Steven M; Lieu, Ricky L; Weldon, Caroline; Torres, Carina; Fine, Cody; Batt, Micheal A; Fitchett, Jonathan R; Glasebrook, Andrew L; Kuhlman, Brian; Demarest, Stephen J

2015-01-01

A myriad of innovative bispecific antibody (BsAb) platforms have been reported. Most require significant protein engineering to be viable from a development and manufacturing perspective. Single-chain variable fragments (scFvs) and diabodies that consist only of antibody variable domains have been used as building blocks for making BsAbs for decades. The drawback with Fv-only moieties is that they lack the native-like interactions with CH1/CL domains that make antibody Fab regions stable and soluble. Here, we utilize a redesigned Fab interface to explore 2 novel Fab-based BsAbs platforms. The redesigned Fab interface designs limit heavy and light chain mixing when 2 Fabs are co-expressed simultaneously, thus allowing the use of 2 different Fabs within a BsAb construct without the requirement of one or more scFvs. We describe the stability and activity of a HER2×HER2 IgG-Fab BsAb, and compare its biophysical and activity properties with those of an IgG-scFv that utilizes the variable domains of the same parental antibodies. We also generated an EGFR × CD3 tandem Fab protein with a similar format to a tandem scFv (otherwise known as a bispecific T cell engager or BiTE). We show that the Fab-based BsAbs have superior biophysical properties compared to the scFv-based BsAbs. Additionally, the Fab-based BsAbs do not simply recapitulate the activity of their scFv counterparts, but are shown to possess unique biological activity.

Twenty-First Century Diseases: Commonly Rare and Rarely Common?

Science.gov (United States)

Daunert, Sylvia; Sittampalam, Gurusingham Sitta; Goldschmidt-Clermont, Pascal J

2017-09-20

Alzheimer's drugs are failing at a rate of 99.6%, and success rate for drugs designed to help patients with this form of dementia is 47 times less than for drugs designed to help patients with cancers ( www.scientificamerican.com/article/why-alzheimer-s-drugs-keep-failing/2014 ). How can it be so difficult to produce a valuable drug for Alzheimer's disease? Each human has a unique genetic and epigenetic makeup, thus endowing individuals with a highly unique complement of genes, polymorphisms, mutations, RNAs, proteins, lipids, and complex sugars, resulting in distinct genome, proteome, metabolome, and also microbiome identity. This editorial is taking into account the uniqueness of each individual and surrounding environment, and stresses the point that a more accurate definition of a "common" disorder could be simply the amalgamation of a myriad of "rare" diseases. These rare diseases are being grouped together because they share a rather constant complement of common features and, indeed, generally respond to empirically developed treatments, leading to a positive outcome consistently. We make the case that it is highly unlikely that such treatments, despite their statistical success measured with large cohorts using standardized clinical research, will be effective on all patients until we increase the depth and fidelity of our understanding of the individual "rare" diseases that are grouped together in the "buckets" of common illnesses. Antioxid. Redox Signal. 27, 511-516.

Testing Students under Cognitive Capitalism: Knowledge Production of Twenty-First Century Skills

Science.gov (United States)

Morgan, Clara

2016-01-01

Scholars studying the global governance of education have noted the increasingly important role corporations play in educational policy making. I contribute to this scholarship by examining the Assessment and Teaching of twenty-first century skills (ATC21S™) project, a knowledge production apparatus operating under cognitive capitalism. I analyze…

Border Crossing in Contemporary Brazilian Culture: Global Perspectives from the Twenty-First Century Literary Scene

Directory of Open Access Journals (Sweden)

Cimara Valim de Melo

2016-06-01

Full Text Available Abstract: This paper investigates the process of internationalisation of Brazilian literature in the twenty-first century from the perspective of the publishing market. For this, we analyse how Brazil has responded to globalisation and what effects of cultural globalisation can be seen in the Brazilian literary scene, focusing on the novel. Observing the movement of the novelists throughout the globe, the reception of Brazilian literature in the United Kingdom and the relations between art and the literary market in Brazil, we intend to provoke some reflections on Brazilian cultural history in the light of the twenty-first century.

Altered specificity of single-chain antibody fragments bound to pandemic H1N1-2009 influenza virus after conversion of the phage-bound to the soluble form

Directory of Open Access Journals (Sweden)

Kaku Yoshihiro

2012-09-01

Full Text Available Abstract Background In 2009, a novel influenza A/H1N1 virus (H1N1pdm quickly spread worldwide and co-circulated with then-existing seasonal H1N1 virus (sH1N1. Distinguishing between these 2 viruses was necessary to better characterize the epidemiological properties of the emergent virus, including transmission patterns, pathogenesis, and anti-influenza drug resistance. This situation prompted us to develop a point-of-care virus differentiation system before entering the 2009–2010 influenza season. Aiming to establish H1N1pdm-specific detection tools rapidly, we employed phage display libraries to select H1N1pdm-specific single-chain variable fragments (scFvs. Findings Human single-fold scFv libraries (Tomlinson I + J underwent selection for the ability to bind H1N1pdm virus particles. Three rounds of panning brought 1152 phage-bound scFvs, of which 58 clones reacted with H1N1pdm specifically or preferentially over sH1N1 in an enzyme-linked immunosorbent assay (ELISA. After conversion of the scFvs to soluble form, 7 clones demonstrating high/stable expression were finally obtained. However, all the soluble scFvs except No. 29 were found to have lost their specificity/preference for H1N1pdm in ELISA. The specificity/preference of No. 29 was also confirmed by immunofluorescence assay and immunoprecipitation, and the viral nucleoprotein was identified by ELISA as its target protein. The change in specificity associated with scFv conversion from phage-bound to soluble form could be due to loss of phage scaffold pIII protein, which likely provides structural support for the scFv antigen-binding site. It is also possible that the similar antigenic properties of H1N1pdm and sH1N1 led to the observed alterations in scFv specificity. Discussion Using a phage display library, we obtained 7 soluble scFv clones reactive against H1N1pdm; however, only 1 showed specificity/preference toward H1N1pdm. Our results confirmed that using phage display

Twenty-first-century medical microbiology services in the UK.

Science.gov (United States)

Duerden, Brian

2005-12-01

With infection once again a high priority for the UK National Health Service (NHS), the medical microbiology and infection-control services require increased technology resources and more multidisciplinary staff. Clinical care and health protection need a coordinated network of microbiology services working to consistent standards, provided locally by NHS Trusts and supported by the regional expertise and national reference laboratories of the new Health Protection Agency. Here, I outline my thoughts on the need for these new resources and the ways in which clinical microbiology services in the UK can best meet the demands of the twenty-first century.

Consciousness: a unique way of processing information.

Science.gov (United States)

Marchetti, Giorgio

2018-02-08

In this article, I argue that consciousness is a unique way of processing information, in that: it produces information, rather than purely transmitting it; the information it produces is meaningful for us; the meaning it has is always individuated. This uniqueness allows us to process information on the basis of our personal needs and ever-changing interactions with the environment, and consequently to act autonomously. Three main basic cognitive processes contribute to realize this unique way of information processing: the self, attention and working memory. The self, which is primarily expressed via the central and peripheral nervous systems, maps our body, the environment, and our relations with the environment. It is the primary means by which the complexity inherent to our composite structure is reduced into the "single voice" of a unique individual. It provides a reference system that (albeit evolving) is sufficiently stable to define the variations that will be used as the raw material for the construction of conscious information. Attention allows for the selection of those variations in the state of the self that are most relevant in the given situation. Attention originates and is deployed from a single locus inside our body, which represents the center of the self, around which all our conscious experiences are organized. Whatever is focused by attention appears in our consciousness as possessing a spatial quality defined by this center and the direction toward which attention is focused. In addition, attention determines two other features of conscious experience: periodicity and phenomenal quality. Self and attention are necessary but not sufficient for conscious information to be produced. Complex forms of conscious experiences, such as the various modes of givenness of conscious experience and the stream of consciousness, need a working memory mechanism to assemble the basic pieces of information selected by attention.

The characterization of twenty sequenced human genomes.

Directory of Open Access Journals (Sweden)

Kimberly Pelak

2010-09-01

Full Text Available We present the analysis of twenty human genomes to evaluate the prospects for identifying rare functional variants that contribute to a phenotype of interest. We sequenced at high coverage ten "case" genomes from individuals with severe hemophilia A and ten "control" genomes. We summarize the number of genetic variants emerging from a study of this magnitude, and provide a proof of concept for the identification of rare and highly-penetrant functional variants by confirming that the cause of hemophilia A is easily recognizable in this data set. We also show that the number of novel single nucleotide variants (SNVs discovered per genome seems to stabilize at about 144,000 new variants per genome, after the first 15 individuals have been sequenced. Finally, we find that, on average, each genome carries 165 homozygous protein-truncating or stop loss variants in genes representing a diverse set of pathways.

Strategies for Teaching Maritime Archaeology in the Twenty First Century

Science.gov (United States)

Staniforth, Mark

2008-12-01

Maritime archaeology is a multi-faceted discipline that requires both theoretical learning and practical skills training. In the past most universities have approached the teaching of maritime archaeology as a full-time on-campus activity designed for ‘traditional’ graduate students; primarily those in their early twenties who have recently come from full-time undergraduate study and who are able to study on-campus. The needs of mature-age and other students who work and live in different places (or countries) and therefore cannot attend lectures on a regular basis (or at all) have largely been ignored. This paper provides a case study in the teaching of maritime archaeology from Australia that, in addition to ‘traditional’ on-campus teaching, includes four main components: (1) learning field methods through field schools; (2) skills training through the AIMA/NAS avocational training program; (3) distance learning topics available through CD-ROM and using the Internet; and (4) practicums, internships and fellowships. The author argues that programs to teach maritime archaeology in the twenty first century need to be flexible and to address the diverse needs of students who do not fit the ‘traditional’ model. This involves collaborative partnerships with other universities as well as government underwater cultural heritage management agencies and museums, primarily through field schools, practicums and internships.

Twenty-first Semiannual Report of the Commission to the Congress, January 1957

Energy Technology Data Exchange (ETDEWEB)

Strauss, Lewis L.

1957-01-31

The document represents the twenty-first semiannual Atomic Energy Commission (AEC) report to Congress. The report sums up the major activities and developments in the national atomic energy program covering the period July - December 1956. A special part two of this semiannual report addresses specifically Radiation Safety in Atomic Energy Activities.

Global Mental Health for Twenty First Century Education

Science.gov (United States)

Moradi Sheykhjan, Tohid; Rajeswari, K.

2016-01-01

Delivering mental health programs and services in education is not a new idea but it is time to bring mental health into focus. Momentum is gaining in terms of raising awareness, increasing understanding, and articulating strategies for advancing and integrating mental health. We need to know that all over the world everything is unique and…

The unique role of halogen substituents in the design of modern agrochemicals.

Science.gov (United States)

Jeschke, Peter

2010-01-01

The past 30 years have witnessed a period of significant expansion in the use of halogenated compounds in the field of agrochemical research and development. The introduction of halogens into active ingredients has become an important concept in the quest for a modern agrochemical with optimal efficacy, environmental safety, user friendliness and economic viability. Outstanding progress has been made, especially in synthetic methods for particular halogen-substituted key intermediates that were previously prohibitively expensive. Interestingly, there has been a rise in the number of commercial products containing 'mixed' halogens, e.g. one or more fluorine, chlorine, bromine or iodine atoms in addition to one or more further halogen atoms. Extrapolation of the current trend indicates that a definite growth is to be expected in fluorine-substituted agrochemicals throughout the twenty-first century. A number of these recently developed agrochemical candidates containing halogen substituents represent novel classes of chemical compounds with new modes of action. However, the complex structure-activity relationships associated with biologically active molecules mean that the introduction of halogens can lead to either an increase or a decrease in the efficacy of a compound, depending on its changed mode of action, physicochemical properties, target interaction or metabolic susceptibility and transformation. In spite of modern design concepts, it is still difficult to predict the sites in a molecule at which halogen substitution will result in optimal desired effects. This review describes comprehensively the successful utilisation of halogens and their unique role in the design of modern agrochemicals, exemplified by various commercial products from Bayer CropScience coming from different agrochemical areas.

Plastic-casting intrinsic-surface unique identifier (tag)

International Nuclear Information System (INIS)

Palm, R.G.; De Volpi, A.

1995-04-01

This report describes the development of an authenticated intrinsic-surf ace tagging method for unique- identification of controlled items. Although developed for control of items limited by an arms control treaty, this method has other potential applications to keep track of critical or high-value items. Each tag (unique-identifier) consists of the intrinsic, microscopic surface topography of a small designated area on a controlled item. It is implemented by making a baseline plastic casting of the designated tag area and usually placing a cover (for example, a bar-code label) over this area to protect the surface from environmental alteration. The plastic casting is returned to a laboratory and prepared for high-resolution scanning electron microscope imaging. Several images are digitized and stored for use as a standard for authentication of castings taken during future inspections. Authentication is determined by numerically comparing digital images. Commercially available hardware and software are used for this tag. Tag parameters are optimized, so unique casting images are obtained from original surfaces, and images obtained from attempted duplicate surfaces are detected. This optimization uses the modulation transfer function, a first principle of image analysis, to determine the parameters. Surface duplication experiments confirmed the optimization

Weeping dragon, a unique ornamenal citrus

Science.gov (United States)

‘Weeping Dragon’ is a new ornamental citrus cultivar developed by intercrossing of two unusual and unique citrus types, Poncirus trifoliata cultivated variety (cv.) Flying Dragon, and Citrus sinensis cv. ‘Cipo’. This new hybrid cultivar combines strongly contorted and weeping growth traits in a smal...

76 FR 72240 - Twenty-Seventh Meeting: RTCA Special Committee 206: Aeronautical Information and Meteorological...

Science.gov (United States)

2011-11-22

... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Twenty-Seventh Meeting: RTCA Special... Administration (FAA), U.S. Department of Transportation (DOT). ACTION: Notice of RTCA Special Committee 206..., 2011 FRAC OSED [[Page 72241

The Summit of «Group of Twenty» – 2016: geopolitical assessments

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O. S. Vonsovych

2016-08-01

Full Text Available The article investigated the geopolitical assessments of the results of the Summit of «Group of Twenty», which took place in Hangzhou from 4 till 5 September, 2016. The main idea of this event was the development of  innovation, healthy, coherent and inclusive economy. Moreover, important for the geopolitical consolidation of efforts of member countries in the context of further development of the world economy was making such documents as: Contours of the innovative growth of «Group of Twenty», Action plan of «Group of Twenty» in connection with a new industrial revolution, Hangzhou action plan, which set out a strategy for overall and confident growth and also initiative of «Group of twenty» in development and cooperation in the field of digital economy. Important thing is that analysis of the Summit’s results for world regions is important from a geopolitical point of view. We can predict that in the future geopolitical dialogue between the EU and the US in the economy will become more vital for both sides, and will enable to contribute to the implementation of more global challenges of the global economy. We should mention that Summit of «Group of Twenty» largely determined the prospects of global economic processes and build a new world economic order with the introduction of innovative approaches and elements of the digital economy. Activity on the functioning of the global economy should be based on the collective efforts of all participants and take into account all the realities on the international stage. No less important is that the Summit proved the presence of leading geopolitical centers that affect not only the balance of power in the world, but also the further development of key economic processes. Each of these centers sees its future not only the global economy but the global system as a whole as well as its geopolitical influence in certain regions and countries. On the one hand, as for the development of

78 FR 20168 - Twenty Fourth Meeting: RTCA Special Committee 203, Unmanned Aircraft Systems

Science.gov (United States)

2013-04-03

... Washington, DC, on March 28, 2013. Paige Williams, Management Analyst, NextGen, Business Operations Group... Introductions Review Meeting Agenda Review/Approval of Twenty Third Plenary Meeting Summary Leadership Update... for Unmanned Aircraft Systems and Minimum Aviation System Performance Standards Other Business Adjourn...

Theoretical Contexts and Conceptual Frames for the Study of Twenty-First Century Capitalism

DEFF Research Database (Denmark)

Hull Kristensen, Peer; Morgan, Glenn

2012-01-01

This chapter argues that the comparative institutionalist approach requires rethinking in the light of developments in the twenty-first century. The chapter emphasizes the following features of the new environment: first, the rise of the BRIC and the emerging economies; secondly, the changed...

METHYLMERCURY BIOACCUMULATION DEPENDENCE ON NORTHERN PIKE AGE AND SIZE IN TWENTY MINNESOTA LAKES

Science.gov (United States)

Mercury accumulation in northern pike muscle tissue (fillets) was found to be directly related to fish age and size. Measurements were made on 173 individual northern pike specimens from twenty lakes across Minnesota. Best fit regressions of mercury fillet concentration (wet wt.)...

Teachers' Critical Reflective Practice in the Context of Twenty-First Century Learning

Science.gov (United States)

Benade, Leon

2015-01-01

In the twenty-first century, learning and teaching at school must prepare young people for engaging in a complex and dynamic world deeply influenced by globalisation and the revolution in digital technology. In addition to the use of digital technologies, is the development of flexible learning spaces. It is claimed that these developments demand,…

On uniqueness in evolution quasivariational inequalities

Czech Academy of Sciences Publication Activity Database

Brokate, M.; Krejčí, Pavel; Schnabel, H.

2004-01-01

Roč. 11, č. 1 (2004), s. 111-130 ISSN 0944-6532 Institutional research plan: CEZ:AV0Z1019905 Keywords : evolution quasivariational inequality * uniqueness * sweeping process Subject RIV: BA - General Mathematics Impact factor: 0.425, year: 2004 http://www.heldermann-verlag.de/jca/jca11/jca0386.pdf

Chemical, Bioactive, and Antioxidant Potential of Twenty Wild Culinary Mushroom Species

OpenAIRE

Sharma, S. K.; Gautam, N.

2015-01-01

The chemical, bioactive, and antioxidant potential of twenty wild culinary mushroom species being consumed by the people of northern Himalayan regions has been evaluated for the first time in the present study. Nutrients analyzed include protein, crude fat, fibres, carbohydrates, and monosaccharides. Besides, preliminary study on the detection of toxic compounds was done on these species. Bioactive compounds evaluated are fatty acids, amino acids, tocopherol content, carotenoids (β-carotene, ...

Automation and robotics for Space Station in the twenty-first century

Science.gov (United States)

Willshire, K. F.; Pivirotto, D. L.

1986-01-01

Space Station telerobotics will evolve beyond the initial capability into a smarter and more capable system as we enter the twenty-first century. Current technology programs including several proposed ground and flight experiments to enable development of this system are described. Advancements in the areas of machine vision, smart sensors, advanced control architecture, manipulator joint design, end effector design, and artificial intelligence will provide increasingly more autonomous telerobotic systems.

Managing the twenty-first century reference department challenges and prospects

CERN Document Server

Katz, Linda S

2014-01-01

Learn the skills needed to update and manage a reference department that efficiently meets the needs of clients today?and tomorrow! Managing the Twenty-First Century Reference Department: Challenges and Prospects provides librarians with the knowledge and skills they need to manage an effective reference service. Full of useful and practical ideas, this book presents successful methods for recruiting and retaining capable reference department staff and management, training new employees and adapting current services to an evolving field. Expert practitioners address the changing role of the r

Trends in CPAP adherence over twenty years of data collection: a flattened curve.

Science.gov (United States)

Rotenberg, Brian W; Murariu, Dorian; Pang, Kenny P

2016-08-19

Obstructive sleep apnea (OSA) is a common disorder, and continuous airway positive pressure (CPAP) is considered to be the gold standard of therapy. CPAP however is known to have problems with adherence, with many patients eventually abandoning the device. The purpose of this paper is to assess secular trends in CPAP adherence over the long term to see if there have been meaningful improvements in adherence in light of the multiple interventions proposed to do so. A comprehensive systematic literature review was conducted using the Medline-Ovid, Embase, and Pubmed databases, searching for data regarding CPAP adherence over a twenty year timeframe (1994-2015). Data was assessed for quality and then extracted. The main outcome measure was reported CPAP non-adherence. Secondary outcomes included changes in CPAP non-adherence when comparing short versus long-term, and changes in terms of behavioral counseling. Eighty-two papers met study inclusion/exclusion criteria. The overall CPAP non-adherence rate based on a 7-h/night sleep time that was reported in studies conducted over the twenty year time frame was 34.1 %. There was no significant improvement over the time frame. Behavioral intervention improved adherence rates by ~1 h per night on average. The rate of CPAP adherence remains persistently low over twenty years worth of reported data. No clinically significant improvement in CPAP adherence was seen even in recent years despite efforts toward behavioral intervention and patient coaching. This low rate of adherence is problematic, and calls into question the concept of CPAP as gold-standard of therapy for OSA.

Holistic Leadership-Nursing's Unique Contribution to Healthcare.

Science.gov (United States)

Clarke, Pamela N; Bleich, Michael R

2018-04-01

This dialogue is focused on holistic leadership from the perspective of a well-known leader in nursing. He frames the changing healthcare environment and nursing's unique contribution on the interprofessional team.

48 CFR 52.211-7 - Alternatives to Government-unique standards.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Alternatives to Government... Government-unique standards. The offeror may propose voluntary consensus standards that meet the Government's... voluntary consensus standard instead of the Government-unique standard if it meets the Government's...

UNiquant, a Program for Quantitative Proteomics Analysis Using Stable Isotope Labeling

Energy Technology Data Exchange (ETDEWEB)

Huang, Xin; Tolmachev, Aleksey V.; Shen, Yulei; Liu, Miao; Huang, Lin; Zhang, Zhixin; Anderson, Gordon A.; Smith, Richard D.; Chan, Wing C.; Hinrichs, Steven; Fu, Kai; Ding, Shi-Jian

2011-03-04

We present UNiquant, a new software program for analyzing stable isotope labeling (SIL) based quantitative proteomics data. UNiquant surpassed the performance of two other platforms, MaxQuant and Mascot Distiller, using complex proteome mixtures having either known or unknown heavy/light ratios. UNiquant is compatible with a broad spectrum of search engines and SIL methods, providing outstanding peptide pair identification and accurate measurement of the relative peptide/protein abundance.

Fluorescent Photo-conversion: A second chance to label unique cells.

Science.gov (United States)

Mellott, Adam J; Shinogle, Heather E; Moore, David S; Detamore, Michael S

2015-03-01

Not all cells behave uniformly after treatment in tissue engineering studies. In fact, some treated cells display no signs of treatment or show unique characteristics not consistent with other treated cells. What if the "unique" cells could be isolated from a treated population, and further studied? Photo-convertible reporter proteins, such as Dendra2 , allow for the ability to selectively identify unique cells with a secondary label within a primary labeled treated population. In the current study, select cells were identified and labeled through photo-conversion of Dendra2 -transfected human Wharton's Jelly cells (hWJCs) for the first time. Robust photo-conversion of green-to-red fluorescence was achieved consistently in arbitrarily selected cells, allowing for precise cell identification of select hWJCs. The current study demonstrates a method that offers investigators the opportunity to selectively label and identify unique cells within a treated population for further study or isolation from the treatment population. Photo-convertible reporter proteins, such as Dendra2 , offer the ability over non-photo-convertible reporter proteins, such as green fluorescent protein, to analyze unique individual cells within a treated population, which allows investigators to gain more meaningful information on how a treatment affects all cells within a target population.

Executive Functions Contribute Uniquely to Reading Competence in Minority Youth

Science.gov (United States)

Jacobson, Lisa A.; Koriakin, Taylor; Lipkin, Paul; Boada, Richard; Frijters, Jan; Lovett, Maureen; Hill, Dina; Willcutt, Erik; Gottwald, Stephanie; Wolf, Maryanne; Bosson-Heenan, Joan; Gruen, Jeffrey R.; Mahone, E. Mark

2018-01-01

Competent reading requires various skills beyond those for basic word reading (i.e., core language skills, rapid naming, phonological processing). Contributing “higher-level” or domain-general processes include information processing speed and executive functions (working memory, strategic problem solving, attentional switching). Research in this area has relied on largely Caucasian samples, with limited representation of children from racial or ethnic minority groups. This study examined contributions of executive skills to reading competence in 761 children of minority backgrounds. Hierarchical linear regressions examined unique contributions of executive functions (EF) to word reading, fluency, and comprehension. EF contributed uniquely to reading performance, over and above reading-related language skills; working memory contributed uniquely to all components of reading; while attentional switching, but not problem solving, contributed to isolated and contextual word reading and reading fluency. Problem solving uniquely predicted comprehension, suggesting that this skill may be especially important for reading comprehension in minority youth. Attentional switching may play a unique role in development of reading fluency in minority youth, perhaps as a result of the increased demand for switching between spoken versus written dialects. Findings have implications for educational and clinical practice with regard to reading instruction, remedial reading intervention, and assessment of individuals with reading difficulty. PMID:26755569

Denture identification using unique identification authority of India barcode

OpenAIRE

Sudhindra Mahoorkar; Anoop Jain

2013-01-01

Over the years, various denture marking systems have been reported in the literature for personal identification. They have been broadly divided into surface marking and inclusion methods. In this technique, patient's unique identification number and barcode printed in the patient's Aadhaar card issued by Unique Identification Authority of India (UIDAI) are used as denture markers. This article describes a simple, quick, and economical method for identification of individual.

Denture identification using unique identification authority of India barcode.

Science.gov (United States)

Mahoorkar, Sudhindra; Jain, Anoop

2013-01-01

Over the years, various denture marking systems have been reported in the literature for personal identification. They have been broadly divided into surface marking and inclusion methods. In this technique, patient's unique identification number and barcode printed in the patient's Aadhaar card issued by Unique Identification Authority of India (UIDAI) are used as denture markers. This article describes a simple, quick, and economical method for identification of individual.

Intranuclear Delivery of a Novel Antibody-Derived Radiosensitizer Targeting the DNA-Dependent Protein Kinase Catalytic Subunit

Energy Technology Data Exchange (ETDEWEB)

Xiong Hairong [Institute of Molecular Medicine and Genetics, Georgia Health Sciences University, Augusta, GA (Georgia); State Key Laboratory of Virology, Institute of Medical Virology, Wuhan University School of Medicine, Wuhan (China); Lee, Robert J. [Division of Pharmaceutics, College of Pharmacy, Ohio State University, Columbus, OH (United States); Haura, Eric B. [Thoracic Oncology and Experimental Therapeutics Programs, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States); Edwards, John G. [Apeliotus Technologies, Inc., Atlanta, GA (United States); Dynan, William S. [Institute of Molecular Medicine and Genetics, Georgia Health Sciences University, Augusta, GA (Georgia); Li Shuyi, E-mail: sli@georgiahealth.edu [Institute of Molecular Medicine and Genetics, Georgia Health Sciences University, Augusta, GA (Georgia); Apeliotus Technologies, Inc., Atlanta, GA (United States)

2012-07-01

Purpose: To inhibit DNA double-strand break repair in tumor cells by delivery of a single-chain antibody variable region fragment (ScFv 18-2) to the cell nucleus. ScFv 18-2 binds to a regulatory region of the DNA-dependent protein kinase (DNA-PK), an essential enzyme in the nonhomologous end-joining pathway, and inhibits DNA end-joining in a cell-free system and when microinjected into single cells. Development as a radiosensitizer has been limited by the lack of a method for intranuclear delivery to target cells. We investigated a delivery method based on folate receptor-mediated endocytosis. Methods and Materials: A recombinant ScFv 18-2 derivative was conjugated to folate via a scissile disulfide linker. Folate-ScFv 18-2 was characterized for its ability to be internalized by tumor cells and to influence the behavior of ionizing radiation-induced repair foci. Radiosensitization was measured in a clonogenic survival assay. Survival curves were fitted to a linear-quadratic model, and between-group differences were evaluated by an F test. Sensitization ratios were determined based on mean inhibitory dose. Results: Human KB and NCI-H292 lung cancer cells treated with folate-conjugated ScFv 18-2 showed significant radiosensitization (p < 0.001). Sensitization enhancement ratios were 1.92 {+-} 0.42 for KB cells and 1.63 {+-} 0.13 for NCI-H292 cells. Studies suggest that treatment inhibits repair of radiation-induced DSBs, as evidenced by the persistence of {gamma}-H2AX-stained foci and by inhibition of staining with anti-DNA-PKcs phosphoserine 2056. Conclusions: Folate-mediated endocytosis is an effective method for intranuclear delivery of an antibody-derived DNA repair inhibitor.

Isolation and characterisation of Ebolavirus-specific recombinant antibody fragments from murine and shark immune libraries.

Science.gov (United States)

Goodchild, Sarah A; Dooley, Helen; Schoepp, Randal J; Flajnik, Martin; Lonsdale, Stephen G

2011-09-01

Members of the genus Ebolavirus cause fulminating outbreaks of disease in human and non-human primate populations with a mortality rate up to 90%. To facilitate rapid detection of these pathogens in clinical and environmental samples, robust reagents capable of providing sensitive and specific detection are required. In this work recombinant antibody libraries were generated from murine (single chain variable domain fragment; scFv) and nurse shark, Ginglymostoma cirratum (IgNAR V) hosts immunised with Zaire ebolavirus. This provides the first recorded IgNAR V response against a particulate antigen in the nurse shark. Both murine scFv and shark IgNAR V libraries were panned by phage display technology to identify useful antibodies for the generation of immunological detection reagents. Two murine scFv were shown to have specificity to the Zaire ebolavirus viral matrix protein VP40. Two isolated IgNAR V were shown to bind to the viral nucleoprotein (NP) and to capture viable Zaire ebolavirus with a high degree of sensitivity. Assays developed with IgNAR V cross-reacted to Reston ebolavirus, Sudan ebolavirus and Bundibugyo ebolavirus. Despite this broad reactivity, neither of IgNAR V showed reactivity to Côte d'Ivoire ebolavirus. IgNAR V was substantially more resistant to irreversible thermal denaturation than murine scFv and monoclonal IgG in a comparative test. The demonstrable robustness of the IgNAR V domains may offer enhanced utility as immunological detection reagents in fieldable biosensor applications for use in tropical or subtropical countries where outbreaks of Ebolavirus haemorrhagic fever occur. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

A novel variable antibody fragment dimerized by leucine zippers with enhanced neutralizing potency against rabies virus G protein compared to its corresponding single-chain variable antibody fragment.

Science.gov (United States)

Li, Zhuang; Cheng, Yue; Xi, Hualong; Gu, Tiejun; Yuan, Ruosen; Chen, Xiaoxu; Jiang, Chunlai; Kong, Wei; Wu, Yongge

2015-12-01

Fatal rabies can be prevented effectively by post-exposure prophylactic (PEP) with rabies immunoglobulin (RIG). Single-chain variable fragments (scFv), which are composed of a variable heavy chain (VH) and a variable light chain (VL) connected by a peptide linker, can potentially be used to replace RIG. However, in our previous study, a scFv (scFV57S) specific for the rabies virus (RV) G protein showed a lower neutralizing potency than that of its parent IgG due to lower stability and altered peptide assembly pattern. In monoclonal antibodies, the VH and VL interact non-covalently, while in scFvs the VH is connected covalently with the VL by the artificial linker. In this study, we constructed and expressed two peptides 57VL-JUN-HIS and 57VH-FOS-HA in Escherichia coli. The well-known Fos and Jun leucine zippers were utilized to dimerize VH and VL similarly to the IgG counterpart. The two peptides assembled to form zipFv57S in vitro. Due to the greater similarity in structure with IgG, the zipFv57S protein showed a higher binding ability and affinity resulting in notable improvement of in vitro neutralizing activity over its corresponding scFv. The zipFv57S protein was also found to be more stable and showed similar protective rate as RIG in mice challenged with a lethal dose of RV. Our results not only indicated zipFv57S as an ideal alternative for RIG in PEP but also offered a novel and efficient hetero-dimerization pattern of VH and VL leading to enhanced neutralizing potency. Copyright © 2015. Published by Elsevier Ltd.

Human antibody fragments specific for Bothrops jararacussu venom reduce the toxicity of other Bothrops sp. venoms.

Science.gov (United States)

Roncolato, Eduardo Crosara; Pucca, Manuela Berto; Funayama, Jaqueline Carlos; Bertolini, Thaís Barboza; Campos, Lucas Benício; Barbosa, José Elpidio

2013-01-01

Approximately 20,000 snakebites are registered each year in Brazil. The classical treatment for venomous snakebite involves the administration of sera obtained from immunized horses. Moreover, the production and care of horses is costly, and the use of heterologous sera can cause hypersensitivity reactions. The production of human antibody fragments by phage display technology is seen as a means of overcoming some of these disadvantages. The studies here attempted to test human monoclonal antibodies specific to Bothrops jararacussu against other Bothrops sp. venoms, using the Griffin.1 library of human single-chain fragment-variable (scFv) phage antibodies. Using the Griffin.1 phage antibody library, this laboratory previously produced scFvs capable of inhibiting the phospholipase and myotoxic activities of Bothrops jararacussu venom. The structural and functional similarities of the various forms of phospholipase A2 (PLA₂) in Bothrops venom served as the basis for the present study wherein the effectiveness of those same scFvs were evaluated against B. jararaca, B. neuwiedi, and B. moojeni venoms. Each clone was found to recognize all three Bothrops venoms, and purified scFvs partially inhibited their in vitro phospholipase activity. In vivo assays demonstrated that the scFv clone P2B7 reduced myotoxicity and increased the survival of animals that received the test venoms. The results here indicate that the scFv P2B7 is a candidate for inclusion in a mixture of specific antibodies to produce a human anti-bothropic sera. This data demonstrates that the human scFv P2B7 represents an alternative therapeutic approach to heterologous anti-bothropic sera available today.

Generation of a Highly Reactive Chicken-Derived Single-Chain Variable Fragment against Fusarium verticillioides by Phage Display

Directory of Open Access Journals (Sweden)

Zu-Quan Hu

2012-06-01

Full Text Available Fusarium verticillioides is the primary causal agent of Fusarium ear and kernel rot in maize, producing fumonisin mycotoxins that are toxic to humans and domestic animals. Rapid detection and monitoring of fumonisin-producing fungi are pivotally important for the prevention of mycotoxins from entering into food/feed products. Chicken-derived single-chain variable fragments (scFvs against cell wall-bound proteins from F. verticillioides were isolated from an immunocompetent phage display library. Comparative phage enzyme-linked immunosorbant assays (ELISAs and sequencing analyses identified four different scFv antibodies with high sensitivity. Soluble antibody ELISAs identified two highly sensitive scFv antibodies, FvCA3 and FvCA4, with the latter being slightly more sensitive. Three-dimensional modeling revealed that the FvCA4 may hold a better overall structure with CDRH3, CDRL1 and CDRL3 centered in the core region of antibody surface compared with that of other scFvs. Immunofluorescence labeling revealed that the binding of FvCA4 antibody was localized to the cell walls of conidiospores and hyphae of F. verticillioides, confirming the specificity of this antibody for a surface target. This scFv antibody was able to detect the fungal mycelium as low as 10⁻² μg/mL and contaminating mycelium at a quantity of 10⁻² mg/g maize. This is the first report that scFv antibodies derived from phage display have a wide application for rapid and accurate detection and monitoring of fumonisin-producing pathogens in agricultural samples.

Flexible and efficient genome tiling design with penalized uniqueness score

Directory of Open Access Journals (Sweden)

Du Yang

2012-12-01

Full Text Available Abstract Background As a powerful tool in whole genome analysis, tiling array has been widely used in the answering of many genomic questions. Now it could also serve as a capture device for the library preparation in the popular high throughput sequencing experiments. Thus, a flexible and efficient tiling array design approach is still needed and could assist in various types and scales of transcriptomic experiment. Results In this paper, we address issues and challenges in designing probes suitable for tiling array applications and targeted sequencing. In particular, we define the penalized uniqueness score, which serves as a controlling criterion to eliminate potential cross-hybridization, and a flexible tiling array design pipeline. Unlike BLAST or simple suffix array based methods, computing and using our uniqueness measurement can be more efficient for large scale design and require less memory. The parameters provided could assist in various types of genomic tiling task. In addition, using both commercial array data and experiment data we show, unlike previously claimed, that palindromic sequence exhibiting relatively lower uniqueness. Conclusions Our proposed penalized uniqueness score could serve as a better indicator for cross hybridization with higher sensitivity and specificity, giving more control of expected array quality. The flexible tiling design algorithm incorporating the penalized uniqueness score was shown to give higher coverage and resolution. The package to calculate the penalized uniqueness score and the described probe selection algorithm are implemented as a Perl program, which is freely available at http://www1.fbn-dummerstorf.de/en/forschung/fbs/fb3/paper/2012-yang-1/OTAD.v1.1.tar.gz.

Nutrients, technological properties and genetic relationships among twenty cowpea landraces cultivated in West Africa

NARCIS (Netherlands)

Madode, Y.E.E.; Linnemann, A.R.; Nout, M.J.R.; Vosman, B.J.; Hounhouigan, D.J.; Boekel, van T.

2012-01-01

The genetic relationships among twenty phenotypically different cowpea landraces were unravelled regarding their suitability for preparing West African dishes. Amplified fragment length polymorphism classified unpigmented landraces (UPs) as highly similar (65%, one cluster), contrary to pigmented

Guide to good practices for operations aspects of unique processes

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-12-01

This Guide to Good Practices is written to enhance understanding of, and provide direction for, Operations Aspects of Facility Chemistry and Unique Processes, Chapter XIII of Department of Energy (DOE) Order 5480.19, Conduct of Operations Requirements for DOE Facilities. The practices in this guide should be considered when planning or reviewing employee training and facility management programs. Contractors are advised to adopt procedures that meet the intent of DOE Order 5480.19. Operations Aspects of Unique Processes is an element of an effective Conduct of Operations program. The complexity and array of activities performed in DOE facilities dictate the necessity for all personnel to coordinate interrelated activities affecting unique processes.

A unique, culture-aware, personalized learning environment

Directory of Open Access Journals (Sweden)

Tillman Swinke

2012-11-01

Full Text Available This paper examines what current learning systems offer towards the idea of a multi- dimensional learning system. It will show the requirements for a multi-dimensional learning system and that no current system is able to meet them. Therefore a new model is proposed that is not only capable of fulfilling the requirements for cultural diversity but also of satisfying the rising demand for personalization that has been rising in the course of the last twenty years. This new model will enable systems, which bring the personalization of e- learning to the next level.

Visual Literacy: Does It Enhance Leadership Abilities Required for the Twenty-First Century?

Science.gov (United States)

Bintz, Carol

2016-01-01

The twenty-first century hosts a well-established global economy, where leaders are required to have increasingly complex skills that include creativity, innovation, vision, relatability, critical thinking and well-honed communications methods. The experience gained by learning to be visually literate includes the ability to see, observe, analyze,…

The Uniqueness of Milton Friedman

OpenAIRE

J. Daniel Hammond

2013-01-01

That there is no Milton Friedman today is not a mystery; the mystery is how Milton Friedman could have been. The facts of Friedman’s biography make him unique among twentieth-century public figures. He had extensive knowledge and expertise in mathematics and statistics. Yet he became a critic of ‘formal’ theory, exemplified by mathematical economics, that failed to engage with real-world facts and data, and of econometric modeling that presumed more knowledge of economic structure than Friedm...

The Turn to Precarity in Twenty-First Century Fiction

Directory of Open Access Journals (Sweden)

Morrison Jago

2014-01-01

Full Text Available Recent years have seen several attempts by writers and critics to understand the changed sensibility in post-9/11 fiction through a variety of new -isms. This essay explores this cultural shift in a different way, finding a ‘turn to precarity’ in twenty-first century fiction characterised by a renewal of interest in the flow and foreclosure of affect, the resurgence of questions about vulnerability and our relationships to the other, and a heightened awareness of the social dynamics of seeing. The essay draws these tendencies together via the work of Judith Butler in Frames of War, in an analysis of Trezza Azzopardi’s quasi-biographical study of precarious life, Remember Me.

High Blood Pressure: Unique to Older Adults

Science.gov (United States)

... our e-newsletter! Aging & Health A to Z High Blood Pressure Hypertension Unique to Older Adults This section provides ... Pressure Targets are Different for Very Old Adults High blood pressure (also called hypertension) increases your chance of having ...

Proceedings of Twenty-Seventh Annual Institute on Mining Health, Safety and Research

Energy Technology Data Exchange (ETDEWEB)

Bockosh, G.R. [ed.] [Pittsburgh Research Center, US Dept. of Energy (United States); Langton, J. [ed.] [Mine Safety and Health Administration, US Dept. of Labor (United States); Karmis, M. [ed.] [Virginia Polytechnic Institute and State University. Dept. of Mining and Minerals Engineering, Blacksburg (United States)

1996-12-31

This Proceedings contains the presentations made during the program of the Twenty-Seventh Annual Institute on Mining Health, Safety and Research held at Virginia Polytechnic Institute and State University, Blacksburg, Virginia, on August 26-28, 1996. The Twenty-Seventh Annual Institute on Mining, Health, Safety and Research was the latest in a series of conferences held at Virginia Polytechnic Institute and State University, cosponsored by the Mine Safety and Health Administration, United States Department of Labor, and the Pittsburgh Research Center, United States Department of Energy (formerly part of the Bureau of Mines, U. S. Department of Interior). The Institute provides an information forum for mine operators, managers, superintendents, safety directors, engineers, inspectors, researchers, teachers, state agency officials, and others with a responsible interest in the important field of mining health, safety and research. In particular, the Institute is designed to help mine operating personnel gain a broader knowledge and understanding of the various aspects of mining health and safety, and to present them with methods of control and solutions developed through research. Selected papers have been processed separately for inclusion in the Energy Science and Technology database.

Unique Protein Signature of Circulating Microparticles in Systemic Lupus Erythematosus

DEFF Research Database (Denmark)

Østergaard, Ole; Nielsen, Christoffer; Iversen, Line V

2013-01-01

To characterize the unique qualities of proteins associated with circulating subcellular material in systemic lupus erythematosus (SLE) patients compared with healthy controls and patients with other chronic autoimmune diseases.......To characterize the unique qualities of proteins associated with circulating subcellular material in systemic lupus erythematosus (SLE) patients compared with healthy controls and patients with other chronic autoimmune diseases....

Addressing Unison and Uniqueness of Reliability and Safety for Better Integration

Science.gov (United States)

Huang, Zhaofeng; Safie, Fayssal

2015-01-01

For a long time, both in theory and in practice, safety and reliability have not been clearly differentiated, which leads to confusion, inefficiency, and sometime counter-productive practices in executing each of these two disciplines. It is imperative to address the uniqueness and the unison of these two disciplines to help both disciplines become more effective and to promote a better integration of the two for enhancing safety and reliability in our products as an overall objective. There are two purposes of this paper. First, it will investigate the uniqueness and unison of each discipline and discuss the interrelationship between the two for awareness and clarification. Second, after clearly understanding the unique roles and interrelationship between the two in a product design and development life cycle, we offer suggestions to enhance the disciplines with distinguished and focused roles, to better integrate the two, and to improve unique sets of skills and tools of reliability and safety processes. From the uniqueness aspect, the paper identifies and discusses the respective uniqueness of reliability and safety from their roles, accountability, nature of requirements, technical scopes, detailed technical approaches, and analysis boundaries. It is misleading to equate unreliable to unsafe, since a safety hazard may or may not be related to the component, sub-system, or system functions, which are primarily what reliability addresses. Similarly, failing-to-function may or may not lead to hazard events. Examples will be given in the paper from aerospace, defense, and consumer products to illustrate the uniqueness and differences between reliability and safety. From the unison aspect, the paper discusses what the commonalities between reliability and safety are, and how these two disciplines are linked, integrated, and supplemented with each other to accomplish the customer requirements and product goals. In addition to understanding the uniqueness in

La nephrolithotomie sur rein unique: a propos de vingt cas ...

African Journals Online (AJOL)

Through a series of 20 patients, we study the feasibility and morbidity of this technique in a solitary kidney. Patients and methods: we retrospectively reviewed a series of twenty patients with a calculus in a solitary kidney during a 9-year period, all treated with (PCNL). The results were analyzed emphasizing complications ...

Word from the CSO - CERN’s unique scientific breadth

CERN Multimedia

2008-01-01

Whilst we are all clearly focused on completion of the LHC and the detectors around it and look forward to a successful start of operations later this year, we should not forget that CERN has yet more to offer in addition to this highest priority programme ‘at the energy frontier’. Indeed, CERN also attracts a large scientific community seizing the opportunities offered by its other facilities. Sometimes I wonder whether we are not too modest and should not emphasize more CERN’s unique scientific breadth. ISOLDE, at the PS Booster, relies on innovative techniques to produce results at the forefront of nuclear physics very cost-effectively. nTOF has provided unique measurements of interest to nuclear technology, nuclear astrophysics and basic nuclear physics, and still has an ambitious programme ahead of it after refurbishment of the target. Another unique facility is the Antiproton Decelerator, at which the study of antimatter is being pursued with ingenious experiment...

Twenty years of energy policy: What should we have learned?

International Nuclear Information System (INIS)

Greene, D.L.

1994-07-01

This report examines the past twenty years of energy market events and energy policies to determine what may be useful for the future. The author focuses on two important lessons that should have been learned but which the author feels have been seriously misunderstood. The first is that oil price shocks were a very big and very real problem for oil importing countries, a problem the has not gone away. The second is that automobile fuel economy regulation has worked and worked effectively to reduce oil consumption and the externalities associated with it, and can still work effectively in the future

Twenty years of energy policy: What should we have learned?

Energy Technology Data Exchange (ETDEWEB)

Greene, D.L. [Oak Ridge National Lab., TN (United States). Center for Transportation Analysis

1994-07-01

This report examines the past twenty years of energy market events and energy policies to determine what may be useful for the future. The author focuses on two important lessons that should have been learned but which the author feels have been seriously misunderstood. The first is that oil price shocks were a very big and very real problem for oil importing countries, a problem the has not gone away. The second is that automobile fuel economy regulation has worked and worked effectively to reduce oil consumption and the externalities associated with it, and can still work effectively in the future.

Duality based direct resolution of unique profiles using zero concentration region information.

Science.gov (United States)

Tavakkoli, Elnaz; Rajkó, Róbert; Abdollahi, Hamid

2018-07-01

Self Modeling Curve Resolution (SMCR) is a class of techniques concerned with estimating pure profiles underlying a set of measurements on chemical systems. In general, the estimated profiles are ambiguous (non-unique) except if some special conditions fulfilled. Implementing the adequate information can reduce the so-called rotational ambiguity effectively, and in the most desirable cases lead to the unique solution. Therefore, studies on circumstances resulting in unique solution are of particular importance. The conditions of unique solution can particularly be studied based on duality principle. In bilinear chemical (e.g., spectroscopic) data matrix, there is a natural duality between its row and column vector spaces using minimal constraints (non-negativity of concentrations and absorbances). In this article, the conditions of the unique solution according to duality concept and using zero concentration region information is intended to show. A simulated dataset of three components and an experimental system with synthetic mixtures containing three amino acids tyrosine, phenylalanine and tryptophan are analyzed. It is shown that in the presence of sufficient information, the reliable unique solution is obtained that is valuable in analytical qualification and for quantitative verification analysis. Copyright © 2018 Elsevier B.V. All rights reserved.

The end of the unique myocardial band

DEFF Research Database (Denmark)

MacIver, David H; Partridge, John B; Agger, Peter

2018-01-01

Two of the leading concepts of mural ventricular architecture are the unique myocardial band and the myocardial mesh model. We have described, in an accompanying article published in this journal, how the anatomical, histological and high-resolution computed tomographic studies strongly favour th...

Twenty-First Century Learning: Communities, Interaction and Ubiquitous Computing

Science.gov (United States)

Leh, Amy S.C.; Kouba, Barbara; Davis, Dirk

2005-01-01

Advanced technology makes 21st century learning, communities and interactions unique and leads people to an era of ubiquitous computing. The purpose of this article is to contribute to the discussion of learning in the 21st century. The paper will review literature on learning community, community learning, interaction, 21st century learning and…

Concentration and mindfulness meditations: unique forms of consciousness?

Science.gov (United States)

Dunn, B R; Hartigan, J A; Mikulas, W L

1999-09-01

Electroencephalographic (EEG) recordings from 19 scalp recording sites were used to differentiate among two posited unique forms of mediation, concentration and mindfulness, and a normal relaxation control condition. Analyzes of all traditional frequency bandwidth data (i.e., delta 1-3 Hz; theta, 4-7 Hz; alpha, 8-12 Hz; beta 1, 13-25 Hz; beta 2, 26-32 Hz) showed strong mean amplitude frequency differences between the two meditation conditions and relaxation over numerous cortical sites. Furthermore, significant differences were obtained between concentration and mindfulness states at all bandwidths. Taken together, our results suggest that concentration and mindfulness "meditations" may be unique forms of consciousness and are not merely degrees of a state of relaxation.

Solitary intraosseous neurofibroma: Report of a unique case

Directory of Open Access Journals (Sweden)

Sagar Satish Jangam

2014-01-01

Full Text Available Neural tumors located centrally in jaw bones are relatively rare compared with soft tissue neurofibromas. Less than 50 cases have been reported in the literature with a predilection for mandible. This article aims to elucidate a unique case of intraosseous neurofibroma of mandible in a 62-year-old edentulous female patient associated with facial asymmetry due to the swelling extending from the right body of mandible to left body of mandible. The uniqueness of this case is related to the age and extensiveness of this lesion. A review of clinical, radiographic, histological, and immunohistochemical features, and the surgical management pertaining to this case are discussed along with a review of the literature.

Unique properties of Drosophila spermatocyte primary cilia

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Maria Giovanna Riparbelli

2013-09-01

The primary cilium is an essential organelle required for animal development and adult homeostasis that is found on most animal cells. The primary cilium contains a microtubule-based axoneme cytoskeleton that typically grows from the mother centriole in G0/G1 phase of the cell cycle as a membrane-bound compartment that protrudes from the cell surface. A unique system of bidirectional transport, intraflagellar transport (IFT, maintains the structure and function of cilia. While the axoneme is dynamic, growing and shrinking at its tip, at the same time it is very stable to the effects of microtubule-targeting drugs. The primary cilia found on Drosophila spermatocytes diverge from the general rules of primary cilium biology in several respects. Among these unique attributes, spermatocyte cilia assemble from all four centrioles in an IFT-independent manner in G2 phase, and persist continuously through two cell divisions. Here, we show that Drosophila spermatocyte primary cilia are extremely sensitive to microtubule-targeting drugs, unlike their mammalian counterparts. Spermatocyte cilia and their axonemes fail to assemble or be maintained upon nocodazole treatment, while centriole replication appears unperturbed. On the other hand, paclitaxel (Taxol, a microtubule-stabilizing drug, disrupted transition zone assembly and anchoring to the plasma membrane while causing spermatocyte primary cilia to grow extensively long during the assembly/elongation phase, but did not overtly affect the centrioles. However, once assembled to their mature length, spermatocyte cilia appeared unaffected by Taxol. The effects of these drugs on axoneme dynamics further demonstrate that spermatocyte primary cilia are endowed with unique assembly properties.

Unique Features of Halophilic Proteins.

Science.gov (United States)

Arakawa, Tsutomu; Yamaguchi, Rui; Tokunaga, Hiroko; Tokunaga, Masao

2017-01-01

Proteins from moderate and extreme halophiles have unique characteristics. They are highly acidic and hydrophilic, similar to intrinsically disordered proteins. These characteristics make the halophilic proteins soluble in water and fold reversibly. In addition to reversible folding, the rate of refolding of halophilic proteins from denatured structure is generally slow, often taking several days, for example, for extremely halophilic proteins. This slow folding rate makes the halophilic proteins a novel model system for folding mechanism analysis. High solubility and reversible folding also make the halophilic proteins excellent fusion partners for soluble expression of recombinant proteins.

Screening for single-chain variable fragment antibodies against multiple Cry1 toxins from an immunized mouse phage display antibody library.

Science.gov (United States)

Dong, Sa; Bo, Zongyi; Zhang, Cunzheng; Feng, Jianguo; Liu, Xianjin

2018-04-01

Single-chain variable fragment (scFv) is a kind of antibody that possess only one chain of the complete antibody while maintaining the antigen-specific binding abilities and can be expressed in prokaryotic system. In this study, scFvs against Cry1 toxins were screened out from an immunized mouse phage displayed antibody library, which was successfully constructed with capacity of 6.25 × 10 7  CFU/mL. Using the mixed and alternative antigen coating strategy and after four rounds of affinity screening, seven positive phage-scFvs against Cry1 toxins were selected and characterized. Among them, clone scFv-3H9 (MG214869) showing relative stable and high binding abilities to six Cry1 toxins was selected for expression and purification. SDS-PAGE indicated that the scFv-3H9 fragments approximately 27 kDa were successfully expressed in Escherichia coli HB2151 strain. The purified scFv-3H9 was used to establish the double antibody sandwich enzyme-linked immunosorbent assay method (DAS-ELISA) for detecting six Cry1 toxins, of which the lowest detectable limits (LOD) and the lowest quantitative limits (LOQ) were 3.14-11.07 and 8.22-39.44 ng mL -1 , respectively, with the correlation coefficient higher than 0.997. The average recoveries of Cry1 toxins from spiked rice leaf samples were ranged from 84 to 95%, with coefficient of variation (CV) less than 8.2%, showing good accuracy for the multi-residue determination of six Cry1 toxins in agricultural samples. This research suggested that the constructed phage display antibody library based on the animal which was immunized with the mixture of several antigens under the same category can be used for the quick and effective screening of generic antibodies.

Unique microstructure and excellent mechanical properties of ADI

Directory of Open Access Journals (Sweden)

Jincheng Liu

2006-11-01

Full Text Available Amongst the cast iron family, ADI has a unique microstructure and an excellent, optimised combination of mechanical properties. The main microstructure of ADI is ausferrite, which is a mixture ofextremely fine acicular ferrite and stable, high carbon austenite. There are two types of austenite in ADI:(1 the coarser and more equiaxed blocks of austenite between non-parallel acicular structures, which exist mainly in the last solidified area, and (2 the thin films of ustenite between the individual ferriteplatelets in the acicular structure. It is this unique microstructure, which gives ADI its excellent static and dynamic properties, and good low temperature impact toughness. The effect of microstructure on the mechanical properties is explained in more detail by examining the microstructure at the atomic scale. Considering the nanometer grain sizes, the unique microstructure, the excellent mechanical properties,good castability, (which enables near net shape components to be produced economically and in large volumes, and the fact that it can be 100% recycled, it is not overemphasized to call ADI a high-tech,nanometer and “green” material. ADI still has the potential to be further improved and its production and the number of applications for ADI will continue to grow, driven by the resultant cost savings over alternative materials.

The Dialectics of Discrimination in the Twenty-First Century

Directory of Open Access Journals (Sweden)

John Stone

2007-12-01

Full Text Available This article explores some of the latest developments in the scholarship on race relations and nationalism that seek to address the impact of globalization and the changed geo-political relations of the first decade of the twenty-first century. New patterns of identification, some of which challenge existing group boundaries and others that reinforce them, can be seen to flow from the effects of global market changes and the political counter-movements against them. The impact of the “war on terrorism”, the limits of the utility of hard power, and the need for new mechanisms of inter-racial and inter-ethnic conflict resolution are evaluated to emphasize the complexity of these group relations in the new world disorder.

Esperanto: A Unique Model for General Linguistics.

Science.gov (United States)

Dulichenko, Aleksandr D.

1988-01-01

Esperanto presents a unique model for linguistic research by allowing the study of language development from project to fully functioning language. Esperanto provides insight into the growth of polysemy and redundancy, as well as into language universals and the phenomenon of social control. (Author/CB)

Ecomorphological correlates of twenty dominant fish species of Amazonian floodplain lakes

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F. K. Siqueira-Souza

Full Text Available Abstract Fishes inhabiting Amazonian floodplain lakes exhibits a great variety of body shape, which was a key advantage to colonize the several habitats that compose these areas adjacent to the large Amazon rivers. In this paper, we did an ecomorphological analysis of twenty abundant species, sampled in May and August 2011, into two floodplain lakes of the lower stretch of the Solimões River. The analysis detected differences among species, which could be probably associated with swimming ability and habitat use preferences.

Twenty natural organic pigments for application in dye sensitized solar cells

Science.gov (United States)

Castillo, D.; Sánchez Juárez, A.; Espinosa Tapia, S.; Guaman, A.; Obregón Calderón, D.

2016-09-01

In this work we present the results of a study of twenty natural pigments obtained from plants and insects from southern Ecuador. Many of them will be considered as a potential natural sensitizer for the construction of DSSCs. The results indicate that these pigments have a good performance in the absorbance and wavelength spectra. Were selected four best pigments for the construction of DSSCs, Rumex tolimensis Wedd, Raphanus sativus, Hibiscus sabdariffa, and Prunus serótina, however the conversion efficiency is lower than 1%.

Existence and uniqueness of solution for a system of equations of ...

African Journals Online (AJOL)

The existence and uniqueness of solution for a system of equations of microwave heating of biologic issue is discussed. Using the Green function approach we establish the existence and uniqueness of solution. Journal of the Nigerian Association of Mathematical Physics Vol. 8 2004: pp. 177-180 ...

Uncertainty in Twenty-First-Century CMIP5 Sea Level Projections

Science.gov (United States)

Little, Christopher M.; Horton, Radley M.; Kopp, Robert E.; Oppenheimer, Michael; Yip, Stan

2015-01-01

The representative concentration pathway (RCP) simulations included in phase 5 of the Coupled Model Intercomparison Project (CMIP5) quantify the response of the climate system to different natural and anthropogenic forcing scenarios. These simulations differ because of 1) forcing, 2) the representation of the climate system in atmosphere-ocean general circulation models (AOGCMs), and 3) the presence of unforced (internal) variability. Global and local sea level rise projections derived from these simulations, and the emergence of distinct responses to the four RCPs depend on the relative magnitude of these sources of uncertainty at different lead times. Here, the uncertainty in CMIP5 projections of sea level is partitioned at global and local scales, using a 164-member ensemble of twenty-first-century simulations. Local projections at New York City (NYSL) are highlighted. The partition between model uncertainty, scenario uncertainty, and internal variability in global mean sea level (GMSL) is qualitatively consistent with that of surface air temperature, with model uncertainty dominant for most of the twenty-first century. Locally, model uncertainty is dominant through 2100, with maxima in the North Atlantic and the Arctic Ocean. The model spread is driven largely by 4 of the 16 AOGCMs in the ensemble; these models exhibit outlying behavior in all RCPs and in both GMSL and NYSL. The magnitude of internal variability varies widely by location and across models, leading to differences of several decades in the local emergence of RCPs. The AOGCM spread, and its sensitivity to model exclusion and/or weighting, has important implications for sea level assessments, especially if a local risk management approach is utilized.

EXOGENOUS CHALLENGES FOR THE TOURISM INDUSTRY IN THE BEGINNING OF THE TWENTY FIRST CENTURY

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Akosz Ozan

2009-05-01

Full Text Available Tourism is one of the fastest growing industries in the world. Besides its sustained growth the tourism industry has shown in the first years of the twenty first century that it can deal with political, military and natural disasters. The present paper ac

Twenty-year trends in the prevalence of Down syndrome and other trisomies in Europe

DEFF Research Database (Denmark)

Loane, Maria; Morris, Joan K; Addor, Marie-Claude

2013-01-01

This study examines trends and geographical differences in total and live birth prevalence of trisomies 21, 18 and 13 with regard to increasing maternal age and prenatal diagnosis in Europe. Twenty-one population-based EUROCAT registries covering 6.1 million births between 1990 and 2009 participa...

SERVICE QUALITY DIMENSIONS IN SPECTATOR SPORT: ANANALYSIS OF THE TWENTY-TWENTYCRICKETLEAGUEMATCHES IN SOUTH AFRICA

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B. A Mokoena

2017-01-01

Full Text Available Since their inception, twenty-twenty (T20 cricket league matches have gainedtremendous popularity and areheralded in South Africa with the potential ofincreasingthespectatorsupport base in cricket. The purpose of this studywastoenhance an understanding of service quality by examining theservice qualitydimensions in T20 cricket events in South Africa. A convenience sample of250T20 cricket spectatorsin the Gauteng provinceofSouth Africa participated in asurveyusingastructuredself-administered questionnaire. The factor analysisprocedure resulted in the extraction of six primarydimensions, namely servicepersonnel, game atmosphere, facility access, facility aesthetics, home team qualityand opposing team characteristics. The model was tested using confirmatory factoranalysis, which showed a good-fit of the data to the model.Among the servicequality dimensions, facility access was rated the most important dimension. Thestudy recommends that managers use the suggested dimensional framework tomeasure service quality in T20 cricket. Managers can also use this framework andmeasurement scale as a diagnostic tool to identify strengths and weaknesses in theirservices, thus providing guidance for potential areas of improvement.

Uniqueness of the gauge invariant action for cosmological perturbations

International Nuclear Information System (INIS)

Prokopec, Tomislav; Weenink, Jan

2012-01-01

In second order perturbation theory different definitions are known of gauge invariant perturbations in single field inflationary models. Consequently the corresponding gauge invariant cubic actions do not have the same form. Here we show that the cubic action for one choice of gauge invariant variables is unique in the following sense: the action for any other, non-linearly related variable can be brought to the same bulk action, plus additional boundary terms. These boundary terms correspond to the choice of hypersurface and generate extra, disconnected contributions to the bispectrum. We also discuss uniqueness of the action with respect to conformal frames. When expressed in terms of the gauge invariant curvature perturbation on uniform field hypersurfaces the action for cosmological perturbations has a unique form, independent of the original Einstein or Jordan frame. Crucial is that the gauge invariant comoving curvature perturbation is frame independent, which makes it extremely helpful in showing the quantum equivalence of the two frames, and therefore in calculating quantum effects in nonminimally coupled theories such as Higgs inflation

Uniqueness of Gibbs states and global Markov property for Euclidean fields

International Nuclear Information System (INIS)

Albeverio, S.; Hoeegh-Krohn, R.

1981-01-01

The authors briefly discuss the proof of the uniqueness of solutions of the DLR equations (uniqueness of Gibbs states) in the class of regular generalized random fields (in the sense of having second moments bounded by those of some Euclidean field), for the Euclidean fields with trigonometric interaction. (Auth.)

Effects of energy constraints on transportation systems. [Twenty-six papers

Energy Technology Data Exchange (ETDEWEB)

Mittal, R. K. [ed.

1977-12-01

Twenty-six papers are presented on a variety of topics including: energy and transportaton facts and figures; long-range planning under energy constraints; technology assessment of alternative fuels; energy efficiency of intercity passenger and freight movement; energy efficiency of intracity passenger movement; federal role; electrification of railroads; energy impact of the electric car in an urban enviroment; research needs and projects in progress--federal viewpoint; research needs in transportation energy conservation--data needs; and energy intensity of various transportation modes--an overview. A separate abstract was prepared for each of the papers for inclusion in Energy Research Abstracts (ERA) and in Energy Abstracts for Policy Analysis (EAPA).

Twenty-five years of post-Bretton Woods experience: some lessons

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H. ASKARI

1999-03-01

Full Text Available In 1971 many academic economists were predicting that the Bretton Woods system of fixed parities would collapse. Some, most notably Milton Friedman, became excited about the possibility of a floating system because the benefits of international capital mobility can only be achieved through the flexibility in the exchange rate. These economists argued that a floating exchange rate system can ensure positive results more than the fixed parities system. Twenty-five years later, however, there is still no consensus on the matter. The author reviews the post-Bretton Woods experience to highlight some policies and approaches that might be helpful for the future.

Marketing the Uniqueness of Small Towns. Revised.

Science.gov (United States)

Dunn, Douglas; Hogg, David H.

The key to marketing a town is determining and promoting the town's "differential advantage" or uniqueness that would make people want to visit or live there. Exercises to help communities gain important insights into the town's competitive edge include a brainstorming session with knowledgeable community members, a visitor…

In vivo tumor targeting and imaging with engineered trivalent antibody fragments containing collagen-derived sequences.

Directory of Open Access Journals (Sweden)

Angel M Cuesta

Full Text Available There is an urgent need to develop new and effective agents for cancer targeting. In this work, a multivalent antibody is characterized in vivo in living animals. The antibody, termed "trimerbody", comprises a single-chain antibody (scFv fragment connected to the N-terminal trimerization subdomain of collagen XVIII NC1 by a flexible linker. As indicated by computer graphic modeling, the trimerbody has a tripod-shaped structure with three highly flexible scFv heads radially outward oriented. Trimerbodies are trimeric in solution and exhibited multivalent binding, which provides them with at least a 100-fold increase in functional affinity than the monovalent scFv. Our results also demonstrate the feasibility of producing functional bispecific trimerbodies, which concurrently bind two different ligands. A trimerbody specific for the carcinoembryonic antigen (CEA, a classic tumor-associated antigen, showed efficient tumor targeting after systemic administration in mice bearing CEA-positive tumors. Importantly, a trimerbody that recognizes an angiogenesis-associated laminin epitope, showed excellent tumor localization in several cancer types, including fibrosarcomas and carcinomas. These results illustrate the potential of this new antibody format for imaging and therapeutic applications, and suggest that some laminin epitopes might be universal targets for cancer targeting.

Analysis of the relationship between end-to-end distance and activity of single-chain antibody against colorectal carcinoma.

Science.gov (United States)

Zhang, Jianhua; Liu, Shanhong; Shang, Zhigang; Shi, Li; Yun, Jun

2012-08-22

We investigated the relationship of End-to-end distance between VH and VL with different peptide linkers and the activity of single-chain antibodies by computer-aided simulation. First, we developed (G4S)n (where n = 1-9) as the linker to connect VH and VL, and estimated the 3D structure of single-chain Fv antibody (scFv) by homologous modeling. After molecular models were evaluated and optimized, the coordinate system of every protein was built and unified into one coordinate system, and End-to-end distances calculated using 3D space coordinates. After expression and purification of scFv-n with (G4S)n as n = 1, 3, 5, 7 or 9, the immunoreactivity of purified ND-1 scFv-n was determined by ELISA. A multi-factorial relationship model was employed to analyze the structural factors affecting scFv: rn=ABn-ABO2+CDn-CDO2+BCn-BCst2. The relationship between immunoreactivity and r-values revealed that fusion protein structure approached the desired state when the r-value = 3. The immunoreactivity declined as the r-value increased, but when the r-value exceeded a certain threshold, it stabilized. We used a linear relationship to analyze structural factors affecting scFv immunoreactivity.

Kinetic analysis of a monoclonal therapeutic antibody and its single-chain homolog by surface plasmon resonance.

Science.gov (United States)

Patel, Rekha; Andrien, Bruce A

2010-01-01

Monoclonal antibodies (mAbs) and antibody fragments have become an emerging class of therapeutics since 1986. Their versatility enables them to be engineered for optimal efficiency and decreased immunogenicity, and the path to market has been set by recent regulatory approvals. One of the initial criteria for success of any protein or antibody therapeutic is to understand its binding characteristics to the target antigen. Surface plasmon resonance (SPR) has been widely used and is an important tool for ligand-antigen binding characterization. In this work, the binding kinetics of a recombinant mAb and its single-chain antibody homolog, single-chain variable fragment (scFv), was analyzed by SPR. These two proteins target the same antigen. The binding kinetics of the mAb (bivalent antibody) and scFv (monovalent scFv) for this antigen was analyzed along with an assessment of the thermodynamics of the binding interactions. Alternative binding configurations were investigated to evaluate potential experimental bias because theoretically experimental binding configuration should have no impact on binding kinetics. Self-association binding kinetics in the proteins' respective formulation solutions and antigen epitope mapping were also evaluated. Functional characterization of monoclonal and single-chain antibodies has become just as important as structural characterization in the biotechnology field.

Efficient Serial and Parallel Algorithms for Selection of Unique Oligos in EST Databases.

Science.gov (United States)

Mata-Montero, Manrique; Shalaby, Nabil; Sheppard, Bradley

2013-01-01

Obtaining unique oligos from an EST database is a problem of great importance in bioinformatics, particularly in the discovery of new genes and the mapping of the human genome. Many algorithms have been developed to find unique oligos, many of which are much less time consuming than the traditional brute force approach. An algorithm was presented by Zheng et al. (2004) which finds the solution of the unique oligos search problem efficiently. We implement this algorithm as well as several new algorithms based on some theorems included in this paper. We demonstrate how, with these new algorithms, we can obtain unique oligos much faster than with previous ones. We parallelize these new algorithms to further improve the time of finding unique oligos. All algorithms are run on ESTs obtained from a Barley EST database.

A unique Fock quantization for fields in non-stationary spacetimes

International Nuclear Information System (INIS)

Cortez, Jerónimo; Marugán, Guillermo A. Mena; Olmedo, Javier; Velhinho, José M.

2010-01-01

In curved spacetimes, the lack of criteria for the construction of a unique quantization is a fundamental problem undermining the significance of the predictions of quantum field theory. Inequivalent quantizations lead to different physics. Recently, however, some uniqueness results have been obtained for fields in non-stationary settings. In particular, for vacua that are invariant under the background symmetries, a unitary implementation of the classical evolution suffices to pick up a unique Fock quantization in the case of Klein-Gordon fields with time-dependent mass, propagating in a static spacetime whose spatial sections are three-spheres. In fact, the field equation can be reinterpreted as describing the propagation in a Friedmann-Robertson-Walker spacetime after a suitable scaling of the field by a function of time. For this class of fields, we prove here an even stronger result about the Fock quantization: the uniqueness persists when one allows for linear time-dependent transformations of the field in order to account for a scaling by background functions. In total, paying attention to the dynamics, there exists a preferred choice of quantum field, and only one SO(4)-invariant Fock representation for it that respects the standard probabilistic interpretation along the evolution. The result has relevant implications e.g. in cosmology

Increasing precipitation volatility in twenty-first-century California

Science.gov (United States)

Swain, Daniel L.; Langenbrunner, Baird; Neelin, J. David; Hall, Alex

2018-05-01

Mediterranean climate regimes are particularly susceptible to rapid shifts between drought and flood—of which, California's rapid transition from record multi-year dryness between 2012 and 2016 to extreme wetness during the 2016-2017 winter provides a dramatic example. Projected future changes in such dry-to-wet events, however, remain inadequately quantified, which we investigate here using the Community Earth System Model Large Ensemble of climate model simulations. Anthropogenic forcing is found to yield large twenty-first-century increases in the frequency of wet extremes, including a more than threefold increase in sub-seasonal events comparable to California's `Great Flood of 1862'. Smaller but statistically robust increases in dry extremes are also apparent. As a consequence, a 25% to 100% increase in extreme dry-to-wet precipitation events is projected, despite only modest changes in mean precipitation. Such hydrological cycle intensification would seriously challenge California's existing water storage, conveyance and flood control infrastructure.

Accelerators for the twenty-first century - a review

International Nuclear Information System (INIS)

Wilson, E.J.N.

1990-01-01

Modern synchrotrons and storage rings are based upon the electrical technology of the 1900s boosted by the microwave radar techniques of World War II. This method of acceleration now seems to be approaching its practical limit. It is high time that we seek a new physical acceleration mechanism to provide the higher energies and luminosities needed to continue particle physics beyond the machines now on the stocks. Twenty years is a short time in which to invent, develop, and construct such a device. Without it, high-energy physics may well come to an end. Particle physicists and astrophysicists are invited to join accelerator specialists in the hunt for this new principle. This report analyses the present limitations of colliders and explores some of the directions in which one might look to find a new principle. Chapters cover proton colliders, electron-positron colliders, linear colliders, and two-beam accelerators; transverse fields, wake-field and beat-wave accelerators, ferroelectric crystals, and acceleration in astrophysics. (orig.)

Changes to injury profile (and recommended cricket injury definitions based on the increased frequency of Twenty20 cricket matches

Directory of Open Access Journals (Sweden)

John Orchard

2010-05-01

Full Text Available John Orchard1, Trefor James2, Alex Kountouris2, Marc Portus21School of Public Health, University of Sydney, Sydney, Australia; 2Cricket Australia, Melbourne, AustraliaAbstract: This study analyzes injuries occurring prospectively in Australian men’s cricket at the state and national levels over 11 seasons (concluding in season 2008–09. In the last four of these seasons, there was more cricket played, with most of the growth being a new form of the game – Twenty20 cricket. Since the introduction of a regular Twenty20 program, injury incidence rates in each form of cricket have been fairly steady. Because of the short match duration, Twenty20 cricket exhibits a high match injury incidence, expressed as injuries per 10,000 hours of play. Expressed as injuries per days of play, Twenty20 cricket injury rates compare more favorably to other forms of cricket. Domestic level Twenty20 cricket resulted in 145 injuries per 1000 days of play (compared to 219 injuries per 1000 days of domestic one day cricket, and 112 injuries per 1000 days of play in first class domestic cricket. It is therefore recommended that match injury incidence measures be expressed in units of injuries per 1000 days of play. Given the high numbers of injuries which are of gradual onset, seasonal injury incidence rates (which typically range from 15–20 injuries per team per defined ‘season’ are probably a superior incidence measure. Thigh and hamstring strains have become clearly the most common injury in the past two years (greater than four injuries per team per season, perhaps associated with the increased amount of Twenty20 cricket. Injury prevalence rates have risen in conjunction with an increase in the density of the cricket calendar. Annual injury prevalence rates (average proportion of players missing through injury have exceeded 10% in the last three years, with the injury prevalence rates for fast bowlers exceeding 18%. As the amount of scheduled cricket is

The Antigerminative Activity of Twenty-Seven Monoterpenes

Directory of Open Access Journals (Sweden)

Laura De Martino

2010-09-01

Full Text Available Monoterpenes, the main constituents of essential oils, are known for their many biological activities. The present work studied the potential biological activity of twenty-seven monoterpenes, including monoterpene hydrocarbons and oxygenated ones, against seed germination and subsequent primary radicle growth of Raphanus sativus L. (radish and Lepidium sativum L. (garden cress, under laboratory conditions. The compounds, belonging to different chemical classes, showed different potency in affecting both parameters evaluated. The assayed compounds demonstrated a good inhibitory activity in a dose-dependent way. In general, radish seed is more sensitive than garden cress and its germination appeares more inhibited by alcohols; at the highest concentration tested, the more active substances were geraniol, borneol, (±-β-citronellol and α-terpineol. Geraniol and carvone inhibited, in a significant way, the germination of garden cress, at the highest concentration tested. Radicle elongation of two test species was inhibited mainly by alcohols and ketones. Carvone inhibited the radicle elongation of both seeds, at almost all concentrations assayed, while 1,8-cineole inhibited their radicle elongation at the lowest concentrations (10−5 M, 10−6 M.

A unique tripartite collision tumor of the esophagus

Science.gov (United States)

Schizas, Dimitrios; Michalinos, Adamantios; Alexandrou, Paraskevi; Moris, Demetrios; Baliou, Evangelia; Tsilimigras, Diamantis; Throupis, Theodore; Liakakos, Theodore

2017-01-01

Abstract Rationale: We report a unique case of a tripartite esophageal collision tumor consisting of three separate histologic types. Patients concerns: Therapeutic dilemmas on the proper treatment of those rare neoplasms remain unanswered considering both proper surgical therapy and adjuvant therapy. Diagnose: In this paper, we report a unique case of a patient with a tripartite esophageal collision tumor consisting of a small cell carcinoma, an adenocarcinoma of medium differentiation and a signet ring cell carcinoma. Diagnosis is difficult as clinical presentation of the patient was undistinguishable from other, commoner tumor types. Interventions: The patient's diagnostic and therapeutic course along with available data on the collisions tumor's biological behavior and treatment are briefly discussed. Outcomes: Esophagectomy is the best treatment options for these patients. Unique nature of this tumor demands aggresive oncologic treatment. Lessons: Collision tumors are rare neoplasms consisting of distinct cell populations developing in juxtaposition to one another without any areas of intermingling. Various cell types can be found. However, collision neoplasms of the esophagus combining adenomatous and neuroendocrine components are exceedingly rare, with only 5 cases described to date in the literature. Given their rarity, limited information is available on their tumorigenesis, biological behavior and clinical course. In general, these tumors are aggressive neoplasms and significantly affect patient treatment and prognosis. PMID:29245236

A unique gesture of sharing

International Nuclear Information System (INIS)

Mustafa, T.

1985-01-01

The Atoms for Peace program was a unique gesture of sharing on the part of the leading industrialized nation, and has very few parallels in modern history. The author says one of the major advantages of the program for developing nations was the much needed stimulation of their indigenous science and technology efforts and the awakening of their governments to the multifaceted benefits of atomic energy. The author discusses how the program benefited Pakistan in the production of electrical energy and in the application of nuclear techniques in the fields of agriculture and medicine, which help to alleviate hunger and combat disease

A unique metal-semiconductor interface and resultant electron transfer phenomenon

OpenAIRE

Taft, S. L.

2012-01-01

An unusual electron transfer phenomenon has been identified from an n-type semiconductor to Schottky metal particles, the result of a unique metal semiconductor interface that results when the metal particles are grown from the semiconductor substrate. The unique interface acts as a one-way (rectifying) open gateway and was first identified in reduced rutile polycrystalline titanium dioxide (an n-type semiconductor) to Group VIII (noble) metal particles. The interface significantly affects th...

A novel strategy for efficient production of anti-V3 human scFvs against HIV-1 clade C

Directory of Open Access Journals (Sweden)

Kumar Rajesh

2012-11-01

Full Text Available Abstract Background Production of human monoclonal antibodies that exhibit broadly neutralizing activity is needed for preventing HIV-1 infection, however only a few such antibodies have been generated till date. Isolation of antibodies by the hybridoma technology is a cumbersome process with fewer yields. Further, the loss of unstable or slowly growing clones which may have unique binding specificities often occurs during cloning and propagation and the strongly positive clones are often lost. This has been avoided by the process described in this paper, wherein, by combining the strategy of EBV transformation and recombinant DNA technology, we constructed human single chain variable fragments (scFvs against the third variable region (V3 of the clade C HIV-1 envelope. Results An antigen specific phage library of 7000 clones was constructed from the enriched V3- positive antibody secreting EBV transformed cells. By ligation of the digested scFv DNA into phagemid vector and bio panning against the HIV-1 consensus C and B V3 peptides followed by random selection of 40 clones, we identified 15 clones that showed V3 reactivity in phage ELISA. DNA fingerprinting analysis and sequencing showed that 13 out of the 15 clones were distinct. Expression of the positive clones was tested by SDS-PAGE and Western blot. All the 13 anti-V3 scFvs showed cross-reactivity against both the clade C and B V3 peptides and did not show any reactivity against other unrelated peptides in ELISA. Preliminary neutralization assays indicated varying degrees of neutralization of clade C and B viruses. EBV transformation, followed by antigen selection of lines to identify specific binders, enabled the selection of phage from un-cloned lines for scFv generation, thus avoiding the problems of hybridoma technology. Moreover, as the clones were pretested for antigen binding, a comparatively small library sufficed for the selection of a considerable number of unique antigen binding

A unique theory of all forces

International Nuclear Information System (INIS)

Di Vecchia, Paolo

1997-01-01

In discussing the construction of a consistent theory of quantum gravity unified with the gauge interactions we are naturally led to a string theory. We review its properties and the five consistent supersymmetric string theories in ten dimensions. We finally discuss the evidence that these theories are actually special limits of a unique 11-dimensional theory, called M-theory, and a recent conjecture for its explicit formulation as a supersymmetric Matrix theory

Is Self-Assessment in Religious Education Unique?

Science.gov (United States)

Brooks, Val; Fancourt, Nigel

2012-01-01

This paper addresses the question: is self-assessment in religious education unique? It first presents an overview of some challenges for assessment from subject differences, and then reviews the generic literature on self-assessment. It builds on earlier empirical research on self-assessment in religious education, carried out in an English state…

Catholic school governance in the twenty-first century: continuity, incongruity and challenge

OpenAIRE

Storr, Christopher John

2007-01-01

This study has two main aspects: first, it reports the results of a survey of ninety nine governors working in Roman Catholic primary and secondary schools situated in four English Catholic dioceses, and publishes hitherto unknown information about them; and, second, it examines how, in seeking to maintain a distinctive educational ethos, these governors are responding both to the legislative changes of the last twenty years, and to changes in English social and cultural attitudes. It shows h...

Why are predictions of general relativity theory for gravitational effects non-unique?

International Nuclear Information System (INIS)

Loskutov, Yu.M.

1990-01-01

Reasons of non-uniqueness of predictions of the general relativity theory (GRT) for gravitational effects are analyzed in detail. To authors' opinion, the absence of comparison mechanism of curved and plane metrics is the reason of non-uniqueness

Uniqueness of flat spherically symmetric spacelike hypersurfaces admitted by spherically symmetric static spacetimes

Science.gov (United States)

Beig, Robert; Siddiqui, Azad A.

2007-11-01

It is known that spherically symmetric static spacetimes admit a foliation by flat hypersurfaces. Such foliations have explicitly been constructed for some spacetimes, using different approaches, but none of them have proved or even discussed the uniqueness of these foliations. The issue of uniqueness becomes more important due to suitability of flat foliations for studying black hole physics. Here, flat spherically symmetric spacelike hypersurfaces are obtained by a direct method. It is found that spherically symmetric static spacetimes admit flat spherically symmetric hypersurfaces, and that these hypersurfaces are unique up to translation under the timelike Killing vector. This result guarantees the uniqueness of flat spherically symmetric foliations for such spacetimes.

78 FR 31627 - Twenty-Second Meeting: RTCA Special Committee 224, Airport Security Access Control Systems

Science.gov (United States)

2013-05-24

..., Management Analyst, NextGen, Business Operations Group, Federal Aviation Administration. [FR Doc. 2013-12460... Welcome, Introductions & Administrative Remarks Review and Approve Summary of the Twenty-first Meeting... Next Meeting Any Other Business Adjourn Attendance is open to the interested public but limited to...

76 FR 21741 - Twenty-First Century Communications and Video Programming Accessibility Act; Announcement of Town...

Science.gov (United States)

2011-04-18

... equipment distribution program for people who are deaf-blind. In addition, the law will fill accessibility... Programming Accessibility Act; Announcement of Town Hall Meeting AGENCY: Federal Communications Commission... The Twenty-First Century Communications and Video Programming Accessibility Act (the Act or CVAA...

Young children's preference for unique owned objects.

Science.gov (United States)

Gelman, Susan A; Davidson, Natalie S

2016-10-01

An important aspect of human thought is the value we place on unique individuals. Adults place higher value on authentic works of art than exact replicas, and young children at times value their original possessions over exact duplicates. What is the scope of this preference in early childhood, and when do children understand its subjective nature? On a series of trials, we asked three-year-olds (N=36) to choose between two toys for either themselves or the researcher: an old (visibly used) toy vs. a new (more attractive) toy matched in type and appearance (e.g., old vs. brand-new blanket). Focal pairs contrasted the child's own toy with a matched new object; Control pairs contrasted toys the child had never seen before. Children preferred the old toys for Focal pairs only, and treated their own preferences as not shared by the researcher. By 3years of age, young children place special value on unique individuals, and understand the subjective nature of that value. Copyright © 2016 Elsevier B.V. All rights reserved.

Event segmentation ability uniquely predicts event memory.

Science.gov (United States)

Sargent, Jesse Q; Zacks, Jeffrey M; Hambrick, David Z; Zacks, Rose T; Kurby, Christopher A; Bailey, Heather R; Eisenberg, Michelle L; Beck, Taylor M

2013-11-01

Memory for everyday events plays a central role in tasks of daily living, autobiographical memory, and planning. Event memory depends in part on segmenting ongoing activity into meaningful units. This study examined the relationship between event segmentation and memory in a lifespan sample to answer the following question: Is the ability to segment activity into meaningful events a unique predictor of subsequent memory, or is the relationship between event perception and memory accounted for by general cognitive abilities? Two hundred and eight adults ranging from 20 to 79years old segmented movies of everyday events and attempted to remember the events afterwards. They also completed psychometric ability tests and tests measuring script knowledge for everyday events. Event segmentation and script knowledge both explained unique variance in event memory above and beyond the psychometric measures, and did so as strongly in older as in younger adults. These results suggest that event segmentation is a basic cognitive mechanism, important for memory across the lifespan. Copyright © 2013 Elsevier B.V. All rights reserved.

Modularity, comparative cognition and human uniqueness

OpenAIRE

Shettleworth, Sara J.

2012-01-01

Darwin's claim ‘that the difference in mind between man and the higher animals … is certainly one of degree and not of kind’ is at the core of the comparative study of cognition. Recent research provides unprecedented support for Darwin's claim as well as new reasons to question it, stimulating new theories of human cognitive uniqueness. This article compares and evaluates approaches to such theories. Some prominent theories propose sweeping domain-general characterizations of the difference ...

Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-etiopathology considerations respecting jaw developmental biology-related unique features

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Schlegel Karl A

2010-10-01

Full Text Available Abstract Background Bone-destructive disease treatments include bisphosphonates and antibodies against the osteoclast differentiator, RANKL (aRANKL; however, osteonecrosis of the jaw (ONJ is a frequent side-effect. Current models fail to explain the restriction of bisphosphonate (BP-related and denosumab (anti-RANKL antibody-related ONJ to jaws. Msx-1 is exclusively expressed in craniofacial structures and pivotal to cranial neural crest (CNC-derived periodontal tissue remodeling. We hypothesised that Msx-1 expression might be impaired in bisphosphonate-related ONJ. The study aim was to elucidate Msx-1 and RANKL-associated signal transduction (BMP-2/4, RANKL in ONJ-altered and healthy periodontal tissue. Methods Twenty ONJ and twenty non-BP exposed periodontal samples were processed for RT-PCR and immunohistochemistry. An automated staining-based alkaline phosphatase-anti-alkaline phosphatase method was used to measure the stained cells:total cell-number ratio (labelling index, Bonferroni adjustment. Real-time RT-PCR was performed on ONJ-affected and healthy jaw periodontal samples (n = 20 each to quantitatively compare Msx-1, BMP-2, RANKL, and GAPDH mRNA levels. Results Semi-quantitative assessment of the ratio of stained cells showed decreased Msx-1 and RANKL and increased BMP-2/4 (all p Conclusions These results explain the sclerotic and osteopetrotic changes of periodontal tissue following BP application and substantiate clinical findings of BP-related impaired remodeling specific to periodontal tissue. RANKL suppression substantiated the clinical finding of impaired bone remodelling in BP- and aRANKL-induced ONJ-affected bone structures. Msx-1 suppression in ONJ-adjacent periodontal tissue suggested a bisphosphonate-related impairment in cellular differentiation that occurred exclusively jaw remodelling. Further research on developmental biology-related unique features of jaw bone structures will help to elucidate pathologies restricted to

Increasing Need for Uniqueness in Contemporary China: Empirical Evidence

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Huajian Cai

2018-05-01

Full Text Available Past research has documented various cultural and psychological changes in contemporary China. In two studies, we examine how Chinese people’s need for uniqueness (NFU also has changed. In Study 1, we found a significant cross-generational increase in Chinese participants’ self-reported NFU. In Study 2, we sampled the names of Chinese newborn babies over the last five decades and found that parents have been increasingly likely to use unique characters to name their children. These findings suggest that the NFU has been rising in China, a historically collectivistic-oriented society. Theoretical and practical implications of our findings were discussed.

A note on unique solvability of the absolute value equation

Directory of Open Access Journals (Sweden)

Taher Lotfi

2014-05-01

Full Text Available It is proved that applying sufficient regularity conditions to the interval matrix $[A-|B|,A+|B|]$‎, ‎we can create a new unique solvability condition for the absolute value equation $Ax+B|x|=b$‎, ‎since regularity of interval matrices implies unique solvability of their corresponding absolute value equation‎. ‎This condition is formulated in terms of positive definiteness of a certain point matrix‎. ‎Special case $B=-I$ is verified too as an application.

Synthetic Biology of Cyanobacteria: Unique Challenges and Opportunities

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Bertram M Berla

2013-08-01

Full Text Available Photosynthetic organisms, and especially cyanobacteria, hold great promise as sources of renewably-produced fuels, bulk and specialty chemicals, and nutritional products. Synthetic biology tools can help unlock cyanobacteria’s potential for these functions, but unfortunately tool development for these organisms has lagged behind that for S. cerevisiae and E. coli. While these organisms may in many cases be more difficult to work with as ‘chassis’ strains for synthetic biology than certain heterotrophs, the unique advantages of autotrophs in biotechnology applications as well as the scientific importance of improved understanding of photosynthesis warrant the development of these systems into something akin to a ‘green E. coli’. In this review, we highlight unique challenges and opportunities for development of synthetic biology approaches in cyanobacteria. We review classical and recently developed methods for constructing targeted mutants in various cyanobacterial strains, and offer perspective on what genetic tools might most greatly expand the ability to engineer new functions in such strains. Similarly, we review what genetic parts are most needed for the development of cyanobacterial synthetic biology. Finally, we highlight recent methods to construct genome-scale models of cyanobacterial metabolism and to use those models to measure properties of autotrophic metabolism. Throughout this paper, we discuss some of the unique challenges of a diurnal, autotrophic lifestyle along with how the development of synthetic biology and biotechnology in cyanobacteria must fit within those constraints.

The design and performance of a twenty barrel hydrogen pellet injector for Alcator C-Mod

International Nuclear Information System (INIS)

Urbahn, J.A.

1994-05-01

A twenty barrel hydrogen pellet injector has been designed, built and tested both in the laboratory and on the Alcator C-Mod Tokamak at MIT. The injector functions by firing pellets of frozen hydrogen or deuterium deep into the plasma discharge for the purpose of fueling the plasma, modifying the density profile and increasing the global energy confinement time. The design goals of the injector are: (1) Operational flexibility, (2) High reliability, (3) Remote operation with minimal maintenance. These requirements have lead to a single stage, pipe gun design with twenty barrels. Pellets are formed by in- situ condensation of the fuel gas, thus avoiding moving parts at cryogenic temperatures. The injector is the first to dispense with the need for cryogenic fluids and instead uses a closed cycle refrigerator to cool the thermal system components. The twenty barrels of the injector produce pellets of four different size groups and allow for a high degree of flexibility in fueling experiments. Operation of the injector is under PLC control allowing for remote operation, interlocked safety features and automated pellet manufacturing. The injector has been extrusively tested and shown to produce pellets reliably with velocities up to 1400 m/sec. During the period from September to November of 1993, the injector was successfully used to fire pellets into over fifty plasma discharges. Experimental results include data on the pellet penetration into the plasma using an advanced pellet tracking diagnostic with improved time and spatial response. Data from the tracker indicates pellet penetrations were between 30 and 86 percent of the plasma minor radius

Uniqueness: skews bit occurrence frequencies in randomly generated fingerprint libraries.

Science.gov (United States)

Chen, Nelson G

2016-08-01

Requiring that randomly generated chemical fingerprint libraries have unique fingerprints such that no two fingerprints are identical causes a systematic skew in bit occurrence frequencies, the proportion at which specified bits are set. Observed frequencies (O) at which each bit is set within the resulting libraries systematically differ from frequencies at which bits are set at fingerprint generation (E). Observed frequencies systematically skew toward 0.5, with the effect being more pronounced as library size approaches the compound space, which is the total number of unique possible fingerprints given the number of bit positions each fingerprint contains. The effect is quantified for varying library sizes as a fraction of the overall compound space, and for changes in the specified frequency E. The cause and implications for this systematic skew are subsequently discussed. When generating random libraries of chemical fingerprints, the imposition of a uniqueness requirement should either be avoided or taken into account.

RUCS: Rapid identification of PCR primers for unique core sequences

DEFF Research Database (Denmark)

Thomsen, Martin Christen Frølund; Hasman, Henrik; Westh, Henrik

2017-01-01

Designing PCR primers to target a specific selection of whole genome sequenced strains can be a long, arduous, and sometimes impractical task. Such tasks would benefit greatly from an automated tool to both identify unique targets, and to validate the vast number of potential primer pairs...... for the targets in silico . Here we present RUCS, a program that will find PCR primer pairs and probes for the unique core sequences of a positive genome dataset complement to a negative genome dataset. The resulting primer pairs and probes are in addition to simple selection also validated through a complex...... in silico PCR simulation. We compared our method, which identifies the unique core sequences, against an existing tool called ssGeneFinder, and found that our method was 6.5-20 times more sensitive. We used RUCS to design primer pairs that would target a set of genomes known to contain the mcr-1 colistin...

A Content Analysis of Unique Selling Propositions of Tobacco Print Ads.

Science.gov (United States)

Johnson Shen, Megan; Banerjee, Smita C; Greene, Kathryn; Carpenter, Amanda; Ostroff, Jamie S

2017-03-01

We describe the unique selling propositions (USPs) (propositions used to convince customers to use a particular brand/product by focusing on the unique benefit) of print tobacco ads. A qualitative content analysis was conducted of print tobacco ads (N = 171) selected from August 2012 to August 2013 for cigarettes, moist snuff, e-cigarettes, cigars, and snus to determine the content and themes of USPs for tobacco ads. Cigarette ad USP themes focused on portraying the product as attractive; moist snuff ads focused on portraying product as masculine; cigar ads focused on selling a "high end product;" and new and emerging tobacco products (e-cigarette, snus) focused on directly comparing these products to cigarettes. Whereas traditional tobacco product ads used USPs focused on themes of enjoyment and pleasure (eg, attractive for cigarettes, "high end product" for cigars), new and emerging tobacco product ads offered the unique benefit (USP) of their product being a better and "safer" alternative to traditional tobacco products. Snuff's USPs focused nearly exclusively on the masculinity of their products. Our results provide targets for potential tobacco regulatory actions that could be implemented to reduce demand for tobacco products by reducing their perceived unique benefits.

Twenty years of JHEP

International Nuclear Information System (INIS)

Amati, Daniele; Bonora, Loriano

2017-01-01

On July 1st of twenty years ago we launched the first issue of JHEP. It was a real challenge to try the adventure of a scientific journal thought and managed by scientists, independent of private or institutional publishers. The idea was that physicists who were performing the work, writing the papers, and refereeing those of their peers, could also edit them in an electronic format. Thus, at a limited cost which could be handled by academic or scientific institutions, giving open access to the published information, and avoiding the heavy burden at that time placed on our libraries. In order to avoid the failure that - as we well remember was predicted to us by publishing companies and institutions, we needed the active support of the scientific community. A support in collaborating to the scrutiny of papers and scientific policies but, mainly, in sending to us their good papers. We contacted in that sense several of our most active and renowned colleagues, restricting of course to our high energy physics field. We received many enthusiastic responses as can be specifically seen from the papers that appear in the first issues of the journal, as well as the respected names listed in the advisory and in the editorial boards featuring in the opening page of the first issue of JHEP attached to this letter. We were optimists, but perhaps not as much as to foresee the success of the journal, which, in his first 20 years, turned out to be one of the most (if not the most) prestigious one in our field. Success for which --- as first project chairman and executive editor - we must essentially thank the scientific community who supported JHEP by considering it ''their journal'', as was our intention from the start. In this occasion we would like to recall the important contribution of Marco Fabbrichesi who designed the software on which the journal is based, and the technical personnel who implemented it and made it work. It is our pleasure to mention

Edges and vertices in a unique signed circle in a signed graph

Directory of Open Access Journals (Sweden)

Richard Behr

2017-12-01

Full Text Available We examine the conditions under which a signed graph contains an edge or a vertex that is contained in a unique negative circle or a unique positive circle. For an edge in a unique signed circle, the positive and negative case require the same structure on the underlying graph, but the requirements on the signature are different. We characterize the structure of the underlying graph necessary to support such an edge in terms of bridges of a circle. We then use the results from the edge version of the problem to help solve the vertex version.

Movies to the Rescue: Keeping the Cold War Relevant for Twenty-First-Century Students

Science.gov (United States)

Gokcek, Gigi; Howard, Alison

2013-01-01

What are the challenges of teaching Cold War politics to the twenty-first-century student? How might the millennial generation be educated about the political science theories and concepts associated with this period in history? A college student today, who grew up in the post-Cold War era with the Internet, Facebook, Twitter, smart phones,…

Being and feeling unique: statistical deviance and psychological marginality.

Science.gov (United States)

Frable, D E

1993-03-01

Two studies tested the hypothesis that people with culturally stigmatized and concealable conditions (e.g., gays, epileptics, juvenile delinquents, and incest victims) would be more likely to feel unique than people with culturally valued or conspicuous conditions (e.g., the physically attractive, the intellectually gifted, the obese, and the facially scarred). In Study 1, culturally stigmatized individuals with concealable conditions were least likely to perceive consensus between their personal preferences and those of others. In Study 2, they were most likely to describe themselves as unique and to make these self-relevant decisions quickly. Marginality is a psychological reality, not just a statistical one, for those with stigmatized and concealable "master status" conditions.

On the Existence and Uniqueness of the Scientific Method.

Science.gov (United States)

Wagensberg, Jorge

2014-01-01

The ultimate utility of science is widely agreed upon: the comprehension of reality. But there is much controversy about what scientific understanding actually means, and how we should proceed in order to gain new scientific understanding. Is there a method for acquiring new scientific knowledge? Is this method unique and universal? There has been no shortage of proposals, but neither has there been a shortage of skeptics about these proposals. This article proffers for discussion a potential scientific method that aspires to be unique and universal and is rooted in the recent and ancient history of scientific thinking. Curiously, conclusions can be inferred from this scientific method that also concern education and the transmission of science to others.

Uniqueness of KMS states for continuous fermion systems

International Nuclear Information System (INIS)

Jaekel, C.D.

1993-01-01

In 1989 Prof H. Narnhofer and Prof. W. Thirring established a (nonlocal) model of fermions with pair interactions. The existence of equilibrium states and the appearance of mixing properties was proofed. If this model reflects the basic facts of nature, one has to expect and to require that at high temperatures there is a unique equilibrium state and at low temperatures there are many different equilibrium states. Uniqueness of the equilibrium state at high temperatures is the topic of this dissertation. One may be astonished, that the proof of the uniqueness requires such a huge machinery, while the existence of KMS-states followes from fairly general conditions. Two states differ, if they can be distinguished by experiment. If one considers now that we have to show that two KMS-states at high temperatures result into the same value in all experiments one can think of, one might get an idea how unhandy this problem is. Even a conscious numeration of all experiments was a problem. Surprisingly only a few principal ideas of the treatment of spin-models survive. The temperature is the leading parameter and therefore it is a good idea to make a high temperature perturbation expansion for the KMS-condition, which fixes an equilibrium state in mathematical terms. But when we choose a generating vector for the perturbation expansion the similarities end. We better use physical considerations: at high temperatures we expect that chemical bounds will be broken up and the interacting equilibrium state will differ only slightly from the equilibrium state for the free time evolution. Roughly spoken, one can expect that high-energetic particles neglect interactions and fly in a straight line. In chapter 2.4 the whole machinery is presented in an easy-to-survey manner on a simple interaction. But in the case of pair interactions every particle interacts with each other and so the author was not able to find an easily accessible form of the developed method for this case

Achievements in the past twenty years and perspective outlook of crop space breeding in China

International Nuclear Information System (INIS)

Liu Luxiang; Guo Huijun; Zhao Linshu; Gu Jiayu; Zhao Shirong

2007-01-01

Space breeding is a novel effective approach to crop mutational improvement, which was firstly founded by the chinese scientists in 1987. A national collaborative research network has been established and significant achievements have been made during the past twenty years. More than forty new mutant varieties derived from space mutagenesis in rice, wheat, cotton, sweet pepper, tomato, sesame and alfalfa have been developed, officially released and put into production. A series of useful rare mutant germplasms which might make a great breakthrough in crop grain yield and/or quality improvement have been obtained. Technique innovations in space breeding and ground simulation of space environmental factors have been made good progresses. Intellective property right protection and industrialization of space mutation techniques and mutant varieties, exploration of the mechanism of space mutation induction have also been stably advanced. In this paper, the main achievements of crop space breeding in the past twenty years had been reviewed. The perspective development strategies of space breeding were also discussed. (authors)

The Relations of Family Members’ Unique and Shared Perspectives of Family Dysfunction to Dyad Adjustment

Science.gov (United States)

Jager, Justin; Yuen, Cynthia X.; Bornstein, Marc H.; Putnick, Diane L.; Hendricks, Charlene

2017-01-01

Among a community sample of families (N = 128), this study examined how family members’ shared and unique perspectives of family dysfunction relate to dyad members’ shared views of dyad adjustment within adolescent-mother, adolescent-father, and mother-father dyads. Independent of a family’s family perspective (shared perspective of family dysfunction), the adolescent’s unique perspective was associated with lower security and higher conflict with both mother and father, the father’s unique perspective was associated with lower security and higher conflict with the adolescent as well as lower marital quality with mother, and the mother unique perspective was associated with lower marital quality with the father. Moreover, for adolescent-parent dyads, compared to the parent unique perspective, the adolescent unique perspective was more strongly associated with dyad adjustment. These findings indicate that both shared and unique views of the family system – the adolescent’s unique view in particular - independently relate to the health of family subsystems. They also suggest that research as well as therapeutic interventions that focus on just the shared view of the family may miss important elements of family dysfunction. PMID:24884682

New Korean Record of Twenty Eight Species of the Family Ichneumonidae (Hymenoptera

Directory of Open Access Journals (Sweden)

Choi, Jin-Kyung

2014-04-01

Full Text Available We report twenty eight ichneumonid species new to Korea. These species belong to seven subfamilies. Among them five subfamilies, Diacritinae Townes, 1965, Microleptinae Townes, 1958, Orthocentrinae F$\\ddot{o} $ 수식 이미지rster, 1869, Orthopelmatinae Schmiedeknecht, 1910, Phrudinae Townes and Townes, 1949, are newly introduced to Korean fauna. All specimens are based on the insect collection of animal systematic laboratory at the Yeungnam University Gyeongsan Campus. Photographs of habitus of newly recorded subfamilies, diagnosis of 28 species and host information are provided.

Marginal and happy? The need for uniqueness predicts the adjustment of marginal immigrants.

Science.gov (United States)

Debrosse, Régine; de la Sablonnière, Roxane; Rossignac-Milon, Maya

2015-12-01

Marginalization is often presented as the strategy associated with the worst adjustment for immigrants. This study identifies a critical variable that buffers marginal immigrants from the negative effects of marginalization on adjustment: The need for uniqueness. In three studies, we surveyed immigrants recruited on university campuses (n = 119, n = 116) and in the field (n = 61). Among marginal immigrants, a higher need for uniqueness predicted higher self-esteem (Study 1), affect (Study 2), and life satisfaction (Study 3), and marginally higher happiness (Study 2) and self-esteem (Study 3). No relationship between the need for uniqueness and adjustment was found among non-marginal immigrants. The adaptive value of the need for uniqueness for marginal immigrants is discussed. © 2015 The British Psychological Society.

The neXtProt peptide uniqueness checker: a tool for the proteomics community.

Science.gov (United States)

Schaeffer, Mathieu; Gateau, Alain; Teixeira, Daniel; Michel, Pierre-André; Zahn-Zabal, Monique; Lane, Lydie

2017-11-01

The neXtProt peptide uniqueness checker allows scientists to define which peptides can be used to validate the existence of human proteins, i.e. map uniquely versus multiply to human protein sequences taking into account isobaric substitutions, alternative splicing and single amino acid variants. The pepx program is available at https://github.com/calipho-sib/pepx and can be launched from the command line or through a cgi web interface. Indexing requires a sequence file in FASTA format. The peptide uniqueness checker tool is freely available on the web at https://www.nextprot.org/tools/peptide-uniqueness-checker and from the neXtProt API at https://api.nextprot.org/. lydie.lane@sib.swiss. © The Author(s) 2017. Published by Oxford University Press.

Ecological restoration should be redefined for the twenty-first century.

Science.gov (United States)

Martin, David M

2017-09-24

Forty years ago, ecological restoration was conceptualized through a natural science lens. Today, ecological restoration has evolved into a social and scientific concept. The duality of ecological restoration is acknowledged in guidance documents on the subject but is not apparent in its definition. Current definitions reflect our views about what ecological restoration does but not why we do it. This viewpoint does not give appropriate credit to contributions from social sciences, nor does it provide compelling goals for people with different motivating rationales to engage in or support restoration. In this study, I give a concise history of the conceptualization and definition of ecological restoration, and I propose an alternative definition and corresponding viewpoint on restoration goal-setting to meet twenty-first century scientific and public inquiry.

On uniqueness in diffuse optical tomography

International Nuclear Information System (INIS)

Harrach, Bastian

2009-01-01

A prominent result of Arridge and Lionheart (1998 Opt. Lett. 23 882–4) demonstrates that it is in general not possible to simultaneously recover both the diffusion (aka scattering) and the absorption coefficient in steady-state (dc) diffusion-based optical tomography. In this work we show that it suffices to restrict ourselves to piecewise constant diffusion and piecewise analytic absorption coefficients to regain uniqueness. Under this condition both parameters can simultaneously be determined from complete measurement data on an arbitrarily small part of the boundary

Assessment of labour market returns in the case of gender unique human capital

OpenAIRE

Paas, Tiiu; Tverdostup, Maryna

2016-01-01

Maryna Tverdostup, Tiiu Paas, ERSA 2016: The paper focuses on the identification of the unique, non-reached by the opposite gender human capital and the analysis of its effect on the earning profiles of unique human capital holders. The overwhelming research aim is to better understand the possible reasons behind gender wage disparities, focusing on the unique features of male and female human capital and their returns. When assessing the gender pay disparities, variation of human capital cha...

Synthesis of Carbon Nano tubes: A Revolution in Material Science for the Twenty-First Century

International Nuclear Information System (INIS)

Allaf, Abd. W.

2003-01-01

The aim of this work is to explain the preparation procedures of single walled carbon nano tubes using arc discharge technique. The optimum conditions of carbon nano tubes synthesis are given. It should be pointed out that this sort of materials would be the twenty-first century materials

Affective and cognitive determinants of intention to consume twenty foods that contribute to fat intake

NARCIS (Netherlands)

Stafleu, A.; Graaf, de C.; Staveren, van W.A.; Burema, J.

2001-01-01

Fishbein and Ajzen's theory of reasoned action was used as a framework to study beliefs and attitudes towards twenty foods that contribute to fat intake in a Netherlands smaple population. Subjects between 18 and 75 years of age (n = 419, response rate 23€filled out a self-administered

Three Unique Implementations of Processes for PyCSP

DEFF Research Database (Denmark)

Friborg, Rune Møllegaard; Bjørndalen, John Markus; Vinter, Brian

2009-01-01

In this work we motivate and describe three unique implementations of processes for PyCSP: process, thread and greenlet based. The overall purpose is to demonstrate the feasibility of Communicating Sequential Processes as a framework for different application types and target platforms. The result...

Differentiating Performance Approach Goals and Their Unique Effects

Science.gov (United States)

Edwards, Ordene V.

2014-01-01

The study differentiates between two types of performance approach goals (competence demonstration performance approach goal and normative performance approach goal) by examining their unique effects on self-efficacy, interest, and fear of failure. Seventy-nine students completed questionnaires that measure performance approach goals,…

Need for Uniqueness Determines Reactions to Web-Based Personalized Advertising.

Science.gov (United States)

Stiglbauer, Barbara; Kovacs, Carrie

2018-01-01

The presented empirical study among a sample of n = 256 participants addressed the relationship between consumers' need for uniqueness and their reactions to web-based personalized advertising. Drawing on regulatory focus theory, we argue that the consumers' need for uniqueness dimensions creative choice and similarity avoidance may relate to promotion and prevention regulatory orientations, respectively. Accordingly, we hypothesized that creative choice and similarity avoidance would differentially predict self-reported approach and avoidance behavior toward personalized advertising. These direct relationships were further expected to be mediated by subjective evaluations of personalized advertising (i.e., perceived value and irritation). In line with these hypotheses, we found that creative choice predicted approach behavior through increased web-based personalized advertising value, whereas similarity avoidance predicted avoidance behavior through increased irritation. Creative choice also predicted decreased irritation, which in turn was related to decreased approach behavior. In sum, the results suggest that the consumers' need for uniqueness dimensions should not be investigated as a composite, as they seem to reflect different regulatory orientations and are therefore likely to evoke different affective, cognitive, and behavioral responses.

The covered distance for twenty five years of the Manche waste storage 1969 - 1994

International Nuclear Information System (INIS)

Gourden, J.M.

2001-01-01

The twenty five years of the Manche plant,are narrated with the difficulties of the beginning, the problems coming from leaks or runoff that have led to improvement in the knowledge of radioactive waste behaviour and the solutions that have been brought. It is from the building of the plant until the radioactive waste management that is related in this book. (N.C.)

Actualizing Unique Type and Token Values as a Solution to the Problem of Evil

Directory of Open Access Journals (Sweden)

Atle Ottesen Søvik

2017-12-01

Full Text Available Concerning the problem of evil, I suggest that God's goodness and omnipotence causes God to want to actualize many different values and things, not solely angels in heaven, but also type unique values like independence, self-formation, creativity, and surprise, and token unique goods like animals and human beings. Such a universe as ours, though, requires undisturbed indeterministic self-formation as actualized by a good God to give those token unique beings access to those type unique values and allow them the opportunity to live forever with God after completion of this self-formation.

Selection and characterization of a human neutralizing antibody to human fibroblast growth factor-2

International Nuclear Information System (INIS)

Tao, Jun; Xiang, Jun-Jian; Li, Dan; Deng, Ning; Wang, Hong; Gong, Yi-Ping

2010-01-01

Compelling evidences suggest that fibroblast growth factor-2 (FGF-2) plays important roles in tumor growth, angiogenesis and metastasis. Molecules blocking the FGF-2 signaling have been proposed as anticancer agents. Through screening of a human scFv phage display library, we have isolated several human single-chain Fv fragments (scFvs) that bind to human FGF-2. After expression and purification in bacteria, one scFv, named 1A2, binds to FGF-2 with a high affinity and specificity, and completes with FGF-2 binding to its receptor. This 1A2 scFv was then cloned into the pIgG1 vector and expressed in 293T cells. The purified hIgG1-1A2 antibody showed a high binding affinity of 8 x 10 -9 M to rhFGF-2. In a set of vitro assays, it inhibited various biological activities of FGF-2 such as the proliferation, migration and tube formation of human umbilical vein endothelial cells. More importantly, hIgG1-1A2 antibody also efficiently blocked the growth while inducing apoptosis of glioma cells. For the first time, we generated a human anti-FGF-2 antibody with proven in vitro anti-tumor activity. It may therefore present a new therapeutic candidate for the treatment of cancers that are dependent on FGF-2 signaling for growth and survival.

Single Chain Antibody Fragment against Venom from the Snake Daboia russelii formosensis

Directory of Open Access Journals (Sweden)

Chi-Hsin Lee

2017-10-01

Full Text Available Russell’s vipers containing hemotoxic and neurotoxic venom commonly cause snake envenomation. Horse-derived antivenom is a specific antidote, but its production is expensive and has side effects. Developing a cost-effective and more tolerable therapeutic strategy is favorable. In this study, using glutaraldehyde-attenuated Daboia russelii formosensis (DRF venom proteins to immunize chickens, polyclonal yolk-immunoglobulin (IgY antibodies were generated and showed a specific binding affinity. Phage display technology was used to generate two antibody libraries of single-chain variable fragments (scFvs containing 3.4 × 107 and 5.5 × 107 transformants, respectively. Phage-based ELISA indicated that specific clones were enriched after bio-panning. The nucleotide sequences of scFv-expressing clones were analyzed and classified into six groups in the short linker and four groups in the long linker. These scFv antibodies specifically bound to DRF proteins, but not other venom proteins. Mass spectrometric data suggested that these scFv antibodies may recognize phospholipase A2 RV-4 or RV-7. In vivo studies showed that anti-DRF IgY exhibited complete protective effects and mixed scFv antibodies increased the survival rate and time of mice challenged with a lethal dose of DRF proteins. These antibodies can be potentially applied in a rapid diagnostic method or for treatment in the future.

Development of a novel monoclonal antibody with reactivity to a wide range of Venezuelan equine encephalitis virus strains

Directory of Open Access Journals (Sweden)

Phelps Amanda L

2009-11-01

Full Text Available Abstract Background There is currently a requirement for antiviral therapies capable of protecting against infection with Venezuelan equine encephalitis virus (VEEV, as a licensed vaccine is not available for general human use. Monoclonal antibodies are increasingly being developed as therapeutics and are potential treatments for VEEV as they have been shown to be protective in the mouse model of disease. However, to be truly effective, the antibody should recognise multiple strains of VEEV and broadly reactive monoclonal antibodies are rarely and only coincidentally isolated using classical hybridoma technology. Results In this work, methods were developed to reliably derive broadly reactive murine antibodies. A phage library was created that expressed single chain variable fragments (scFv isolated from mice immunised with multiple strains of VEEV. A broadly reactive scFv was identified and incorporated into a murine IgG2a framework. This novel antibody retained the broad reactivity exhibited by the scFv but did not possess virus neutralising activity. However, the antibody was still able to protect mice against VEEV disease induced by strain TrD when administered 24 h prior to challenge. Conclusion A monoclonal antibody possessing reactivity to a wide range of VEEV strains may be of benefit as a generic antiviral therapy. However, humanisation of the murine antibody will be required before it can be tested in humans. Crown Copyright © 2009

Generation of human antibody fragments recognizing distinct epitopes of the nucleocapsid (N SARS-CoV protein using a phage display approach

Directory of Open Access Journals (Sweden)

Grasso Felicia

2005-09-01

Full Text Available Abstract Background Severe acute respiratory syndrome (SARS-CoV is a newly emerging virus that causes SARS with high mortality rate in infected people. Successful control of the global SARS epidemic will require rapid and sensitive diagnostic tests to monitor its spread, as well as, the development of vaccines and new antiviral compounds including neutralizing antibodies that effectively prevent or treat this disease. Methods The human synthetic single-chain fragment variable (scFv ETH-2 phage antibody library was used for the isolation of scFvs against the nucleocapsid (N protein of SARS-CoV using a bio panning-based strategy. The selected scFvs were characterized under genetics-molecular aspects and for SARS-CoV N protein detection in ELISA, western blotting and immunocytochemistry. Results Human scFv antibodies to N protein of SARS-CoV can be easily isolated by selecting the ETH-2 phage library on immunotubes coated with antigen. These in vitro selected human scFvs specifically recognize in ELISA and western blotting studies distinct epitopes in N protein domains and detect in immunohistochemistry investigations SARS-CoV particles in infected Vero cells. Conclusion The human scFv antibodies isolated and described in this study represent useful reagents for rapid detection of N SARS-CoV protein and SARS virus particles in infected target cells.

Single Chain Antibody Fragment against Venom from the Snake Daboia russelii formosensis.

Science.gov (United States)

Lee, Chi-Hsin; Lee, Yu-Ching; Lee, Yueh-Lun; Leu, Sy-Jye; Lin, Liang-Tzung; Chen, Chi-Ching; Chiang, Jen-Ron; Mwale, Pharaoh Fellow; Tsai, Bor-Yu; Hung, Ching-Sheng; Yang, Yi-Yuan

2017-10-27

Russell's vipers containing hemotoxic and neurotoxic venom commonly cause snake envenomation. Horse-derived antivenom is a specific antidote, but its production is expensive and has side effects. Developing a cost-effective and more tolerable therapeutic strategy is favorable. In this study, using glutaraldehyde-attenuated Daboia russelii formosensis (DRF) venom proteins to immunize chickens, polyclonal yolk-immunoglobulin (IgY) antibodies were generated and showed a specific binding affinity. Phage display technology was used to generate two antibody libraries of single-chain variable fragments (scFvs) containing 3.4 × 10⁷ and 5.5 × 10⁷ transformants, respectively. Phage-based ELISA indicated that specific clones were enriched after bio-panning. The nucleotide sequences of scFv-expressing clones were analyzed and classified into six groups in the short linker and four groups in the long linker. These scFv antibodies specifically bound to DRF proteins, but not other venom proteins. Mass spectrometric data suggested that these scFv antibodies may recognize phospholipase A2 RV-4 or RV-7. In vivo studies showed that anti-DRF IgY exhibited complete protective effects and mixed scFv antibodies increased the survival rate and time of mice challenged with a lethal dose of DRF proteins. These antibodies can be potentially applied in a rapid diagnostic method or for treatment in the future.

A Content Analysis of Unique Selling Propositions of Tobacco Print Ads

Science.gov (United States)

Shen, Megan Johnson; Banerjee, Smita C.; Greene, Kathryn; Carpenter, Amanda; Ostroff, Jamie S.

2017-01-01

Objectives The present study described the unique selling propositions (USPs) (propositions used to convince customers to use a particular brand/product by focusing on the unique benefit) of print tobacco ads. Methods A qualitative content analysis was conducted of print tobacco ads (N = 171) selected from August 2012-August 2013 for cigarettes, moist snuff, e-cigarettes, cigars, and snus to determine the content and themes of USPs for tobacco ads. Results Cigarette ad USP themes focused on portraying the product as attractive; moist snuff ads focused on portraying product as masculine; cigar ads focused on selling a “high end product;” and new and emerging tobacco products (e-cigarette, snus) focused on directly comparing these products to cigarettes. Conclusions Whereas traditional tobacco product ads used USPs focused on themes of enjoyment and pleasure (eg, attractive for cigarettes, “high end product” for cigars), new and emerging tobacco product ads offered the unique benefit (USP) of their product being a better and “safer” alternative to traditional tobacco products. Snuff’s USPs focused nearly exclusively on the masculinity of their products. Results of this study provide targets for potential tobacco regulatory actions that could be implemented to reduce demand for tobacco products by reducing their perceived unique benefits. PMID:28452697

Logic without unique readability - a study of semantic and syntactic ambiguity

DEFF Research Database (Denmark)

Bentzen, Martin Mose

One of the main reasons for introducing a formal language is to remove ambiguity, the possibility of assigning several meanings to a linguistic expression. Typically, this is achieved through ensuring unique readability of formulas by using brackets (or another convention, such as Polish notation...... not hold true universally. Whereas e.g. scope ambiguities in natural languages have been studied extensively, ambiguous formal languages have not been the focus of in depth research. Here, we lift the assumption of unique readability by omitting the brackets from propositional logic, making it possible...... to formally distinguish between syntactic and semantic ambiguity. A valuation then amounts to a semantic disambiguation, and rather than a unique valuation (truth value), there is a set of valuations corresponding to ways a formula could have been constructed. We show what happens to familiar concepts...

Uniqueness and zeros of q-shift difference polynomials

Indian Academy of Sciences (India)

In this paper, we consider the zero distributions of -shift difference polynomials of meromorphic functions with zero order, and obtain two theorems that extend the classical Hayman results on the zeros of differential polynomials to -shift difference polynomials. We also investigate the uniqueness problem of -shift ...

Leadership for Twenty-First-Century Schools and Student Achievement: Lessons Learned from Three Exemplary Cases

Science.gov (United States)

Schrum, Lynne; Levin, Barbara B.

2013-01-01

The purpose of this research was to understand ways exemplary award winning secondary school leaders have transformed their schools for twenty-first-century education and student achievement. This article presents three diverse case studies and identifies ways that each school's leader and leadership team reconfigured its culture and expectations,…

Speaking American: Comparing Supreme Court and Hollywood Racial Interpretation in the Early Twenty-First Century

Science.gov (United States)

Hawkins, Paul Henry

2010-01-01

Apprehending that race is social, not biological, this study examines U.S. racial formation in the early twenty-first century. In particular, Hollywood and Supreme Court texts are analyzed as media for gathering, shaping and transmitting racial ideas. Representing Hollywood, the 2004 film "Crash" is analyzed. Representing the Supreme Court, the…

Teaching and Learning in the Twenty-First Century: What Is an "Institute of Education" for?

Science.gov (United States)

Husbands, Chris

2012-01-01

As we begin the twenty-first century, schools and teachers are subject to enormous pressures for change. The revolution in digital technologies, the pressure to develop consistently high-performing schools systems, and the drive between excellence and equity all combine to raise profound questions about the nature of successful teaching and…

The Role of Visual Working Memory in Attentive Tracking of Unique Objects

Science.gov (United States)

Makovski, Tal; Jiang, Yuhong V.

2009-01-01

When tracking moving objects in space humans usually attend to the objects' spatial locations and update this information over time. To what extent do surface features assist attentive tracking? In this study we asked participants to track identical or uniquely colored objects. Tracking was enhanced when objects were unique in color. The benefit…

Non-unique factorizations algebraic, combinatorial and analytic theory

CERN Document Server

Geroldinger, Alfred

2006-01-01

From its origins in algebraic number theory, the theory of non-unique factorizations has emerged as an independent branch of algebra and number theory. Focused efforts over the past few decades have wrought a great number and variety of results. However, these remain dispersed throughout the vast literature. For the first time, Non-Unique Factorizations: Algebraic, Combinatorial, and Analytic Theory offers a look at the present state of the theory in a single, unified resource.Taking a broad look at the algebraic, combinatorial, and analytic fundamentals, this book derives factorization results and applies them in concrete arithmetical situations using appropriate transfer principles. It begins with a basic introduction that can be understood with knowledge of standard basic algebra. The authors then move to the algebraic theory of monoids, arithmetic theory of monoids, the structure of sets of lengths, additive group theory, arithmetical invariants, and the arithmetic of Krull monoids. They also provide a s...

Large anterior temporal Virchow-Robin spaces: unique MR imaging features

Energy Technology Data Exchange (ETDEWEB)

Lim, Anthony T. [Monash University, Neuroradiology Service, Monash Imaging, Monash Health, Melbourne, Victoria (Australia); Chandra, Ronil V. [Monash University, Neuroradiology Service, Monash Imaging, Monash Health, Melbourne, Victoria (Australia); Monash University, Department of Surgery, Faculty of Medicine, Nursing and Health Sciences, Melbourne (Australia); Trost, Nicholas M. [St Vincent' s Hospital, Neuroradiology Service, Melbourne (Australia); McKelvie, Penelope A. [St Vincent' s Hospital, Anatomical Pathology, Melbourne (Australia); Stuckey, Stephen L. [Monash University, Neuroradiology Service, Monash Imaging, Monash Health, Melbourne, Victoria (Australia); Monash University, Southern Clinical School, Faculty of Medicine, Nursing and Health Sciences, Melbourne (Australia)

2015-05-01

Large Virchow-Robin (VR) spaces may mimic cystic tumor. The anterior temporal subcortical white matter is a recently described preferential location, with only 18 reported cases. Our aim was to identify unique MR features that could increase prospective diagnostic confidence. Thirty-nine cases were identified between November 2003 and February 2014. Demographic, clinical data and the initial radiological report were retrospectively reviewed. Two neuroradiologists reviewed all MR imaging; a neuropathologist reviewed histological data. Median age was 58 years (range 24-86 years); the majority (69 %) was female. There were no clinical symptoms that could be directly referable to the lesion. Two thirds were considered to be VR spaces on the initial radiological report. Mean maximal size was 9 mm (range 5-17 mm); majority (79 %) had perilesional T2 or fluid-attenuated inversion recovery (FLAIR) hyperintensity. The following were identified as potential unique MR features: focal cortical distortion by an adjacent branch of the middle cerebral artery (92 %), smaller adjacent VR spaces (26 %), and a contiguous cerebrospinal fluid (CSF) intensity tract (21 %). Surgery was performed in three asymptomatic patients; histopathology confirmed VR spaces. Unique MR features were retrospectively identified in all three patients. Large anterior temporal lobe VR spaces commonly demonstrate perilesional T2 or FLAIR signal and can be misdiagnosed as cystic tumor. Potential unique MR features that could increase prospective diagnostic confidence include focal cortical distortion by an adjacent branch of the middle cerebral artery, smaller adjacent VR spaces, and a contiguous CSF intensity tract. (orig.)

Protein nanoparticle: A unique system as drug delivery vehicles

African Journals Online (AJOL)

STORAGESEVER

2008-12-29

Dec 29, 2008 ... Nanobiotechnology Research Center, Faculty of Chemical Engineering, Babol University of Technology, Iran. ... as potential carriers with unique advantages including ..... for intracellular uptake in BT/20 human breast cancer.

Historical Approach to the Role of Women in the Legislation of Iran: A Case Study on the Twenty-First Parliament

Directory of Open Access Journals (Sweden)

Sarah Sheibani

2017-01-01

Full Text Available One hundred and ten years ago, men and women took constitutionalism to achieve justice in Iran. National Council was the result of the Iranian people's struggle for justice, both women and men. Men policies from the beginning of legislation put women as minors and lunatics and bankrupted and banned them from vote. However, the Constitutional Revolution as a turning point and a national revolution played a key role in changing attitudes to women and structural context of their participation provided. In this paper, with the use of descriptive-analytical as well as quantitative methods, we sought to answer the question that what was the position of women in the twenty-first Parliament. The results of this study suggest that when Iranian women were allowed to participate politics, they have achieved to show their ability in politics as we saw examples in the twenty-first Parliament in which women had twenty-two percent participation.

Hepatoblastoma Biology Using Isotope Ratio Mass Spectrometry: Utility of a Unique Technique for the Analysis of Oncological Specimens.

Science.gov (United States)

Taran, Katarzyna; Frączek, Tomasz; Sitkiewicz, Anna; Sikora-Szubert, Anita; Kobos, Józef; Paneth, Piotr

2016-07-07

Hepatoblastoma is the most common primary liver tumor in children. However, it occurs rarely, with an incidence of 0.5-1.5 cases per million children. There is no clear explanation of the relationship between clinicopathologic features, therapy, and outcome in hepatoblastoma cases, so far. One of the most widely accepted prognostic factors in hepatoblastoma is histology of the tumor. The aim of the study was to determine the potential differences in biology of hepatoblastoma histological subtypes at the atomic level using the unique method of isotope ratio mass spectrometry, which is especially valuable in examination of small groups of biological samples. Twenty-four measurements of nitrogen stable isotope ratio, carbon stable isotope ratio and total carbon to nitrogen mass ratio in fetal and embryonal hepatoblastoma tissue were performed using a Sercon 20-22 Continuous Flow Isotope Ratio Mass Spectrometer (CF-IRMS) coupled with a Sercon SL elemental analyzer for simultaneous carbon-nitrogen-sulfur (NCS) analysis. A difference of about 1.781‰ in stable nitrogen isotope 15N/14N ratio was found between examined hepatoblastoma histological subtypes. The prognosis in liver tumors cases in children may be challenging particularly because of the lack of versatile methods of its evaluation. Isotope ratio mass spectrometry allows one to determine the difference between hepatoblastoma histological subtypes and clearly indicates the cases with the best outcome.

Evaluation of glycodendron and synthetically-modified dextran clearing agents for multi-step targeting of radioisotopes for molecular imaging and radioimmunotherapy

Science.gov (United States)

Cheal, Sarah M.; Yoo, Barney; Boughdad, Sarah; Punzalan, Blesida; Yang, Guangbin; Dilhas, Anna; Torchon, Geralda; Pu, Jun; Axworthy, Don B.; Zanzonico, Pat; Ouerfelli, Ouathek; Larson, Steven M.

2014-01-01

A series of N-acetylgalactosamine-dendrons (NAG-dendrons) and dextrans bearing biotin moieties were compared for their ability to complex with and sequester circulating bispecific anti-tumor antibody (scFv4) streptavidin (SA) fusion protein (scFv4-SA) in vivo, to improve tumor to normal tissue concentration ratios for targeted radioimmunotherapy and diagnosis. Specifically, a total of five NAG-dendrons employing a common synthetic scaffold structure containing 4, 8, 16, or 32 carbohydrate residues and a single biotin moiety were prepared (NAGB), and for comparative purposes, a biotinylated-dextran with average molecular weight (MW) of 500 kD was synthesized from amino-dextran (DEXB). One of the NAGB compounds, CA16, has been investigated in humans; our aim was to determine if other NAGB analogs (e.g. CA8 or CA4) were bioequivalent to CA16 and/or better suited as MST reagents. In vivo studies included dynamic positron-emission tomography (PET) imaging of 124I-labelled-scFv4-SA clearance and dual-label biodistribution studies following multi-step targeting (MST) directed at subcutaneous (s.c.) human colon adenocarcinoma xenografts in mice. The MST protocol consists of three injections: first, a bispecific antibody specific for an anti-tumor associated glycoprotein (TAG-72) single chain genetically-fused with SA (scFv4-SA); second, CA16 or other clearing agent; and third, radiolabeled biotin. We observed using PET imaging of 124I-labelled-scFv4-SA clearance that the spatial arrangement of ligands conjugated to NAG (i.e. biotin) can impact the binding to antibody in circulation and subsequent liver uptake of the NAG-antibody complex. Also, NAGB CA32-LC or CA16-LC can be utilized during MST to achieve comparable tumor- to-blood ratios and absolute tumor uptake seen previously with CA16. Finally, DEXB was equally effective as NAGB CA32-LC at lowering scFv4-SA in circulation, but at the expense of reducing absolute tumor uptake of radiolabeled biotin. PMID:24219178

Unique features of space reactors

International Nuclear Information System (INIS)

Buden, D.

1990-01-01

This paper reports on space reactors that are designed to meet a unique set of requirements; they must be sufficiently compact to be launched in a rocket to their operational location, operate for many years without maintenance and servicing, operate in extreme environments, and reject heat by radiation to space. To meet these restrictions, operating temperatures are much greater than in terrestrial power plants, and the reactors tend to have a fast neutron spectrum. Currently, a new generation of space reactor power plants is being developed. The major effort is in the SP-100 program, where the power plant is being designed for seven years of full power, and no maintenance operation at a reactor outlet operating temperature of 1350 K

Twenty-second Fungal Genetics Conference - Asilomar, 2003

Energy Technology Data Exchange (ETDEWEB)

Jonathan D. Walton

2003-06-30

The purpose of the Twenty Second Fungal Genetics Conference is to bring together scientists and students who are interested in genetic approaches to studying the biology of filamentous fungi. It is intended to stimulate thinking and discussion in an atmosphere that supports interactions between scientists at different levels and in different disciplines. Topics range from the basic to the applied. Filamentous fungi impact human affairs in many ways. In the environment they are the most important agents of decay and nutrient turnover. They are used extensively in the food industry for the production of food enzymes such as pectinase and food additives such as citric acid. They are used in the production of fermented foods such as alcoholic drinks, bread, cheese, and soy sauce. More than a dozen species of mushrooms are used as foods directly. Many of our most important antibiotics, such as penicillin, cyclosporin, and lovastatin, come from fungi. Fungi also have many negative impacts on human health and economics. Fungi are serious pathogens in immuno-compromised patients. Fungi are the single largest group of plant pathogens and thus a serious limit on crop productivity throughout the world. Many fungi are allergenic, and mold contamination of residences and commercial buildings is now recognized as a serious public health threat. As decomposers, fungi cause extensive damage to just about all natural and synthetic materials.

Nuclear energy into the twenty-first century

International Nuclear Information System (INIS)

Hammond, G.P.

1996-01-01

The historical development of the civil nuclear power generation industry is examined in the light of the need to meet conflicting energy-supply and environmental pressures over recent decades. It is suggested that fission (thermal and fast) reactors will dominate the market up to the period 2010-2030, with fusion being relegated to the latter part of the twenty-first century. A number of issues affecting the use of nuclear electricity generation in Western Europe are considered including its cost, industrial strategy needs, and the public acceptability of nuclear power. The contribution of nuclear power stations to achieving CO2 targets aimed at relieving global warming is discussed in the context of alternative strategies for sustainable development, including renewable energy sources and energy-efficiency measures. Trends in the generation of nuclear electricity from fission reactors are finally considered in terms of the main geopolitical groupings that make up the world in the mid-1990s. Several recent, but somewhat conflicting, forecasts of the role of nuclear power in the fuel mix to about 2020 are reviewed. It is argued that the only major expansion in generating capacity will take place on the Asia-Pacific Rim and not in the developing countries generally. Nevertheless, the global nuclear industry overall will continue to be dominated by a small number of large nuclear electricity generating countries; principally the USA, France and Japan. (UK)

A Unique Case of Muscle Invasive Metastatic Breast Cancer Mimicking Myositis

Science.gov (United States)

2017-06-28

TYPE 08/ 03/20 17 Publ ication/Journal 4. TITLE AND SUBTITLE A unique case of muscle-invasive metastatic breast cancer mimicking myositis 6...Rev. 8/98) Prescnbed by ANSI Std Z39. 18 Adobe Profes11on11 7.0 Title: A Unique Case of M uscle-Invasive Metastatic Breast Cancer M imicking...an 84-year-old female who presented with neck swelling and upper airway obstruction due to metastatic breast cancer invading the sternocleidomastoid

Twenty years of environmental opposition in the electric sector

International Nuclear Information System (INIS)

Molocchi, Andrea

1997-01-01

This article aims to provide a framework for analysing social opposition In Italy against the construction and management of electric power plants (nuclear and thermoelectric) and big electricity power lines in the past twenty years. First The author provide a history of social environmental opposition in the electric sector. This is followed by a typology of reason for opposition in terms of risk perception, which has been applied to about forty cases of social opposition against electric plants. This study an original experimental methodology which could also yield useful results when applied to other complex social phenomena. In the third phase of the study the author analyse the various roles of the social and institutional actors involved in the opposition, and the obstacles to future consensus building. The most interesting result of the study is the not only social but political nature opposition. This factor necessitates integration of the traditional individual risk perception approach with an approach which analyses political and social action of NGO's

Comparative evaluation of twenty pilot workload assessment measure using a psychomotor task in a moving base aircraft simulator

Science.gov (United States)

Connor, S. A.; Wierwille, W. W.

1983-01-01

A comparison of the sensitivity and intrusion of twenty pilot workload assessment techniques was conducted using a psychomotor loading task in a three degree of freedom moving base aircraft simulator. The twenty techniques included opinion measures, spare mental capacity measures, physiological measures, eye behavior measures, and primary task performance measures. The primary task was an instrument landing system (ILS) approach and landing. All measures were recorded between the outer marker and the middle marker on the approach. Three levels (low, medium, and high) of psychomotor load were obtained by the combined manipulation of windgust disturbance level and simulated aircraft pitch stability. Six instrument rated pilots participated in four seasons lasting approximately three hours each.

Three times twenty by twenty-twenty

International Nuclear Information System (INIS)

Heller, W.

2007-01-01

Under the German presidency, the European Council adopted a program of climate protection and energy policy on March 9, 2007. It contains these 3 objectives: (1) By 2020, greenhouse gas emissions in the EU will be reduced by at least 20 percent from their 1990 level. (2) The share of renewable energies in primary energy consumption in the EU will be raised to 20 percent by 2020. (3) To enhance energy efficiency, energy consumption in the EU is to be reduced by 20 percent relative to the forecasts for 2020. The reason given by the European Council for the ambitious energy efficiency goal is its conviction that, in addition to the considerable increase in renewables, a major improvement in energy efficiency will enhance the security of energy supply, attenuate the forecast rise in energy prices, and diminish greenhouse gas emissions. Nuclear power is mentioned only in passing and as a topic for national decisionmaking, which is absolutely unsatisfactory in the light of what nuclear power currently is, and could go on, contributing to the security of supply, the climate protection, and reasonably priced electricity supply. On the whole, the package of energy and environmental policy measures devised by the European Council may be termed ambitious. (orig.)

Twenty-One Genome Sequences from Pseudomonas Species and 19 Genome Sequences from Diverse Bacteria Isolated from the Rhizosphere and Endosphere of Populus deltoides

Energy Technology Data Exchange (ETDEWEB)

Brown, Steven D [ORNL; Utturkar, Sagar M [ORNL; Klingeman, Dawn Marie [ORNL; Johnson, Courtney M [ORNL; Martin, Stanton [ORNL; Land, Miriam L [ORNL; Lu, Tse-Yuan [ORNL; Schadt, Christopher Warren [ORNL; Doktycz, Mitchel John [ORNL; Pelletier, Dale A [ORNL

2012-01-01

To aid in the investigation of the Populus deltoides microbiome we generated draft genome sequences for twenty one Pseudomonas and twenty one other diverse bacteria isolated from Populus deltoides roots. Genome sequences for isolates similar to Acidovorax, Bradyrhizobium, Brevibacillus, Burkholderia, Caulobacter, Chryseobacterium, Flavobacterium, Herbaspirillum, Novosphingobium, Pantoea, Phyllobacterium, Polaromonas, Rhizobium, Sphingobium and Variovorax were generated.

Preparing Teacher-Students for Twenty-First-Century Learning Practices (PREP 21): A Framework for Enhancing Collaborative Problem-Solving and Strategic Learning Skills

Science.gov (United States)

Häkkinen, Päivi; Järvelä, Sanna; Mäkitalo-Siegl, Kati; Ahonen, Arto; Näykki, Piia; Valtonen, Teemu

2017-01-01

With regard to the growing interest in developing teacher education to match the twenty-first-century skills, while many assumptions have been made, there has been less theoretical elaboration and empirical research on this topic. The aim of this article is to present our pedagogical framework for the twenty-first-century learning practices in…

Evolutionary theory, human uniqueness and the image of God

Directory of Open Access Journals (Sweden)

Gijsbert van den Brink

2012-10-01

Full Text Available In this article, I examined what might be called the evolutionary argument against human uniqueness and human dignity. After having rehearsed briefly the roots of the classical Judeo- Christian view on human uniqueness and human dignity in the first chapters of Genesis, I went on to explore and delineate the nature of the evolutionary argument against this view. Next, I examined whether Christian theology might widen the concept of imago Dei so as to include other beings as well as humans, thus giving up the idea of human uniqueness. I concluded, however, that this move is deeply problematic. Therefore, I turned to a discussion of some recent attempts to define both human uniqueness and the image of God in theological rather than empirical terms. One of these, which is based on the concept of incarnation, is found wanting, but another one is construed in such a way that it enables us to reconcile the idea of human uniqueness as encapsulated in the doctrine of the imago Dei with contemporary evolutionary theory. Thus, this article can be seen as an exercise in bringing classical Christian theology to terms with evolution, further highlighting this theology’s ongoing vitality. Evolusieteorie, menslike uniekheid and die beeld van God. In hierdie artikel ondersoek ek die sogenaamde evolusionêre argument teen menslike uniekheid en menswaardigheid. Na ‘n kort oorsig oor die oorsprong van die klassieke Joods-Christelike siening van menslike uniekheid en menswaardigheid soos uit die eerste vyf hoofstukke van Genesis blyk, ondersoek en beeld ek die aard van die evolusionêre argument hierteenoor uit. Vervolgens word die vraag ondersoek of die Christelike teologie die konsep van imago Dei sodanig kan verbreed dat dit ook ander wesens behalwe mense kan insluit, waardeur die idee van menslike uniekheid dus prysgegee word. Ek kom egter tot die slotsom dat hierdie skuif hoogs problematies is. Daarom wend ek my tot ’n bespreking van onlangse pogings om

Target Choice and Unique Synergies in Global Mobile Telephony

DEFF Research Database (Denmark)

Claussen, Jörg; Köhler, Rebecca; Kretschmer, Tobias

2018-01-01

their foresight to select specific targets: First, they lower integration costs by selecting geographically close targets. This effect is stronger when buyer and target are in the same country, but only if the market is not so concentrated that it provokes regulatory interventions. Second, they select targets......The success of acquisitions rests on detecting and realizing unique synergies between buyer and target through their dyadic relationships. We study the role of unique dyad-specific synergies in the selection of takeover targets in the global mobile telecommunications industry. Firms use...... that can be acquired at a modest bid premium because they have asymmetric bargaining power. Finally, they select targets which can generate significant synergies due to technological synergies. Our work expands the existing target selection literature by studying dyad-specific factors within a single...

Unique Outcomes in the Narratives of Young Adults Who Experienced Dating Violence as Adolescents.

Science.gov (United States)

Draucker, Claire Burke; Smith, Carolyn; Mazurczyk, Jill; Thomas, Destini; Ramirez, Patricia; McNealy, Kim; Thomas, Jade; Martsolf, Donna S

2016-01-01

Narrative therapy, an approach based on the reauthoring of life narratives, may be a useful psychotherapeutic strategy for youth who have experienced dating violence. A cornerstone of narrative therapy is the concept of unique outcomes, which are moments that stand in contrast to a client's otherwise problem-saturated narratives. The purpose of this study was to identify and categorize unique outcomes embedded in narratives about adolescent dating violence. Text units representing unique outcomes were extracted from transcripts of interviews with 88 young adults who had experienced dating violence and were categorized using standard content analytic techniques. Six categories of unique outcome stories were identified: facing-facts stories, standing-up-for-myself stories, cutting-it-off stories, cutting-'em-loose stories, getting-back-on-track stories, and changing-it-up stories. This typology of unique outcomes can inform clinicians who work with clients who have a history of adolescent dating violence. © The Author(s) 2015.

Uniqueness of the joint measurement and the structure of the set of compatible quantum measurements

Science.gov (United States)

Guerini, Leonardo; Terra Cunha, Marcelo

2018-04-01

We address the problem of characterising the compatible tuples of measurements that admit a unique joint measurement. We derive a uniqueness criterion based on the method of perturbations and apply it to show that extremal points of the set of compatible tuples admit a unique joint measurement, while all tuples that admit a unique joint measurement lie in the boundary of such a set. We also provide counter-examples showing that none of these properties are both necessary and sufficient, thus completely describing the relation between the joint measurement uniqueness and the structure of the compatible set. As a by-product of our investigations, we completely characterise the extremal and boundary points of the set of general tuples of measurements and of the subset of compatible tuples.

Secondary metabolites from the unique bamboo, Melocanna baccifera.

Science.gov (United States)

Govindan, Balaji; Johnson, Anil John; Viswanathan, Gayathri; Ramaswamy, Venkataraman; Koshy, Konnath Chacko; Baby, Sabulal

2018-02-15

Phytochemistry of fruits and leaves of the unique bamboo Melocanna baccifera resulted in the isolation of 27 secondary metabolites, including 4-Oxabicyclo[3.2.2]nona-1(7),5,8-triene and Verbacine. Biological activity studies of Verbacine revealed it as an inhibitor of acetylcholinesterase and as cytotoxic against C6 cancer cells.

Determining hydraulic parameters of a karst aquifer using unique ...

African Journals Online (AJOL)

2014-07-15

Jul 15, 2014 ... 1 Faculty of Natural Sciences, Potchefstroom Campus, North-West University, ... a first-ever attempt to utilise various sets of unique historical data ..... Even though the aquifer shows characteristics of all major ...... Earth Sci.

Symmetry breaking and uniqueness for the incompressible Navier-Stokes equations

International Nuclear Information System (INIS)

Dascaliuc, Radu; Thomann, Enrique; Waymire, Edward C.; Michalowski, Nicholas

2015-01-01

The present article establishes connections between the structure of the deterministic Navier-Stokes equations and the structure of (similarity) equations that govern self-similar solutions as expected values of certain naturally associated stochastic cascades. A principle result is that explosion criteria for the stochastic cascades involved in the probabilistic representations of solutions to the respective equations coincide. While the uniqueness problem itself remains unresolved, these connections provide interesting problems and possible methods for investigating symmetry breaking and the uniqueness problem for Navier-Stokes equations. In particular, new branching Markov chains, including a dilogarithmic branching random walk on the multiplicative group (0, ∞), naturally arise as a result of this investigation

Symmetry breaking and uniqueness for the incompressible Navier-Stokes equations.

Science.gov (United States)

Dascaliuc, Radu; Michalowski, Nicholas; Thomann, Enrique; Waymire, Edward C

2015-07-01

The present article establishes connections between the structure of the deterministic Navier-Stokes equations and the structure of (similarity) equations that govern self-similar solutions as expected values of certain naturally associated stochastic cascades. A principle result is that explosion criteria for the stochastic cascades involved in the probabilistic representations of solutions to the respective equations coincide. While the uniqueness problem itself remains unresolved, these connections provide interesting problems and possible methods for investigating symmetry breaking and the uniqueness problem for Navier-Stokes equations. In particular, new branching Markov chains, including a dilogarithmic branching random walk on the multiplicative group (0, ∞), naturally arise as a result of this investigation.

Stationary Black Holes: Uniqueness and Beyond

Directory of Open Access Journals (Sweden)

Heusler Markus

1998-01-01

Full Text Available The spectrum of known black hole solutions to the stationary Einstein equations has increased in an unexpected way during the last decade. In particular, it has turned out that not all black hole equilibrium configurations are characterized by their mass, angular momentum and global charges. Moreover, the high degree of symmetry displayed by vacuum and electro-vacuum black hole space-times ceases to exist in self-gravitating non-linear field theories. This text aims to review some of the recent developments and to discuss them in the light of the uniqueness theorem for the Einstein-Maxwell system.

Stationary Black Holes: Uniqueness and Beyond

Directory of Open Access Journals (Sweden)

Piotr T. Chruściel

2012-05-01

Full Text Available The spectrum of known black-hole solutions to the stationary Einstein equations has been steadily increasing, sometimes in unexpected ways. In particular, it has turned out that not all black-hole-equilibrium configurations are characterized by their mass, angular momentum and global charges. Moreover, the high degree of symmetry displayed by vacuum and electro vacuum black-hole spacetimes ceases to exist in self-gravitating non-linear field theories. This text aims to review some developments in the subject and to discuss them in light of the uniqueness theorem for the Einstein-Maxwell system.

Twenty-first century learning after school: the case of Junior Achievement Worldwide.

Science.gov (United States)

Box, John M

2006-01-01

Efforts to increase after-school programming indicate the nation's concern about how youth are engaged during out-of-school time. There are clear benefits to extending the learning that goes on during the school day. Research from the U.S. Departments of Education and Justice shows that after-school participants do better in school and have stronger expectations for the future than youth who are not occupied after school. And the need is evident: 14.3 million students return to an empty house after school, yet only 6.5 million children are currently enrolled in after-school programs. If an after-school program were available, parents of 15.3 million would enroll their child. JA Worldwide began in 1919 and has been rooted in the afterschool arena from its origins. Its after-school programs teach students about the free enterprise system through curriculum focusing on business, citizenship, economics, entrepreneurship, ethics and character, financial literacy, and career development. At the same time, JA Worldwide incorporates hands-on learning and engagement with adults as role models, both key elements to a successful after-school program. Now focused on developing curriculum emphasizing skills needed for the twenty-first century, JA adopted the key elements laid out for after-school programs by the Partnership for 21st Century Skills. To ensure that the next generation of students enters the workforce prepared, America's education system must provide the required knowledge, skills, and attitudes. Programs such as JA Worldwide serve as models of how to provide the twenty-first century skills that all students need to succeed.

2010 Critical Success Factors for the North Carolina Community College System. Twenty First Annual Report

Science.gov (United States)

North Carolina Community College System (NJ1), 2010

2010-01-01

First mandated by the North Carolina General Assembly in 1989 (S.L. 1989; C. 752; S. 80), the Critical Success Factors report has evolved into the major accountability document for the North Carolina Community College System. This twenty first annual report on the critical success factors is the result of a process undertaken to streamline and…

Essential Soft Skills for Success in the Twenty-First Century Workforce as Perceived by Business Educators

Science.gov (United States)

Mitchell, Geana W.; Skinner, Leane B.; White, Bonnie J.

2010-01-01

Background: Soft skills describe career attributes that individuals should possess, such as team skills, communication skills, ethics, time-management skills, and an appreciation for diversity. In the twenty-first century workforce, soft skills are important in every business sector. However, employers in business continuously report that new…

Twenty-First Century Instructional Classroom Practices and Reading Motivation: Probing the Effectiveness of Interventional Reading Programs

Science.gov (United States)

Boulhrir, Taoufik

2017-01-01

Twenty-first century education has undoubtedly witnessed changes of the definition of literacy to cope with the economic, social, and intellectual trends. Technological advances, which include skills of communication, creativity, critical thinking, and collaboration have become key in education, especially when dealing with literacy and reading…

Neurogenetics in Child Neurology: Redefining a Discipline in the Twenty-first Century.

Science.gov (United States)

Kaufmann, Walter E

2016-12-01

Increasing knowledge on genetic etiology of pediatric neurologic disorders is affecting the practice of the specialty. I reviewed here the history of pediatric neurologic disorder classification and the role of genetics in the process. I also discussed the concept of clinical neurogenetics, with its role in clinical practice, education, and research. Finally, I propose a flexible model for clinical neurogenetics in child neurology in the twenty-first century. In combination with disorder-specific clinical programs, clinical neurogenetics can become a home for complex clinical issues, repository of genetic diagnostic advances, educational resource, and research engine in child neurology.

Twenty years' application of agricultural countermeasures following the Chernobyl accident: lessons learned

International Nuclear Information System (INIS)

Fesenko, S V; Alexakhin, R M; Balonov, M I; Bogdevich, I M; Howard, B J; Kashparov, V A; Sanzharova, N I; Panov, A V; Voigt, G; Zhuchenka, Yu M

2006-01-01

The accident at the Chernobyl NPP (nuclear power plant) was the most serious ever to have occurred in the history of nuclear energy. The consumption of contaminated foodstuffs in affected areas was a significant source of irradiation for the population. A wide range of different countermeasures have been used to reduce exposure of people and to mitigate the consequences of the Chernobyl accident for agriculture in affected regions in Belarus, Russia and Ukraine. This paper for the first time summarises key data on countermeasure application over twenty years for all three countries and describes key lessons learnt from this experience. (review)

Twenty years of „post-communism”: the radiography of a political failure

Directory of Open Access Journals (Sweden)

Aurora Martin

2011-11-01

Full Text Available This empirical view on the current „state” of Romania has as main objective to emphasize that the contemporary economic crisis actually revealed some other escalated crises in the very heart of the Romanian society. The vicious circle determined by three crises – one political, another social-institutional and last, but not least, a cultural one, continuously weakened the state for the last twenty years. Romania will overcome the economic crisis but the key for walking out of the above-mentioned circle would be the real transformation of its core systems – political, institutional and educational.

Autonomous Robotic Weapons: US Army Innovation for Ground Combat in the Twenty-First Century

Science.gov (United States)

2015-05-21

1 Introduction Today the robot is an accepted fact, but the principle has not been pushed far enough. In the twenty-first century the...2013, accessed March 29, 2015, http://www.bbc.com/news/magazine-21576376?print=true. 113 Steven Kotler , “Say Hello to Comrade Terminator: Russia’s...of autonomous robotic weapons, black- marketed directed energy weapons, and or commercially available software, potential adversaries may find

Analysis of the projected regional sea-ice changes in the Southern Ocean during the twenty-first century

Energy Technology Data Exchange (ETDEWEB)

Lefebvre, W.; Goosse, H. [Universite Catholique de Louvain, Institut d' Astronomie et de Geophysique Georges Lemaitre, Louvain-la-Neuve (Belgium)

2008-01-15

Using the set of simulations performed with atmosphere-ocean general circulation models (AOGCMs) for the Fourth Assessment Report of the Intergovernmental Panel on Climate Change (IPCC AR4), the projected regional distribution of sea ice for the twenty-first century has been investigated. Averaged over all those model simulations, the current climate is reasonably well reproduced. However, this averaging procedure hides the errors from individual models. Over the twentieth century, the multimodel average simulates a larger sea-ice concentration decrease around the Antarctic Peninsula compared to other regions, which is in qualitative agreement with observations. This is likely related to the positive trend in the Southern Annular Mode (SAM) index over the twentieth century, in both observations and in the multimodel average. Despite the simulated positive future trend in SAM, such a regional feature around the Antarctic Peninsula is absent in the projected sea-ice change for the end of the twenty-first century. The maximum decrease is indeed located over the central Weddell Sea and the Amundsen-Bellingshausen Seas. In most models, changes in the oceanic currents could play a role in the regional distribution of the sea ice, especially in the Ross Sea, where stronger southward currents could be responsible for a smaller sea-ice decrease during the twenty-first century. Finally, changes in the mixed layer depth can be found in some models, inducing locally strong changes in the sea-ice concentration. (orig.)

[Reactance proneness, collectivism, uniqueness, and resistance to persuasion].

Science.gov (United States)

Imajo, Shuzo

2002-10-01

This study examined the reliability and validity of Japanese psychological reactance scales. A total of 167 undergraduates completed a questionnaire of Therapeutic Reactance Scale (TRS), the Hong Reactance Scale (HRS), the Uniqueness Scale, and the Collectivism Scale. They also received messages involving three persuasion situations that were either high or low in terms of threat, and were asked to describe their reactions to them. The author categorized the reactions into three: acceptance, indirect resistance, and direct resistance. Reliabilities of the reactance scales were satisfactory. Their scores positively correlated with uniqueness scores, and negatively with collectivism scores. Those high on reactance proneness were less persuaded in two of the three situations. But in the third, an HRS by threat interaction was observed, indicating that only those who were high on reactance proneness under the high-threat condition showed resistance to persuasion. These results suggest that the Japanese versions of reactance scale were reliable and valid. However, the assertiveness aspect of TRS may not be appropriate for the definition of reactance. The influence of culture on psychological reactance was also discussed.

Unique identification code for medical fundus images using blood vessel pattern for tele-ophthalmology applications.

Science.gov (United States)

Singh, Anushikha; Dutta, Malay Kishore; Sharma, Dilip Kumar

2016-10-01

Identification of fundus images during transmission and storage in database for tele-ophthalmology applications is an important issue in modern era. The proposed work presents a novel accurate method for generation of unique identification code for identification of fundus images for tele-ophthalmology applications and storage in databases. Unlike existing methods of steganography and watermarking, this method does not tamper the medical image as nothing is embedded in this approach and there is no loss of medical information. Strategic combination of unique blood vessel pattern and patient ID is considered for generation of unique identification code for the digital fundus images. Segmented blood vessel pattern near the optic disc is strategically combined with patient ID for generation of a unique identification code for the image. The proposed method of medical image identification is tested on the publically available DRIVE and MESSIDOR database of fundus image and results are encouraging. Experimental results indicate the uniqueness of identification code and lossless recovery of patient identity from unique identification code for integrity verification of fundus images. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Binding of HIV-1 gp41-directed neutralizing and non-neutralizing fragment antibody binding domain (Fab and single chain variable fragment (ScFv antibodies to the ectodomain of gp41 in the pre-hairpin and six-helix bundle conformations.

Directory of Open Access Journals (Sweden)

John M Louis

Full Text Available We previously reported a series of antibodies, in fragment antigen binding domain (Fab formats, selected from a human non-immune phage library, directed against the internal trimeric coiled-coil of the N-heptad repeat (N-HR of HIV-1 gp41. Broadly neutralizing antibodies from that series bind to both the fully exposed N-HR trimer, representing the pre-hairpin intermediate state of gp41, and to partially-exposed N-HR helices within the context of the gp41 six-helix bundle. While the affinities of the Fabs for pre-hairpin intermediate mimetics vary by only 2 to 20-fold between neutralizing and non-neutralizing antibodies, differences in inhibition of viral entry exceed three orders of magnitude. Here we compare the binding of neutralizing (8066 and non-neutralizing (8062 antibodies, differing in only four positions within the CDR-H2 binding loop, in Fab and single chain variable fragment (ScFv formats, to several pre-hairpin intermediate and six-helix bundle constructs of gp41. Residues 56 and 58 of the mini-antibodies are shown to be crucial for neutralization activity. There is a large differential (≥ 150-fold in binding affinity between neutralizing and non-neutralizing antibodies to the six-helix bundle of gp41 and binding to the six-helix bundle does not involve displacement of the outer C-terminal helices of the bundle. The binding stoichiometry is one six-helix bundle to one Fab or three ScFvs. We postulate that neutralization by the 8066 antibody is achieved by binding to a continuum of states along the fusion pathway from the pre-hairpin intermediate all the way to the formation of the six-helix bundle, but prior to irreversible fusion between viral and cellular membranes.

Effects of Twenty-four Move Shadow Boxing Combined with psychosomatic relaxation on Depression and Anxiety in Patients with Type-2 Diabetes.

Science.gov (United States)

Zheng, Yingying; Zhou, Yiyi; Lai, Qiujia

2015-06-01

The aim of the current study was to observe the effects of Twenty-four Move Shadow Boxing combined with psychosomatic relaxation on depression and anxiety in patients with Type-2 Diabetes. One hundred and twenty (120) patients with Type-2 Diabetes and depressive/anxious symptoms were divided into intervention group (60 cases) and control group (60 cases) according to the minimum distribution principle of unbalanced indicators. Twenty-four Move Shadow Boxing group used this intervention combined with psychosomatic relaxation. Control group underwent conventional treatment. All the patients in the two groups completed the Self-rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) before and after treatment. Among the 52 people included in the statistical analysis, the recovery rate was 13.3%. The differences between depression and anxiety scores in the intervention group before and after treatment were statistically significant (PBoxing and psychosomatic relaxation has a beneficial auxiliary therapeutic effect on depression and anxiety accompanying Type-2 Diabetes.

Comparing Unique Title Coverage of Web of Science and Scopus in Earth and Atmospheric Sciences

Science.gov (United States)

Barnett, Philip; Lascar, Claudia

2012-01-01

The current journal titles in earth and atmospheric sciences, that are unique to each of two databases, Web of Science and Scopus, were identified using different methods. Comparing by subject category shows that Scopus has hundreds of unique titles, and Web of Science just 16. The titles unique to each database have low SCImago Journal Rank…

Somatic cell nuclear transfer: Infinite reproduction of a unique diploid genome

International Nuclear Information System (INIS)

Kishigami, Satoshi; Wakayama, Sayaka; Hosoi, Yoshihiko; Iritani, Akira; Wakayama, Teruhiko

2008-01-01

In mammals, a diploid genome of an individual following fertilization of an egg and a spermatozoon is unique and irreproducible. This implies that the generated unique diploid genome is doomed with the individual ending. Even as cultured cells from the individual, they cannot normally proliferate in perpetuity because of the 'Hayflick limit'. However, Dolly, the sheep cloned from an adult mammary gland cell, changes this scenario. Somatic cell nuclear transfer (SCNT) enables us to produce offspring without germ cells, that is, to 'passage' a unique diploid genome. Animal cloning has also proven to be a powerful research tool for reprogramming in many mammals, notably mouse and cow. The mechanism underlying reprogramming, however, remains largely unknown and, animal cloning has been inefficient as a result. More momentously, in addition to abortion and fetal mortality, some cloned animals display possible premature aging phenotypes including early death and short telomere lengths. Under these inauspicious conditions, is it really possible for SCNT to preserve a diploid genome? Delightfully, in mouse and recently in primate, using SCNT we can produce nuclear transfer ES cells (ntES) more efficiently, which can preserve the eternal lifespan for the 'passage' of a unique diploid genome. Further, new somatic cloning technique using histone-deacetylase inhibitors has been developed which can significantly increase the previous cloning rates two to six times. Here, we introduce SCNT and its value as a preservation tool for a diploid genome while reviewing aging of cloned animals on cellular and individual levels

Somatic cell nuclear transfer: infinite reproduction of a unique diploid genome.

Science.gov (United States)

Kishigami, Satoshi; Wakayama, Sayaka; Hosoi, Yoshihiko; Iritani, Akira; Wakayama, Teruhiko

2008-06-10

In mammals, a diploid genome of an individual following fertilization of an egg and a spermatozoon is unique and irreproducible. This implies that the generated unique diploid genome is doomed with the individual ending. Even as cultured cells from the individual, they cannot normally proliferate in perpetuity because of the "Hayflick limit". However, Dolly, the sheep cloned from an adult mammary gland cell, changes this scenario. Somatic cell nuclear transfer (SCNT) enables us to produce offspring without germ cells, that is, to "passage" a unique diploid genome. Animal cloning has also proven to be a powerful research tool for reprogramming in many mammals, notably mouse and cow. The mechanism underlying reprogramming, however, remains largely unknown and, animal cloning has been inefficient as a result. More momentously, in addition to abortion and fetal mortality, some cloned animals display possible premature aging phenotypes including early death and short telomere lengths. Under these inauspicious conditions, is it really possible for SCNT to preserve a diploid genome? Delightfully, in mouse and recently in primate, using SCNT we can produce nuclear transfer ES cells (ntES) more efficiently, which can preserve the eternal lifespan for the "passage" of a unique diploid genome. Further, new somatic cloning technique using histone-deacetylase inhibitors has been developed which can significantly increase the previous cloning rates two to six times. Here, we introduce SCNT and its value as a preservation tool for a diploid genome while reviewing aging of cloned animals on cellular and individual levels.

Loss of uniqueness in poro-mechanical model with enhanced media

International Nuclear Information System (INIS)

Sieffert, Y.; Marinelli, F.; Chambon, R.

2010-01-01

Document available in extended abstract form only. These paper deals with the problem of uniqueness in simulation the behavior of geo-materials with enhanced media to controlled the widths of bands. In the last 10 years, the loss of uniqueness has been clearly demonstrated in some initial boundary value problems involving constitutive equations modeling the degradation of the strength of materials. First in theoretical aspect with a simple test for a one dimensional problem of traction in a bar where the analytical solutions can be developed. In this article, It was also demonstrated that it is possible to retrieve all the analytical solutions in numerical simulations, only by using different starting guesses in the Newton's method. Then thanks to some classical numerical and experimental tests in geomechanical the non uniqueness is proved: the biaxial test and the borehole problem. However in all theses study, the geo-material is assumed to be monophasic. That's why is relevant to investigated the problem of uniqueness in taken into account the fluid part in the media. We deals in the framework of poro-mechanical model where the mechanical part is obeying a second gradient theory (not local) to ensure a regularization of the localisation pattern. This work is realized within the framework of the European Project TIMODAZ (Thermal Impact on the Damaged Zone Around a Radioactive Waste Disposal in Clay Host Rocks, http:// www.timodaz.eu/). As one benchmark in this project, the classical mechanical part is a Druecker-Prager model with a softening in the cohesion and a hardening in the frictional angle. It is a non-associated plasticity model for limited dilatancy. The parameters of this model are the same of this benchmark to simulated the Boom Clay material. Finally this paper demonstrates that several numerical solutions could be obtained as monophasic for the biaxial test modelling. (authors)

Nephrotic syndrome induced by dibasic sodium phosphate injections for twenty-eight days in rats.

Science.gov (United States)

Tsuchiya, Noriko; Torii, Mikinori; Narama, Isao; Matsui, Takane

2009-04-01

Sprague-Dawley rats received once daily tail-vein injections of 360 mM dibasic sodium phosphate solution at 8 mL/kg for fourteen or twenty-eight days. Clinical examination revealed persistent proteinuria from three days after the first dosing and thereafter severe proteinuria from eight days or later in the phosphate-treated groups. Proteinuria developed without remission even after fourteen-day withdrawal in the fourteen-day dosed group. Phosphate-treated animals developed lipemia, hypercholesterolemia, anemia, higher serum fibrinogen levels, and lower serum albumin/globulin ratios on day 29. Renal weight increased significantly compared with control animals, and the kidneys appeared pale and enlarged with a rough surface. Histopathologically, glomerular changes consisted of mineralization in whole glomeruli, glomerular capillary dilatation, partial adhesion of glomerular tufts to Bowman's capsule, and mesangiolysis. Ultrastructural lesions such as an increased number of microvilli, effacement of foot processes, and thickening of the glomerular basement membrane, and immunocytochemical changes in podocytes, mainly decreased podoplanin-positive cells and increased desmin expression, were also conspicuous in the phosphate-treated rats for twenty-eight days. Marked tubulointerstitial lesions were tubular regeneration and dilatation, protein casts, mineralization in the basement membrane, focal interstitial inflammation, and fibrosis in the cortex. These clinical and morphological changes were similar to features of human nephrotic syndrome.

Zeros and uniqueness of Q-difference polynomials of meromorphic ...

Indian Academy of Sciences (India)

Meromorphic functions; Nevanlinna theory; logarithmic order; uniqueness problem; difference-differential polynomial. Abstract. In this paper, we investigate the value distribution of -difference polynomials of meromorphic function of finite logarithmic order, and study the zero distribution of difference-differential polynomials ...

Index to the Twenty-first Semiannual Report of the Commission to the Congress. July 1956 - December 1956

Energy Technology Data Exchange (ETDEWEB)

Strauss, Lewis L.

1957-01-31

This volume contains a name and subject indext for the twenty-first semiannual report of the United States Atomic Energy Commission to Congress. The full semiannual report covers the major unclassified activities of the Commission from July 1956 through December 1956.

An Association of Unique microRNA Turnover Machinery with Prostate Cancer Progression

Science.gov (United States)

2017-10-01

targeting of critical androgen receptor -604 coregulator interactions in prostate cancer . Nature communications 4, 1923, 605 doi:10.1038/ncomms2912 (2013...AWARD NUMBER: W81XWH-16-1-0474 TITLE: An Association of Unique microRNA Turnover Machinery with Prostate Cancer Progression PRINCIPAL INVESTIGATOR...14 Sep 2017 4. Title An Association of Unique microRNA Turnover Machinery with Prostate Cancer Progression 5a. CONTRACT NUMBER 5b. GRANT NUMBER

Unmanned Aerial Vehicles unique cost estimating requirements

Science.gov (United States)

Malone, P.; Apgar, H.; Stukes, S.; Sterk, S.

Unmanned Aerial Vehicles (UAVs), also referred to as drones, are aerial platforms that fly without a human pilot onboard. UAVs are controlled autonomously by a computer in the vehicle or under the remote control of a pilot stationed at a fixed ground location. There are a wide variety of drone shapes, sizes, configurations, complexities, and characteristics. Use of these devices by the Department of Defense (DoD), NASA, civil and commercial organizations continues to grow. UAVs are commonly used for intelligence, surveillance, reconnaissance (ISR). They are also use for combat operations, and civil applications, such as firefighting, non-military security work, surveillance of infrastructure (e.g. pipelines, power lines and country borders). UAVs are often preferred for missions that require sustained persistence (over 4 hours in duration), or are “ too dangerous, dull or dirty” for manned aircraft. Moreover, they can offer significant acquisition and operations cost savings over traditional manned aircraft. Because of these unique characteristics and missions, UAV estimates require some unique estimating methods. This paper describes a framework for estimating UAV systems total ownership cost including hardware components, software design, and operations. The challenge of collecting data, testing the sensitivities of cost drivers, and creating cost estimating relationships (CERs) for each key work breakdown structure (WBS) element is discussed. The autonomous operation of UAVs is especially challenging from a software perspective.

Unique Features of Mobile Commerce

Institute of Scientific and Technical Information of China (English)

DING Xiaojun; IIJIMA Junichi; HO Sho

2004-01-01

While the market potentials and impacts of web-based e-commerce are still in the ascendant, the advances in wireless technologies and mobile networks have brought about a new business opportunity and research attention, what is termed mobile commerce. Commonly, mobile commerce is considered to be another new application of existing web-based e-commerce onto wireless networks, but as an independent business area, mobile commerce has its own advantages and challenges as opposed to traditional e-commerce applications. This paper focuses on exploring the unique features of mobile commerce as. Compared with traditional e-commerce. Also, there are still some limitations arisen in m-commerce in contrast to web-based e-commerce. Finally, current state of mobile commerce in Japan is presented in brief, with an introduction of several cases involving mobile commerce applications in today 's marketplace.

The Uniqueness of Islamic Culture

Directory of Open Access Journals (Sweden)

Sinan YILMAZ

2014-12-01

Full Text Available Abstract This paper examines the main reasons behind why Islamic culture is different than other cultures. In the introduction part of the paper, the usage area of the words culture and civilization were tackled. In the first part of the paper, an evaluation of the uniqueness of Islamic culture was made and examples about this were given. In the second part of the paper, evaluations about how Islamic culture has struggled with modernization and secularization and how it has shaped itself as a result of this were made. In the third part of the paper, the situation in which Islamic civilization has regressed against the Western civilization causing emerging arguments and the current situation in Islamic civilization have been addressed by making evaluations on culture and civilization. In the final part, evaluations on thesis this paper has used were made.

Regional cluster policy between best practices and cultural uniqueness

NARCIS (Netherlands)

Hospers, Gerrit J.; Beugelsdijk, S.; Boneschansker, E.; van Dijk, J.; Jansma, L.G.J.; Verhaar, K.H.A.

2004-01-01

This chapter deals with an intriguing paradox in current regional economic policy: whereas unique local factors are increasingly seen as the determinants of regional economic success, more and more governments simultaneously try to copy policy experiences that have proved successful in a particular

Unique Migraine Subtypes, Rare Headache Disorders, and Other Disturbances.

Science.gov (United States)

Goadsby, Peter J

2015-08-01

The medical aphorism that common things happen commonly makes unique (and less common) migraine subtypes especially appropriate to review for the general neurologist. This article also identifies some rare headache disorders and other disturbances, and offers strategies to manage them. This article discusses migraine with brainstem aura, which is troublesome clinically and has had a change in terminology in the International Classification of Headache Disorders, Third Edition, beta version (ICHD-3 beta), and hemiplegic migraine, which is also troublesome in practice. The rare headache disorder hypnic headache and the exploding head syndrome are also discussed. When hypnic headache is recognized, it is eminently treatable, while exploding head syndrome is a benign condition with no reported consequences. Unique migraine subtypes, rare headache disorders, and other disturbances present to neurologists. When recognized, they can often be managed very well, which offers significant benefits to patients and practice satisfaction to neurologists.

Uniqueness plots: A simple graphical tool for identifying poor peak fits in X-ray photoelectron spectroscopy

International Nuclear Information System (INIS)

Singh, Bhupinder; Diwan, Anubhav; Jain, Varun; Herrera-Gomez, Alberto; Terry, Jeff; Linford, Matthew R.

2016-01-01

Highlights: • Uniqueness plots are introduced as a new tool for identifying poor XPS peak fits. • Uniqueness plots are demonstrated on real XPS data sets. • A horizontal line in a uniqueness plot indicates a poor fit, i.e., fit parameter correlation. • A parabolic shape in a uniqueness plot indicates that a fit may be appropriate. - Abstract: Peak fitting is an essential part of X-ray photoelectron spectroscopy (XPS) narrow scan analysis, and the Literature contains both good and bad examples of peak fitting. A common cause of poor peak fitting is the inclusion of too many fit parameters, often without a sound chemical and/or physical basis for them, and/or the failure to reasonably constrain them. Under these conditions, fit parameters are often correlated, and therefore lacking in statistical meaning. Here we introduce the uniqueness plot as a simple graphical tool for identifying bad peak fits in XPS, i.e., fit parameter correlation. These plots are widely used in spectroscopic ellipsometry. We illustrate uniqueness plots with two data sets: a C 1s narrow scan from ozone-treated carbon nanotube forests and an Si 2p narrow scan from an air-oxidized silicon wafer. For each fit, we consider different numbers of parameters and constraints on them. As expected, the uniqueness plots are parabolic when fewer fit parameters and/or more constraints are applied. However, they fan out and eventually become horizontal lines as more unconstrained parameters are included in the fits. Uniqueness plots are generated by plotting the chi squared (χ 2 ) value for a fit vs. a systematically varied value of a parameter in the fit. The Abbe criterion is also considered as a figure of merit for uniqueness plots in the Supporting Information. We recommend that uniqueness plots be used by XPS practitioners for identifying inappropriate peak fits.

Uniqueness plots: A simple graphical tool for identifying poor peak fits in X-ray photoelectron spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Singh, Bhupinder; Diwan, Anubhav; Jain, Varun [Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, 84606 (United States); Herrera-Gomez, Alberto [CINVESTAV-Unidad Queretaro, Queretaro, 76230 (Mexico); Terry, Jeff [Department of Physics, Illinois Institute of Technology, Chicago, IL, 60616 (United States); Linford, Matthew R., E-mail: mrlinford@chem.byu.edu [Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, 84606 (United States)

2016-11-30

Highlights: • Uniqueness plots are introduced as a new tool for identifying poor XPS peak fits. • Uniqueness plots are demonstrated on real XPS data sets. • A horizontal line in a uniqueness plot indicates a poor fit, i.e., fit parameter correlation. • A parabolic shape in a uniqueness plot indicates that a fit may be appropriate. - Abstract: Peak fitting is an essential part of X-ray photoelectron spectroscopy (XPS) narrow scan analysis, and the Literature contains both good and bad examples of peak fitting. A common cause of poor peak fitting is the inclusion of too many fit parameters, often without a sound chemical and/or physical basis for them, and/or the failure to reasonably constrain them. Under these conditions, fit parameters are often correlated, and therefore lacking in statistical meaning. Here we introduce the uniqueness plot as a simple graphical tool for identifying bad peak fits in XPS, i.e., fit parameter correlation. These plots are widely used in spectroscopic ellipsometry. We illustrate uniqueness plots with two data sets: a C 1s narrow scan from ozone-treated carbon nanotube forests and an Si 2p narrow scan from an air-oxidized silicon wafer. For each fit, we consider different numbers of parameters and constraints on them. As expected, the uniqueness plots are parabolic when fewer fit parameters and/or more constraints are applied. However, they fan out and eventually become horizontal lines as more unconstrained parameters are included in the fits. Uniqueness plots are generated by plotting the chi squared (χ{sup 2}) value for a fit vs. a systematically varied value of a parameter in the fit. The Abbe criterion is also considered as a figure of merit for uniqueness plots in the Supporting Information. We recommend that uniqueness plots be used by XPS practitioners for identifying inappropriate peak fits.

Twenty years on: Poverty and hardship in urban Fiji

Directory of Open Access Journals (Sweden)

Jenny Bryant-Tokalau

2012-09-01

Full Text Available Through ‘official statistics’, academic and donor interpretations as well as the eyes of Suva residents, this paper presents an overview and case study of twenty years of growing poverty and hardship in the contemporary Pacific. Focusing on the past two decades, the paper notes how much, and yet so little, has changed for those attempting to make a living in the rapidly developing towns and cities. Changing interpretations of poverty and hardship are presented, moving from the ‘no such thing’ view, to simplification, and finally to an understanding that Pacific island countries, especially Fiji, are no longer an ‘extension’ of Australia and New Zealand, but independent nations actively trying to find solutions to their issues of economic, social and political hardship whilst facing challenges to traditional institutions and networks. Fiji is in some respects a very particular case as almost half of the population has limited access to secure land, but the very nature of that vulnerability to hardship and poverty holds useful lessons for wider analysis.

Crystal structure and size-dependent neutralization properties of HK20, a human monoclonal antibody binding to the highly conserved heptad repeat 1 of gp41.

Science.gov (United States)

Sabin, Charles; Corti, Davide; Buzon, Victor; Seaman, Mike S; Lutje Hulsik, David; Hinz, Andreas; Vanzetta, Fabrizia; Agatic, Gloria; Silacci, Chiara; Mainetti, Lara; Scarlatti, Gabriella; Sallusto, Federica; Weiss, Robin; Lanzavecchia, Antonio; Weissenhorn, Winfried

2010-11-18

The human monoclonal antibody (mAb) HK20 neutralizes a broad spectrum of primary HIV-1 isolates by targeting the highly conserved heptad repeat 1 (HR1) of gp41, which is transiently exposed during HIV-1 entry. Here we present the crystal structure of the HK20 Fab in complex with a gp41 mimetic 5-Helix at 2.3 Å resolution. HK20 employs its heavy chain CDR H2 and H3 loops to bind into a conserved hydrophobic HR1 pocket that is occupied by HR2 residues in the gp41 post fusion conformation. Compared to the previously described HR1-specific mAb D5, HK20 approaches its epitope with a different angle which might favor epitope access and thus contribute to its higher neutralization breadth and potency. Comparison of the neutralization activities of HK20 IgG, Fab and scFv employing both single cycle and multiple cycle neutralization assays revealed much higher potencies for the smaller Fab and scFv over IgG, implying that the target site is difficult to access for complete antibodies. Nevertheless, two thirds of sera from HIV-1 infected individuals contain significant titers of HK20-inhibiting antibodies. The breadth of neutralization of primary isolates across all clades, the higher potencies for C-clade viruses and the targeting of a distinct site as compared to the fusion inhibitor T-20 demonstrate the potential of HK20 scFv as a therapeutic tool.

An unusual cysteine VL87 affects the antibody fragment conformations without interfering with the disulfide bond formation.

Science.gov (United States)

Attallah, Carolina; Aguilar, María Fernanda; Garay, A Sergio; Herrera, Fernando E; Etcheverrigaray, Marina; Oggero, Marcos; Rodrigues, Daniel E

2017-10-01

The Cys residues are almost perfectly conserved in all antibodies. They contribute significantly to the antibody fragment stability. The relevance of two natural contiguous Cys residues of an anti-recombinant human-follicle stimulation hormone (rhFSH) in a format of single-chain variable fragment (scFv) was studied. This scFv contains 5 Cys residues: V H 22 and V H 92 in the variable heavy chain (V H ) and V L 23, V L 87 and V L 88 in the variable light chain (V L ). The influence of two unusual contiguous Cys at positions V L 87 and V L 88 was studied by considering the wild type fragment and mutant variants: V L -C88S, V L -C87S, V L -C87Y. The analysis was carried out using antigen-binding ability measurement by indirect specific ELISA and a detailed molecular modeling that comprises homology methods, long molecular dynamics simulations and docking. We found that V L -C87 affected the antibody fragment stability without interfering with the disulfide bond formation. The effect of mutating the V L -C87 by a usual residue at this position like Tyr caused distant structural changes at the V H region that confers a higher mobility to the V H -CDR2 and V H -CDR3 loops improving the scFv binding to the antigen. Copyright © 2017 Elsevier Ltd. All rights reserved.

Public Heath in Colonial and Post-Colonial Ghana: Lesson-Drawing for The Twenty-First Century

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Adu-Gyamfi, Samuel

2017-06-01

Full Text Available Public health in twenty-first century Ghana is mired with several issues ranging from the inadequacy of public health facilities, improper settlement planning, insanitary conditions, and the inadequacy of laws and their implementation. This situation compared to the colonial era is a direct contradiction. Development in the pre-colonial era to the colonial era sought to make the prevention of diseases a priority in the colonial administration. This was begun with the establishment of the health branch in 1909 as a response to the bubonic plague that was fast spreading in the colony. From here public health policies and strategies were enacted to help the diseases prevention cause. Various public health boards, the medical research institute or the laboratory branch, the waste management department, the use of preventive medicine and maintenance of good settlement planning and sanitation were public health measures in the colonial era. This research seeks to analyse the public health system in the colonial era so as to draw basic lessons for twenty-first century Ghana. Archival data and other secondary sources are reviewed and analysed to help draw these lessons. Richard Rose’s lesson-drawing approach was used to draw the lessons.

review article how unique is south african military integration?

African Journals Online (AJOL)

Roy Licklider

Rutgers University. The study of civil war ... South Africa has a strong case to be the poster child of military integration after civil violence.6 In a .... One aspect of the South African response to this problem was unique: a. Defence White Paper ...

La autoidentidad. Problemas metodológicos del Twenty Statements Test

Directory of Open Access Journals (Sweden)

MODESTO ESCOBAR

1983-01-01

Full Text Available Se evalúa críticamente el Twenty Statements Test (TST desarrollado por la Iowa School para el estudio empírico de la autoidentidad, basado en la teoría clásica de George Herbert Mead. Para ello se entregó dicho test a una muestra representativa (372 de estudiantes de la Universidad Complutense durante el curso académico 79/80. Las hipótesis de trabajo eran : la autopercepción varía a lo largo de la dimensión consensualiad ; el componente consensual de las actitudes hacia sí mismo es el más sobresaliente ; los sujetos tienden a contestar en primer lugar las referencias consensuales. Sin embargo, los resultados no corroboraron las hipótesis. Las razones hay que buscarlas la imprecisión teórica de la dimensión de consensualidad.

Harnessing insulin- and leptin-induced oxidation of PTP1B for therapeutic development.

Science.gov (United States)

Krishnan, Navasona; Bonham, Christopher A; Rus, Ioana A; Shrestha, Om Kumar; Gauss, Carla M; Haque, Aftabul; Tocilj, Ante; Joshua-Tor, Leemor; Tonks, Nicholas K

2018-01-18

The protein tyrosine phosphatase PTP1B is a major regulator of glucose homeostasis and energy metabolism, and a validated target for therapeutic intervention in diabetes and obesity. Nevertheless, it is a challenging target for inhibitor development. Previously, we generated a recombinant antibody (scFv45) that recognizes selectively the oxidized, inactive conformation of PTP1B. Here, we provide a molecular basis for its interaction with reversibly oxidized PTP1B. Furthermore, we have identified a small molecule inhibitor that mimics the effects of scFv45. Our data provide proof-of-concept that stabilization of PTP1B in an inactive, oxidized conformation by small molecules can promote insulin and leptin signaling. This work illustrates a novel paradigm for inhibiting the signaling function of PTP1B that may be exploited for therapeutic intervention in diabetes and obesity.

Hepatoblastoma Biology Using Isotope Ratio Mass Spectrometry: Utility of a Unique Technique for the Analysis of Oncological Specimens

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Katarzyna Taran

2016-07-01

Full Text Available Introduction: Hepatoblastoma is the most common primary liver tumor in children. However, it occurs rarely, with an incidence of 0.5-1.5 cases per million children. There is no clear explanation of the relationship between clinicopathologic features, therapy, and outcome in hepatoblastoma cases, so far. One of the most widely accepted prognostic factors in hepatoblastoma is histology of the tumor. The aim of the study was to determine the potential differences in biology of hepatoblastoma histological subtypes at the atomic level using the unique method of isotope ratio mass spectrometry, which is especially valuable in examination of small groups of biological samples.Material/Methods: Twenty-four measurements of nitrogen stable isotope ratio, carbon stable isotope ratio and total carbon to nitrogen mass ratio in fetal and embryonal hepatoblastoma tissue were performed using a Sercon 20-22 Continuous Flow Isotope Ratio Mass Spectrometer (CF-IRMS coupled with a Sercon SL elemental analyzer for simultaneous carbon-nitrogen-sulfur (NCS analysis.Results: A difference of about 1.781‰ in stable nitrogen isotope 15N/14N ratio was found between examined hepatoblastoma histological subtypes.Conclusions: The prognosis in liver tumors cases in children may be challenging particularly because of the lack of versatile methods of its evaluation. Isotope ratio mass spectrometry allows one to determine the difference between hepatoblastoma histological subtypes and clearly indicates the cases with the best outcome.

Unique Approach to Dental Management of Children with Hearing Impairment.

Science.gov (United States)

Renahan, Navanith; Varma, R Balagopal; Kumaran, Parvathy; Xavier, Arun M

2017-01-01

The number of deaf children has dramatically increased in the past few decades. These children present to the pediatric dentist a unique set of challenges mostly pertaining to the establishment of communication with them. There have been very few attempts in the past to break down these challenges and formulate a strategy on how to manage them effectively. This is a case report of a child who was successfully managed using two different modes of communication. Finally, the advantages and disadvantages are mentioned, and a common strategy incorporating the positives of both the methods has been devised. Renahan N, Varma RB, Kumaran P, Xavier AM. Unique Approach to Dental Management of Children with Hearing Impairment. Int J Clin Pediatr Dent 2017;10(1):107-110.

A Unique Climate and Energy Policy - Key Problems and Possible Solutions

International Nuclear Information System (INIS)

Granic, G.

2016-01-01

This paper analyses problems of independent application of climate and energy policy. In order to accomplish the goals from The Paris Climate Agreement, an agreement about the goals and measures for climate preservation from 2015, a unique climate and energy policy is suggested, as well as the measures for the implementation of it. To achieve no CO2 and GHG emissions in the energy sector, to have it be completely market based, energy efficient and technologically approved, a unique climate and energy policy is a necessary option and the only viable option to accomplish previously agreed climate goals.(author).

The generalized Schwinger-DeWitt technique and the unique effective action in quantum gravity

International Nuclear Information System (INIS)

Barvinsky, A.O.; Vilkovisky, G.A.

1983-01-01

We consider the one-loop approximation to the recently proposed unique effective action in gauge theory. The Schwinger-DeWitt technique is generalized and applied to the computation of the unique gravitational counterterms. The issue of asymptotic freedom is reexamined. (orig.)

Why Is Family Firms' Internationalization Unique? : A Meta-Analysis

NARCIS (Netherlands)

Arregle, Jean-Luc; Duran, Patricio; Hitt, Michael A.; van Essen, M.

Despite its importance, there is no clear understanding of the uniqueness of family firms' internationalization. This article sheds new light on this issue with a meta-analysis of 76 studies covering 41 countries. We show that the considerable study and cross-country differences in the relationship

When a Celebrity Endorser is Disgraced: A Twenty Five Year Event Study

NARCIS (Netherlands)

Bratz, S.; Molchanov, A.E.; Stork, P.A.

2013-01-01

This paper investigates how the announcement of negative information about a celebrity endorser impacts firm value, as measured by abnormal stock returns. The unique data sample consists of 93 celebrity disgraces that occurred between 1986 and 2011, affecting firms listed on US stock exchanges. Some

A Commentary on "Updating the Duplex Design for Test-Based Accountability in the Twenty-First Century"

Science.gov (United States)

Brandt, Steffen

2010-01-01

This article presents the author's commentary on "Updating the Duplex Design for Test-Based Accountability in the Twenty-First Century," in which Isaac I. Bejar and E. Aurora Graf propose the application of a test design--the duplex design (which was proposed in 1988 by Bock and Mislevy) for application in current accountability assessments.…

Dissociative absorption: An empirically unique, clinically relevant, dissociative factor.

Science.gov (United States)

Soffer-Dudek, Nirit; Lassri, Dana; Soffer-Dudek, Nir; Shahar, Golan

2015-11-01

Research of dissociative absorption has raised two questions: (a) Is absorption a unique dissociative factor within a three-factor structure, or a part of one general dissociative factor? Even when three factors are found, the specificity of the absorption factor is questionable. (b) Is absorption implicated in psychopathology? Although commonly viewed as "non-clinical" dissociation, absorption was recently hypothesized to be specifically associated with obsessive-compulsive symptoms. To address these questions, we conducted exploratory and confirmatory factor analyses on 679 undergraduates. Analyses supported the three-factor model, and a "purified" absorption scale was extracted from the original inclusive absorption factor. The purified scale predicted several psychopathology scales. As hypothesized, absorption was a stronger predictor of obsessive-compulsive symptoms than of general psychopathology. In addition, absorption was the only dissociative scale that longitudinally predicted obsessive-compulsive symptoms. We conclude that absorption is a unique and clinically relevant dissociative tendency that is particularly meaningful to obsessive-compulsive symptoms. Copyright © 2015 Elsevier Inc. All rights reserved.

Questions of uniqueness and resolution in reconstruction from projections

CERN Document Server

Katz, Myron Bernard

1978-01-01

Reconstruction from projections has revolutionized radiology and as now become one of the most important tools of medical diagnosi- he E. M. I. Scanner is one example. In this text, some fundamental heoretical and practical questions are resolved. Despite recent research activity in the area, the crucial subject ·f the uniqueness of the reconstruction and the effect of noise in the ata posed some unsettled fundamental questions. In particular, Kennan mith proved that if we describe an object by a C~ function, i. e. , nfinitely differentiable with compact support, then there are other bjects with the same shape, i. e. , support, which can differ almost rhitrarily and still have the same projections in finitely many direc­ ions. On the other hand, he proved that objects in finite dimensional unction spaces are uniquely determined by a single projection for almost 11 angles, i. e. , except on a set of measure zero. Along these lines, erman and Rowland in [41) showed that reconstructions obtained from he common...

The Italian National Register of infants with congenital hypothyroidism: twenty years of surveillance and study of congenital hypothyroidism

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Olivieri Antonella

2009-02-01

Full Text Available Abstract All the Italian Centres in charge of screening, diagnosis, and follow-up of infants with congenital hypothyroidism participate in the Italian National Registry of affected infants, which performs the nationwide surveillance of the disease. It was established in 1987 as a program of the Health Ministry and is coordinated by the Istituto Superiore di Sanità. The early diagnosis performed by the nationwide newborn screening programme, the prompt treatment and the appropriate clinical management of the patients carried out by the Follow-up Centres, and the surveillance of the disease performed by the National Register of infants with congenital hypothyroidism are the components of an integrated approach to the disease which has been successfully established in our country. The aim of the Register is to monitor efficiency and effectiveness of neonatal screening, to provide disease surveillance and to allow identification of possible aetiological risk factors for the disease. During the past twenty years the active and continuous collaboration between the Register and the Italian Screening and Follow up Centres for Congenital Hypothyroidism allowed to perform a standardization of screening procedures and considerable improvements in the time at starting treatment and in the dose of therapy. Furthermore, the large amount and the high quality of information collected in the Register provided a unique opportunity for research into the disease. This because data collected in the Register are highly representative as referred to the entire Italian population with congenital hypothyroidism. The results derived from the epidemiological studies performed in these years, by using the Register database, contributed to deepen the knowledge of congenital hypothyroidism, to start identifying the most important risk factors for the disease, and to orient molecular studies aimed at identifying new genes involved in the aetiology of this condition.

Structure determination of human Lck unique and SH3 domains by nuclear magnetic resonance spectroscopy

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Willbold Dieter

2003-05-01

Full Text Available Abstract Background Protein tyrosine kinases are involved in signal transduction pathways that regulate cell growth, differentiation, activation and transformation. Human lymphocyte specific kinase (Lck is a 56 kDa protein involved in T-cell- and IL2-receptor signaling. Three-dimensional structures are known for SH3, SH2 and kinase domains of Lck as well as for other tyrosine kinases. No structure is known for the unique domain of any Src-type tyrosine kinase. Results Lck(1–120 comprising unique and SH3 domains was structurally investigated by nuclear magnetic resonance spectroscopy. We found the unique domain, in contrast to the SH3 part, to have basically no defined structural elements. The solution structure of the SH3 part could be determined with very high precision. It does not show significant differences to Lck SH3 in the absence of the unique domain. Minor differences were observed to the X-ray structure of Lck SH3. Conclusion The unique domain of Lck does not contain any defined structure elements in the absence of ligands and membranes. Presence of the unique domain is not relevant to the three-dimensional structure of the Lck SH3 domain.

Is physical space unique or optional

International Nuclear Information System (INIS)

Ekstein, H.; Centre National de la Recherche Scientifique, 13 - Marseille

1975-02-01

There are two concepts of the physical space-time. One, S(F), is that of a fixed arena in which events take place. The other S(D), is that of a space-time shaped by events. The second depends on the state (initial conditions) or on the external field, the first does not. The main assertions of the present paper are: 1) the fixed space-time S(F) is neither incompatibles with nor made superfluous, by Einstein's theory. S(F) is experimentally explorable, unique, and probably identical with Minkowski space M. 2) The dynamical space S(D) is largely optional. It can be chosen to be M, but the natural choice is Einstein's pseudo-Riemanian manifold [fr

MRI: unique costing and pricing issues.

Science.gov (United States)

Schwartz, H W; Jarl, D F

1985-01-01

Acquisition of magnetic resonance imaging (MRI) involves a plethora of costs not traditionally encountered in radiology procedure cost accounting models. Experiences with MRI gained at the University of Minnesota Hospitals and Clinics during 1984 uncovered a wide variety of unique costing issues which were eventually identified at the time when the MRI hospital charge was being established. Our experience at UMHC can provide those radiology departments now acquiring MRI with an earlier awareness of these special costing issues, hopefully resulting in better and more timely data collection. Current reimbursement and pricing issues are also having a dramatic impact on MRI costs at each institution and must be assessed in terms of third-party payor intentions.

The unique ethics of sports medicine.

Science.gov (United States)

Johnson, Rob

2004-04-01

The ethical code by which physicians traditionally conduct themselves is based on the relationship between the physician and the patient: both work toward the goal of improving or maintaining health. Constraints on this relationship may be behaviors of patient choice (tobacco use, excessive alcohol use, sedentary behavior, and so on). The athlete-physician relationship is ethically different. Influences such as the physician's employer, the athlete's desire to play with pain and injury, and the economic consequences of playing or not complicate medical decisions. This perspective suggests something different and even unique about the ethics of the sports medicine practitioner. This article explores the differences fostering the ethical tight ropes that sports physicians walk in their sports medicine practices.

Relative mRNA expression of prostate-derived E-twenty-six factor and E-twenty-six variant 4 transcription factors, and of uridine phosphorylase-1 and thymidine phosphorylase enzymes, in benign and malignant prostatic tissue

Science.gov (United States)

CAVAZZOLA, LUCIANE ROSTIROLA; CARVALHAL, GUSTAVO FRANCO; DEVES, CANDIDA; RENCK, DAIANA; ALMEIDA, RICARDO; SANTOS, DIóGENES SANTIAGO

2015-01-01

Prostate cancer is the most frequent urological tumor, and the second most common cancer diagnosed in men. Incidence and mortality are variable and appear to depend on behavioral factors and genetic predisposition. The prostate-derived E-twenty-six factor (PDEF) and E-twenty-six variant 4 (ETV4) transcription factors, and the thymidine phosphorylase (TP) and uridine phosphorylase-1 (UP-1) enzymes, are reported to be components of the pathways leading to tumorigenesis and/or metastasis in a number of tumors. The present study aimed to analyze the mRNA expression levels of these proteins in prostatic cancerous and benign tissue, and their association with clinical and pathological variables. Using quantitative reverse transcription polymerase chain reaction, the mRNA expression levels of PDEF, ETV4, TP and UP-1 were studied in 52 tissue samples (31 of benign prostatic hyperplasia and 21 of prostate adenocarcinomas) obtained from patients treated by transurethral resection of the prostate or by radical prostatectomy. Relative expression was assessed using the ∆-CT method. Data was analyzed using Spearman's tests for correlation. Pbenign and malignant prostatic tissues. Further studies are necessary to define the role of these proteins as therapeutic targets in prostate cancer. PMID:26137165

On the Existence of Unique Equilibria in Location Models

NARCIS (Netherlands)

Webers, H.M.

1996-01-01

In this paper, we study a two-stage location-then-price game where consumers are distributed piecewise uniformly, each piece being referred to as an interval.Although the firms face a coordination problem, it is obvious that, for any given locations and prices, there is a unique indifferent

Marketing the Uniqueness of Small Towns. Small Town Strategy.

Science.gov (United States)

Hogg, David H.; Dunn, Douglas

A small town can strengthen its local economy as a result of business people and concerned citizens collectively identifying that community's uniqueness and then capitalizing on it via advertising, personal selling, sales promotion, or publicity. This publication relates the science of marketing to communities. Seven simple techniques are provided…

Meeting Each Student's Unique Potential: One Approach to Education.

Science.gov (United States)

Gauld, Joseph W.

1996-01-01

By championing extrinsic motivation, the achievement-reward system short-circuits individuals' innate inner power. Achievement-oriented adults rely on their knowledge, skills, and abilities, not their deeper potential. Hyde School, in Bath, Maine, solves this problem by committing the entire school community to development of unique potential via…

Determining hydraulic parameters of a karst aquifer using unique ...

African Journals Online (AJOL)

Although karst aquifers constitute some of the most important water resources worldwide, generally accepted methods for reliably characterising their hydraulic properties are still elusive. This paper aims at contributing to the discussion by a first-ever attempt to utilise various sets of unique historical data derived from ...

A Meta-Analysis of Motivational Interviewing: Twenty-Five Years of Empirical Studies

Science.gov (United States)

Lundahl, Brad W.; Kunz, Chelsea; Brownell, Cynthia; Tollefson, Derrik; Burke, Brian L.

2010-01-01

Objective: The authors investigated the unique contribution motivational interviewing (MI) has on counseling outcomes and how MI compares with other interventions. Method: A total of 119 studies were subjected to a meta-analysis. Targeted outcomes included substance use (tobacco, alcohol, drugs, marijuana), health-related behaviors (diet,…

Unique supply function equilibrium with capacity constraints

International Nuclear Information System (INIS)

Holmberg, Paer

2008-01-01

Consider a market where producers submit supply functions to a procurement auction with uncertain demand, e.g. an electricity auction. In the Supply Function Equilibrium (SFE), every firm commits to the supply function that maximises expected profit in the one-shot game given the supply functions of competitors. A basic weakness of the SFE is the presence of multiple equilibria. This paper shows that with (i) symmetric producers, (ii) perfectly inelastic demand, (iii) a price cap, and (iv) capacity constraints that bind with a positive probability, there exists a unique, symmetric SFE. (author)

Problem of uniqueness in the renewal process generated by the uniform distribution

Directory of Open Access Journals (Sweden)

D. Ugrin-Šparac

1992-01-01

Full Text Available The renewal process generated by the uniform distribution, when interpreted as a transformation of the uniform distribution into a discrete distribution, gives rise to the question of uniqueness of the inverse image. The paper deals with a particular problem from the described domain, that arose in the construction of a complex stochastic test intended to evaluate pseudo-random number generators. The connection of the treated problem with the question of a unique integral representation of Gamma-function is also mentioned.

Chromatically unique 6-bridge graph theta(a,a,a,b,b,c

Directory of Open Access Journals (Sweden)

N.S.A. Karim

2016-04-01

Full Text Available For a graph $G$, let $P(G,\\lambda$ denote the chromatic polynomial of $G$. Two graphs $G$ and $H$ are chromatically equivalent if they share the same chromatic polynomial. A graph $G$ is chromatically unique if for any graph chromatically equivalent to $G$ is isomorphic to $G$. In this paper, the chromatically unique of a new family of 6-bridge graph $\\theta(a,a,a,b,b,c$ where $2\\le a\\le b\\le c$ is investigated.

Uniqueness for inverse problems of determining orders of multi-term time-fractional derivatives of diffusion equation

OpenAIRE

Li, Zhiyuan; Yamamoto, Masahiro

2014-01-01

This article proves the uniqueness for two kinds of inverse problems of identifying fractional orders in diffusion equations with multiple time-fractional derivatives by pointwise observation. By means of eigenfunction expansion and Laplace transform, we reduce the uniqueness for our inverse problems to the uniqueness of expansions of some special function and complete the proof.

Black Hats and White Hats: The Effect of Organizational Culture and Institutional Identity on the Twenty-third Air Force

National Research Council Canada - National Science Library

Koskinas, Ioannis

2006-01-01

.... Although brief, the Twenty-third Air Force's experience provides sufficient data for a thorough analysis of the effect of organizational culture and institutional agendas on the evolution of a nascent organization...

Dirac fields in flat FLRW cosmology: Uniqueness of the Fock quantization

Energy Technology Data Exchange (ETDEWEB)

Cortez, Jerónimo, E-mail: jacq@ciencias.unam.mx [Departamento de Física, Facultad de Ciencias, Universidad Nacional Autónoma de México, México D.F. 04510 (Mexico); Elizaga Navascués, Beatriz, E-mail: beatriz.elizaga@iem.cfmac.csic.es [Instituto de Estructura de la Materia, IEM-CSIC, Serrano 121, 28006 Madrid (Spain); Martín-Benito, Mercedes, E-mail: m.martin@hef.ru.nl [Radboud University Nijmegen, Institute for Mathematics, Astrophysics and Particle Physics, Heyendaalseweg 135, NL-6525 AJ Nijmegen (Netherlands); Mena Marugán, Guillermo A., E-mail: mena@iem.cfmac.csic.es [Instituto de Estructura de la Materia, IEM-CSIC, Serrano 121, 28006 Madrid (Spain); Velhinho, José M., E-mail: jvelhi@ubi.pt [Universidade da Beira Interior, Rua Marquês d’Ávila e Bolama, 6201-001, Covilhã (Portugal)

2017-01-15

We address the issue of the infinite ambiguity that affects the construction of a Fock quantization of a Dirac field propagating in a cosmological spacetime with flat compact sections. In particular, we discuss a physical criterion that restricts to a unique possibility (up to unitary equivalence) the infinite set of available vacua. We prove that this desired uniqueness is guaranteed, for any possible choice of spin structure on the spatial sections, if we impose two conditions. The first one is that the symmetries of the classical system must be implemented quantum mechanically, so that the vacuum is invariant under the symmetry transformations. The second and more important condition is that the constructed theory must have a quantum dynamics that is implementable as a (non-trivial) unitary operator in Fock space. Actually, this unitarity of the quantum dynamics leads us to identify as explicitly time dependent some very specific contributions of the Dirac field. In doing that, we essentially characterize the part of the dynamics governed by the Dirac equation that is unitarily implementable. The uniqueness of the Fock vacuum is attained then once a physically motivated convention for the concepts of particles and antiparticles is fixed.

Dirac fields in flat FLRW cosmology: Uniqueness of the Fock quantization

International Nuclear Information System (INIS)

Cortez, Jerónimo; Elizaga Navascués, Beatriz; Martín-Benito, Mercedes; Mena Marugán, Guillermo A.; Velhinho, José M.

2017-01-01

We address the issue of the infinite ambiguity that affects the construction of a Fock quantization of a Dirac field propagating in a cosmological spacetime with flat compact sections. In particular, we discuss a physical criterion that restricts to a unique possibility (up to unitary equivalence) the infinite set of available vacua. We prove that this desired uniqueness is guaranteed, for any possible choice of spin structure on the spatial sections, if we impose two conditions. The first one is that the symmetries of the classical system must be implemented quantum mechanically, so that the vacuum is invariant under the symmetry transformations. The second and more important condition is that the constructed theory must have a quantum dynamics that is implementable as a (non-trivial) unitary operator in Fock space. Actually, this unitarity of the quantum dynamics leads us to identify as explicitly time dependent some very specific contributions of the Dirac field. In doing that, we essentially characterize the part of the dynamics governed by the Dirac equation that is unitarily implementable. The uniqueness of the Fock vacuum is attained then once a physically motivated convention for the concepts of particles and antiparticles is fixed.

Parieto-occipital encephalomalacia in children; clinical and electrophysiological features of twenty-seven cases.

Science.gov (United States)

Karaoğlu, Pakize; Polat, Ayşe İpek; Yiş, Uluç; Hız, Semra

2015-01-01

Brain injuries occurring at a particular time may cause damages in well-defined regions of brain. Perinatal hypoxic ischemic encephalopathy and hypoglycemia are some of the most common types of brain injuries. Neonatal hypoglycemia can cause abnormal myelination in parietal and occipital lobes resulting in parieto-occipital encephalomalacia. There is a small number of studies about clinical and electroencephalographic (EEG) features of children with parieto-occipital encephalomalacia. They might have important neurologic sequelae such as cortical visual loss, seizures, and psychomotor retardation. We aimed to evaluate the causes of parieto-occipital encephalomalacia and evaluate the clinical and electrophysiological features of children with parieto-occipital encephalomalacia. We evaluated clinical features and EEGs of 27 children with parieto-occipital encephalomalacia. Descriptive statistics were used. Hospitalization during the neonatal period was the most common cause (88.9%) of parieto-occipital brain injury. Eleven patients (40.7%) had a history of neonatal hypoglycemia. Twenty-three patients (85.2%) had epilepsy and nine of the epileptic patients (39%) had refractory seizures. Most of the patients had bilateral (50%) epileptic discharges originating from temporal, parietal, and occipital lobes (56.2%). However, some patients had frontal sharp waves and some had continuous spike and wave discharges during sleep. Visual abnormalities were evident in 15 (55.6%) patients. Twenty-two (81.5%) had psychomotor retardation. Fine motor skills, social contact and language development were impaired more than gross motor skills. In our study, most of the patients with parieto-occipital encephalomalacia had an eventful perinatal history. Epilepsy, psychomotor retardation, and visual problems were common neurologic complications.

Unique relations among anxiety sensitivity factors and anxiety, depression, and suicidal ideation.

Science.gov (United States)

Allan, Nicholas P; Capron, Daniel W; Raines, Amanda M; Schmidt, Norman B

2014-03-01

Anxiety sensitivity (AS) is composed of three lower-order dimensions, cognitive concerns, physical concerns, and social concerns. We examined the relations between AS dimensions using a more adequate assessment of subscales (ASI-3) than has previously been used, and measures of anxiety and mood disorders as well as suicidal ideation in a sample of 256 (M age = 37.10 years, SD = 16.40) treatment-seeking individuals using structural equation modeling. AS cognitive concerns was uniquely associated with generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), major depressive disorder (MDD), post-traumatic stress disorder (PTSD), and suicidal ideation. AS physical concerns was uniquely associated with OCD, social anxiety disorder (SAD), panic disorder (PD), and specific phobia. AS social concerns was uniquely associated with SAD, GAD, OCD, and MDD. These results highlight the importance of considering the lower-order AS dimensions when examining the relations between AS and psychopathology. Copyright © 2013 Elsevier Ltd. All rights reserved.

CHID: a unique health information and education database.

OpenAIRE

Lunin, L F; Stein, R S

1987-01-01

The public's growing interest in health information and the health professions' increasing need to locate health education materials can be answered in part by the new Combined Health Information Database (CHID). This unique database focuses on materials and programs in professional and patient education, general health education, and community risk reduction. Accessible through BRS, CHID suggests sources for procuring brochures, pamphlets, articles, and films on community services, programs ...

Nonlinear Pedagogy and Its Role in Encouraging Twenty-First Century Competencies through Physical Education: A Singapore Experience

Science.gov (United States)

Lee, Miriam Chang Yi; Chow, Jia Yi; Button, Chris; Tan, Clara Wee Keat

2017-01-01

Nonlinear Pedagogy is an exploratory approach to teaching and learning Physical Education that can be potentially effective to help children acquire relevant twenty-first century competencies. Underpinned by Ecological Dynamics, the focus of Nonlinear Pedagogy is on the learner and includes the provision of less prescriptive instructions and…

Rethinking Teaching and Learning Pedagogy for Education in the Twenty-First Century: Blended Learning in Music Education

Science.gov (United States)

Crawford, Renée

2017-01-01

In an increasingly technologically driven world, there is proliferate discussion among education and government authorities about the necessity to rethink education in the twenty-first century. The evolution of technology and its pervasive influence on the needs and requirements of society is central to this mindset. Innovations in online…

The method of selecting an integrated development territory for the high-rise unique constructions

Science.gov (United States)

Sheina, Svetlana; Shevtsova, Elina; Sukhinin, Alexander; Priss, Elena

2018-03-01

On the basis of data provided by the Department of architecture and urban planning of the city of Rostov-on-don, the problem of the choice of the territory for complex development that will be in priority for the construction of high-rise and unique buildings is solved. The objective of the study was the development of a methodology for selection of the area and the implementation of the proposed method on the example of evaluation of four-territories complex development. The developed method along with standard indicators of complex evaluation considers additional indicators that assess the territory from the position of high-rise unique building. The final result of the study is the rankings of the functional priority areas that takes into account the construction of both residential and public and business objects of unique high-rise construction. The use of the developed methodology will allow investors and customers to assess the investment attractiveness of the future unique construction project on the proposed site.

Twenty Years of Research on RNS for DSP: Lessons Learned and Future Perspectives

DEFF Research Database (Denmark)

Albicocco, Pietro; Cardarilli, Gian Carlo; Nannarelli, Alberto

2014-01-01

In this paper, we discuss a number of issues emerged from our twenty-year long experience in applying the Residue Number System (RNS) to DSP systems. In early days, RNS was mainly used to reach the maximum performance in speed. Today, RNS is also used to obtain powerefficient (tradeoffs speed......-power) and reliable systems (redundant RNS). Advances in microelectronics and CAD tools play an important role in favoring one technology over another, and a winning choice of the past may become at disadvantage today. In this paper, we address a number of factors influencing the choice of RNS as the winning solution...

Twenty years' application of agricultural countermeasures following the Chernobyl accident: lessons learned

Energy Technology Data Exchange (ETDEWEB)

Fesenko, S V [International Atomic Energy Agency, 1400 Vienna (Austria); Alexakhin, R M [Russian Institute of Agricultural Radiology and Agroecology, 249020 Obninsk (Russian Federation); Balonov, M I [International Atomic Energy Agency, 1400 Vienna (Austria); Bogdevich, I M [Research Institute for Soil Science and Agrochemistry, Minsk (Belarus); Howard, B J [Centre for Ecology and Hydrology, Lancaster Environment Centre, Library Avenue, Bailrigg, Lancaster LAI 4AP (United Kingdom); Kashparov, V A [Ukrainian Institute of Agricultural Radiology (UIAR), Mashinostroiteley Street 7, Chabany, Kiev Region 08162 (Ukraine); Sanzharova, N I [Russian Institute of Agricultural Radiology and Agroecology, 249020 Obninsk (Russian Federation); Panov, A V [Russian Institute of Agricultural Radiology and Agroecology, 249020 Obninsk (Russian Federation); Voigt, G [International Atomic Energy Agency, 1400 Vienna (Austria); Zhuchenka, Yu M [Research Institute of Radiology, 246000 Gomel (Belarus)

2006-12-15

The accident at the Chernobyl NPP (nuclear power plant) was the most serious ever to have occurred in the history of nuclear energy. The consumption of contaminated foodstuffs in affected areas was a significant source of irradiation for the population. A wide range of different countermeasures have been used to reduce exposure of people and to mitigate the consequences of the Chernobyl accident for agriculture in affected regions in Belarus, Russia and Ukraine. This paper for the first time summarises key data on countermeasure application over twenty years for all three countries and describes key lessons learnt from this experience. (review)

Unique morphology of dispersed clay particles in a polymer nanocomposite

CSIR Research Space (South Africa)

Malwela, T

2011-02-01

Full Text Available This communication reports a unique morphology of dispersed clay particles in a polymer nanocomposite. A nanocomposite of poly[butylene succinate)-co-adipate] (PBSA) with 3 wt% of organically modified montmorillonite was prepared by melt...

Twenty years of experience with central softening in The Netherlands : Water quality – Environmental benefits – Costs

NARCIS (Netherlands)

Hofman, J.A.M.H.; Kramer, O.J.I.; van der Hoek, J.P.; Nederlof, M; Groenendijk, M

2006-01-01

Central softening has been utilized by the Dutch water utilities since the late 1970s. It was introduced in the water treatment process as a method to supply water with an optimum water composition to prevent lead and copper release and to prevent excessive scaling. Twenty years of experience show

Retinoblastoma-independent antiproliferative activity of novel intracellular antibodies against the E7 oncoprotein in HPV 16-positive cells

International Nuclear Information System (INIS)

Accardi, Luisa; Tommasino, Massimo; Banks, Lawrence; Chirullo, Barbara; Giorgi, Colomba; Donà, Maria Gabriella; Mileo, Anna M; Paggi, Marco G; Federico, Antonio; Torreri, Paola; Petrucci, Tamara C; Accardi, Rosita; Pim, David

2011-01-01

'High risk' Human Papillomavirus strains are the causative agents of the vast majority of carcinomas of the uterine cervix. In these tumors, the physical integration of the HPV genome is a frequent, though not invariable occurrence, but the constitutive expression of the E6 and E7 viral genes is always observed, suggesting key roles for the E6 and E7 oncoproteins in the process of malignant transformation. The 'intracellular antibody' technology using recombinant antibodies in single-chain format offers the possibility of targeting a protein in its intracellular environment even at the level of definite domains thus representing a valuable strategy to 'knock out' the function of specific proteins. In this study, we investigate the in vitro activity of two single-chain antibody fragments directed against the 'high-risk' HPV 16 E7 oncoprotein, scFv 43M2 and scFv 51. These scFvs were expressed by retroviral system in different cell compartments of the HPV16-positive SiHa cells, and cell proliferation was analyzed by Colony Formation Assay and EZ4U assay. The binding of these scFvs to E7, and their possible interference with the interaction between E7 and its main target, the tumor suppressor pRb protein, were then investigated by immunoassays, PepSet™technology and Surface Plasmon Resonance. The expression of the two scFvs in the nucleus and the endoplasmic reticulum of SiHa cells resulted in the selective growth inhibition of these cells. Analysis of binding showed that both scFvs bind E7 via distinct but overlapping epitopes not corresponding to the pRb binding site. Nevertheless, the binding of scFv 43M2 to E7 was inhibited by pRb in a non-competitive manner. Based on the overall results, the observed inhibition of HPV-positive SiHa cells proliferation could be ascribed to an interaction between scFv and E7, involving non-pRb targets. The study paves the way for the employment of specific scFvs in immunotherapeutic

The twenty-five maiden ladies' tomb and predicaments of the feminist movement in Taiwan

OpenAIRE

Lee, Anru; Tang, Wen-hui Anna

2010-01-01

“The Twenty-five Maiden Ladies’ Tomb” is the collective burial site of the female workers who died in a ferry accident on their way to work in 1973. The fact that of the more than 70 passengers on board all 25 who died were unmarried young women, and the taboo in Taiwanese culture that shuns unmarried female ghosts, made the Tomb a fearsome place. Feminists in Gaoxiong (高雄) had for some years wanted the city government to change the tomb’s public image....

Methanophosphagen: Unique cyclic pyrophosphate isolated from Methanobacterium thermoautotrophicum

OpenAIRE

Kanodia, Sushila; Roberts, Mary Fedarko

1983-01-01

A unique cyclic pyrophosphate compound has been detected at 10-12 mM intracellular concentration in Methanobacterium thermoautotrophicum by in vivo31P NMR. This compound has been extracted from cells and purified by anion-exchange chromatography. Studies with 1H, 13C, and 31P NMR and fast-atom-bombardment mass spectrometry have identified it as 2,3-cyclopyrophosphoglycerate, an intramolecularly cyclized pyrophosphate of 2,3-diphosphoglycerate. Chemical degradation to 2,3-diphosphoglycerate an...

ROMANIA'S MACROECONOMIC ACHIEVEMENTS FOR JOINING THE UNIQUE EUROPEAN CURENCY

Directory of Open Access Journals (Sweden)

SILVIA POPESCU

2011-04-01

Full Text Available The Romanian government has announced plans to join the eurozone by 2015. Currently, the leu is not yet part of ERM II but plans to join in 2010-2012. The economic advantages of the monetary union grow with expansion of the Euro zone. There is also a high level of skepticism; the main fear about the Euro is the inflation –that is considerable promoted by the Euro currency’s exchange rate in comparison with 2002; another restraint is due to member states inability to establish their own interest rates. The IMF arose the option of joining the Euro zone criteria relaxing. A one-sided Euro’s joining was suggested by International Monetary Fund on March-April 2009, in a confidential report mentioned by The Financial Times as the emergent states in Central and Eastern Europe to be able to pass to the unique currency, but not being represented in the Central European Bank Board. By its side, CEB considers that emergent states of the European Union must not pass to the unique currency unilaterally, because such a fact could under-mine the trust in Euro currency worldwide. This option would hardly deepen the macroeconomic controversies inside the Euro zone and would contradict the previous conditions already imposed. An acceptable solution could be the fastening of emergent countries joining the Exchange Rate Mechanism 2, after they are aware of risks arisen by such a step. The European Commission endorses in the Convergence Report on 2010 that Romania doesn’t meet any criteria needed by passing to the unique European currency, respectively: prices stability; budget position of the government; stability of exchange rate; interest convergence on long run and there are also law impediments. Our paper discusses arguments for a faster passing to the Euro currency versus arguments for a late joining the Euro currency in Romania.

Uniqueness of inverse scattering problem in local quantum physics

Energy Technology Data Exchange (ETDEWEB)

Schroer, Bert [Centro Brasileiro de Pesquisas Fisicas (CBPF), Rio de Janeiro, RJ (Brazil)]. E-mail: schroer@cbpf.br

2001-06-01

It is shown that the a Bisognano-Wichmann-Unruh inspired formulation of local quantum physics which starts from wedge-localized algebras, leads to a uniqueness proof for the scattering problem. The important mathematical tool is the thermal KMS aspect of localization and its strengthening by the requirement of crossing symmetry for generalized formfactors. (author)

TIME SERIES ANALYSIS USING A UNIQUE MODEL OF TRANSFORMATION

Directory of Open Access Journals (Sweden)

Goran Klepac

2007-12-01

Full Text Available REFII1 model is an authorial mathematical model for time series data mining. The main purpose of that model is to automate time series analysis, through a unique transformation model of time series. An advantage of this approach of time series analysis is the linkage of different methods for time series analysis, linking traditional data mining tools in time series, and constructing new algorithms for analyzing time series. It is worth mentioning that REFII model is not a closed system, which means that we have a finite set of methods. At first, this is a model for transformation of values of time series, which prepares data used by different sets of methods based on the same model of transformation in a domain of problem space. REFII model gives a new approach in time series analysis based on a unique model of transformation, which is a base for all kind of time series analysis. The advantage of REFII model is its possible application in many different areas such as finance, medicine, voice recognition, face recognition and text mining.

Common processes at unique volcanoes – a volcanological conundrum

Directory of Open Access Journals (Sweden)

Katharine eCashman

2014-11-01

Full Text Available An emerging challenge in modern volcanology is the apparent contradiction between the perception that every volcano is unique, and classification systems based on commonalities among volcano morphology and eruptive style. On the one hand, detailed studies of individual volcanoes show that a single volcano often exhibits similar patterns of behaviour over multiple eruptive episodes; this observation has led to the idea that each volcano has its own distinctive pattern of behaviour (or personality. In contrast, volcano classification schemes define eruption styles referenced to type volcanoes (e.g. Plinian, Strombolian, Vulcanian; this approach implicitly assumes that common processes underpin volcanic activity and can be used to predict the nature, extent and ensuing hazards of individual volcanoes. Actual volcanic eruptions, however, often include multiple styles, and type volcanoes may experience atypical eruptions (e.g., violent explosive eruptions of Kilauea, Hawaii1. The volcanological community is thus left with a fundamental conundrum that pits the uniqueness of individual volcanic systems against generalization of common processes. Addressing this challenge represents a major challenge to volcano research.

The Tankwa Karoo National Park feral goat population: A unique ...

African Journals Online (AJOL)

The Tankwa Karoo National Park feral goat population: A unique genetic ... The feral goats from Tankwa Karoo National Park in the Northern Cape, South Africa, ... Park and former Tankwa goats, now kept on a private farm were genotyped, ...

Crossover Can Be Constructive When Computing Unique Input Output Sequences

DEFF Research Database (Denmark)

Lehre, Per Kristian; Yao, Xin

2010-01-01

Unique input output (UIO) sequences have important applications in conformance testing of finite state machines (FSMs). Previous experimental and theoretical research has shown that evolutionary algorithms (EAs) can compute UIOs efficiently on many FSM instance classes, but fail on others. However...

The UNIQUe Label: Supporting a Culture of Innovation and Quality in Higher Education

Science.gov (United States)

Boonen, Annemie; Bijnens, Helena

European higher education institutions will need significant reforms, in order to guarantee their leading role in a globalized knowledge economy. These reforms can be enhanced by improving the way in which traditional universities integrate new technologies both in their educational activities and throughout their strategic and operational processes. The UNIQUe institutional accreditation scheme, analyzed and described in this chapter, intends to support this process of integrating the use of new technologies in higher education. With its specific open approach to quality in e-Learning, UNIQUe emphasizes innovation and creativity in a process that includes self-assessment and constructive dialog with peers and stakeholders involved. UNIQUe intends to use the institutional quality label as a catalyst for continuous improvement and change while setting up collaborative bench learning processes among universities for the adoption and integration of e-Learning.

Unique associations between young adult men's emotional functioning and their body dissatisfaction and disordered eating.

Science.gov (United States)

Griffiths, Scott; Angus, Douglas; Murray, Stuart B; Touyz, Stephen

2014-03-01

Research on emotional functioning, body dissatisfaction, and disordered eating in males is predominated by studies of negative affect and emotion regulation. Other aspects of emotional functioning, namely emotion recognition and attentional biases toward emotional stimuli, have received little empirical attention. The present study investigated the unique associations between different aspects of men's emotional functioning and their disordered eating attitudes, muscularity dissatisfaction, and body fat dissatisfaction. Results from 132 male undergraduates showed that muscularity dissatisfaction was uniquely associated with both emotion regulation difficulties and an attentional bias toward rejecting faces. Body fat dissatisfaction was not uniquely associated with any aspect of emotional functioning. Disordered eating was uniquely associated with emotion regulation difficulties. Collectively, the results indicate differences in the patterns of associations between men's emotional functioning and their body dissatisfaction and disordered eating. Copyright © 2013 Elsevier Ltd. All rights reserved.

Greenland Surface Mass Balance as Simulated by the Community Earth System Model. Part II: Twenty-First-Century Changes

NARCIS (Netherlands)

Vizcaino, M.; Lipscomb, W.H.; Sacks, W.J.; van den Broeke, M.R.

2014-01-01

This study presents the first twenty-first-century projections of surface mass balance (SMB) changes for the Greenland Ice Sheet (GIS) with the Community Earth System Model (CESM), which includes a new ice sheet component. For glaciated surfaces, CESM includes a sophisticated calculation of energy

Multilingual domain modeling in Twenty-One: automatic creation of a bi-directional translation lexicon from a parallel corpus

NARCIS (Netherlands)

Hiemstra, Djoerd

1998-01-01

Within the project Twenty-One, which aims at the effective dissemination of information on ecology and sustainable development, a sytem is developed that supports cross-language information retrieval in any of the four languages Dutch, English, French and German. Knowledge of this application domain

The method of selecting an integrated development territory for the high-rise unique constructions

Directory of Open Access Journals (Sweden)

Sheina Svetlana

2018-01-01

Full Text Available On the basis of data provided by the Department of architecture and urban planning of the city of Rostov-on-don, the problem of the choice of the territory for complex development that will be in priority for the construction of high-rise and unique buildings is solved. The objective of the study was the development of a methodology for selection of the area and the implementation of the proposed method on the example of evaluation of four-territories complex development. The developed method along with standard indicators of complex evaluation considers additional indicators that assess the territory from the position of high-rise unique building. The final result of the study is the rankings of the functional priority areas that takes into account the construction of both residential and public and business objects of unique high-rise construction. The use of the developed methodology will allow investors and customers to assess the investment attractiveness of the future unique construction project on the proposed site.

EXISTENCE AND UNIQUENESS OF THE ENTROPY SOLUTION TO A NONLINEAR HYPERBOLIC EQUATION

Institute of Scientific and Technical Information of China (English)

R.EYMARD; T.Gallouёt; R.Herbin

1995-01-01

This work is concerned with the proof of the existence and uniqueness of the entropy weak solution to the following nonlinear hyperbolic equation: ut+div(vf(u)） = 0 in IRN×（0, T）, with initial data u(-, 0) = u0(-) in IRN, where u0 ∈ L∞（IRN) is a given function, v is a divergence-free bounded fnnction of class C1 from IRN × [0, T] to IRN, and f is a 5motion of class C1 from IR to IR. It also gives a result of convergence of a numerical scheme for the discretization of this equation. The authors first show the existence of a “process” solution (which generalizes the concept of entropy weak solutions, and can be obtained by passing to the limit of solutions ofthe numerical scheme). The uniqueness of this entropy process solution is then proven; it isalso proven that the entropy process solution is in fact an entropy weak solution. Hence the existence and uniqueness of the entropy weak solution are proven.

Diophantine and minimal but not uniquely ergodic (almost)

International Nuclear Information System (INIS)

Kwapisz, Jaroslaw; Mathison, Mark

2012-01-01

We demonstrate that minimal non-uniquely ergodic behaviour can be generated by slowing down a simple harmonic oscillator with diophantine frequency, in contrast with the known examples where the frequency is well approximable by the rationals. The slowing is effected by a singular time change that brings one phase point to rest. The time one-map of the flow has uncountably many invariant measures yet every orbit is dense, with the minor exception of the rest point

Crystal structure and size-dependent neutralization properties of HK20, a human monoclonal antibody binding to the highly conserved heptad repeat 1 of gp41.

Directory of Open Access Journals (Sweden)

Charles Sabin

Full Text Available The human monoclonal antibody (mAb HK20 neutralizes a broad spectrum of primary HIV-1 isolates by targeting the highly conserved heptad repeat 1 (HR1 of gp41, which is transiently exposed during HIV-1 entry. Here we present the crystal structure of the HK20 Fab in complex with a gp41 mimetic 5-Helix at 2.3 Å resolution. HK20 employs its heavy chain CDR H2 and H3 loops to bind into a conserved hydrophobic HR1 pocket that is occupied by HR2 residues in the gp41 post fusion conformation. Compared to the previously described HR1-specific mAb D5, HK20 approaches its epitope with a different angle which might favor epitope access and thus contribute to its higher neutralization breadth and potency. Comparison of the neutralization activities of HK20 IgG, Fab and scFv employing both single cycle and multiple cycle neutralization assays revealed much higher potencies for the smaller Fab and scFv over IgG, implying that the target site is difficult to access for complete antibodies. Nevertheless, two thirds of sera from HIV-1 infected individuals contain significant titers of HK20-inhibiting antibodies. The breadth of neutralization of primary isolates across all clades, the higher potencies for C-clade viruses and the targeting of a distinct site as compared to the fusion inhibitor T-20 demonstrate the potential of HK20 scFv as a therapeutic tool.

Hydrogel Tethering Enhances Interdomain Stabilization of Single-Chain Antibodies

Energy Technology Data Exchange (ETDEWEB)

Xiong, Yijia [Department; Ford, Nicole R. [Marine; Hecht, Karen A. [Marine; Roesijadi, Guritno [Marine; Department; Squier, Thomas C. [Department

2017-10-12

Self-assembly of recombinant proteins within the biosilica of living diatoms represents a means to construct functional materials in a reproducible and scalable manner that enable applications that harness the inherent specificities of proteins to sense and respond to environmental cues. Here we describe the use of a silaffin-derived lysine-rich 39 amino-acid targeting sequence (Sil3T8) to direct a single chain fragment variable (scFv) antibody or an enhanced green fluorescent protein (EGFP) to assemble within the biosilica frustule, resulting in abundances in excess of 200,000 proteins per frustule. The fluorescence of either a derivative of trinitrotoluene (TNT) bound to the scFv or the endogenous fluorescence of EGFP was used to monitor pro-tein conformational dynamics, accessibility to external quenchers, binding affinity, and conformational stability. We find that proteins within isolated frustules undergo isotropic rotational motions with two-fold increases in rotational correlation times, which are indicative of weak macromolecular associations within the biosilica. Solvent accessibilities and high-affinity (pM) binding are comparable to those in solution. In contrast to solution conditions, scFv antibod-ies within the biosilica matrix retain their binding affinity in the presence of chaotropic agents (i.e., 8 M urea). These results argue that dramatic increases in protein conforma-tional stability within the biosilica frustule matrices arise through molecular crowding, acting to retain native protein folds and associated functionality to allow the utility of engineered proteins under a range of harsh environmental conditions associated with environmental sensing and industrial catalytic transformations.