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Sample records for display human scfv

  1. A novel lentiviral scFv display library for rapid optimization and selection of high affinity antibodies.

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    Qudsia, Sehar; Merugu, Siva B; Mangukiya, Hitesh B; Hema, Negi; Wu, Zhenghua; Li, Dawei

    2018-04-30

    Antibody display libraries have become a popular technique to screen monoclonal antibodies for therapeutic purposes. An important aspect of display technology is to generate an optimization library by changing antibody affinity to antigen through mutagenesis and screening the high affinity antibody. In this study, we report a novel lentivirus display based optimization library antibody in which Agtuzumab scFv is displayed on cell membrane of HEK-293T cells. To generate an optimization library, hotspot mutagenesis was performed to achieve diverse antibody library. Based on sequence analysis of randomly selected clones, library size was estimated approximately to be 1.6 × 10 6 . Lentivirus display vector was used to display scFv antibody on cell surface and flow cytometery was performed to check the antibody affinity to antigen. Membrane bound scFv antibodies were then converted to secreted antibody through cre/loxP recombination. One of the mutant clones, M8 showed higher affinity to antigen in flow cytometery analysis. Further characterization of cellular and secreted scFv through western blot showed that antibody affinity was increased by three fold after mutagenesis. This study shows successful construction of a novel antibody library and suggests that hotspot mutagenesis could prove a useful and rapid optimization tool to generate similar libraries with various degree of antigen affinity. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Baculovirus display of single chain antibody (scFv using a novel signal peptide

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    Gonzalez Gaëlle

    2010-11-01

    Full Text Available Abstract Background Cells permissive to virus can become refractory to viral replication upon intracellular expression of single chain fragment variable (scFv antibodies directed towards viral structural or regulatory proteins, or virus-coded enzymes. For example, an intrabody derived from MH-SVM33, a monoclonal antibody against a conserved C-terminal epitope of the HIV-1 matrix protein (MAp17, was found to exert an inhibitory effect on HIV-1 replication. Results Two versions of MH-SVM33-derived scFv were constructed in recombinant baculoviruses (BVs and expressed in BV-infected Sf9 cells, N-myristoylation-competent scFvG2/p17 and N-myristoylation-incompetent scFvE2/p17 protein, both carrying a C-terminal HA tag. ScFvG2/p17 expression resulted in an insoluble, membrane-associated protein, whereas scFvE2/p17 was recovered in both soluble and membrane-incorporated forms. When coexpressed with the HIV-1 Pr55Gag precursor, scFvG2/p17 and scFvE2/p17 did not show any detectable negative effect on virus-like particle (VLP assembly and egress, and both failed to be encapsidated in VLP. However, soluble scFvE2/p17 isolated from Sf9 cell lysates was capable of binding to its specific antigen, in the form of a synthetic p17 peptide or as Gag polyprotein-embedded epitope. Significant amounts of scFvE2/p17 were released in the extracellular medium of BV-infected cells in high-molecular weight, pelletable form. This particulate form corresponded to BV particles displaying scFvE2/p17 molecules, inserted into the BV envelope via the scFv N-terminal region. The BV-displayed scFvE2/p17 molecules were found to be immunologically functional, as they reacted with the C-terminal epitope of MAp17. Fusion of the N-terminal 18 amino acid residues from the scFvE2/p17 sequence (N18E2 to another scFv recognizing CD147 (scFv-M6-1B9 conferred the property of BV-display to the resulting chimeric scFv-N18E2/M6. Conclusion Expression of scFvE2/p17 in insect cells using a BV

  3. Improved Soluble ScFv ELISA Screening Approach for Antibody Discovery Using Phage Display Technology.

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    Tohidkia, Mohammad R; Sepehri, Maryam; Khajeh, Shirin; Barar, Jaleh; Omidi, Yadollah

    2017-09-01

    Phage display technology (PDT) is a powerful tool for the isolation of recombinant antibody (Ab) fragments. Using PDT, target molecule-specific phage-Ab clones are enriched through the "biopanning" process. The individual specific binders are screened by the monoclonal scFv enzyme-linked immunosorbent assay (ELISA) that may associate with inevitable false-negative results. Thus, in this study, three strategies were investigated for optimization of the scFvs screening using Tomlinson I and J libraries, including (1) optimizing the expression of functional scFvs, (2) improving the sensitivity of ELISA, and (3) preparing different samples containing scFvs. The expression of all scFv Abs was significantly enhanced when scFv clones were cultivated in the terrific broth (TB) medium at the optimum temperature of 30 °C. The protein A-conjugated with horseradish peroxidase (HRP) was found to be a well-suited reagent for the detection of Ag-bound scFvs in comparison with either anti-c-myc Ab or the mixing procedure. Based on our findings, it seems there is no universal media supplement for an improved expression of all scFvs derived from both Tomlinson I and J libraries. We thus propose that expression of scFv fragments in a microplate scale is largely dependent on a variety of parameters, in particular the scFv clones and relevant sequences.

  4. 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.

  5. Radiosensitization and growth inhibition of cancer cells mediated by an scFv antibody gene against DNA-PKcs in vitro and in vivo

    International Nuclear Information System (INIS)

    Du, Li; Zhou, Ping-Kun; Zhou, Li-Jun; Pan, Xiu-Jie; Wang, Yu-Xiao; Xu, Qin-Zhi; Yang, Zhi-Hua; Wang, Yu; Liu, Xiao-Dan; Zhu, Mao-Xiang

    2010-01-01

    Overexpression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is commonly occurred in cancers and causes radioresistance and poor prognosis. In present study, the single-chain variable antibody fragments (scFv) targeting DNA-PKcs was developed for the application of radiosensitization in vitro and in vivo. A humanized semisynthetic scFv library and the phage-display antibodies technology were employed to screen DNA-PKcs scFv antibody. DNA-PKcs epitopes were predicted and cloned. A humanized semisynthetic scFv library and the phage-display antibodies technology were employed to screen DNA-PKcs scFv antibody. DNA damage repair was analyzed by comet assay and immunofluorescence detection of γH2AX foci. The radiosensitization in vivo was determined on Balb/c athymic mice transplanted tumours of HeLa cells. Four epitopes of DNA-PKcs have been predicted and expressed as the antigens, and a specific human anti-DNA-PKcs scFv antibody gene, anti-DPK3-scFv, was obtained by screening the phage antibody library using the DNA-PKcs peptide DPK3. The specificity of anti-DPK3-scFv was verified, in vitro. Transfection of HeLa cells with the anti-DPK3-scFv gene resulted in an increased sensitivity to IR, decreased repair capability of DNA double-strand breaks (DSB) detected by comet assay and immunofluorescence detection of γH2AX foci. Moreover, the kinase activity of DNA-PKcs was inhibited by anti-DPK3-scFv, which was displayed by the decreased phosphorylation levels of its target Akt/S473 and the autophosphorylation of DNA-PKcs on S2056 induced by radiation. Measurement of the growth and apoptosis rates showed that anti-DPK3-scFv enhanced the sensitivity of tumours transplanted in Balb/c athymic mice to radiation therapy. The antiproliferation and radiosensitizing effects of anti-DPK3-scFv via targeting DNA-PKcs make it very appealing for the development as a novel biological radiosensitizer for cancer therapeutic potential

  6. 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.

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

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    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.

  8. Development of single chain variable fragment (scFv) antibodies against Xylella fastidiosa subsp. pauca by phage display.

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    Yuan, Qing; Jordan, Ramon; Brlansky, Ronald H; Istomina, Olga; Hartung, John

    2015-10-01

    Xylella fastidiosa is a member of the gamma proteobacteria. It is fastidious, insect-vectored and xylem-limited and causes a variety of diseases, some severe, on a wide range of economically important perennial crops, including grape and citrus. Antibody based detection assays are commercially available for X. fastidiosa, and are effective at the species, but not at the subspecies level. We have made a library of scFv antibody fragments directed against X. fastidiosa subsp. pauca strain 9a5c (citrus) by using phage display technology. Antibody gene repertoires were PCR-amplified using 23 primers for the heavy chain variable region (V(H)) and 21 primers for the light chain variable region (V(L)). The V(H) and V(L) were joined by overlap extension PCR, and then the genes of the scFv library were ligated into the phage vector pKM19. The library contained 1.2×10(7) independent clones with full-length scFv inserts. In each of 3cycles of affinity-selection with 9a5c, about 1.0×10(12) phage were used for panning with 4.1×10(6), 7.1×10(6), 2.1×10(7) phage recovered after the first, second and third cycles, respectively. Sixty-six percent of clones from the final library bound X. fastidiosa 9a5c in an ELISA. Some of these scFv antibodies recognized strain 9a5c and did not recognize X. fastidiosa strains that cause Pierce's disease of grapevine. Published by Elsevier B.V.

  9. Production of a germline-humanized cetuximab scFv and evaluation of its activity in recognizing EGFR- overexpressing cancer cells.

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    Banisadr, Arsham; Safdari, Yaghoub; Kianmehr, Anvarsadat; Pourafshar, Mahdieh

    2018-04-03

    The aim of this study was to produce a humanized single chain antibody (scFv) as a potential improved product design to target EGFR (Epidermal Growth Factor Receptor) overexpressing cancer cells. To this end, CDR loops of cetuximab (an FDA-approved anti-EGFR antibody) were grafted on framework regions derived from type 3 (VH3 and VL3 kappa) human germline sequences to obtain recombinant VH and VL domainslinked together with a flexible linker [(Gly 4 Ser) 3 ] to form a scFv. Codon optimized synthetic gene encoding the scFv (with NH2-VH-linker-VL-COOH orientation) was expressed in E. coli Origami™ 2(DE3) cells and the resultant scFv purified by using Ni-NTA affinity chromatography. The scFv, called cet.Hum scFv, was evaluated in ELISA and immunoblot to determine whether it can recognize EGFR. The scFv was able to recognize EGFR over-expressing cancer cells (A-431) but failed to detect cancer cells with low levels of EGFR (MCF-7 cells). Although the affinity of the scFv forA-431 cells was 9 fold lower than that of cetuximab, it was strong enough to recognize these cells. Considering its ability to bind EGFR molecules, the scFv may exhibit a potential application for the detection of EGFR-overexpressing cancer cells.

  10. Isolation and characterization of anti c-met single chain fragment variable (scFv) antibodies.

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    Qamsari, Elmira Safaie; Sharifzadeh, Zahra; Bagheri, Salman; Riazi-Rad, Farhad; Younesi, Vahid; Abolhassani, Mohsen; Ghaderi, Sepideh Safaei; Baradaran, Behzad; Somi, Mohammad Hossein; Yousefi, Mehdi

    2017-12-01

    The receptor tyrosine kinase (RTK) Met is the cell surface receptor for hepatocyte growth factor (HGF) involved in invasive growth programs during embryogenesis and tumorgenesis. There is compelling evidence suggesting important roles for c-Met in colorectal cancer proliferation, migration, invasion, angiogenesis, and survival. Hence, a molecular inhibitor of an extracellular domain of c-Met receptor that blocks c-Met-cell surface interactions could be of great thera-peutic importance. In an attempt to develop molecular inhibitors of c-Met, single chain variable fragment (scFv) phage display libraries Tomlinson I + J against a specific synthetic oligopeptide from the extracellular domain of c-Met receptor were screened; selected scFv were then characterized using various immune techniques. Three c-Met specific scFv (ES1, ES2, and ES3) were selected following five rounds of panning procedures. The scFv showed specific binding to c-Met receptor, and significantly inhibited proliferation responses of a human colorectal carcinoma cell line (HCT-116). Moreover, anti- apoptotic effects of selected scFv antibodies on the HCT-116 cell line were also evaluated using Annexin V/PI assays. The results demonstrated rates of apoptotic cell death of 46.0, 25.5, and 37.8% among these cells were induced by use of ES1, ES2, and ES3, respectively. The results demonstrated ability to successfully isolate/char-acterize specific c-Met scFv that could ultimately have a great therapeutic potential in immuno-therapies against (colorectal) cancers.

  11. Construction of human antibody gene libraries and selection of antibodies by phage display.

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    Frenzel, André; Kügler, Jonas; Wilke, Sonja; Schirrmann, Thomas; Hust, Michael

    2014-01-01

    Antibody phage display is the most commonly used in vitro selection technology and has yielded thousands of useful antibodies for research, diagnostics, and therapy.The prerequisite for successful generation and development of human recombinant antibodies using phage display is the construction of a high-quality antibody gene library. Here, we describe the methods for the construction of human immune and naive scFv gene libraries.The success also depends on the panning strategy for the selection of binders from these libraries. In this article, we describe a panning strategy that is high-throughput compatible and allows parallel selection in microtiter plates.

  12. 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 ...

  13. 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

  14. 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.

  15. Lentivirus display: stable expression of human antibodies on the surface of human cells and virus particles.

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    Ran Taube

    Full Text Available BACKGROUND: Isolation of human antibodies using current display technologies can be limited by constraints on protein expression, folding and post-translational modifications. Here we describe a discovery platform that utilizes self-inactivating (SIN lentiviral vectors for the surface display of high-affinity single-chain variable region (scFv antibody fragments on human cells and lentivirus particles. METHODOLOGY/PRINCIPAL FINDINGS: Bivalent scFvFc human antibodies were fused in frame with different transmembrane (TM anchoring moieties to allow efficient high-level expression on human cells and the optimal TM was identified. The addition of an eight amino acid HIV-1 gp41 envelope incorporation motif further increased scFvFc expression on human cells and incorporation into lentiviral particles. Both antibody-displaying human cells and virus particles bound antigen specifically. Sulfation of CDR tyrosine residues, a property recently shown to broaden antibody binding affinity and antigen recognition was also demonstrated. High level scFvFc expression and stable integration was achieved in human cells following transduction with IRES containing bicistronic SIN lentivectors encoding ZsGreen when scFvFc fusion proteins were expressed from the first cassette. Up to 10(6-fold enrichment of antibody expressing cells was achieved with one round of antigen coupled magnetic bead pre-selection followed by FACS sorting. Finally, the scFvFc displaying human cells could be used directly in functional biological screens with remarkable sensitivity. CONCLUSIONS/SIGNIFICANCE: This antibody display platform will complement existing technologies by virtue of providing properties unique to lentiviruses and antibody expression in human cells, which, in turn, may aid the discovery of novel therapeutic human mAbs.

  16. Surface expression of anti-CD3scfv stimulates locoregional immunotherapy against hepatocellular carcinoma depending on the E1A-engineered human umbilical cord mesenchymal stem cells.

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    Zhang, Qing; Yuan, Xiang-Fei; Lu, Yang; Li, Zhen-Zhen; Bao, Shi-Qi; Zhang, Xiao-Long; Yang, Yuan-Yuan; Fan, Dong-Mei; Zhang, Yi-Zhi; Wu, Chen-Xuan; Guo, Hong-Xing; Zhang, Yan-Jun; Ye, Zhou; Xiong, Dong-Sheng

    2017-10-01

    Tumor antigens is at the core of cancer immunotherapy, however, the ideal antigen selection is difficult especially in poorly immunogenic tumors. In this study, we designed a strategy to modify hepatocellular carcinoma (HCC) cells by surface expressing anti-CD3scfv within the tumor site strictly, which depended on the E1A-engineered human umbilical cord mesenchymal stem cells (HUMSC.E1A) delivery system. Subsequently, membrane-bound anti-CD3scfv actived the lymphocytes which lysed HCC cells bypassing the expression of antigens or MHC restriction. First, we constructed the anti-CD3scfv gene driven by human α-fetoprotein (AFP) promoter into an adenoviral vector and the E1A gene into the lentiviral vector. Our results showed that anti-CD3scfv could specifically express on the surface of HCC cells and activate the lymphocytes to kill target cells effectively in vitro. HUMSC infected by AdCD3scfv followed by LentiR.E1A could support the adenoviral replication and packaging in vitro 36 h after LentiR.E1A infection. Using a subcutaneous HepG2 xenograft model, we confirmed that AdCD3scfv and LentiR.E1A co-transfected HUMSC could migrate selectively to the tumor site and produce considerable adenoviruses. The new generated AdCD3scfv infected and modified tumor cells successfully. Mice injected with the MSC.E1A.AdCD3scfv and lymphocytes significantly inhibited the tumor growth compared with control groups. Furthermore, 5-fluorouracil (5-FU) could sensitize adenovirus infection at low MOI resulting in improved lymphocytes cytotoxicity in vitro and in vivo. In summary, this study provides a promising strategy for solid tumor immunotherapy. © 2017 UICC.

  17. 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.

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    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.

  18. A novel fusion protein of IP10-scFv retains antibody specificity and chemokine function

    International Nuclear Information System (INIS)

    Guo Junqing; Chen Liu; Ai Hongwu; Jing Jiannian; Zhou Jiyong; Zhang Chuyu; You Shangyou

    2004-01-01

    We combined the specificity of tumor-specific antibody with the chemokine function of interferon-γ inducible protein 10 (IP-10) to recruit immune effector cells in the vicinity of tumor cells. A novel fusion protein of IP10-scFv was constructed by fusing mouse IP-10 to V H region of single-chain Fv fragment (scFv) against acidic isoferritin (AIF), and expressed in NS0 murine myeloma cells. The IP10-scFv fusion protein was shown to maintain the specificity of the antiAIF scFv with similar affinity constant, and bind to the human hepatocarcinoma SMMC 7721 cells secreting AIF as well as the activated mouse T lymphocytes expressing CXCR3 receptor. Furthermore, the IP10-scFv protein either in solution or bound on the surface of SMMC 7721 cells induced significant chemotaxis of mouse T cells in vitro. The results indicate that the IP10-scFv fusion protein possesses both bioactivities of the tumor-specific antibody and IP-10 chemokine, suggesting its possibility to induce an enhanced immune response against the residual tumor cells in vivo

  19. 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.

  20. A novel fusion protein of IP10-scFv retains antibody specificity and chemokine function

    Energy Technology Data Exchange (ETDEWEB)

    Junqing, Guo; Liu, Chen; Hongwu, Ai; Jiannian, Jing; Jiyong, Zhou; Chuyu, Zhang; Shangyou, You

    2004-07-23

    We combined the specificity of tumor-specific antibody with the chemokine function of interferon-{gamma} inducible protein 10 (IP-10) to recruit immune effector cells in the vicinity of tumor cells. A novel fusion protein of IP10-scFv was constructed by fusing mouse IP-10 to V{sub H} region of single-chain Fv fragment (scFv) against acidic isoferritin (AIF), and expressed in NS0 murine myeloma cells. The IP10-scFv fusion protein was shown to maintain the specificity of the antiAIF scFv with similar affinity constant, and bind to the human hepatocarcinoma SMMC 7721 cells secreting AIF as well as the activated mouse T lymphocytes expressing CXCR3 receptor. Furthermore, the IP10-scFv protein either in solution or bound on the surface of SMMC 7721 cells induced significant chemotaxis of mouse T cells in vitro. The results indicate that the IP10-scFv fusion protein possesses both bioactivities of the tumor-specific antibody and IP-10 chemokine, suggesting its possibility to induce an enhanced immune response against the residual tumor cells in vivo.

  1. Effective single chain antibody (scFv) concentrations in vivo via adenoviral vector mediated expression of secretory scFv

    NARCIS (Netherlands)

    Arafat, WO; Gomez-Navarro, J; Buchsbaum, DJ; Xiang, J; Casado, E; Barker, SD; Mahasreshti, PJ; Haisma, HJ; Barnes, MN; Siegal, GP; Alvarez, RD; Hemminki, A; Nettelbeck, DM; Curiel, DT

    Single chain antibodies (scFv) represent powerful interventional agents for the achievement of targeted therapeutics. The practical utility of these agents have been limited, however, by difficulties related to production of recombinant scFv and the achievement of effective and sustained levels of

  2. Modular Construction of Large Non-Immune Human Antibody Phage-Display Libraries from Variable Heavy and Light Chain Gene Cassettes.

    Science.gov (United States)

    Lee, Nam-Kyung; Bidlingmaier, Scott; Su, Yang; Liu, Bin

    2018-01-01

    Monoclonal antibodies and antibody-derived therapeutics have emerged as a rapidly growing class of biological drugs for the treatment of cancer, autoimmunity, infection, and neurological diseases. To support the development of human antibodies, various display techniques based on antibody gene repertoires have been constructed over the last two decades. In particular, scFv-antibody phage display has been extensively utilized to select lead antibodies against a variety of target antigens. To construct a scFv phage display that enables efficient antibody discovery, and optimization, it is desirable to develop a system that allows modular assembly of highly diverse variable heavy chain and light chain (Vκ and Vλ) repertoires. Here, we describe modular construction of large non-immune human antibody phage-display libraries built on variable gene cassettes from heavy chain and light chain repertoires (Vκ- and Vλ-light can be made into independent cassettes). We describe utility of such libraries in antibody discovery and optimization through chain shuffling.

  3. Production of in vivo biotinylated scFv specific to almond (Prunus dulcis) proteins by recombinant Pichia pastoris.

    Science.gov (United States)

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

    2016-06-10

    The methylotropic yeast Pichia pastoris has demonstrated its suitability for large-scale production of recombinant proteins. As an eukaryotic organism P. pastoris presents a series of advantages at expression and processing of heterologous proteins when compared with Escherichia coli. In this work, P. pastoris has been used to express a scFv from a human synthetic library previously shown to bind almond proteins. In order to facilitate purification and post processing manipulations, the scFv was engineered with a C-terminal tag and biotinylated in vivo. After purification, biotinylated scFv were bound to avidin conjugated with HRP producing a multimeric scFv. The multimeric scFv showed to maintain their ability to recognize almond protein when assayed in ELISA, reaching a LOD of 470mgkg(-1). This study describes an easy method to produce large quantities of in vivo biotinylated scFv in P. pastoris. By substituting the enzyme or fluorochromes linked to avidin, it will be possible to generate a diverse number of multimeric scFv as probes to suit different analytical platforms in the detection of almond in food products. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. 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.

  5. 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.

  6. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    International Nuclear Information System (INIS)

    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.

  10. 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.

  11. 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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  14. Human antibody fragments specific for the epidermal growth factor receptor selected from large non-immunised phage display libraries.

    Science.gov (United States)

    Souriau, Christelle; Rothacker, Julie; Hoogenboom, Hennie R; Nice, Edouard

    2004-09-01

    Antibodies to EGFR have been shown to display anti-tumour effects mediated in part by inhibition of cellular proliferation and angiogenesis, and by enhancement of apoptosis. Humanised antibodies are preferred for clinical use to reduce complications with HAMA and HAHA responses frequently seen with murine and chimaeric antibodies. We have used depletion and subtractive selection strategies on cells expressing the EGFR to sample two large antibody fragment phage display libraries for the presence of human antibodies which are specific for the EGFR. Four Fab fragments and six scFv fragments were identified, with affinities of up to 2.2nM as determined by BIAcore analysis using global fitting of the binding curves to obtain the individual rate constants (ka and kd). This overall approach offers a generic screening method for the identification of growth factor specific antibodies and antibody fragments from large expression libraries and has potential for the rapid development of new therapeutic and diagnostic reagents.

  15. Targeted Multiplex Imaging Mass Spectrometry with Single Chain Fragment Variable (scfv) Recombinant Antibodies

    Science.gov (United States)

    Thiery, Gwendoline; Mernaugh, Ray L.; Yan, Heping; Spraggins, Jeffrey M.; Yang, Junhai; Parl, Fritz F.; Caprioli, Richard M.

    2012-10-01

    Recombinant scfv antibodies specific for CYP1A1 and CYP1B1 P450 enzymes were combined with targeted imaging mass spectrometry to simultaneously detect the P450 enzymes present in archived, paraffin-embedded, human breast cancer tissue sections. By using CYP1A1 and CYP1B1 specific scfv, each coupled to a unique reporter molecule (i.e., a mass tag) it was possible to simultaneously detect multiple antigens within a single tissue sample with high sensitivity and specificity using mass spectrometry. The capability of imaging multiple antigens at the same time is a significant advance that overcomes technical barriers encountered when using present day approaches to develop assays that can simultaneously detect more than a single antigen in the same tissue sample.

  16. 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...

  17. Construction of a Single Chain Variable Fragment Antibody (scFv) against Carbaryl and Its Interaction with Carbaryl.

    Science.gov (United States)

    Xiuyuan, Zhang; Zhihong, Huang; Lixia, Wang; Xiaonan, Liu

    2015-05-01

    Carbaryl is a low molecular weight insecticide that inhibits cholinesterase. Residues of carbaryl in food and the environment have damaged human health. A high-specificity scFv that can identify carbaryl is still lacking. In the present study, an anti-carbaryl scFv gene was prepared by cloning VL and VH genes from hybridoma cells secreting monoclonal antibody, then VH and VL were fused together using splicing by overlap extension (SOE) PCR with a flexible polypeptide linker connector (Gly4Ser)3, and then the scFv-pET-26b recombinant plasmid was constructed and transformed into E. coli BL21 for expression using IPTG as an inducer. The expressed recombinant protein was identified by SDS-PAGE and ELISA. The three-dimensional structure of the anti-carbaryl scFv was constructed by computer modeling, and carbaryl was docked to the scFv model to obtain the structure of the binding complex. The binding site was composed of Ala51, Ser52, Ile51, Gly54, Ser56, Arg98, and Gly100. This helps to understand the mechanism of interaction between anti-carbaryl antibody and antigen. Furthermore, it provides guidance for in vitro affinity maturation of anti-carbaryl antibody.

  18. Fast conversion of scFv to Fab antibodies using type IIs restriction enzymes.

    Science.gov (United States)

    Sanmark, Hanna; Huovinen, Tuomas; Matikka, Tero; Pettersson, Tiina; Lahti, Maria; Lamminmäki, Urpo

    2015-11-01

    Single chain variable fragment (scFv) antibody libraries are widely used for developing novel bioaffinity reagents, although Fab or IgG molecules are the preferred antibody formats in many final applications. Therefore, rapid conversion methods for combining multiple DNA fragments are needed to attach constant domains to the scFv derived variable domains. In this study we describe a fast and easy cloning method for the conversion of single framework scFv fragments to Fab fragments using type IIS restriction enzymes. All cloning steps excluding plating of the Fab transformants can be done in 96 well plates and the procedure can be completed in one working day. The concept was tested by converting 69 scFv clones into Fab format on 96 well plates, which resulted in 93% success rate. The method is particularly useful as a high-throughput tool for the conversion of the chosen scFv clones into Fab molecules in order to analyze them as early as possible, as the conversion can significantly affect the binding properties of the chosen clones. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

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

    Science.gov (United States)

    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.

  3. 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.

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

    Science.gov (United States)

    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.

  5. 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

  6. 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

  7. Recombinant norovirus-specific scFv inhibit virus-like particle binding to cellular ligands

    Directory of Open Access Journals (Sweden)

    Hardy Michele E

    2008-01-01

    Full Text Available Abstract Background Noroviruses cause epidemic outbreaks of gastrointestinal illness in all age-groups. The rapid onset and ease of person-to-person transmission suggest that inhibitors of the initial steps of virus binding to susceptible cells have value in limiting spread and outbreak persistence. We previously generated a monoclonal antibody (mAb 54.6 that blocks binding of recombinant norovirus-like particles (VLP to Caco-2 intestinal cells and inhibits VLP-mediated hemagglutination. In this study, we engineered the antigen binding domains of mAb 54.6 into a single chain variable fragment (scFv and tested whether these scFv could function as cell binding inhibitors, similar to the parent mAb. Results The scFv54.6 construct was engineered to encode the light (VL and heavy (VH variable domains of mAb 54.6 separated by a flexible peptide linker, and this recombinant protein was expressed in Pichia pastoris. Purified scFv54.6 recognized native VLPs by immunoblot, inhibited VLP-mediated hemagglutination, and blocked VLP binding to H carbohydrate antigen expressed on the surface of a CHO cell line stably transfected to express α 1,2-fucosyltransferase. Conclusion scFv54.6 retained the functional properties of the parent mAb with respect to inhibiting norovirus particle interactions with cells. With further engineering into a form deliverable to the gut mucosa, norovirus neutralizing antibodies represent a prophylactic strategy that would be valuable in outbreak settings.

  8. 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.

  9. 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.

  10. CARbodies: Human Antibodies Against Cell Surface Tumor Antigens Selected From Repertoires Displayed on T Cell Chimeric Antigen Receptors

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    Vanesa Alonso-Camino

    2013-01-01

    Full Text Available A human single-chain variable fragment (scFv antibody library was expressed on the surface of human T cells after transduction with lentiviral vectors (LVs. The repertoire was fused to a first-generation T cell receptor ζ (TCRζ-based chimeric antigen receptor (CAR. We used this library to isolate antibodies termed CARbodies that recognize antigens expressed on the tumor cell surface in a proof-of-principle system. After three rounds of activation-selection there was a clear repertoire restriction, with the emergence dominant clones. The CARbodies were purified from bacterial cultures as soluble and active proteins. Furthermore, to validate its potential application for adoptive cell therapy, human T cells were transduced with a LV encoding a second-generation costimulatory CAR (CARv2 bearing the selected CARbodies. Transduced human primary T cells expressed significant levels of the CARbodies-based CARv2 fusion protein on the cell surface, and importantly could be specifically activated, after stimulation with tumor cells. This approach is a promising tool for the generation of antibodies fully adapted to the display format (CAR and the selection context (cell synapse, which could extend the scope of current adoptive cell therapy strategies with CAR-redirected T cells.

  11. 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.

    Science.gov (United States)

    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.

  12. Development of human antibody fragments using antibody phage display for the detection and diagnosis of Venezuelan equine encephalitis virus (VEEV

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    Hust Michael

    2008-09-01

    Full Text Available Abstract Background Venezuelan equine encephalitis virus (VEEV belongs to the Alphavirus group. Several species of this family are also pathogenic to humans and are recognized as potential agents of biological warfare and terrorism. The objective of this work was the generation of recombinant antibodies for the detection of VEEV after a potential bioterrorism assault or an natural outbreak of VEEV. Results In this work, human anti-VEEV single chain Fragments variable (scFv were isolated for the first time from a human naïve antibody gene library using optimized selection processes. In total eleven different scFvs were identified and their immunological specificity was assessed. The specific detection of the VEEV strains TC83, H12/93 and 230 by the selected antibody fragments was proved. Active as well as formalin inactivated virus particles were recognized by the selected antibody fragments which could be also used for Western blot analysis of VEEV proteins and immunohistochemistry of VEEV infected cells. The anti-VEEV scFv phage clones did not show any cross-reactivity with Alphavirus species of the Western equine encephalitis virus (WEEV and Eastern equine encephalitis virus (EEEV antigenic complex, nor did they react with Chikungunya virus (CHIKV, if they were used as detection reagent. Conclusion For the first time, this study describes the selection of antibodies against a human pathogenic virus from a human naïve scFv antibody gene library using complete, active virus particles as antigen. The broad and sensitive applicability of scFv-presenting phage for the immunological detection and diagnosis of Alphavirus species was demonstrated. The selected antibody fragments will improve the fast identification of VEEV in case of a biological warfare or terroristic attack or a natural outbreak.

  13. Antibody engineering using phage display with a coiled-coil heterodimeric Fv antibody fragment.

    Directory of Open Access Journals (Sweden)

    Xinwei Wang

    Full Text Available A Fab-like antibody binding unit, ccFv, in which a pair of heterodimeric coiled-coil domains was fused to V(H and V(L for Fv stabilization, was constructed for an anti-VEGF antibody. The anti-VEGF ccFv showed the same binding affinity as scFv but significantly improved stability and phage display level. Furthermore, phage display libraries in the ccFv format were constructed for humanization and affinity maturation of the anti-VEGF antibody. A panel of V(H frameworks and V(H-CDR3 variants, with a significant improvement in affinity and expressibility in both E. coli and yeast systems, was isolated from the ccFv phage libraries. These results demonstrate the potential application of the ccFv antibody format in antibody engineering.

  14. 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.

  15. Construction and sequencing analysis of scFv antibody fragment derived from monoclonal antibody against norfloxacin (Nor155

    Directory of Open Access Journals (Sweden)

    J. Mala

    2017-06-01

    Full Text Available Norfloxacin belongs to the group of fluoroquinolone antibiotics which has been approved for treatment in animals. However, its residues in animal products can pose adverse side effects to consumer. Therefore, detection of the residue in different food matrices must be concerned. In this study, a single chain variable fragment (scFv that recognizes norfloxacin antibiotic was constructed. The cDNA was synthesized from total RNA of hybridoma cells against norfloxacin. Genes encoding VH and VL regions of monoclonal antibody against norfloxacin (Nor155 were amplified and size of VH and VL fragments was 402 bp and 363 bp, respectively. The scFv of Nor155 was constructed by an addition of (Gly4Ser3 as a linker between VH and VL regions and subcloned into pPICZαA, an expression vector of Pichia pastoris. The sequence of scFv Nor155 (GenBank No. AJG06891.1 was confirmed by sequencing analysis. The complementarity determining regions (CDR I, II, and III of VH and VL were specified by Kabat method. The obtained recombinant plasmid will be useful for production of scFv antibody against norfloxacin in P. pastoris and further engineer scFv antibody against fluoroquinolone antibiotics.

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

    Science.gov (United States)

    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.

  17. 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.

  18. Fab is the most efficient format to express functional antibodies by yeast surface display.

    Science.gov (United States)

    Sivelle, Coline; Sierocki, Raphaël; Ferreira-Pinto, Kelly; Simon, Stéphanie; Maillere, Bernard; Nozach, Hervé

    2018-04-30

    Multiple formats are available for engineering of monoclonal antibodies (mAbs) by yeast surface display, but they do not all lead to efficient expression of functional molecules. We therefore expressed four anti-tumor necrosis factor and two anti-IpaD mAbs as single-chain variable fragment (scFv), antigen-binding fragment (Fab) or single-chain Fabs and compared their expression levels and antigen-binding efficiency. Although the scFv and scFab formats are widely used in the literature, 2 of 6 antibodies were either not or weakly expressed. In contrast, all 6 antibodies expressed as Fab revealed strong binding and high affinity, comparable to that of the soluble form. We also demonstrated that the variations in expression did not affect Fab functionality and were due to variations in light chain display and not to misfolded dimers. Our results suggest that Fab is the most versatile format for the engineering of mAbs.

  19. Therapeutic monoclonal antibodies: scFv patents as a marker of a new class of potential biopharmaceuticals

    Directory of Open Access Journals (Sweden)

    Manuela Berto Pucca

    2011-03-01

    Full Text Available Monoclonal antibodies represent the fastest growing class of biopharmaceutical products and have a host of applications in medical research, diagnosis, therapy, and basic science. The production of recombinant monoclonal antibodies has revolutionized the generation of immunoglobulins, and their use represents a strategic breakthrough, affecting the global pharmaceutical market for therapeutic proteins. In the present work, a review of scFv, and the number of related patents, has been carried out. The results show that several countries have scFv patents, most notably the United States, China and United Kingdom. The target of these scFv antibodies was also assessed and the results demonstrate that most are directed toward cancer therapy.Anticorpos monoclonais representam a classe de maior crescimento em produtos de biofármacos e possuem várias aplicações em pesquisa médica, diagnóstico, terapias e ciência básica. A produção de anticorpos monoclonais recombinantes revolucionou a geração de imunoglobulinas e sua utilização implica em avanço estratégico, afetando o mercado farmacêutico global de proteínas terapêuticas. No presente trabalho, uma revisão sobre scFv e a relação do seu número de patentes foi analisada. Os resultados mostram que vários países apresentam patentes de scFv com destaque para os Estados Unidos, China e Reino Unido. Os alvos desses anticorpos também foram avaliados e as análises revelaram que a maioria é destinado a terapias contra o câncer.

  20. An efficient method for isolating antibody fragments against small peptides by antibody phage display

    DEFF Research Database (Denmark)

    Duan, Zhi; Siegumfeldt, Henrik

    2010-01-01

    We generated monoclonal scFv (single chain variable fragment) antibodies from an antibody phage display library towards three small synthetic peptides derived from the sequence of s1-casein. Key difficulties for selection of scFv-phages against small peptides were addressed. Small peptides do....... The scFvs were sequenced and characterized, and specificity was characterized by ELISA. The methods developed in this study are universally applicable for antibody phage display to efficiently produce antibody fragments against small peptides....

  1. Characterization of Anti-Citrinin Specific ScFvs Selected from Non-Immunized Mouse Splenocytes by Eukaryotic Ribosome Display.

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    Haiwei Cheng

    Full Text Available Single chain variable fragments (scFvs against citrinin (CIT were selected from a scFv library constructed from the splenocytes of non-immunized mice by an improved eukaryotic ribosome display technology in this study. Bovine serum albumin (BSA/ CIT-BSA and ovalbumin (OVA/ CIT-OVA were used as the antigens to select specific anti-CIT scFvs. Eukaryotic in situ RT-PCR method was used to recover the selected mRNA after every affinity selection. After six rounds of ribosome display, expression vector pTIG-TRX carrying specific scFv DNAs were constructed and transformed into Escherichia coli BL21 (DE3 for protein expression. Thirteen positive clones were selected out of which three (designated 23, 68 and 109 showed high binding activity and specificity to CIT by indirect ELISA, while no clone showed binding activity with carrier proteins. The three scFvs showed high specificity to CIT and the cross reactivity with other mycotoxins was below 0.01% as determined by indirect competitive ELISA. These specific scFvs offer a potential novel immunoassay method for CIT residues. This study confirmed the effectiveness of the improved eukaryotic ribosome display system and could be used as a reference for the selection of scFvs specific to other small molecules using ribosome display.

  2. Phage display selection of fully human antibody fragments to inhibit growth-promoting effects of glycine-extended gastrin 17 on human colorectal cancer cells.

    Science.gov (United States)

    Khajeh, Shirin; Tohidkia, Mohammad Reza; Aghanejad, Ayuob; Mehdipour, Tayebeh; Fathi, Farzaneh; Omidi, Yadollah

    2018-06-09

    Glycine-extended gastrin 17 (G17-Gly), a dominant processing intermediate of gastrin gene, has been implicated in the development or maintenance of colorectal cancers (CRCs). Hence, neutralizing G17-Gly activity by antibody entities can provide a potential therapeutic strategy in the patients with CRCs. To this end, we isolated fully human antibody fragments from a phage antibody library through biopanning against different epitopes of G17-Gly in order to obtain the highest possible antibody diversity. ELISA screening and sequence analysis identified 2 scFvs and 4 V L antibody fragments. Kinetic analysis of the antibody fragments by SPR revealed K D values to be in the nanomolar range (87.9-334 nM). The selected anti-G17-Gly antibody fragments were analyzed for growth inhibition and apoptotic assays in a CRC cell line, HCT-116, which is well-characterized for expressing gastrin intermediate species but not amidated gastrin. The antibody fragments exhibited significant inhibition of HCT-116 cells proliferation ranging from 36.5 to 73% of controls. Further, Annexin V/PI staining indicated that apoptosis rates of scFv H8 and V L G8 treated cells were 45.8 and 63%, respectively. Based on these results, we for the first time, demonstrated the isolation of anti-G17-Gly human scFv and V L antibodies with potential therapeutic applications in G17-Gly-responsive tumors.

  3. 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.

  4. 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...

  5. DARPA Antibody Technology Program. Standardized Test Bed for Antibody Characterization: Characterization of an MS2 ScFv Antibody Produced by Illumina

    Science.gov (United States)

    2016-08-01

    ECBC-TR-1395 DARPA ANTIBODY TECHNOLOGY PROGRAM STANDARDIZED TEST BED FOR... ANTIBODY CHARACTERIZATION: CHARACTERIZATION OF AN MS2 SCFV ANTIBODY PRODUCED BY ILLUMINA Patricia E. Buckley Alena M. Calm Heather Welsh Roy...4. TITLE AND SUBTITLE DARPA Antibody Technology Program Standardized Test Bed for Antibody Characterization: Characterization of an MS2 ScFv

  6. 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.

  7. 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.

  8. Human Factors Military Lexicon: Auditory Displays

    National Research Council Canada - National Science Library

    Letowski, Tomasz

    2001-01-01

    .... In addition to definitions specific to auditory displays, speech communication, and audio technology, the lexicon includes several terms unique to military operational environments and human factors...

  9. 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.

  10. 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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  14. Human factors guidelines for large-screen displays

    International Nuclear Information System (INIS)

    Collier, Steve

    2005-09-01

    Any control-room project (including upgrades or evolutionary improvements to existing control-rooms) is well advised at the outset first to gather and update related background material for the design. This information-gathering exercise should also take into account experience from similar projects and operating experience. For these reasons, we decided to use our research, and experience in large-screen display design with several clients to update human factors guidance for large-screen displays, to take into account new ergonomics guidelines, operating experience, and work from similar projects. To write the updated guidelines, we drew on much of our experience across several departments at IFE, including research funded by the HRP programme, and experience with individual clients. Guidance here is accordingly focused mainly on recent areas of technical and human innovations in the man-machine interface. One particular area of focus was on the increasing use of large-screen display systems in modern control-rooms, and on how guidelines could be adapted and supplemented for their design. Guidance or reference to recommended sources is also given for control suite arrangement and layout, control-room layout, workstation layout, design of displays and controls, and design of the work environment, especially insofar as these ergonomic issues interact with the effectiveness of modern displays, in particular large screen displays. The work shows that there can be synergy between HRP research and bilateral activities: the one side offers a capability to develop tools and guidelines, while the other side gives an opportunity to test and refine these in practice, to the benefit of both parties. (Author)

  15. Human factors guidelines for large-screen displays

    Energy Technology Data Exchange (ETDEWEB)

    Collier, Steve

    2005-09-15

    Any control-room project (including upgrades or evolutionary improvements to existing control-rooms) is well advised at the outset first to gather and update related background material for the design. This information-gathering exercise should also take into account experience from similar projects and operating experience. For these reasons, we decided to use our research, and experience in large-screen display design with several clients to update human factors guidance for large-screen displays, to take into account new ergonomics guidelines, operating experience, and work from similar projects. To write the updated guidelines, we drew on much of our experience across several departments at IFE, including research funded by the HRP programme, and experience with individual clients. Guidance here is accordingly focused mainly on recent areas of technical and human innovations in the man-machine interface. One particular area of focus was on the increasing use of large-screen display systems in modern control-rooms, and on how guidelines could be adapted and supplemented for their design. Guidance or reference to recommended sources is also given for control suite arrangement and layout, control-room layout, workstation layout, design of displays and controls, and design of the work environment, especially insofar as these ergonomic issues interact with the effectiveness of modern displays, in particular large screen displays. The work shows that there can be synergy between HRP research and bilateral activities: the one side offers a capability to develop tools and guidelines, while the other side gives an opportunity to test and refine these in practice, to the benefit of both parties. (Author)

  16. 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.

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

    Science.gov (United States)

    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

  18. Conformal displays: human factor analysis of innovative landing aids

    Science.gov (United States)

    Schmerwitz, Sven; Lueken, Thomas; Doehler, Hans-Ullrich; Peinecke, Niklas; Ernst, Johannes M.; da Silva Rosa, David L.

    2017-05-01

    In the past couple of years, research on display content for helicopter operations headed in a new direction. The already reached goals could evolve into a paradigm change for information visualization. Technology advancements allow implementing three-dimensional and conformal content on a helmet-mounted see-through device. This superimposed imagery inherits the same optical flow as the environment. It is supposed to ease switching between display information and environmental cues. The concept is neither pathbreaking nor new, but it has not been successfully established in aviation yet. Nevertheless, there are certainly some advantages to expect-at least from perspective of a human-centered system design. Within the following pages, the next generation displays will be presented and discussed with a focus on human factors. Beginning with recalling some human factor related research facts, an experiment comparing the former two-dimensional research displays will be presented. Before introducing the DLR conformal symbol set and the three experiments about an innovative drift, indication related research activities toward conformal symbol sets will be addressed.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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.

  1. Human Engineering of Space Vehicle Displays and Controls

    Science.gov (United States)

    Whitmore, Mihriban; Holden, Kritina L.; Boyer, Jennifer; Stephens, John-Paul; Ezer, Neta; Sandor, Aniko

    2010-01-01

    Proper attention to the integration of the human needs in the vehicle displays and controls design process creates a safe and productive environment for crew. Although this integration is critical for all phases of flight, for crew interfaces that are used during dynamic phases (e.g., ascent and entry), the integration is particularly important because of demanding environmental conditions. This panel addresses the process of how human engineering involvement ensures that human-system integration occurs early in the design and development process and continues throughout the lifecycle of a vehicle. This process includes the development of requirements and quantitative metrics to measure design success, research on fundamental design questions, human-in-the-loop evaluations, and iterative design. Processes and results from research on displays and controls; the creation and validation of usability, workload, and consistency metrics; and the design and evaluation of crew interfaces for NASA's Crew Exploration Vehicle are used as case studies.

  2. 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.

  3. Reliable cloning of functional antibody variable domains from hybridomas and spleen cell repertoires employing a reengineered phage display system.

    Science.gov (United States)

    Krebber, A; Bornhauser, S; Burmester, J; Honegger, A; Willuda, J; Bosshard, H R; Plückthun, A

    1997-02-14

    A prerequisite for the use of recombinant antibody technologies starting from hybridomas or immune repertoires is the reliable cloning of functional immunoglobulin genes. For this purpose, a standard phage display system was optimized for robustness, vector stability, tight control of scFv-delta geneIII expression, primer usage for PCR amplification of variable region genes, scFv assembly strategy and subsequent directional cloning using a single rare cutting restriction enzyme. This integrated cloning, screening and selection system allowed us to rapidly obtain antigen binding scFvs derived from spleen-cell repertoires of mice immunized with ampicillin as well as from all hybridoma cell lines tested to date. As representative examples, cloning of monoclonal antibodies against a his tag, leucine zippers, the tumor marker EGP-2 and the insecticide DDT is presented. Several hybridomas whose genes could not be cloned in previous experimental setups, but were successfully obtained with the present system, expressed high amounts of aberrant heavy and light chain mRNAs, which were amplified by PCR and greatly exceeded the amount of binding antibody sequences. These contaminating variable region genes were successfully eliminated by employing the optimized phage display system, thus avoiding time consuming sequencing of non-binding scFv genes. To maximize soluble expression of functional scFvs subsequent to cloning, a compatible vector series to simplify modification, detection, multimerization and rapid purification of recombinant antibody fragments was constructed.

  4. 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

  5. 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.

  6. Human factors engineering in the design of colour-graphic displays

    International Nuclear Information System (INIS)

    Fenton, E.F.

    1985-01-01

    The operator interface for Ontario Hydro's Darlington Nuclear Generating Station will rely extensively on the use of coloured graphic display formats. These are used for the presentation of both control and monitoring information. The displays are organized in a hierarchical relationship and a simple interactive selection method using light pens has been implemented. The application of human factors engineering principles has been a major factor in all aspects of the design. This paper describes the system and the human factors engineering function

  7. Display analysis with the optimal control model of the human operator. [pilot-vehicle display interface and information processing

    Science.gov (United States)

    Baron, S.; Levison, W. H.

    1977-01-01

    Application of the optimal control model of the human operator to problems in display analysis is discussed. Those aspects of the model pertaining to the operator-display interface and to operator information processing are reviewed and discussed. The techniques are then applied to the analysis of advanced display/control systems for a Terminal Configured Vehicle. Model results are compared with those obtained in a large, fixed-base simulation.

  8. 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

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

    Science.gov (United States)

    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.

  10. Development of exosome surface display technology in living human cells

    International Nuclear Information System (INIS)

    Stickney, Zachary; Losacco, Joseph; McDevitt, Sophie; Zhang, Zhiwen; Lu, Biao

    2016-01-01

    Surface display technology is an emerging key player in presenting functional proteins for targeted drug delivery and therapy. Although a number of technologies exist, a desirable mammalian surface display system is lacking. Exosomes are extracellular vesicles that facilitate cell–cell communication and can be engineered as nano-shuttles for cell-specific delivery. In this study, we report the development of a novel exosome surface display technology by exploiting mammalian cell secreted nano-vesicles and their trans-membrane protein tetraspanins. By constructing a set of fluorescent reporters for both the inner and outer surface display on exosomes at two selected sites of tetraspanins, we demonstrated the successful exosomal display via gene transfection and monitoring fluorescence in vivo. We subsequently validated our system by demonstrating the expected intracellular partitioning of reporter protein into sub-cellular compartments and secretion of exosomes from human HEK293 cells. Lastly, we established the stable engineered cells to harness the ability of this robust system for continuous production, secretion, and uptake of displayed exosomes with minimal impact on human cell biology. In sum, our work paved the way for potential applications of exosome, including exosome tracking and imaging, targeted drug delivery, as well as exosome-mediated vaccine and therapy.

  11. Development of exosome surface display technology in living human cells

    Energy Technology Data Exchange (ETDEWEB)

    Stickney, Zachary, E-mail: zstickney@scu.edu; Losacco, Joseph, E-mail: jlosacco@scu.edu; McDevitt, Sophie, E-mail: smmcdevitt@scu.edu; Zhang, Zhiwen, E-mail: zzhang@scu.edu; Lu, Biao, E-mail: blu2@scu.edu

    2016-03-25

    Surface display technology is an emerging key player in presenting functional proteins for targeted drug delivery and therapy. Although a number of technologies exist, a desirable mammalian surface display system is lacking. Exosomes are extracellular vesicles that facilitate cell–cell communication and can be engineered as nano-shuttles for cell-specific delivery. In this study, we report the development of a novel exosome surface display technology by exploiting mammalian cell secreted nano-vesicles and their trans-membrane protein tetraspanins. By constructing a set of fluorescent reporters for both the inner and outer surface display on exosomes at two selected sites of tetraspanins, we demonstrated the successful exosomal display via gene transfection and monitoring fluorescence in vivo. We subsequently validated our system by demonstrating the expected intracellular partitioning of reporter protein into sub-cellular compartments and secretion of exosomes from human HEK293 cells. Lastly, we established the stable engineered cells to harness the ability of this robust system for continuous production, secretion, and uptake of displayed exosomes with minimal impact on human cell biology. In sum, our work paved the way for potential applications of exosome, including exosome tracking and imaging, targeted drug delivery, as well as exosome-mediated vaccine and therapy.

  12. The human factors of CRT displays for nuclear power plant control

    International Nuclear Information System (INIS)

    Danchak, M.M.

    1984-01-01

    This chapter attempts to show how the Cathode Ray Tube (CRT) can be used to effectively present information to the operator rather than just data. The capabilities of the human as a sensing and information processing subsystem are discussed with CRT displays in mind. The display system is described in terms of its hardware and functioning. The interface between the two is examined by providing substantive guidelines for the effective design of CRT displays for nuclear power plant control. Alphanumeric displays, graphic displays, and representational displays are treated. The design of CRT displays for nuclear power plant control requires an extensive knowledge of cognitive psychology, computer display systems and the process being controlled

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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

  15. 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.

  16. Human factors considerations for the use of color in display systems

    Science.gov (United States)

    Demars, S. A.

    1975-01-01

    Identified and assessed are those human factor considerations impacting an operator's ability to perform when information is displayed in color as contrasted to monochrome (black and white only). The findings provide valuable guidelines for the assessment of the advantages (and disadvantages) of using a color display system. The use of color provides an additional sensory channel (color perception) which is not available with black and white. The degree to which one can exploit the use of this channel is highly dependent on available display technology, mission information display requirements, and acceptable operational modes.

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

    Science.gov (United States)

    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.

  18. 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.

  19. A novel anti-alpha-fetoprotein single-chain variable fragment displays anti-tumor effects in HepG2 cells as a single agent or in combination with paclitaxel.

    Science.gov (United States)

    Ji, Xiaonan; Shen, Yanli; Sun, Hao; Gao, Xiangdong

    2016-08-01

    Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival time. The function of alpha-fetoprotein (AFP) as a regulatory factor in the growth of HCC cells has been well defined. The aim of this study was to investigate the use of a novel AFP-specific single-chain variable fragment that blocked AFP and inhibited HCC cell growth. The results indicated that the anti-AFP single-chain variable fragment (scFv) induced growth inhibition of AFP-expressing HCC cell lines in vitro through induction of G1 cell cycle arrest and apoptosis. The mechanism of apoptosis probably involved with blocking AFP internalization and regulation of the PTEN/PI3K/Akt signaling network. Moreover, the anti-AFP-scFv also effectively sensitized the HepG2 cells to paclitaxel (PTX) at a lower concentration. The combination effect of PTX and anti-AFP-scFv displayed a synergistic effect on HepG2 cells both in vitro and in vivo. Our results demonstrated that targeting AFP by specific antibodies has potential immunotherapeutic efficacy in human HCC.

  20. 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.

  1. Human factors engineering design review acceptance criteria for the safety parameter display

    International Nuclear Information System (INIS)

    McGevna, V.; Peterson, L.R.

    1981-01-01

    This report contains human factors engineering design review acceptance criteria developed by the Human Factors Engineering Branch (HFEB) of the Nuclear Regulatory Commission (NRC) to use in evaluating designs of the Safety Parameter Display System (SPDS). These criteria were developed in response to the functional design criteria for the SPDS defined in NUREG-0696, Functional Criteria for Emergency Response Facilities. The purpose of this report is to identify design review acceptance criteria for the SPDS installed in the control room of a nuclear power plant. Use of computer driven cathode ray tube (CRT) displays is anticipated. General acceptance criteria for displays of plant safety status information by the SPDS are developed. In addition, specific SPDS review criteria corresponding to the SPDS functional criteria specified in NUREG-0696 are established

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

  4. 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

  5. Development of a new high-affinity human antibody with antitumor activity against solid and blood malignancies.

    Science.gov (United States)

    Sioud, Mouldy; Westby, Phuong; Vasovic, Vlada; Fløisand, Yngvar; Peng, Qian

    2018-04-16

    mAbs have emerged as a promising strategy for the treatment of cancer. However, in several malignancies, no effective antitumor mAbs are yet available. Identifying therapeutic mAbs that recognize common tumor antigens could render the treatment widely applicable. Here, a human single-chain variable fragment (scFv) antibody library was sequentially affinity selected against a panel of human cancer cell lines and an antibody fragment (named MS5) that bound to solid and blood cancer cells was identified. The MS5 scFv was fused to the human IgG1 Fc domain to generate an antibody (MS5-Fc fusion) that induced antibody-dependent cellular cytotoxicity and phagocytosis of cancer cells by macrophages. In addition, the MS5-Fc antibody bound to primary leukemia cells and induced antibody-dependent cellular cytotoxicity. In the majority of analyzed cancer cells, the MS5-Fc antibody induced cell surface redistribution of the receptor complexes, but not internalization, thus maximizing the accessibility of the IgG1 Fc domain to immune effector cells. In vitro stability studies showed that the MS5-Fc antibody was stable after 6 d of incubation in human serum, retaining ∼60% of its initial intact form. After intravenous injections, the antibody localized into tumor tissues and inhibited the growth of 3 different human tumor xenografts (breast, lymphoma, and leukemia). These antitumor effects were associated with tumor infiltration by macrophages and NK cells. In the Ramos B-cell lymphoma xenograft model, the MS5-Fc antibody exhibited a comparable antitumor effect as rituximab, a chimeric anti-CD20 IgG1 mAb. These results indicate that human antibodies with pan-cancer abilities can be generated from phage display libraries, and that the engineered MS5-Fc antibody could be an attractive agent for further clinical investigation.-Sioud, M., Westby, P., Vasovic, V., Fløisand, Y., Peng, Q. Development of a new high-affinity human antibody with antitumor activity against solid and

  6. Development of HANARO human factors management plan and evaluation of BCS display

    International Nuclear Information System (INIS)

    Oh, I. S.; Lee, J. W.; Lee, Y. H.

    2004-01-01

    In this study, human factors evaluation of BCS display design was performed. We adopted the suitability of design elements of BCS display as human factors evaluation measure. And, we also adopted guideline based evaluation, field survey and expert evaluation as evaluation method. The checklist was utilized for the evaluation, and the results of evaluation were well arranged in the evaluation format. We did not find out the HED (Human Engineering Discrepancy) impede safety of HANARO, except some necessary items to improve during short periods. We also provide some items of improvement for the enhancement of safety and operator's performance in the aspect of long periods. If the proposed improvement items were completely fulfilled, the more improved safety of HANARO will be secured

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Phage-display libraries of murine and human antibody Fab fragments

    DEFF Research Database (Denmark)

    Engberg, J; Andersen, P S; Nielsen, L K

    1996-01-01

    We provide efficient and detailed procedures for construction, expression, and screening of comprehensive libraries of murine or human antibody Fab fragments displayed on the surface of filamentous phage. In addition, protocols for producing and using ultra-electrocompetent cells, for producing Fab...

  9. 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

  10. Human engineering design considerations for the use of signal color enhancement in ASW displays

    Energy Technology Data Exchange (ETDEWEB)

    Banks, W.W.

    1990-11-01

    The Lawrence Livermore National Laboratory (LLNL) was requested to examine and define man-machine limits as part of the Office of Naval Technology's High Gain Initiative program (HGI). As an initial investigative area, LLNL's Systems and Human Performance effort focused upon color display interfaces and the use of color enhancement techniques to define human and system interface limits in signal detection and discrimination tasks. The knowledgeable and prudent use of color in different types of display is believed to facilitate human visual detection, discrimination and recognition in complex visual tasks. The consideration and understanding of the complex set of interacting variables associated with the prudent use of color is essential to optimize human performance, especially in the ASW community. The designers of advanced display technology and signal processing algorithms may be eventually called upon to present pre-processed information to ASW operators and researchers using the latest color enhancement techniques. These techniques, however, may be limited if one does not understand the complexity and limits of human information processing which reflects the assessed state of knowledge relevant to the use of color in displays. The initial sections of this report discuss various aspects of color presentation and the problems typically encountered, while the last section deals with a specific research proposal required to further our understanding and proper use of color enhancement methods.

  11. Human engineering guidelines for the evaluation and assessment of Video Display Units

    International Nuclear Information System (INIS)

    Gilmore, W.E.

    1985-07-01

    This report provides the Nuclear Regulatory Commission with a single source that documents known guidelines for conducting formal Human Factors evaluations of Video Display Units (VDUs). The handbook is a ''cookbook'' of acceptance guidelines for the reviewer faced with the task of evaluating VDUs already designed or planned for service in the control room. The areas addressed are video displays, controls, control/display integration, and workplace layout. Guidelines relevant to each of those areas are presented. The existence of supporting research is also indicated for each guideline. A Comment section and Method for Assessment section are provided for each set of guidelines

  12. Selection of diethylstilbestrol-specific single-chain antibodies from a non-immunized mouse ribosome display library.

    Directory of Open Access Journals (Sweden)

    Yanan Sun

    Full Text Available Single chain variable fragments (scFvs against diethylstilbestrol (DES were selected from the splenocytes of non-immunized mice by ribosome display technology. A naive library was constructed and engineered to allow in vitro transcription and translation using an E. coli lysate system. Alternating selection in solution and immobilization in microtiter wells was used to pan mRNA-ribosome-antibody (ARM complexes. After seven rounds of ribosome display, the expression vector pTIG-TRX containing the selected specific scFv DNAs were transformed into Escherichia coli BL21 (DE3 for expression. Twenty-six positive clones were screened and five clones had high antibody affinity and specificity to DES as evidenced by indirect competitive ELISA. Sequence analysis showed that these five DES-specific scFvs had different amino acid sequences, but the CDRs were highly similar. Surface plasmon resonance (SPR analysis was used to determine binding kinetics of one clone (30-1. The measured K(D was 3.79 µM. These results indicate that ribosome display technology can be used to efficiently isolate hapten-specific antibody (Ab fragments from a naive library; this study provides a methodological framework for the development of novel immunoassays for multiple environmental pollutants with low molecular weight detection using recombinant antibodies.

  13. Human factors review of CFMS displays for Ulchin Nuclear Power Unit 3 and 4

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yong Hee; Baek, Seung Min; Kim, Jung Taek; Park, Jae Chang; Lee, Jung Woon; Oh, In Suk; Lee, Joon Whan; Jung, Kwang Tae; Cha, Hye Young [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1996-11-01

    This report describes the human factors review of CFMS displays for Ulchin 3 and 4 by the following four subjects; At first, by reviewing issues regarding the design process of present CFMS, human factors engineering program plan (HFEPP) and human factors verification and validation plan Were proposed to accomplish the completeness of design word; Secondly, researches and developments were integrated into the review results at the point of suitability of CFMS design concept and basic function; For the third, availability and suitability were assessed according to human factors evaluation criteria on the CFMS display design, and overall effectiveness was also evaluated in parts; For the fourth, recommendations were made to human factors problems in accordance with their importance and an implementation plan was suggested for the resolution of problems. 54 refs., 34 tabs., 42 figs. (author)

  14. Human factors considerations in the design and evaluation of flight deck displays and controls

    Science.gov (United States)

    2013-11-01

    The objective of this effort is to have a single source document for human factors regulatory and guidance material for flight deck displays and controls, in the interest of improving aviation safety. This document identifies guidance on human factor...

  15. Effects of Viewing Displays from Different Distances on Human Visual System

    Directory of Open Access Journals (Sweden)

    Mohamed Z. Ramadan

    2017-11-01

    Full Text Available The current stereoscopic 3D displays have several human-factor issues including visual-fatigue symptoms such as eyestrain, headache, fatigue, nausea, and malaise. The viewing time and viewing distance are factors that considerably affect the visual fatigue associated with 3D displays. Hence, this study analyzes the effects of display type (2D vs. 3D and viewing distance on visual fatigue during a 60-min viewing session based on electroencephalogram (EEG relative beta power, and alpha/beta power ratio. In this study, twenty male participants watched four videos. The EEGs were recorded at two occipital lobes (O1 and O2 of each participant in the pre-session (3 min, post-session (3 min, and during a 60-min viewing session. The results showed that the decrease in relative beta power of the EEG and the increase in the alpha/beta ratio from the start until the end of the viewing session were significantly higher when watching the 3D display. When the viewing distance was increased from 1.95 m to 3.90 m, the visual fatigue was decreased in the case of the 3D-display, whereas the fatigue was increased in the case of the 2D-display. Moreover, there was approximately the same level of visual fatigue when watching videos in 2D or 3D from a long viewing distance (3.90 m.

  16. Human-scale interaction for virtual model displays: a clear case for real tools

    Science.gov (United States)

    Williams, George C.; McDowall, Ian E.; Bolas, Mark T.

    1998-04-01

    We describe a hand-held user interface for interacting with virtual environments displayed on a Virtual Model Display. The tool, constructed entirely of transparent materials, is see-through. We render a graphical counterpart of the tool on the display and map it one-to-one with the real tool. This feature, combined with a capability for touch- sensitive, discrete input, results in a useful spatial input device that is visually versatile. We discuss the tool's design and interaction techniques it supports. Briefly, we look at the human factors issues and engineering challenges presented by this tool and, in general, by the class of hand-held user interfaces that are see-through.

  17. [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.

  18. Augmenting digital displays with computation

    Science.gov (United States)

    Liu, Jing

    As we inevitably step deeper and deeper into a world connected via the Internet, more and more information will be exchanged digitally. Displays are the interface between digital information and each individual. Naturally, one fundamental goal of displays is to reproduce information as realistically as possible since humans still care a lot about what happens in the real world. Human eyes are the receiving end of such information exchange; therefore it is impossible to study displays without studying the human visual system. In fact, the design of displays is rather closely coupled with what human eyes are capable of perceiving. For example, we are less interested in building displays that emit light in the invisible spectrum. This dissertation explores how we can augment displays with computation, which takes both display hardware and the human visual system into consideration. Four novel projects on display technologies are included in this dissertation: First, we propose a software-based approach to driving multiview autostereoscopic displays. Our display algorithm can dynamically assign views to hardware display zones based on multiple observers' current head positions, substantially reducing crosstalk and stereo inversion. Second, we present a dense projector array that creates a seamless 3D viewing experience for multiple viewers. We smoothly interpolate the set of viewer heights and distances on a per-vertex basis across the arrays field of view, reducing image distortion, crosstalk, and artifacts from tracking errors. Third, we propose a method for high dynamic range display calibration that takes into account the variation of the chrominance error over luminance. We propose a data structure for enabling efficient representation and querying of the calibration function, which also allows user-guided balancing between memory consumption and the amount of computation. Fourth, we present user studies that demonstrate that the ˜ 60 Hz critical flicker fusion

  19. Design and Development of Functionally Effective Human-Machine Interfaces for Firing Room Displays

    Science.gov (United States)

    Cho, Henry

    2013-01-01

    This project involves creating software for support equipment used on the Space Launch System (SLS). The goal is to create applications and displays that will be used to remotely operate equipment from the firing room and will continue to support the SLS launch vehicle to the extent of its program. These displays include design practices that help to convey information effectively, such as minimizing distractions at normal operating state and displaying intentional distractions during a warning or alarm state. The general practice for creating an operator display is to reduce the detail of unimportant aspects of the display and promote focus on data and dynamic information. These practices include using minimalist design, using muted tones for background colors, using a standard font at a readable text size, displaying alarms visible for immediate attention, grouping data logically, and displaying data appropriately varying on the type of data. Users of these displays are more likely to stay focused on operating for longer periods by using design practices that reduce eye strain and fatigue. Effective operator displays will improve safety by reducing human errors during operation, which will help prevent catastrophic accidents. This report entails the details of my work on developing remote displays for the Hypergolic fuel servicing system. Before developing a prototype display, the design and requirements of the system are outlined and compiled into a document. Then each subsystem has schematic representations drawn that meet the specifications detailed in the document. The schematics are then used as the outline to create display representations of each subsystem. Each display is first tested individually. Then the displays are integrated with a prototype of the master system, and they are tested in a simulated environment then retested in the real environment. Extensive testing is important to ensure the displays function reliably as intended.

  20. Techniques for optimizing human-machine information transfer related to real-time interactive display systems

    Science.gov (United States)

    Granaas, Michael M.; Rhea, Donald C.

    1989-01-01

    In recent years the needs of ground-based researcher-analysts to access real-time engineering data in the form of processed information has expanded rapidly. Fortunately, the capacity to deliver that information has also expanded. The development of advanced display systems is essential to the success of a research test activity. Those developed at the National Aeronautics and Space Administration (NASA), Western Aeronautical Test Range (WATR), range from simple alphanumerics to interactive mapping and graphics. These unique display systems are designed not only to meet basic information display requirements of the user, but also to take advantage of techniques for optimizing information display. Future ground-based display systems will rely heavily not only on new technologies, but also on interaction with the human user and the associated productivity with that interaction. The psychological abilities and limitations of the user will become even more important in defining the difference between a usable and a useful display system. This paper reviews the requirements for development of real-time displays; the psychological aspects of design such as the layout, color selection, real-time response rate, and interactivity of displays; and an analysis of some existing WATR displays.

  1. Re-engineering of the PAM1 phage display monoclonal antibody to produce a soluble, versatile anti-homogalacturonan scFv

    DEFF Research Database (Denmark)

    Manfield, I. W.; Bernal Giraldo, Adriana Jimena; Møller, I.

    2006-01-01

    Antibody phage display is an increasingly important alternative method for the production of monoclonal antibodies (mAbs) and involves the expression of antibody fragments (scFvs) at the surface of bacteriophage particles. We have previously used this technique to generate a phage mAb (PAM1phage...

  2. 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

  3. Generation of human antibody fragments against Streptococcus mutans using a phage display chain shuffling approach

    Directory of Open Access Journals (Sweden)

    Barth Stefan

    2005-01-01

    Full Text Available Abstract Background Common oral diseases and dental caries can be prevented effectively by passive immunization. In humans, passive immunotherapy may require the use of humanized or human antibodies to prevent adverse immune responses against murine epitopes. Therefore we generated human single chain and diabody antibody derivatives based on the binding characteristics of the murine monoclonal antibody Guy's 13. The murine form of this antibody has been used successfully to prevent Streptococcus mutans colonization and the development of dental caries in non-human primates, and to prevent bacterial colonization in human clinical trials. Results The antibody derivatives were generated using a chain-shuffling approach based on human antibody variable gene phage-display libraries. Like the parent antibody, these derivatives bound specifically to SAI/II, the surface adhesin of the oral pathogen S. mutans. Conclusions Humanization of murine antibodies can be easily achieved using phage display libraries. The human antibody fragments bind the antigen as well as the causative agent of dental caries. In addition the human diabody derivative is capable of aggregating S. mutans in vitro, making it a useful candidate passive immunotherapeutic agent for oral diseases.

  4. Combining EL4-B5-based B-cell stimulation and phage display technology for the successful isolation of human anti-Scl-70 autoantibody fragments.

    Science.gov (United States)

    Weber, Malte; Weiss, Etienne; Engel, Alfred M

    2003-07-01

    Scl-70 is the major antigen recognised by autoantibodies in the sera of patients with systemic sclerosis (SSc). The autoantibodies that specifically react with Scl-70 are highly characteristic of the disease and represent valuable markers for the diagnosis of SSc. We describe a novel strategy for cloning autoantibody fragments starting with a small blood sample from an SSc patient. B cells isolated from the collected peripheral blood mononuclear cells (PBMCs) were cultured in vitro using the EL4-B5 system. Anti-Scl-70 IgG-producing cells were pooled for RNA preparation followed by the generation of phagemid libraries of approximately 10(7) independent single-chain Fvs (scFvs). The screening of these libraries by phage display allowed us to isolate four anti-Scl-70 scFvs following three rounds of biopanning. About 10 times more starting blood material was needed to generate scFv libraries of similar size from PBMCs of an SSc patient and only two anti-Scl-70 scFvs were isolated after three rounds of phage selection. Together, this work shows that functional autoantibody fragments can be advantageously cloned after in vitro expansion of B cells. The isolated anti-Scl-70 autoantibody fragments represent useful tools for calibrating SSc diagnostic assays.

  5. 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.

  6. P1-32: Response of Human Visual System to Paranormal Stimuli Appearing in Three-Dimensional Display

    Directory of Open Access Journals (Sweden)

    Jisoo Hong

    2012-10-01

    Full Text Available Three-dimensional (3D display became one of indispensable features of commercial TVs in recent years. However, the 3D content displayed by 3D display may contain the abrupt change of depth when the scene changes, which might be considered as a paranormal stimulus. Because the human visual system is not accustomed to such paranormal stimuli in natural conditions, they can cause unexpected responses which usually induce discomfort. Following the change of depth expressed by 3D display, the eyeballs rotate to match the convergence to the new 3D image position. The amount of rotation varies according to the initial longitudinal location and depth displacement of 3D image. Because the change of depth is abrupt, there is delay in human visual system following the change and such delay can be a source of discomfort. To guarantee the safety in watching 3D TV, the acceptable level of displacement in the longitudinal direction should be revealed quantitatively. Additionally, the artificially generated scenes also can provide paranormal stimuli such as periodic depth variations. In the presentation, we investigate the response of human visual system to such paranormal stimuli given by 3D display system. Using the result of investigation, we can give guideline to creating the 3D content to minimize the discomfort coming from the paranormal stimuli.

  7. The Effect of Information Analysis Automation Display Content on Human Judgment Performance in Noisy Environments

    Science.gov (United States)

    Bass, Ellen J.; Baumgart, Leigh A.; Shepley, Kathryn Klein

    2014-01-01

    Displaying both the strategy that information analysis automation employs to makes its judgments and variability in the task environment may improve human judgment performance, especially in cases where this variability impacts the judgment performance of the information analysis automation. This work investigated the contribution of providing either information analysis automation strategy information, task environment information, or both, on human judgment performance in a domain where noisy sensor data are used by both the human and the information analysis automation to make judgments. In a simplified air traffic conflict prediction experiment, 32 participants made probability of horizontal conflict judgments under different display content conditions. After being exposed to the information analysis automation, judgment achievement significantly improved for all participants as compared to judgments without any of the automation's information. Participants provided with additional display content pertaining to cue variability in the task environment had significantly higher aided judgment achievement compared to those provided with only the automation's judgment of a probability of conflict. When designing information analysis automation for environments where the automation's judgment achievement is impacted by noisy environmental data, it may be beneficial to show additional task environment information to the human judge in order to improve judgment performance. PMID:24847184

  8. The Effect of Information Analysis Automation Display Content on Human Judgment Performance in Noisy Environments.

    Science.gov (United States)

    Bass, Ellen J; Baumgart, Leigh A; Shepley, Kathryn Klein

    2013-03-01

    Displaying both the strategy that information analysis automation employs to makes its judgments and variability in the task environment may improve human judgment performance, especially in cases where this variability impacts the judgment performance of the information analysis automation. This work investigated the contribution of providing either information analysis automation strategy information, task environment information, or both, on human judgment performance in a domain where noisy sensor data are used by both the human and the information analysis automation to make judgments. In a simplified air traffic conflict prediction experiment, 32 participants made probability of horizontal conflict judgments under different display content conditions. After being exposed to the information analysis automation, judgment achievement significantly improved for all participants as compared to judgments without any of the automation's information. Participants provided with additional display content pertaining to cue variability in the task environment had significantly higher aided judgment achievement compared to those provided with only the automation's judgment of a probability of conflict. When designing information analysis automation for environments where the automation's judgment achievement is impacted by noisy environmental data, it may be beneficial to show additional task environment information to the human judge in order to improve judgment performance.

  9. Generation of human scFvs antibodies recognizing a prion protein epitope expressed on the surface of human lymphoblastoid cells

    Directory of Open Access Journals (Sweden)

    Imperiale Valentina

    2007-07-01

    Full Text Available Abstract Background A hallmark of prion disease is the transformation of normal cellular prion protein (PrPc into an infectious disease-associated isoform, (PrPsc. Anti-prion protein monoclonal antibodies are invaluable for structure-function studies of PrP molecules. Furthermore recent in vitro and in vivo studies indicate that anti-PrP monoclonal antibodies can prevent the incorporation of PrPc into propagating prions. In the present article, we show two new human phage antibodies, isolated on recombinant hamster prion protein (rHaPrP. Results We adopted an antibody phage display strategy to isolate specific human antibodies directed towards rHaPrP which has been used as a bait for panning the synthetic ETH-2 antibody phage library. Two phage antibodies clones named MA3.B4 and MA3.G3 were isolated and characterized under genetic biochemical and immunocytochemical aspects. The clones were found to recognize the prion protein in ELISA studies. In flow-cytometry studies, these human single chain Fragment variable (scFv phage-antibodies show a well defined pattern of reactivity on human lymphoblastoid and myeloid cells. Conclusion Sequence analysis of the gene encoding for the antibody fragments and antigen recognition patterns determined by flow-cytometry analysis indicate that the isolated scFvs recognize novel epitopes in the PrPc molecule. These new anti PrPc human antibodies are unique reagents for prion protein detection and may represent a biologic platform to develop new reagents to treat PrPsc associated disease.

  10. Enhancement of antitumor activity by using a fully human gene encoding a single-chain fragmented antibody specific for carcinoembryonic antigen

    Directory of Open Access Journals (Sweden)

    Shibaguchi H

    2017-08-01

    Full Text Available Hirotomo Shibaguchi,1,* Naixiang Luo,1,* Naoto Shirasu,1,* Motomu Kuroki,2 Masahide Kuroki1 1Department of Biochemistry, Faculty of Medicine, Fukuoka University, Fukuoka, Japan; 2School of Nursing, Faculty of Medicine, Fukuoka University, Fukuoka, Japan *These authors equally contributed to this work Abstract: Human leukocyte antigen and/or costimulatory molecules are frequently lacking in metastatic tumor cells, and thus tumor cells are able to escape from the immune system. Although lymphocytes with a chimeric antigen receptor (CAR is a promising approach for overcoming this challenge in cancer immunotherapy, administration of modified T cells alone often demonstrates little efficacy in patients. Therefore, in order to enhance the antitumor activity of immune cells in the cancer microenvironment, we used lymphocytes expressing CAR in combination with a fusion protein of IL-2 that contained the single-chain fragmented antibody (scFv specific for the carcinoembryonic antigen. Among a series of CAR constructs, with or without a spacer and the intracellular domain of CD28, the CAR construct containing CD8α, CD28, and CD3ζ most effectively activated and expressed INF-γ in CAR-bearing T cells. Furthermore, in comparison with free IL-2, the combination of peripheral blood mononuclear cells expressing CAR and the fusion protein containing IL-2 significantly enhanced the antitumor activity against MKN-45 cells, a human gastric cancer cell line. In conclusion, this novel combination therapy of CAR and a fusion protein consisting of a functional cytokine and a fully human scFv may be a promising approach for adoptive cancer immunotherapy. Keywords: chimeric antigen receptor, fusion protein, human scFv, CEA, combination therapy

  11. Self-assembling complexes of quantum dots and scFv antibodies for cancer cell targeting and imaging.

    Directory of Open Access Journals (Sweden)

    Tatiana A Zdobnova

    Full Text Available Semiconductor quantum dots represent a novel class of fluorophores with unique physical and chemical properties which could enable a remarkable broadening of the current applications of fluorescent imaging and optical diagnostics. Complexes of quantum dots and antibodies are promising visualising agents for fluorescent detection of selective biomarkers overexpressed in tumor tissues. Here we describe the construction of self-assembling fluorescent complexes of quantum dots and anti-HER1 or anti-HER2/neu scFv antibodies and their interactions with cultured tumor cells. A binding strategy based on a very specific non-covalent interaction between two proteins, barnase and barstar, was used to connect quantum dots and the targeting antibodies. Such a strategy allows combining the targeting and visualization functions simply by varying the corresponding modules of the fluorescent complex.

  12. Rise and Fall of an Anti-MUC1 Specific Antibody

    Science.gov (United States)

    Li, Jiandong; von Wasielewski, Reinhard; Bastert, Gunther; Schirrmann, Thomas; Esteves, Isabel Tourais; Behrens, Christian K.; Fournes, Bénédict; Fournier, Nathalie; de Romeuf, Christophe; Hust, Michael; Dübel, Stefan

    2011-01-01

    Background So far, human antibodies with good affinity and specificity for MUC1, a transmembrane protein overexpressed on breast cancers and ovarian carcinomas, and thus a promising target for therapy, were very difficult to generate. Results A human scFv antibody was isolated from an immune library derived from breast cancer patients immunised with MUC1. The anti-MUC1 scFv reacted with tumour cells in more than 80% of 228 tissue sections of mamma carcinoma samples, while showing very low reactivity with a large panel of non-tumour tissues. By mutagenesis and phage display, affinity of scFvs was increased up to 500fold to 5,7×10−10 M. Half-life in serum was improved from below 1 day to more than 4 weeks and was correlated with the dimerisation tendency of the individual scFvs. The scFv bound to T47D and MCF-7 mammalian cancer cell lines were recloned into the scFv-Fc and IgG format resulting in decrease of affinity of one binder. The IgG variants with the highest affinity were tested in mouse xenograft models using MCF-7 and OVCAR tumour cells. However, the experiments showed no significant decrease in tumour growth or increase in the survival rates. To study the reasons for the failure of the xenograft experiments, ADCC was analysed in vitro using MCF-7 and OVCAR3 target cells, revealing a low ADCC, possibly due to internalisation, as detected for MCF-7 cells. Conclusions Antibody phage display starting with immune libraries and followed by affinity maturation is a powerful strategy to generate high affinity human antibodies to difficult targets, in this case shown by the creation of a highly specific antibody with subnanomolar affinity to a very small epitope consisting of four amino acids. Despite these “best in class” binding parameters, the therapeutic success of this antibody was prevented by the target biology. PMID:21264246

  13. Rise and fall of an anti-MUC1 specific antibody.

    Directory of Open Access Journals (Sweden)

    Holger Thie

    2011-01-01

    Full Text Available So far, human antibodies with good affinity and specificity for MUC1, a transmembrane protein overexpressed on breast cancers and ovarian carcinomas, and thus a promising target for therapy, were very difficult to generate.A human scFv antibody was isolated from an immune library derived from breast cancer patients immunised with MUC1. The anti-MUC1 scFv reacted with tumour cells in more than 80% of 228 tissue sections of mamma carcinoma samples, while showing very low reactivity with a large panel of non-tumour tissues. By mutagenesis and phage display, affinity of scFvs was increased up to 500fold to 5,7×10(-10 M. Half-life in serum was improved from below 1 day to more than 4 weeks and was correlated with the dimerisation tendency of the individual scFvs. The scFv bound to T47D and MCF-7 mammalian cancer cell lines were recloned into the scFv-Fc and IgG format resulting in decrease of affinity of one binder. The IgG variants with the highest affinity were tested in mouse xenograft models using MCF-7 and OVCAR tumour cells. However, the experiments showed no significant decrease in tumour growth or increase in the survival rates. To study the reasons for the failure of the xenograft experiments, ADCC was analysed in vitro using MCF-7 and OVCAR3 target cells, revealing a low ADCC, possibly due to internalisation, as detected for MCF-7 cells.Antibody phage display starting with immune libraries and followed by affinity maturation is a powerful strategy to generate high affinity human antibodies to difficult targets, in this case shown by the creation of a highly specific antibody with subnanomolar affinity to a very small epitope consisting of four amino acids. Despite these "best in class" binding parameters, the therapeutic success of this antibody was prevented by the target biology.

  14. What is 3D good for? A review of human performance on stereoscopic 3D displays

    Science.gov (United States)

    McIntire, John P.; Havig, Paul R.; Geiselman, Eric E.

    2012-06-01

    This work reviews the human factors-related literature on the task performance implications of stereoscopic 3D displays, in order to point out the specific performance benefits (or lack thereof) one might reasonably expect to observe when utilizing these displays. What exactly is 3D good for? Relative to traditional 2D displays, stereoscopic displays have been shown to enhance performance on a variety of depth-related tasks. These tasks include judging absolute and relative distances, finding and identifying objects (by breaking camouflage and eliciting perceptual "pop-out"), performing spatial manipulations of objects (object positioning, orienting, and tracking), and navigating. More cognitively, stereoscopic displays can improve the spatial understanding of 3D scenes or objects, improve memory/recall of scenes or objects, and improve learning of spatial relationships and environments. However, for tasks that are relatively simple, that do not strictly require depth information for good performance, where other strong cues to depth can be utilized, or for depth tasks that lie outside the effective viewing volume of the display, the purported performance benefits of 3D may be small or altogether absent. Stereoscopic 3D displays come with a host of unique human factors problems including the simulator-sickness-type symptoms of eyestrain, headache, fatigue, disorientation, nausea, and malaise, which appear to effect large numbers of viewers (perhaps as many as 25% to 50% of the general population). Thus, 3D technology should be wielded delicately and applied carefully; and perhaps used only as is necessary to ensure good performance.

  15. Regression of established renal cell carcinoma in nude mice using lentivirus-transduced human T cells expressing a human anti-CAIX chimeric antigen receptor

    Directory of Open Access Journals (Sweden)

    Agnes Shuk-Yee Lo

    2014-01-01

    Full Text Available Carbonic anhydrase IX (CAIX is a tumor-associated antigen and marker of hypoxia that is overexpressed on > 90% of clear-cell type renal cell carcinoma (RCC but not on neighboring normal kidney tissue. Here, we report on the construction of two chimeric antigen receptors (CARs that utilize a carbonic anhydrase (CA domain mapped, human single chain antibody (scFv G36 as a targeting moiety but differ in their capacity to provide costimulatory signaling for optimal T cell proliferation and tumor cell killing. The resulting anti-CAIX CARs were expressed on human primary T cells via lentivirus transduction. CAR-transduced T cells (CART cells expressing second-generation G36-CD28-TCRζ exhibited more potent in vitro antitumor effects on CAIX+ RCC cells than first-generation G36-CD8-TCRζ including cytotoxicity, cytokine secretion, proliferation, and clonal expansion. Adoptive G36-CD28-TCRζ CART cell therapy combined with high-dose interleukin (IL-2 injection also lead to superior regression of established RCC in nude mice with evidence of tumor cell apoptosis and tissue necrosis. These results suggest that the fully human G36-CD28-TCRζ CARs should provide substantial improvements over first-generation mouse anti-CAIX CARs in clinical use through reduced human anti-mouse antibody responses against the targeting scFv and administration of lower doses of T cells during CART cell therapy of CAIX+ RCC.

  16. Isolation and expression of recombinant antibody fragments to the biological warfare pathogen Brucella melitensis.

    Science.gov (United States)

    Hayhurst, Andrew; Happe, Scott; Mabry, Robert; Koch, Zephyr; Iverson, Brent L; Georgiou, George

    2003-05-01

    Brucella melitensis is a highly infectious animal pathogen able to cause a recurring debilitating disease in humans and is therefore high on the list of biological warfare agents. Immunoglobulin genes from mice immunized with gamma-irradiated B. melitensis strain 16M were used to construct a library that was screened by phage display against similarly prepared bacteria. The selected phage particles afforded a strong enzyme-linked immunosorbent assay (ELISA) signal against gamma-irradiated B. melitensis cells. However, extensive efforts to express the respective single chain antibody variable region fragment (scFv) in soluble form failed due to: (i) poor solubility and (ii) in vivo degradation of the c-myc tag used for the detection of the recombinant antibodies. Both problems could be addressed by: (i) fusing a human kappa light chain constant domain (Ck) chain to the scFv to generate single chain antibody fragment (scAb) antibody fragments and (ii) by co-expression of the periplasmic chaperone Skp. While soluble, functional antibodies could be produced in this manner, phage-displaying scFvs or scAbs were still found to be superior ELISA reagents for immunoassays, due to the large signal amplification afforded by anti-phage antibodies. The isolated phage antibodies were shown to be highly specific to B. melitensis and did not recognize Yersinia pseudotuberculosis in contrast to the existing diagnostic monoclonal YST 9.2.1.

  17. Integrated multimodal human-computer interface and augmented reality for interactive display applications

    Science.gov (United States)

    Vassiliou, Marius S.; Sundareswaran, Venkataraman; Chen, S.; Behringer, Reinhold; Tam, Clement K.; Chan, M.; Bangayan, Phil T.; McGee, Joshua H.

    2000-08-01

    We describe new systems for improved integrated multimodal human-computer interaction and augmented reality for a diverse array of applications, including future advanced cockpits, tactical operations centers, and others. We have developed an integrated display system featuring: speech recognition of multiple concurrent users equipped with both standard air- coupled microphones and novel throat-coupled sensors (developed at Army Research Labs for increased noise immunity); lip reading for improving speech recognition accuracy in noisy environments, three-dimensional spatialized audio for improved display of warnings, alerts, and other information; wireless, coordinated handheld-PC control of a large display; real-time display of data and inferences from wireless integrated networked sensors with on-board signal processing and discrimination; gesture control with disambiguated point-and-speak capability; head- and eye- tracking coupled with speech recognition for 'look-and-speak' interaction; and integrated tetherless augmented reality on a wearable computer. The various interaction modalities (speech recognition, 3D audio, eyetracking, etc.) are implemented a 'modality servers' in an Internet-based client-server architecture. Each modality server encapsulates and exposes commercial and research software packages, presenting a socket network interface that is abstracted to a high-level interface, minimizing both vendor dependencies and required changes on the client side as the server's technology improves.

  18. Surface Immobilization of Human Arginase-1 with an Engineered Ice Nucleation Protein Display System in E. coli.

    Directory of Open Access Journals (Sweden)

    Zhen Zhang

    Full Text Available Ice nucleation protein (INP is frequently used as a surface anchor for protein display in gram-negative bacteria. Here, MalE and TorA signal peptides, and three charged polypeptides, 6×Lys, 6×Glu and 6×Asp, were anchored to the N-terminus of truncated INP (InaK-N to improve its surface display efficiency for human Arginase1 (ARG1. Our results indicated that the TorA signal peptide increased the surface translocation of non-protein fused InaK-N and human ARG1 fused InaK-N (InaK-N/ARG1 by 80.7% and 122.4%, respectively. Comparably, the MalE signal peptide decreased the display efficiencies of both the non-protein fused InaK-N and InaK-N/ARG1. Our results also suggested that the 6×Lys polypeptide significantly increased the surface display efficiency of K6-InaK-N/ARG1 by almost 2-fold, while also practically abolishing the surface translocation of non-protein fused InaK-N, indicating the interesting roles of charged polypeptides in bacteria surface display systems. Cell surface-immobilized K6-InaK-N/ARG1 presented an arginase activity of 10.7 U/OD600 under the optimized conditions of 40°C, pH 10.0 and 1 mM Mn2+, which could convert more than 95% of L-Arginine (L-Arg to L-Ornithine (L-Orn in 16 hours. The engineered InaK-Ns expanded the INP surface display system, which aided in the surface immobilization of human ARG1 in E. coli cells.

  19. Circular displays: control/display arrangements and stereotype strength with eight different display locations.

    Science.gov (United States)

    Chan, Alan H S; Hoffmann, Errol R

    2015-01-01

    Two experiments are reported that were designed to investigate control/display arrangements having high stereotype strengths when using circular displays. Eight display locations relative to the operator and control were tested with rotational and translational controls situated on different planes according to the Frame of Reference Transformation Tool (FORT) model of Wickens et al. (2010). (Left. No, Right! Development of the Frame of Reference Transformation Tool (FORT), Proceedings of the Human Factors and Ergonomics Society 54th Annual Meeting, 54: 1022-1026). In many cases, there was little effect of display locations, indicating the importance of the Worringham and Beringer (1998. Directional stimulus-response compatibility: a test of three alternative principles. Ergonomics, 41(6), 864-880) Visual Field principle and an extension of this principle for rotary controls (Hoffmann and Chan (2013). The Worringham and Beringer 'visual field' principle for rotary controls. Ergonomics, 56(10), 1620-1624). The initial indicator position (12, 3, 6 and 9 o'clock) had a major effect on control/display stereotype strength for many of the six controls tested. Best display/control arrangements are listed for each of the different control types (rotational and translational) and for the planes on which they are mounted. Data have application where a circular display is used due to limited display panel space and applies to space-craft, robotics operators, hospital equipment and home appliances. Practitioner Summary: Circular displays are often used when there is limited space available on a control panel. Display/control arrangements having high stereotype strength are listed for four initial indicator positions. These arrangements are best for design purposes.

  20. Identification of human embryonic progenitor cell targeting peptides using phage display.

    Directory of Open Access Journals (Sweden)

    Paola A Bignone

    Full Text Available Human pluripotent stem (hPS cells are capable of differentiation into derivatives of all three primary embryonic germ layers and can self-renew indefinitely. They therefore offer a potentially scalable source of replacement cells to treat a variety of degenerative diseases. The ability to reprogram adult cells to induced pluripotent stem (iPS cells has now enabled the possibility of patient-specific hPS cells as a source of cells for disease modeling, drug discovery, and potentially, cell replacement therapies. While reprogramming technology has dramatically increased the availability of normal and diseased hPS cell lines for basic research, a major bottleneck is the critical unmet need for more efficient methods of deriving well-defined cell populations from hPS cells. Phage display is a powerful method for selecting affinity ligands that could be used for identifying and potentially purifying a variety of cell types derived from hPS cells. However, identification of specific progenitor cell-binding peptides using phage display may be hindered by the large cellular heterogeneity present in differentiating hPS cell populations. We therefore tested the hypothesis that peptides selected for their ability to bind a clonal cell line derived from hPS cells would bind early progenitor cell types emerging from differentiating hPS cells. The human embryonic stem (hES cell-derived embryonic progenitor cell line, W10, was used and cell-targeting peptides were identified. Competition studies demonstrated specificity of peptide binding to the target cell surface. Efficient peptide targeted cell labeling was accomplished using multivalent peptide-quantum dot complexes as detected by fluorescence microscopy and flow cytometry. The cell-binding peptides were selective for differentiated hPS cells, had little or no binding on pluripotent cells, but preferential binding to certain embryonic progenitor cell lines and early endodermal hPS cell derivatives. Taken

  1. Performance evaluation of phage-displayed synthetic human single-domain antibody libraries: A retrospective analysis.

    Science.gov (United States)

    Henry, Kevin A; Tanha, Jamshid

    2018-05-01

    Fully human synthetic single-domain antibodies (sdAbs) are desirable therapeutic molecules but their development is a considerable challenge. Here, using a retrospective analysis of in-house historical data, we examined the parameters that impact the outcome of screening phage-displayed synthetic human sdAb libraries to discover antigen-specific binders. We found no evidence for a differential effect of domain type (V H or V L ), library randomization strategy, incorporation of a stabilizing disulfide linkage or sdAb display format (monovalent vs. multivalent) on the probability of obtaining any antigen-binding human sdAbs, instead finding that the success of library screens was primarily related to properties of target antigens, especially molecular mass. The solubility and binding affinity of sdAbs isolated from successful screens depended both on properties of the sdAb libraries (primarily domain type) and the target antigens. Taking attrition of sdAbs with major manufacturability concerns (aggregation; low expression) and sdAbs that do not recognize native cell-surface antigens as independent probabilities, we calculate the overall likelihood of obtaining ≥1 antigen-binding human sdAb from a single library-target screen as ~24%. Successful library-target screens should be expected to yield ~1.3 human sdAbs on average, each with average binding affinity of ~2 μM. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Human oxidation-specific antibodies reduce foam cell formation and atherosclerosis progression

    DEFF Research Database (Denmark)

    Tsimikas, Sotirios; Miyanohara, Atsushi; Hartvigsen, Karsten

    2011-01-01

    We sought to assess the in vivo importance of scavenger receptor (SR)-mediated uptake of oxidized low-density lipoprotein (OxLDL) in atherogenesis and to test the efficacy of human antibody IK17-Fab or IK17 single-chain Fv fragment (IK17-scFv), which lacks immunologic properties of intact antibod...... antibodies other than the ability to inhibit uptake of OxLDL by macrophages, to inhibit atherosclerosis....

  3. Development of a 'mouse and human cross-reactive' affinity-matured exosite inhibitory human antibody specific to TACE (ADAM17) for cancer immunotherapy.

    Science.gov (United States)

    Kwok, Hang Fai; Botkjaer, Kenneth A; Tape, Christopher J; Huang, Yanchao; McCafferty, John; Murphy, Gillian

    2014-06-01

    We previously showed that a human anti-TACE antibody, D1(A12), is a potent inhibitor of TNF-α converting enzyme (TACE) ectodomain proteolysis and has pharmacokinetic properties suitable for studies of the inhibition of TACE-dependent growth factor shedding in relation to possible therapeutic applications. However, the lack of murine TACE immunoreactivity limits pre-clinical in vivo studies to human xenograft models which are poor analogies to in situ pathology and are not considered clinically predictive. Here, to overcome these limitations, we set out to develop a 'mouse and human cross-reactive' specific anti-TACE antibody. We first re-investigated the originally selected anti-TACE ectodomain phage-display clones, and isolated a lead 'mouse-human cross-reactive' anti-TACE scFv, clone A9. We reformatted scFv-A9 into an IgG2 framework for comprehensive biochemical and cellular characterization and further demonstrated that A9 is an exosite TACE inhibitor. However, surface plasmon resonance analysis and quenched-fluorescent (QF) peptide assay indicated that IgG reformatting of A9 caused low binding affinity and an 80-fold reduction in TACE ectodomain inhibition, severely limiting its efficacy. To address this, we constructed second generation phage-display randomization libraries focused on the complementarity-determining region 3, and carried out affinity selections shuffling between human and mouse TACE ectodomain as antigen in addition to an off-rate selection to increase the chance of affinity improvement. The bespoke 'three-step' selections enabled a 100-fold affinity enhancement of A9 IgG, and also improved its IC50 in a QF peptide assay to 0.2 nM. In human and mouse cancer cell assays, matured A9 IgG showed significant cell-surface TACE inhibition as a monotherapy or combination therapy with chemotherapeutic agent. Collectively, these data suggest that we successfully developed an exosite inhibitor of TACE with sub-nanomolar affinity, which possesses both

  4. The Effect of Information Analysis Automation Display Content on Human Judgment Performance in Noisy Environments

    OpenAIRE

    Bass, Ellen J.; Baumgart, Leigh A.; Shepley, Kathryn Klein

    2012-01-01

    Displaying both the strategy that information analysis automation employs to makes its judgments and variability in the task environment may improve human judgment performance, especially in cases where this variability impacts the judgment performance of the information analysis automation. This work investigated the contribution of providing either information analysis automation strategy information, task environment information, or both, on human judgment performance in a domain where noi...

  5. 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.

  6. 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

  7. Development of an Indirect Competitive Enzyme-Linked Immunosorbent Assay for Glycocholic Acid Based on Chicken Single-Chain Variable Fragment Antibodies.

    Science.gov (United States)

    Cui, Xiping; Vasylieva, Natalia; Wu, Panpan; Barnych, Bogdan; Yang, Jun; Shen, Ding; He, Qiyi; Gee, Shirley J; Zhao, Suqing; Hammock, Bruce D

    2017-10-17

    Glycocholic acid (GCA) is an important metabolite of bile acids, whose urine levels are expected to be a specific diagnostic biomarker for hepatocellular carcinoma (HCC). A high-throughput immunoassay for determination of GCA would be of significant advantage and useful for primary diagnosis, surveillance, and early detection of HCC. Single-chain variable fragment (scFv) antibodies have several desirable characteristics and are an attractive alternative to traditional antibodies for the immunoassay. Because chicken antibodies possess single heavy and light variable functional domains, they are an ideal framework for simplified generation of recombinant antibodies for GCA detection. However, chicken scFvs have rarely been used to detect GCA. In this study, a scFv library was generated from chickens immunized with a GCA hapten coupled to bovine serum albumin (BSA), and anti-GCA scFvs were isolated by a phage-displayed method. Compared to the homologous coating antigen, use of a heterologous coating antigen resulted in about an 85-fold improvement in sensitivity of the immunoassay. This assay, under optimized conditions, had a linear range of 0.02-0.18 μg/mL, with an IC 50 of 0.06 μg/mL. The assay showed negligible cross-reactivity with various related bile acids, except for taurocholic acid. The detection of GCA from spiked human urine samples ranged from 86.7% to 123.3%. These results, combined with the advantages of scFv antibodies, indicated that a chicken scFv-based enzyme-linked immunosorbent assay is a suitable method for high-throughput screening of GCA in human urine.

  8. Handbook of Visual Display Technology

    CERN Document Server

    Cranton, Wayne; Fihn, Mark

    2012-01-01

    The Handbook of Visual Display Technology is a unique work offering a comprehensive description of the science, technology, economic and human interface factors associated with the displays industry. An invaluable compilation of information, the Handbook will serve as a single reference source with expert contributions from over 150 international display professionals and academic researchers. All classes of display device are covered including LCDs, reflective displays, flexible solutions and emissive devices such as OLEDs and plasma displays, with discussion of established principles, emergent technologies, and particular areas of application. The wide-ranging content also encompasses the fundamental science of light and vision, image manipulation, core materials and processing techniques, display driving and metrology.

  9. Effect of display location on control-display stereotype strength for translational and rotational controls with linear displays.

    Science.gov (United States)

    Chan, Alan H S; Hoffmann, Errol R

    2015-01-01

    Experiments were designed to investigate the effects of control type and display location, relative to the operator, on the strength of control/display stereotypes. The Worringham and Beringer Visual Field principle and an extension of this principle for rotary controls (Hoffmann E.R., and Chan A.H.S. 2013). "The Worringham and Beringer 'Visual Field' Principle for Rotary Controls. Ergonomics." 56 (10): 1620-1624) indicated that, for a number of different control types (rotary and lever) on different planes, there should be no significant effect of the display location relative to the seated operator. Past data were surveyed and stereotype strengths listed. Experiments filled gaps where data are not available. Six different control types and seven display locations were used, as in the Frame of Reference Transformation Tool (FORT) model of Wickens et al. (Wickens, C.D., Keller, J.W., and Small, R.L. (2010). "Left. No, Right! Development of the Frame of Reference Transformation Tool (FORT)." Proceedings of the Human Factors and Ergonomics Society 54th Annual Meeting September 2010, 54: 1022-1026). Control/display arrangements with high stereotype strengths were evaluated yielding data for designers of complex control/display arrangements where the control and display are in different planes and for where the operator is moving. It was found possible to predict display/control arrangements with high stereotype strength, based on past data. Practitioner Summary: Controls and displays in complex arrangements need to have high compatibility. These experiments provide arrangements for six different controls (rotary and translational) and seven different display locations relative to the operator.

  10. Affinity Maturation of an Anti-V Antigen IgG Expressed In Situ Via Adenovirus Gene Delivery Confers Enhanced Protection Against Yersinia pestis Challenge

    Science.gov (United States)

    Van Blarcom, Thomas J.; Sofer-Podesta, Carolina; Ang, John; Boyer, Julie L.; Crystal, Ronald G.; Georgiou, George

    2013-01-01

    Genetic transfer of neutralizing antibodies has been shown to confer strong and persistent protection against bacterial and viral infectious agents. While it is well established that for many exogenous neutralizing antibodies increased antigen affinity correlates with protection, the effect of antigen affinity on antibodies produced in situ following adenoviral gene transfer has not been examined. The mouse IgG2b monoclonal antibody 2C12.4 recognizes the Yersinia pestis Type III secretion apparatus protein LcrV (V antigen) and confers protection in mice when administered as an IgG intraperitoneally or, following genetic immunization with engineered, replication-defective serotype 5 human adenovirus (Ad) 1. 2C12.4 was expressed as a scFv fragment in E. coli and was shown to display a KD=3.5 nM by surface plasmon resonance (SPR) analysis. The 2C12.4 scFv was subjected to random mutagenesis and variants with increased affinity were isolated by flow cytometry using the Anchored Periplasmic Expression (APEx) bacterial display system. After a single round of mutagenesis, variants displaying up to 35-fold lower KD values (H8, KD=100 pM) were isolated. The variable domains of the H8 scFv were used to replace those of the parental 2C12.4 IgG encoded in the Ad vector, AdαV giving rise to AdαV.H8. The two adenoviral vectors resulted in similar titers of anti-V antigen antibodies 3 days post-immunization with 109, 1010 or 1011 particle units. Following intranasal challenge with 363 LD50Y. pestis CO92, 54% of the mice immunized with 1010 pu of AdαV.H8 survived at the 14 day end point compared to only 15% survivors for the group immunized with AdαV expressing the lower affinity 2C12.4 (Pgenetic transfer may confer increased protection not only for Y. pestis challenge but possibly for other pathogens. PMID:20393511

  11. Ribosome display: next-generation display technologies for production of antibodies in vitro.

    Science.gov (United States)

    He, Mingyue; Khan, Farid

    2005-06-01

    Antibodies represent an important and growing class of biologic research reagents and biopharmaceutical products. They can be used as therapeutics in a variety of diseases. With the rapid expansion of proteomic studies and biomarker discovery, there is a need for the generation of highly specific binding reagents to study the vast number of proteins encoded by the genome. Display technologies provide powerful tools for obtaining antibodies. Aside from the preservation of natural antibody repertoires, they are capable of exploiting diversity by DNA recombination to create very large libraries for selection of novel molecules. In contrast to in vivo immunization processes, display technologies allow selection of antibodies under in vitro-defined selection condition(s), resulting in enrichment of antibodies with desired properties from large populations. In addition, in vitro selection enables the isolation of antibodies against difficult antigens including self-antigens, and this can be applied to the generation of human antibodies against human targets. Display technologies can also be combined with DNA mutagenesis for antibody evolution in vitro. Some methods are amenable to automation, permitting high-throughput generation of antibodies. Ribosome display is considered as representative of the next generation of display technologies since it overcomes the limitations of cell-based display methods by using a cell-free system, offering advantages of screening larger libraries and continuously expanding new diversity during selection. Production of display-derived antibodies can be achieved by choosing one of a variety of prokaryotic and eukaryotic cell-based expression systems. In the near future, cell-free protein synthesis may be developed as an alternative for large-scale generation of antibodies.

  12. Interactive displays natural human-interface technologies

    CERN Document Server

    Bhowmik, Achintya K

    2014-01-01

    One of the first books to provide an in-depth discussion of the technologies, applications and trends in the rapidly emerging field of interactive displays (touch, gesture & voice) The book will cover the technologies, applications and trends in the field of interactive displays, namely interfaces based on touch, gesture and voice and those using a combination of these technologies. The book will be split into 4 main parts with each being dedicated to a specific user interface. Part 1 ''Touch Interfaces'' will provide a review of the currently deployed touch-screen technologies and applications. It will also cover the recent developments towards achieving thinner, lightweight and cost-reduced touch screen panels in the future via integration of touch functionalities. Part 2 ''Gesture Interfaces'' will examine techniques and applications in stereoscopic 3D computer vision, structured-light 3D computer vision and time-of-flight 3D computer vision in gesture interfaces. Part 3 ''Voice Interfaces'' will revie...

  13. A recombinant, fully human monoclonal antibody with antitumor activity constructed from phage-displayed antibody fragments

    NARCIS (Netherlands)

    Huls, GA; Heijnen, IAFM; Cuomo, ME; Koningsberger, JC; Boel, E; de Vries, ARV; Loyson, SAJ; Helfrich, W; Henegouwen, GPV; van Meijer, M; de Kruif, J; Logtenberg, T

    A single-chain Fv antibody fragment specific for the tumor-associated Ep-CAM molecule was isolated from a semisynthetic phage display library and converted into an intact, fully human IgG1 monoclonal antibody (huMab), The purified huMab had an affinity of 5 nM and effectively mediated tumor cell

  14. 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 ...

  15. Human factors considerations in the design and evaluation of flight deck displays and controls : version 2.0

    Science.gov (United States)

    2016-12-01

    The objective of this effort is to have a single source reference document for human factors regulatory and guidance material for flight deck displays and controls, in the interest of improving aviation safety. This document identifies guidance on hu...

  16. USING OLFACTORY DISPLAYS AS A NONTRADITIONAL INTERFACE IN HUMAN COMPUTER INTERACTION

    Directory of Open Access Journals (Sweden)

    Alper Efe

    2017-07-01

    Full Text Available Smell has its limitations and disadvantages as a display medium, but it also has its strengths and many have recognized its potential. At present, in communications and virtual technologies, smell is either forgotten or improperly stimulated, because non controlled odorants present in the physical space surrounding the user. Nonetheless a controlled presentation of olfactory information can give advantages in various application fields. Therefore, two enabling technologies, electronic noses and especially olfactory displays are reviewed. Scenarios of usage are discussed together with relevant psycho-physiological issues. End-to-end systems including olfactory interfaces are quantitatively characterised under many respects. Recent works done by the authors on field are reported. The article will touch briefly on the control of scent emissions; an important factor to consider when building scented computer systems. As a sample application SUBSMELL system investigated. A look at areas of human computer interaction where olfaction output may prove useful will be presented. The article will finish with some brief conclusions and discuss some shortcomings and gaps of the topic. In particular, the addition of olfactory cues to a virtual environment increased the user's sense of presence and memory of the environment. Also, this article discusses the educational aspect of the subsmell systems.

  17. Touch sensitive electrorheological fluid based tactile display

    Science.gov (United States)

    Liu, Yanju; Davidson, Rob; Taylor, Paul

    2005-12-01

    A tactile display is programmable device whose controlled surface is intended to be investigated by human touch. It has a great number of potential applications in the field of virtual reality and elsewhere. In this research, a 5 × 5 tactile display array including electrorheological (ER) fluid has been developed and investigated. Force responses of the tactile display array have been measured while a probe was moved across the upper surface. The purpose of this was to simulate the action of touch performed by human finger. Experimental results show that the sensed surface information could be controlled effectively by adjusting the voltage activation pattern imposed on the tactels. The performance of the tactile display is durable and repeatable. The touch sensitivity of this ER fluid based tactile display array has also been investigated in this research. The results show that it is possible to sense the touching force normal to the display's surface by monitoring the change of current passing through the ER fluid. These encouraging results are helpful for constructing a new type of tactile display based on ER fluid which can act as both sensor and actuator at the same time.

  18. Facial Displays Are Tools for Social Influence.

    Science.gov (United States)

    Crivelli, Carlos; Fridlund, Alan J

    2018-05-01

    Based on modern theories of signal evolution and animal communication, the behavioral ecology view of facial displays (BECV) reconceives our 'facial expressions of emotion' as social tools that serve as lead signs to contingent action in social negotiation. BECV offers an externalist, functionalist view of facial displays that is not bound to Western conceptions about either expressions or emotions. It easily accommodates recent findings of diversity in facial displays, their public context-dependency, and the curious but common occurrence of solitary facial behavior. Finally, BECV restores continuity of human facial behavior research with modern functional accounts of non-human communication, and provides a non-mentalistic account of facial displays well-suited to new developments in artificial intelligence and social robotics. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. White constancy method for mobile displays

    Science.gov (United States)

    Yum, Ji Young; Park, Hyun Hee; Jang, Seul Ki; Lee, Jae Hyang; Kim, Jong Ho; Yi, Ji Young; Lee, Min Woo

    2014-03-01

    In these days, consumer's needs for image quality of mobile devices are increasing as smartphone is widely used. For example, colors may be perceived differently when displayed contents under different illuminants. Displayed white in incandescent lamp is perceived as bluish, while same content in LED light is perceived as yellowish. When changed in perceived white under illuminant environment, image quality would be degraded. Objective of the proposed white constancy method is restricted to maintain consistent output colors regardless of the illuminants utilized. Human visual experiments are performed to analyze viewers'perceptual constancy. Participants are asked to choose the displayed white in a variety of illuminants. Relationship between the illuminants and the selected colors with white are modeled by mapping function based on the results of human visual experiments. White constancy values for image control are determined on the predesigned functions. Experimental results indicate that propsed method yields better image quality by keeping the display white.

  20. Volume scanning three-dimensional display with an inclined two-dimensional display and a mirror scanner

    Science.gov (United States)

    Miyazaki, Daisuke; Kawanishi, Tsuyoshi; Nishimura, Yasuhiro; Matsushita, Kenji

    2001-11-01

    A new three-dimensional display system based on a volume-scanning method is demonstrated. To form a three-dimensional real image, an inclined two-dimensional image is rapidly moved with a mirror scanner while the cross-section patterns of a three-dimensional object are displayed sequentially. A vector-scan CRT display unit is used to obtain a high-resolution image. An optical scanning system is constructed with concave mirrors and a galvanometer mirror. It is confirmed that three-dimensional images, formed by the experimental system, satisfy all the criteria for human stereoscopic vision.

  1. 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

  2. Color speckle in laser displays

    Science.gov (United States)

    Kuroda, Kazuo

    2015-07-01

    At the beginning of this century, lighting technology has been shifted from discharge lamps, fluorescent lamps and electric bulbs to solid-state lighting. Current solid-state lighting is based on the light emitting diodes (LED) technology, but the laser lighting technology is developing rapidly, such as, laser cinema projectors, laser TVs, laser head-up displays, laser head mounted displays, and laser headlamps for motor vehicles. One of the main issues of laser displays is the reduction of speckle noise1). For the monochromatic laser light, speckle is random interference pattern on the image plane (retina for human observer). For laser displays, RGB (red-green-blue) lasers form speckle patterns independently, which results in random distribution of chromaticity, called color speckle2).

  3. Characterization of an engineered human purine nucleoside phosphorylase fused to an anti-her2/neu single chain Fv for use in ADEPT

    Directory of Open Access Journals (Sweden)

    Wu Anna M

    2009-12-01

    Full Text Available Abstract Background Antibody Directed Enzyme Prodrug Therapy (ADEPT can be used to generate cytotoxic agents at the tumor site. To date non-human enzymes have mainly been utilized in ADEPT. However, these non-human enzymes are immunogenic limiting the number of times that ADEPT can be administered. To overcome the problem of immunogenicity, a fully human enzyme, capable of converting a non-toxic prodrug to cytotoxic drug was developed and joined to a human tumor specific scFv yielding a fully human targeting agent. Methods A double mutant of human purine nucleoside phosphorylase (hDM was developed which unlike the human enzyme can cleave adenosine-based prodrugs. For tumor-specific targeting, hDM was fused to the human anti-HER2/neu single chain Fv (scFv, C6 MH3B1. Enzymatic activity of hDM with its natural substrates and prodrugs was determined using spectrophotomeric approaches. A cell proliferation assay was used to assess the cytotoxicity generated following conversion of prodrug to drug as a result of enzymatic activity of hDM. Affinity of the targeting scFv, C6 MH3B1 fused to hDM to Her2/neu was confirmed using affinity chromatography, surface plasmon resonance, and flow-cytometry. Results In vitro hDM-C6 MH3B1 binds specifically to HER2/neu expressing tumor cells and localizes hDM to tumor cells, where the enzymatic activity of hDM-C6 MH3B1, but not the wild type enzyme, results in phosphorolysis of the prodrug, 2-fluoro-2'-deoxyadenosine to the cytotoxic drug 2-fluoroadenine (F-Ade causing inhibition of tumor cell proliferation. Significantly, the toxic small drug diffuses through the cell membrane of HER2/neu expressing cells as well as cells that lack the expression of HER2/neu, causing a bystander effect. F-Ade is toxic to cells irrespective of their growth rate; therefore, both the slowly dividing tumor cells and the non-dividing neighboring stromal cells that support tumor growth should be killed. Analysis of potential novel MHCII

  4. Effect of display size on visual attention.

    Science.gov (United States)

    Chen, I-Ping; Liao, Chia-Ning; Yeh, Shih-Hao

    2011-06-01

    Attention plays an important role in the design of human-machine interfaces. However, current knowledge about attention is largely based on data obtained when using devices of moderate display size. With advancement in display technology comes the need for understanding attention behavior over a wider range of viewing sizes. The effect of display size on test participants' visual search performance was studied. The participants (N = 12) performed two types of visual search tasks, that is, parallel and serial search, under three display-size conditions (16 degrees, 32 degrees, and 60 degrees). Serial, but not parallel, search was affected by display size. In the serial task, mean reaction time for detecting a target increased with the display size.

  5. Cellular Immunotherapy for Carcinoma Using Genetically Modified EGFR-Specific T Lymphocytes

    Directory of Open Access Journals (Sweden)

    Xikun Zhou

    2013-05-01

    Full Text Available Epidermal growth factor receptor (EGFR is overexpressed in a variety of human malignancies, including pancreatic cancer, breast cancer, colon cancer, and non-small cell lung cancer. Overexpression of EGFR is a predictive marker of therapeutic response and several lines of evidence suggest that EGFR is an excellent target for tumor therapy. However, the effective antitumor capacity of EGFR-specific T cells against EGFR-overexpressing tumor cells has not been fully elucidated. In our previous study, we identified an anti-EGFR single-chain variable fragment (scFv with specific and high affinity after screening by ribosome display. In this study, the anticancer potential of anti-EGFR scFv was investigated on the basis of cell-targeted therapy. A chimeric antigen receptor (CAR targeting EGFR was constructed and expressed on the cell membrane of T lymphocytes. These CAR-modified T cells demonstrated antitumor efficacy both in vitro and in vivo. In addition, the safety evaluation showed that CAR-modified lymphocytes have no or very minimal acute systemic toxicity. Taken together, our study provided the experimental basis for clinical application of genetically engineered lymphocytes; moreover, we also evaluate a new and interesting cell therapy protocol.

  6. Selection and Characterization of Single Chain Antibody Fragments Specific for Hsp90 as a Potential Cancer Targeting Molecule

    Directory of Open Access Journals (Sweden)

    Edyta Petters

    2015-08-01

    Full Text Available Heat shock proteins play an essential role in facilitating malignant transformation and they have been recognized as important factors in human cancers. One of the key elements of the molecular chaperones machinery is Hsp90 and it has recently become a target for anticancer therapeutic approaches. The potential and importance of Hsp90-directed agents becomes apparent when one realizes that disruption of Hsp90 function may influence over 200 oncogenic client proteins. Here, we described the selection and characterization of Hsp90-specific antibody fragments from commercially available Tomlinson I and J phage display libraries. The affinities of Hsp90-binding scFv variants were measured using SPR method. Then, based on the best clone selected, we performed the affinity maturation procedure and obtained valuable Hsp90-specific clones. The selected binders were expressed and applied for immunostaining, ELISA and SPR analysis using model cancer cell lines. All performed experiments confirmed the ability of selected antibodies to interact with the Hsp90. Therefore, the presented Hsp90-specific scFv, might be a starting point for the development of a novel antibody-based strategy targeting cancer.

  7. Development of an Evaluation Method for the Design Complexity of Computer-Based Displays

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyoung Ju; Lee, Seung Woo; Kang, Hyun Gook; Seong, Poong Hyun [KAIST, Daejeon (Korea, Republic of); Park, Jin Kyun [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2011-10-15

    The importance of the design of human machine interfaces (HMIs) for human performance and the safety of process industries has long been continuously recognized for many decades. Especially, in the case of nuclear power plants (NPPs), HMIs have significant implications for the safety of the NPPs because poor HMIs can impair the decision making ability of human operators. In order to support and increase the decision making ability of human operators, advanced HMIs based on the up-to-date computer technology are provided. Human operators in advanced main control room (MCR) acquire information through video display units (VDUs) and large display panel (LDP), which is required for the operation of NPPs. These computer-based displays contain a huge amount of information and present it with a variety of formats compared to those of a conventional MCR. For example, these displays contain more display elements such as abbreviations, labels, icons, symbols, coding, etc. As computer-based displays contain more information, the complexity of advanced displays becomes greater due to less distinctiveness of each display element. A greater understanding is emerging about the effectiveness of designs of computer-based displays, including how distinctively display elements should be designed. This study covers the early phase in the development of an evaluation method for the design complexity of computer-based displays. To this end, a series of existing studies were reviewed to suggest an appropriate concept that is serviceable to unravel this problem

  8. [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.

  9. Novel IgE Inhibitors for the Treatment of Food Allergies

    Science.gov (United States)

    2016-10-01

    our chances of identifying inhibitors of the IgE:FcR Figure 4. Yeast surface display and selection of mutated anti-IgE scFv clone 18 from an error...complex was used to generate a point mutation in the IgE-Fc, yielding an omalizumab-resistant IgE. Omalizumab-resistant IgE, in combination with...display experiments with wt and mutant IgE-Fc Month 10 Obtained yeast display library, generated selection reagents (IgE), completed anti-IgE

  10. Use of human factors in the integration of a safety parameter display system (SPDS) and emergency response facility (ERF) capabilities for the James A. Fitzpatrick nuclear power plant

    International Nuclear Information System (INIS)

    Fish, H.C. Jr.; Gutierrez, R.

    1987-01-01

    In 1987, New York Power Authority's Emergency and Process Information Computer (EPIC) System will be operational. The EPIC system was designed to perform two distinct functions: to serve as an advanced replacement for the existing plant process computer and to assist in providing the JAFNPP operations staff with information during plant emergency conditions. Besides meeting the operational and regulatory goals of NYPA, EPIC was designed to meet NYPA human factors criteria. Using human factors literature, industry standards and guidelines, a Human Factors Criteria document was prepared for the EPIC project. This document served as the bases for all hardware, display, and documentation design applicable to EPIC. The major tasks of the EPIC human factors plan include integration of past and present applicable human factors information, establishment of a user definition using data gathered from control room observations (startup and shutdown of JAFNPP), survey of computer programs used by the operators, and obtaining input from licensed operators. These major tasks played a role in the design of the design of the control room configuration, the design and development of computer generated displays, and the format in which the displayed and hard copy information would be presented to the user. This paper presents an overview of the human factors work performed and the documents researched or developed in the design of EPIC displays, software, and hardware. The location and operation of this new computer based information system, like the displays was based on the systematic application of operations and human factors principles

  11. 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.

  12. Full-color wide field-of-view holographic helmet-mounted display for pilot/vehicle interface development and human factors studies

    Science.gov (United States)

    Burley, James R., II; LaRussa, Joseph A.

    1990-10-01

    A Helmet-Mounted Display (HMD) which utilizes highly efficient trichromatic holographic elements has been designed to support pilot vechicle interface development and human factors studies at the NASA-Langley Research Center. While the optics are fully color corrected, the miniature CRT's are monochromatic. This design provides an upgrade path to full-color when miniature display technology matures to color. The optical design conforms to the helmet shape and provides a 50 degree field-of-view (FOV) to each eye. Built-in adjustments allow each ocular to be independently moved so that the overall horizontal FOV may be varied from 50 degrees to 100 degrees with a corresponding change in the stereo overlap region. The helmet design and interpupillary adjustment allow for the 5th through 95th percentile male and female wearer. Total head-borne weight is approximately 4.2 pounds. The high-resolution monochromatic CRTs are driven by a set of multisync electronics with a maximum video bandwidth of 88 Mhz and supports bith raster and stroke modes. The electronics are designed to be compatiable with the Silicon Graphics IRIS 4D graphics workstations and the ADAGE 340 stroke graphics computer. A Polhemus magnetic tracking device is used to determine the helmet line-of-sight. The helmet will be used to develop innovative new display concepts for the F- 1 8 High-Alpha Research Vehicle (HARV) which make use of the unique display properties of the HMD. Pictorial displays, which convey the appropriate information intuitively, are envisioned. Human factors studies are also planned to evaluate the utility of stereopsis and determine the FOV requirements for different tasks. Concepts proven in the simulator will be carried to flight test in 1993 with a lighter weight, "hardened" version of this HMD design.

  13. Tandem bispecific neutralizing antibody eliminates HIV-1 infection in humanized mice.

    Science.gov (United States)

    Wu, Xilin; Guo, Jia; Niu, Mengyue; An, Minghui; Liu, Li; Wang, Hui; Jin, Xia; Zhang, Qi; Lam, Ka Shing; Wu, Tongjin; Wang, Hua; Wang, Qian; Du, Yanhua; Li, Jingjing; Cheng, Lin; Tang, Hang Ying; Shang, Hong; Zhang, Linqi; Zhou, Paul; Chen, Zhiwei

    2018-04-23

    The discovery of an HIV-1 cure remains a medical challenge because the virus rebounds quickly after the cessation of combination antiretroviral therapy (cART). Here, we investigate the potential of an engineered tandem bispecific broadly neutralizing antibody (bs-bnAb) as an innovative product for HIV-1 prophylactic and therapeutic interventions. We discovered that by preserving 2 single-chain variable fragment (scFv) binding domains of each parental bnAb, a single gene-encoded tandem bs-bnAb, BiIA-SG, displayed substantially improved breadth and potency. BiIA-SG neutralized all 124 HIV-1-pseudotyped viruses tested, including global subtypes/recombinant forms, transmitted/founder viruses, variants not susceptible to parental bnAbs and to many other bnAbs with an average IC50 value of 0.073 μg/ml (range HIV-1 stains. Moreover, whereas BiIA-SG delayed viral rebound in a short-term therapeutic setting when combined with cART, a single injection of adeno-associated virus-transferred (AAV-transferred) BiIA-SG gene resulted dose-dependently in prolonged in vivo expression of BiIA-SG, which was associated with complete viremia control and subsequent elimination of infected cells in humanized mice. These results warrant the clinical development of BiIA-SG as a promising bs-bnAb-based biomedical intervention for the prevention and treatment of HIV-1 infection.

  14. Human health and ecological toxicity potentials due to heavy metal content in waste electronic devices with flat panel displays

    International Nuclear Information System (INIS)

    Lim, Seong-Rin; Schoenung, Julie M.

    2010-01-01

    Display devices such as cathode-ray tube (CRT) televisions and computer monitors are known to contain toxic substances and have consequently been banned from disposal in landfills in the State of California and elsewhere. New types of flat panel display (FPD) devices, millions of which are now purchased each year, also contain toxic substances, but have not previously been systematically studied and compared to assess the potential impact that could result from their ultimate disposal. In the current work, the focus is on the evaluation of end-of-life toxicity potential from the heavy metal content in select FPD devices with the intent to inform material selection and design-for-environment (DfE) decisions. Specifically, the metals antimony, arsenic, barium, beryllium, cadmium, chromium, cobalt, copper, lead, mercury, molybdenum, nickel, selenium, silver, vanadium, and zinc in plasma TVs, LCD (liquid crystal display) TVs, LCD computer monitors and laptop computers are considered. The human health and ecotoxicity potentials are evaluated through a life cycle assessment perspective by combining data on the respective heavy metal contents, the characterization factors in the U.S. EPA Tool for the Reduction and Assessment of Chemical and other environmental Impacts (TRACI), and a pathway and impact model. Principal contributors to the toxicity potentials are lead, arsenic, copper, and mercury. Although the heavy metal content in newer flat panel display devices creates less human health toxicity potential than that in CRTs, for ecological toxicity, the new devices are worse, especially because of the mercury in LCD TVs and the copper in plasma TVs.

  15. Guidelines for the use of vibro-tactile displays in human computer interaction

    NARCIS (Netherlands)

    Erp, J.B.F. van

    2002-01-01

    Vibro-tactile displays convey messages by presenting vibration to the user's skin. In recent years, the interest in and application of vibro-tactile displays is growing. Vibratory displays are introduced in mobile devices, desktop applications and even in aircraft [1]. Despite the growing interest,

  16. Polyvalent Display of Biomolecules on Live Cells.

    Science.gov (United States)

    Shi, Peng; Zhao, Nan; Lai, Jinping; Coyne, James; Gaddes, Erin R; Wang, Yong

    2018-06-04

    Surface display of biomolecules on live cells offers new opportunities to treat human diseases and perform basic studies. Existing methods are primarily focused on monovalent functionalization, that is, the display of single biomolecules across the cell surface. Here we show that the surface of live cells can be functionalized to display polyvalent biomolecular structures through two-step reactions under physiological conditions. This polyvalent functionalization enables the cell surface to recognize the microenvironment one order of magnitude more effectively than with monovalent functionalization. Thus, polyvalent display of biomolecules on live cells holds great potential for various biological and biomedical applications. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Volumetric 3D display using a DLP projection engine

    Science.gov (United States)

    Geng, Jason

    2012-03-01

    In this article, we describe a volumetric 3D display system based on the high speed DLPTM (Digital Light Processing) projection engine. Existing two-dimensional (2D) flat screen displays often lead to ambiguity and confusion in high-dimensional data/graphics presentation due to lack of true depth cues. Even with the help of powerful 3D rendering software, three-dimensional (3D) objects displayed on a 2D flat screen may still fail to provide spatial relationship or depth information correctly and effectively. Essentially, 2D displays have to rely upon capability of human brain to piece together a 3D representation from 2D images. Despite the impressive mental capability of human visual system, its visual perception is not reliable if certain depth cues are missing. In contrast, volumetric 3D display technologies to be discussed in this article are capable of displaying 3D volumetric images in true 3D space. Each "voxel" on a 3D image (analogous to a pixel in 2D image) locates physically at the spatial position where it is supposed to be, and emits light from that position toward omni-directions to form a real 3D image in 3D space. Such a volumetric 3D display provides both physiological depth cues and psychological depth cues to human visual system to truthfully perceive 3D objects. It yields a realistic spatial representation of 3D objects and simplifies our understanding to the complexity of 3D objects and spatial relationship among them.

  18. 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.

  19. User interface design in safety parameter display systems

    International Nuclear Information System (INIS)

    Schultz, E.E. Jr.; Johnson, G.L.

    1988-01-01

    The extensive installation of computerized safety Parameter Display Systems (SPDSs) in nuclear power plants since the Three-Mile Island accident has enhanced plant safety. It has also raised new issues of how best to ensure an effective interface between human operators and the plant via computer systems. New developments in interface technologies since the current generation of SPDSs was installed can contribute to improving display interfaces. These technologies include new input devices, three-dimensional displays, delay indicators, and auditory displays. Examples of how they might be applied to improve current SPDSs are given. These examples illustrate how the new use interface technology could be applied to future nuclear plant displays

  20. Ultraminiature, Micropower Multipurpose Display, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — High information content electronic displays remain the most difficult element of the human-machine interface to effectively miniaturize. Mobile applications need a...

  1. Immune TB Antibody Phage Display Library as a Tool To Study B Cell Immunity in TB Infections.

    Science.gov (United States)

    Hamidon, Nurul Hamizah; Suraiya, Siti; Sarmiento, Maria E; Acosta, Armando; Norazmi, Mohd Nor; Lim, Theam Soon

    2018-03-01

    B cells and in particular antibodies has always played second fiddle to cellular immunity in regard to tuberculosis (TB). However, recent studies has helped position humoral immunity especially antibodies back into the foray in relation to TB immunity. Therefore, the ability to correlate the natural antibody responses of infected individuals toward TB antigens would help strengthen this concept. Phage display is an intriguing approach that can be utilized to study antibody-mediated responses against a particular infection via harvesting the B cell repertoire from infected individuals. The development of disease-specific antibody libraries or immune libraries is useful to better understand antibody-mediated immune responses against specific disease antigens. This study describes the generation of an immune single-chain variable fragment (scFv) library derived from TB-infected individuals. The immune library with an estimated diversity of 10 9 independent clones was then applied for the identification of monoclonal antibodies against Mycobacterium tuberculosis α-crystalline as a model antigen. Biopanning of the library isolated three monoclonal antibodies with unique gene usage. This strengthens the role of antibodies in TB immunity in addition to the role played by cellular immunity. The developed library can be applied against other TB antigens and aid antibody-derived TB immunity studies in the future.

  2. An Investigation of Interval Management Displays

    Science.gov (United States)

    Swieringa, Kurt A.; Wilson, Sara R.; Shay, Rick

    2015-01-01

    NASA's first Air Traffic Management (ATM) Technology Demonstration (ATD-1) was created to transition the most mature ATM technologies from the laboratory to the National Airspace System. One selected technology is Interval Management (IM), which uses onboard aircraft automation to compute speeds that help the flight crew achieve and maintain precise spacing behind a preceding aircraft. Since ATD-1 focuses on a near-term environment, the ATD-1 flight demonstration prototype requires radio voice communication to issue an IM clearance. Retrofit IM displays will enable pilots to both enter information into the IM avionics and monitor IM operation. These displays could consist of an interface to enter data from an IM clearance and also an auxiliary display that presents critical information in the primary field-of-view. A human-in-the-loop experiment was conducted to examine usability and acceptability of retrofit IM displays, which flight crews found acceptable. Results also indicate the need for salient alerting when new speeds are generated and the desire to have a primary field of view display available that can display text and graphic trend indicators.

  3. Nuclear Medicine Image Display. Chapter 14

    Energy Technology Data Exchange (ETDEWEB)

    Bergmann, H. [Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna (Austria)

    2014-12-15

    The final step in a medical imaging procedure is to display the image(s) on a suitable display system where it is presented to the medical specialist for diagnostic interpretation. The display of hard copy images on X ray film or photographic film has largely been replaced today by soft copy image display systems with cathode ray tube (CRT) or liquid crystal display (LCD) monitors as the image rendering device. Soft copy display requires a high quality display monitor and a certain amount of image processing to optimize the image both with respect to the properties of the display device and to some psychophysiological properties of the human visual system. A soft copy display system, therefore, consists of a display workstation providing some basic image processing functions and the display monitor as the intrinsic display device. Display devices of lower quality may be used during intermediate steps of the acquisition and analysis of a patient study. Display monitors with a quality suitable for diagnostic reading by the specialist medical doctor are called primary devices, also known as diagnostic devices. Monitors with lower quality but good enough to be used for positioning, processing of studies, presentation of images in the wards, etc. are referred to as secondary devices or clinical devices. Nuclear medicine images can be adequately displayed even for diagnostic purposes on secondary devices. However, the increasing use of X ray images on which to report jointly with images from nuclear medicine studies, such as those generated by dual modality imaging, notably by positron emission tomography (PET)/computed tomography (CT) and single photon emission computed tomography (SPECT)/CT, requires display devices capable of visualizing high resolution grey scale images at diagnostic quality, i.e. primary display devices. Both grey scale and colour display devices are used, the latter playing an important role in the display of processed nuclear medicine images and

  4. Nuclear Medicine Image Display. Chapter 14

    International Nuclear Information System (INIS)

    Bergmann, H.

    2014-01-01

    The final step in a medical imaging procedure is to display the image(s) on a suitable display system where it is presented to the medical specialist for diagnostic interpretation. The display of hard copy images on X ray film or photographic film has largely been replaced today by soft copy image display systems with cathode ray tube (CRT) or liquid crystal display (LCD) monitors as the image rendering device. Soft copy display requires a high quality display monitor and a certain amount of image processing to optimize the image both with respect to the properties of the display device and to some psychophysiological properties of the human visual system. A soft copy display system, therefore, consists of a display workstation providing some basic image processing functions and the display monitor as the intrinsic display device. Display devices of lower quality may be used during intermediate steps of the acquisition and analysis of a patient study. Display monitors with a quality suitable for diagnostic reading by the specialist medical doctor are called primary devices, also known as diagnostic devices. Monitors with lower quality but good enough to be used for positioning, processing of studies, presentation of images in the wards, etc. are referred to as secondary devices or clinical devices. Nuclear medicine images can be adequately displayed even for diagnostic purposes on secondary devices. However, the increasing use of X ray images on which to report jointly with images from nuclear medicine studies, such as those generated by dual modality imaging, notably by positron emission tomography (PET)/computed tomography (CT) and single photon emission computed tomography (SPECT)/CT, requires display devices capable of visualizing high resolution grey scale images at diagnostic quality, i.e. primary display devices. Both grey scale and colour display devices are used, the latter playing an important role in the display of processed nuclear medicine images and

  5. Ocular Tolerance of Contemporary Electronic Display Devices.

    Science.gov (United States)

    Clark, Andrew J; Yang, Paul; Khaderi, Khizer R; Moshfeghi, Andrew A

    2018-05-01

    Electronic displays have become an integral part of life in the developed world since the revolution of mobile computing a decade ago. With the release of multiple consumer-grade virtual reality (VR) and augmented reality (AR) products in the past 2 years utilizing head-mounted displays (HMDs), as well as the development of low-cost, smartphone-based HMDs, the ability to intimately interact with electronic screens is greater than ever. VR/AR HMDs also place the display at much closer ocular proximity than traditional electronic devices while also isolating the user from the ambient environment to create a "closed" system between the user's eyes and the display. Whether the increased interaction with these devices places the user's retina at higher risk of damage is currently unclear. Herein, the authors review the discovery of photochemical damage of the retina from visible light as well as summarize relevant clinical and preclinical data regarding the influence of modern display devices on retinal health. Multiple preclinical studies have been performed with modern light-emitting diode technology demonstrating damage to the retina at modest exposure levels, particularly from blue-light wavelengths. Unfortunately, high-quality in-human studies are lacking, and the small clinical investigations performed to date have failed to keep pace with the rapid evolutions in display technology. Clinical investigations assessing the effect of HMDs on human retinal function are also yet to be performed. From the available data, modern consumer electronic displays do not appear to pose any acute risk to vision with average use; however, future studies with well-defined clinical outcomes and illuminance metrics are needed to better understand the long-term risks of cumulative exposure to electronic displays in general and with "closed" VR/AR HMDs in particular. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:346-354.]. Copyright 2018, SLACK Incorporated.

  6. Large Display Interaction Using Mobile Devices

    OpenAIRE

    Bauer, Jens

    2015-01-01

    Large displays become more and more popular, due to dropping prices. Their size and high resolution leverages collaboration and they are capable of dis- playing even large datasets in one view. This becomes even more interesting as the number of big data applications increases. The increased screen size and other properties of large displays pose new challenges to the Human- Computer-Interaction with these screens. This includes issues such as limited scalability to the number of users, diver...

  7. 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.

  8. Head-Mounted Display Technology for Low Vision Rehabilitation and Vision Enhancement

    Science.gov (United States)

    Ehrlich, Joshua R.; Ojeda, Lauro V.; Wicker, Donna; Day, Sherry; Howson, Ashley; Lakshminarayanan, Vasudevan; Moroi, Sayoko E.

    2017-01-01

    Purpose To describe the various types of head-mounted display technology, their optical and human factors considerations, and their potential for use in low vision rehabilitation and vision enhancement. Design Expert perspective. Methods An overview of head-mounted display technology by an interdisciplinary team of experts drawing on key literature in the field. Results Head-mounted display technologies can be classified based on their display type and optical design. See-through displays such as retinal projection devices have the greatest potential for use as low vision aids. Devices vary by their relationship to the user’s eyes, field of view, illumination, resolution, color, stereopsis, effect on head motion and user interface. These optical and human factors considerations are important when selecting head-mounted displays for specific applications and patient groups. Conclusions Head-mounted display technologies may offer advantages over conventional low vision aids. Future research should compare head-mounted displays to commonly prescribed low vision aids in order to compare their effectiveness in addressing the impairments and rehabilitation goals of diverse patient populations. PMID:28048975

  9. Structure-based engineering to restore high affinity binding of an isoform-selective anti-TGFβ1 antibody

    Science.gov (United States)

    Honey, Denise M.; Best, Annie; Qiu, Huawei

    2018-01-01

    ABSTRACT Metelimumab (CAT192) is a human IgG4 monoclonal antibody developed as a TGFβ1-specific antagonist. It was tested in clinical trials for the treatment of scleroderma but later terminated due to lack of efficacy. Subsequent characterization of CAT192 indicated that its TGFβ1 binding affinity was reduced by ∼50-fold upon conversion from the parental single-chain variable fragment (scFv) to IgG4. We hypothesized this result was due to decreased conformational flexibility of the IgG that could be altered via engineering. Therefore, we designed insertion mutants in the elbow region and screened for binding and potency. Our results indicated that increasing the elbow region linker length in each chain successfully restored the isoform-specific and high affinity binding of CAT192 to TGFβ1. The crystal structure of the high binding affinity mutant displays large conformational rearrangements of the variable domains compared to the wild-type antigen-binding fragment (Fab) and the low binding affinity mutants. Insertion of two glycines in both the heavy and light chain elbow regions provided sufficient flexibility for the variable domains to extend further apart than the wild-type Fab, and allow the CDR3s to make additional interactions not seen in the wild-type Fab structure. These interactions coupled with the dramatic conformational changes provide a possible explanation of how the scFv and elbow-engineered Fabs bind TGFβ1 with high affinity. This study demonstrates the benefits of re-examining both structure and function when converting scFv to IgG molecules, and highlights the potential of structure-based engineering to produce fully functional antibodies. PMID:29333938

  10. A variable-collimation display system

    Science.gov (United States)

    Batchko, Robert; Robinson, Sam; Schmidt, Jack; Graniela, Benito

    2014-03-01

    Two important human depth cues are accommodation and vergence. Normally, the eyes accommodate and converge or diverge in tandem; changes in viewing distance cause the eyes to simultaneously adjust both focus and orientation. However, ambiguity between accommodation and vergence cues is a well-known limitation in many stereoscopic display technologies. This limitation also arises in state-of-the-art full-flight simulator displays. In current full-flight simulators, the out-the-window (OTW) display (i.e., the front cockpit window display) employs a fixed collimated display technology which allows the pilot and copilot to perceive the OTW training scene without angular errors or distortions; however, accommodation and vergence cues are limited to fixed ranges (e.g., ~ 20 m). While this approach works well for long-range, the ambiguity of depth cues at shorter range hinders the pilot's ability to gauge distances in critical maneuvers such as vertical take-off and landing (VTOL). This is the first in a series of papers on a novel, variable-collimation display (VCD) technology that is being developed under NAVY SBIR Topic N121-041 funding. The proposed VCD will integrate with rotary-wing and vertical take-off and landing simulators and provide accurate accommodation and vergence cues for distances ranging from approximately 3 m outside the chin window to ~ 20 m. A display that offers dynamic accommodation and vergence could improve pilot safety and training, and impact other applications presently limited by lack of these depth cues.

  11. 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.

  12. Multimethods approach to safety-parameter-display evaluation

    International Nuclear Information System (INIS)

    Banks, W.W.; Blackman, H.S.; Gertman, D.I.; Petersen, R.J.

    1982-01-01

    The Human Factors Engineering Office of EG and G Idaho performed this NRC-funded study to assist the NRC in objectively assessing licensee-developed safety parameter display (SPD) formats and designs. The purpose of this study was to quantitatively measure the degree to which a tachistoscopic method of display evaluation would correlate with the results of a multidimensional rating approach to display evaluation. Results of the following three experiments will be presented; (a) tachistoscopic, (b) multidimensional rating scale, and (c) the combined results of a and b. The test material for all experiments consisted of three multivariate data display formats all under development as SPDs for reactor control rooms presenting safety parameter display data at the loss-of-fluid test (LOFT) facility. The three display formats studied were stars, deviation bar graphs, and meters. Eighteen adult volunteers were used as subjects. All were currently qualified reactor operators from the LOFT reactor plant, with a mean of 9.4 years reactor operating experience

  13. Bacterial surface-displayed GII.4 human norovirus capsid proteins bound to surface of Romaine lettuce through HBGA-like molecules

    Science.gov (United States)

    Human Noroviruses (HuNoVs) are the main cause of nonbacterial gastroenteritis. Contaminated produce is a main vehicle for dissemination of HuNoVs. In this study, we used an ice nucleation protein (INP) mediated surface display system to present the protruding domain of GII.4 HuNoV capsid protein (G...

  14. Advanced image display systems in radiology

    International Nuclear Information System (INIS)

    Wendler, T.

    1987-01-01

    Advanced image display systems for the fully digital diagnostic imaging departments of the future will be far more than simple replacements of the traditional film-viewing equipment. The new capabilities of very high resolution and highly dynamic displays offer a userfriendly and problem-oriented way of image interpretation. Advanced harware-, software- and human-machine interaction-concepts have been outlined. A scenario for a future way of handling and displaying images, reflecting a new image viewing paradigm in radiology is sketched which has been realized in an experimental image workstation model in the laboratory which, despite its technical complexity, offers a consistent strategy for fast and convenient interaction with image objects. The perspective of knowledge based techniques for workstation control software with object-oriented programming environments and user- and task-adaptive behavior leads to more advanced display properties and a new quality of userfriendliness. 2 refs.; 5 figs

  15. Isolation of Anti-Ricin Protective Antibodies Exhibiting High Affinity from Immunized Non-Human Primates

    Directory of Open Access Journals (Sweden)

    Tal Noy-Porat

    2016-03-01

    Full Text Available Ricin, derived from the castor bean plant Ricinus communis, is one of the most potent and lethal toxins known, against which there is no available antidote. To date, the use of neutralizing antibodies is the most promising post-exposure treatment for ricin intoxication. The aim of this study was to isolate high affinity anti-ricin antibodies that possess potent toxin-neutralization capabilities. Two non-human primates were immunized with either a ricin-holotoxin- or subunit-based vaccine, to ensure the elicitation of diverse high affinity antibodies. By using a comprehensive set of primers, immune scFv phage-displayed libraries were constructed and panned. A panel of 10 antibodies (five directed against the A subunit of ricin and five against the B subunit was isolated and reformatted into a full-length chimeric IgG. All of these antibodies were found to neutralize ricin in vitro, and several conferred full protection to ricin-intoxicated mice when given six hours after exposure. Six antibodies were found to possess exceptionally high affinity toward the toxin, with KD values below pM (koff < 1 × 10−7 s−1 that were well correlated with their ability to neutralize ricin. These antibodies, alone or in combination, could be used for the development of a highly-effective therapeutic preparation for post-exposure treatment of ricin intoxication.

  16. Monkeys preferentially process body information while viewing affective displays.

    Science.gov (United States)

    Bliss-Moreau, Eliza; Moadab, Gilda; Machado, Christopher J

    2017-08-01

    Despite evolutionary claims about the function of facial behaviors across phylogeny, rarely are those hypotheses tested in a comparative context-that is, by evaluating how nonhuman animals process such behaviors. Further, while increasing evidence indicates that humans make meaning of faces by integrating contextual information, including that from the body, the extent to which nonhuman animals process contextual information during affective displays is unknown. In the present study, we evaluated the extent to which rhesus macaques (Macaca mulatta) process dynamic affective displays of conspecifics that included both facial and body behaviors. Contrary to hypotheses that they would preferentially attend to faces during affective displays, monkeys looked for longest, most frequently, and first at conspecifics' bodies rather than their heads. These findings indicate that macaques, like humans, attend to available contextual information during the processing of affective displays, and that the body may also be providing unique information about affective states. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  17. Application of the Decomposition Method to the Design Complexity of Computer-based Display

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyoung Ju; Lee, Seung Woo; Seong, Poong Hyun [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of); Park, Jin Kyun [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2012-05-15

    The importance of the design of human machine interfaces (HMIs) for human performance and safety has long been recognized in process industries. In case of nuclear power plants (NPPs), HMIs have significant implications for the safety of the NPPs since poor implementation of HMIs can impair the operators' information searching ability which is considered as one of the important aspects of human behavior. To support and increase the efficiency of the operators' information searching behavior, advanced HMIs based on computer technology are provided. Operators in advanced main control room (MCR) acquire information through video display units (VDUs), and large display panel (LDP) required for the operation of NPPs. These computer-based displays contain a very large quantity of information and present them in a variety of formats than conventional MCR. For example, these displays contain more elements such as abbreviations, labels, icons, symbols, coding, and highlighting than conventional ones. As computer-based displays contain more information, complexity of the elements becomes greater due to less distinctiveness of each element. A greater understanding is emerging about the effectiveness of designs of computer-based displays, including how distinctively display elements should be designed. And according to Gestalt theory, people tend to group similar elements based on attributes such as shape, color or pattern based on the principle of similarity. Therefore, it is necessary to consider not only human operator's perception but the number of element consisting of computer-based display

  18. Application of the Decomposition Method to the Design Complexity of Computer-based Display

    International Nuclear Information System (INIS)

    Kim, Hyoung Ju; Lee, Seung Woo; Seong, Poong Hyun; Park, Jin Kyun

    2012-01-01

    The importance of the design of human machine interfaces (HMIs) for human performance and safety has long been recognized in process industries. In case of nuclear power plants (NPPs), HMIs have significant implications for the safety of the NPPs since poor implementation of HMIs can impair the operators' information searching ability which is considered as one of the important aspects of human behavior. To support and increase the efficiency of the operators' information searching behavior, advanced HMIs based on computer technology are provided. Operators in advanced main control room (MCR) acquire information through video display units (VDUs), and large display panel (LDP) required for the operation of NPPs. These computer-based displays contain a very large quantity of information and present them in a variety of formats than conventional MCR. For example, these displays contain more elements such as abbreviations, labels, icons, symbols, coding, and highlighting than conventional ones. As computer-based displays contain more information, complexity of the elements becomes greater due to less distinctiveness of each element. A greater understanding is emerging about the effectiveness of designs of computer-based displays, including how distinctively display elements should be designed. And according to Gestalt theory, people tend to group similar elements based on attributes such as shape, color or pattern based on the principle of similarity. Therefore, it is necessary to consider not only human operator's perception but the number of element consisting of computer-based display

  19. Preliminary study of gaze toward humans in photographs by individuals with autism, Down syndrome, or other intellectual disabilities: implications for design of visual scene displays.

    Science.gov (United States)

    Wilkinson, Krista M; Light, Janice

    2014-06-01

    Visual scene displays (VSDs) are a form of augmentative and alternative communication display in which language concepts are embedded into an image of a naturalistic event. VSDs are based on the theory that language learning occurs through interactions with other people, and recommendations for VSD design have emphasized using images of these events that include humans. However, many VSDs also include other items that could potentially be distracting. We examined gaze fixation in 18 school-aged participants with and without severe intellectual/developmental disabilities (i.e., individuals with typical development, autism, Down syndrome and other intellectual disabilities) while they viewed photographs with human figures of various sizes and locations in the image, appearing alongside other interesting, and potentially distracting items. In all groups, the human figures attracted attention rapidly (within 1.5 seconds). The proportions of each participant's own fixation time spent on the human figures were similar across all groups, as were the proportions of total fixations made to the human figures. Although the findings are preliminary, this initial evidence supports the inclusion of humans in VSD images.

  20. [Peptide phage display in biotechnology and biomedicine].

    Science.gov (United States)

    Kuzmicheva, G A; Belyavskaya, V A

    2016-07-01

    To date peptide phage display is one of the most common combinatorial methods used for identifying specific peptide ligands. Phage display peptide libraries containing billions different clones successfully used for selection of ligands with high affinity and selectivity toward wide range of targets including individual proteins, bacteria, viruses, spores, different kind of cancer cells and variety of nonorganic targets (metals, alloys, semiconductors etc.) Success of using filamentous phage in phage display technologies relays on the robustness of phage particles and a possibility to genetically modify its DNA to construct new phage variants with novel properties. In this review we are discussing characteristics of the most known non-commercial peptide phage display libraries of different formats (landscape libraries in particular) and their successful applications in several fields of biotechnology and biomedicine: discovery of peptides with diagnostic values against different pathogens, discovery and using of peptides recognizing cancer cells, trends in using of phage display technologies in human interactome studies, application of phage display technologies in construction of novel nano materials.

  1. Antiviral Activity of HIV gp120 Targeting Bispecific T Cell Engager (BiTE®) Antibody Constructs.

    Science.gov (United States)

    Brozy, Johannes; Schlaepfer, Erika; Mueller, Christina K S; Rochat, Mary-Aude; Rampini, Silvana K; Myburgh, Renier; Raum, Tobias; Kufer, Peter; Baeuerle, Patrick A; Muenz, Markus; Speck, Roberto F

    2018-05-02

    Today's gold standard in HIV therapy is the combined antiretroviral therapy (cART). It requires strict adherence by patients and life-long medication, which can lower the viral load below detection limits and prevent HIV-associated immunodeficiency, but cannot cure patients. The bispecific T cell engaging (BiTE®) antibody technology has demonstrated long-term relapse-free outcomes in patients with relapsed and refractory acute lymphocytic leukemia. We here generated BiTE® antibody constructs that target the HIV-1 envelope protein gp120 (HIV gp120) using either the scFv B12 or VRC01, the first two extracellular domains (1+2) of human CD4 alone or joined to the single chain variable fragment (scFv) of the antibody 17b fused to an anti-human CD3ϵ scFv. These engineered human BiTE® antibody constructs showed engagement of T cells for redirected lysis of HIV gp120-transfected CHO cells. Furthermore, they substantially inhibited HIV-1 replication in PBMCs as well as in macrophages co-cultured with autologous CD8+ T-cells, the most potent being the human CD4(1+2) BiTE® antibody construct and the CD4(1+2)L17b BiTE® antibody construct. The CD4(1+2) h BiTE® antibody construct promoted HIV infection of human CD4-/CD8+ T cells. In contrast, the neutralizing B12 and the VRC01 BiTE® antibody constructs as well as the CD4(1+2)L17b BiTE® antibody construct did not. Thus, BiTE® antibody constructs targeting HIV gp120 are very promising for constraining HIV and warrant further development as novel antiviral therapy with curative potential. Importance HIV is a chronic infection well controlled with the current cART. However, we lack cure of HIV, and the HIV pandemic goes on. Here we showed in vitro and ex vivo t hat a bispecific T-cell engaging (BiTE®) antibody construct targeting HIV gp120 resulted in substantially reduced HIV replication. In addition, these BiTE® antibody constructs display efficient killing of gp120 expressing cells and inhibited replication in ex vivo

  2. 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.

  3. Dance choreography is coordinated with song repertoire in a complex avian display.

    Science.gov (United States)

    Dalziell, Anastasia H; Peters, Richard A; Cockburn, Andrew; Dorland, Alexandra D; Maisey, Alex C; Magrath, Robert D

    2013-06-17

    All human cultures have music and dance, and the two activities are so closely integrated that many languages use just one word to describe both. Recent research points to a deep cognitive connection between music and dance-like movements in humans, fueling speculation that music and dance have coevolved and prompting the need for studies of audiovisual displays in other animals. However, little is known about how nonhuman animals integrate acoustic and movement display components. One striking property of human displays is that performers coordinate dance with music by matching types of dance movements with types of music, as when dancers waltz to waltz music. Here, we show that a bird also temporally coordinates a repertoire of song types with a repertoire of dance-like movements. During displays, male superb lyrebirds (Menura novaehollandiae) sing four different song types, matching each with a unique set of movements and delivering song and dance types in a predictable sequence. Crucially, display movements are both unnecessary for the production of sound and voluntary, because males sometimes sing without dancing. Thus, the coordination of independently produced repertoires of acoustic and movement signals is not a uniquely human trait. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Color and Visual Factors in ATC Displays

    National Research Council Canada - National Science Library

    Xing, Jing

    2006-01-01

    .... While the advantages of color may be apparent, many display designs suggest that ATC technology developers have not used basic human factors and color principles to optimize the advantages of color...

  5. Nanobodies and Nanobody-Based Human Heavy Chain Antibodies As Antitumor Therapeutics

    Directory of Open Access Journals (Sweden)

    Peter Bannas

    2017-11-01

    Full Text Available Monoclonal antibodies have revolutionized cancer therapy. However, delivery to tumor cells in vivo is hampered by the large size (150 kDa of conventional antibodies. The minimal target recognition module of a conventional antibody is composed of two non-covalently associated variable domains (VH and VL. The proper orientation of these domains is mediated by their hydrophobic interface and is stabilized by their linkage to disulfide-linked constant domains (CH1 and CL. VH and VL domains can be fused via a genetic linker into a single-chain variable fragment (scFv. scFv modules in turn can be fused to one another, e.g., to generate a bispecific T-cell engager, or they can be fused in various orientations to antibody hinge and Fc domains to generate bi- and multispecific antibodies. However, the inherent hydrophobic interaction of VH and VL domains limits the stability and solubility of engineered antibodies, often causing aggregation and/or mispairing of V-domains. Nanobodies (15 kDa and nanobody-based human heavy chain antibodies (75 kDa can overcome these limitations. Camelids naturally produce antibodies composed only of heavy chains in which the target recognition module is composed of a single variable domain (VHH or Nb. Advantageous features of nanobodies include their small size, high solubility, high stability, and excellent tissue penetration in vivo. Nanobodies can readily be linked genetically to Fc-domains, other nanobodies, peptide tags, or toxins and can be conjugated chemically at a specific site to drugs, radionuclides, photosensitizers, and nanoparticles. These properties make them particularly suited for specific and efficient targeting of tumors in vivo. Chimeric nanobody-heavy chain antibodies combine advantageous features of nanobodies and human Fc domains in about half the size of a conventional antibody. In this review, we discuss recent developments and perspectives for applications of nanobodies and nanobody

  6. Nanobodies and Nanobody-Based Human Heavy Chain Antibodies As Antitumor Therapeutics.

    Science.gov (United States)

    Bannas, Peter; Hambach, Julia; Koch-Nolte, Friedrich

    2017-01-01

    Monoclonal antibodies have revolutionized cancer therapy. However, delivery to tumor cells in vivo is hampered by the large size (150 kDa) of conventional antibodies. The minimal target recognition module of a conventional antibody is composed of two non-covalently associated variable domains (VH and VL). The proper orientation of these domains is mediated by their hydrophobic interface and is stabilized by their linkage to disulfide-linked constant domains (CH1 and CL). VH and VL domains can be fused via a genetic linker into a single-chain variable fragment (scFv). scFv modules in turn can be fused to one another, e.g., to generate a bispecific T-cell engager, or they can be fused in various orientations to antibody hinge and Fc domains to generate bi- and multispecific antibodies. However, the inherent hydrophobic interaction of VH and VL domains limits the stability and solubility of engineered antibodies, often causing aggregation and/or mispairing of V-domains. Nanobodies (15 kDa) and nanobody-based human heavy chain antibodies (75 kDa) can overcome these limitations. Camelids naturally produce antibodies composed only of heavy chains in which the target recognition module is composed of a single variable domain (VHH or Nb). Advantageous features of nanobodies include their small size, high solubility, high stability, and excellent tissue penetration in vivo . Nanobodies can readily be linked genetically to Fc-domains, other nanobodies, peptide tags, or toxins and can be conjugated chemically at a specific site to drugs, radionuclides, photosensitizers, and nanoparticles. These properties make them particularly suited for specific and efficient targeting of tumors in vivo . Chimeric nanobody-heavy chain antibodies combine advantageous features of nanobodies and human Fc domains in about half the size of a conventional antibody. In this review, we discuss recent developments and perspectives for applications of nanobodies and nanobody-based human heavy

  7. Safety parameter display systems' effect on operator performance

    International Nuclear Information System (INIS)

    Cerven, F.; Ford, R.E.; Blackman, H.S.

    1983-01-01

    Computer generated displays are a powerful and flexible tool for presenting data to the operators of nuclear power plants. Such displays are currently being developed in industry for use as safety parameter displays and for use in advanced control rooms. There exists a need for methods to objectively evaluate the effect of these displays, positive or negative, on the performance of control room personnel. Results of developing one such method, noninteractive simulation, and the two experiments that were performed to determine if it can be used as a method for evaluating computer displays are presented. This method is more objective and powerful than pencil and paper methods because it measures human performance rather than opinion or perference, has excellent control of the experimental variables, and has a higher fidelity to the control room environment. The results of these experiments indicates that the present methodology does not differentiate among the display types tested at a statistically significant level. In other words, all display types tested worked equally well in providing operators needed information

  8. Experimental study on display-control stereotype and development of human factors guidelines

    International Nuclear Information System (INIS)

    Lee, Jung Woon; Lee, Yong Hee; Oh, In Seok; Lee, Hyun Chul; Cha, Woo Chang

    2003-01-01

    It is very important to develop the design guidelines which can be applicable for Korean operators for the purpose of designing the KSNP more safely. The objective of this project is to provide the standards, guidelines and bases applicable for HF-010 through the within-subject experiment for obtaining Korean operators' population stereotype for direction-of-movement of controls associated with displays on the control panels. Through the survey of researches on display compatibility and the classification of types of displays and controls in the main control room of Uljin units 3 and 4, methods for an experiment on the stereotype were established. Experimental interface prototypes for a total of 108 combinations of display and control types were implemented. Experimental data collection and analysis system was built in association with the interface prototypes. The experiment was performed with participation of 250 students as subjects. About 20 guideline items were developed based on the results obtained from our analysis of experimental data

  9. Experimental study on display-control stereotype and development of human factors guidelines

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Lee, Yong Hee; Oh, In Seok; Lee, Hyun Chul [KAERI, Taejon (Korea, Republic of); Cha, Woo Chang [Kumoh National Univ. of Technolgy, Gumi (Korea, Republic of)

    2003-01-01

    It is very important to develop the design guidelines which can be applicable for Korean operators for the purpose of designing the KSNP more safely. The objective of this project is to provide the standards, guidelines and bases applicable for HF-010 through the within-subject experiment for obtaining Korean operators' population stereotype for direction-of-movement of controls associated with displays on the control panels. Through the survey of researches on display compatibility and the classification of types of displays and controls in the main control room of Uljin units 3 and 4, methods for an experiment on the stereotype were established. Experimental interface prototypes for a total of 108 combinations of display and control types were implemented. Experimental data collection and analysis system was built in association with the interface prototypes. The experiment was performed with participation of 250 students as subjects. About 20 guideline items were developed based on the results obtained from our analysis of experimental data.

  10. Visual displays and Neuro-Linguistic Programming

    Energy Technology Data Exchange (ETDEWEB)

    Brown-VanHoozer, S.A. [Argonne National Lab., Idaho Falls, ID (United States); VanHoozer, W.R. [Tranceformations Unlimited, Rigby, ID (United States)

    1994-10-01

    Advancement of computer technology is forthcoming at such a rapid pace that the research concerning the interplay of humans and computer technology is lagging far behind. One area of particular concern is the design of visual displays that are pragmatic, ``user friendly,`` and ``user assisting.`` When engineers design visual displays, they generally do so methodically and logically, but only from within their own individual perspective or ``model of the world.`` They select the human aspects which make sense to them and not necessarily to non-engineers, operators, and others. The model design is what the engineer chooses to relate, based on his or her perspective of reality. These choices limit the model design thereby excluding the users` perspective. A set of techniques which can be used to assist the designers in expanding their choices and include the users` model is Neuro-Linguistic Programming (NLP).

  11. Preliminary Investigation of Visual Attention to Human Figures in Photographs: Potential Considerations for the Design of Aided AAC Visual Scene Displays

    Science.gov (United States)

    Wilkinson, Krista M.; Light, Janice

    2011-01-01

    Purpose: Many individuals with complex communication needs may benefit from visual aided augmentative and alternative communication systems. In visual scene displays (VSDs), language concepts are embedded into a photograph of a naturalistic event. Humans play a central role in communication development and might be important elements in VSDs.…

  12. Directed Selection of Recombinant Human Monoclonal Antibodies to Herpes Simplex Virus Glycoproteins from Phage Display Libraries

    Science.gov (United States)

    Sanna, Pietro Paolo; Williamson, R. Anthony; de Logu, Alessandro; Bloom, Floyd E.; Burton, Dennis R.

    1995-07-01

    Human monoclonal antibodies have considerable potential in the prophylaxis and treatment of viral disease. However, only a few such antibodies suitable for clinical use have been produced to date. We have previously shown that large panels of human recombinant monoclonal antibodies against a plethora of infectious agents, including herpes simplex virus types 1 and 2, can be established from phage display libraries. Here we demonstrate that facile cloning of recombinant Fab fragments against specific viral proteins in their native conformation can be accomplished by panning phage display libraries against viral glycoproteins "captured" from infected cell extracts by specific monoclonal antibodies immobilized on ELISA plates. We have tested this strategy by isolating six neutralizing recombinant antibodies specific for herpes simplex glycoprotein gD or gB, some of which are against conformationally sensitive epitopes. By using defined monoclonal antibodies for the antigen-capture step, this method can be used for the isolation of antibodies to specific regions and epitopes within the target viral protein. For instance, monoclonal antibodies to a nonneutralizing epitope can be used in the capture step to clone antibodies to neutralizing epitopes, or antibodies to a neutralizing epitope can be used to clone antibodies to a different neutralizing epitope. Furthermore, by using capturing antibodies to more immunodominant epitopes, one can direct the cloning to less immunogenic ones. This method should be of value in generating antibodies to be used both in the prophylaxis and treatment of viral infections and in the characterization of the mechanisms of antibody protective actions at the molecular level.

  13. 3D display system using monocular multiview displays

    Science.gov (United States)

    Sakamoto, Kunio; Saruta, Kazuki; Takeda, Kazutoki

    2002-05-01

    A 3D head mounted display (HMD) system is useful for constructing a virtual space. The authors have researched the virtual-reality systems connected with computer networks for real-time remote control and developed a low-priced real-time 3D display for building these systems. We developed a 3D HMD system using monocular multi-view displays. The 3D displaying technique of this monocular multi-view display is based on the concept of the super multi-view proposed by Kajiki at TAO (Telecommunications Advancement Organization of Japan) in 1996. Our 3D HMD has two monocular multi-view displays (used as a visual display unit) in order to display a picture to the left eye and the right eye. The left and right images are a pair of stereoscopic images for the left and right eyes, then stereoscopic 3D images are observed.

  14. Generation of recombinant antibodies to rat GABAA receptor subunits by affinity selection on synthetic peptides.

    Directory of Open Access Journals (Sweden)

    Sujatha P Koduvayur

    Full Text Available The abundance and physiological importance of GABAA receptors in the central nervous system make this neurotransmitter receptor an attractive target for localizing diagnostic and therapeutic biomolecules. GABAA receptors are expressed within the retina and mediate synaptic signaling at multiple stages of the visual process. To generate monoclonal affinity reagents that can specifically recognize GABAA receptor subunits, we screened two bacteriophage M13 libraries, which displayed human scFvs, by affinity selection with synthetic peptides predicted to correspond to extracellular regions of the rat α1 and β2 GABAA subunits. We isolated three anti-β2 and one anti-α1 subunit specific scFvs. Fluorescence polarization measurements revealed all four scFvs to have low micromolar affinities with their cognate peptide targets. The scFvs were capable of detecting fully folded GABAA receptors heterologously expressed by Xenopus laevis oocytes, while preserving ligand-gated channel activity. Moreover, A10, the anti-α1 subunit-specific scFv, was capable of detecting native GABAA receptors in the mouse retina, as observed by immunofluorescence staining. In order to improve their apparent affinity via avidity, we dimerized the A10 scFv by fusing it to the Fc portion of the IgG. The resulting scFv-Fc construct had a Kd of ∼26 nM, which corresponds to an approximately 135-fold improvement in binding, and a lower detection limit in dot blots, compared to the monomeric scFv. These results strongly support the use of peptides as targets for generating affinity reagents to membrane proteins and encourage investigation of molecular conjugates that use scFvs as anchoring components to localize reagents of interest at GABAA receptors of retina and other neural tissues, for studies of receptor activation and subunit structure.

  15. Isolation of Osteosarcoma-Associated Human Antibodies from a Combinatorial Fab Phage Display Library

    Directory of Open Access Journals (Sweden)

    Carmela Dantas-Barbosa

    2009-01-01

    Full Text Available Osteosarcoma, a highly malignant disease, is the most common primary bone tumor and is frequently found in children and adolescents. In order to isolate antibodies against osteosarcoma antigens, a combinatorial osteosarcoma Fab library displayed on the surface of phages was used. After three rounds of selection on the surface of tumor cells, several osteosarcoma-reactive Fabs were detected. From these Fabs, five were better characterized, and despite having differences in their VH (heavy chain variable domain and Vκ (kappa chain variable domain regions, they all bound to a protein with the same molecular mass. Further analysis by cell ELISA and immunocytochemistry suggested that the Fabs recognize a membrane-associated tumor antigen expressed in higher amounts in neoplasic cells than in normal tissue. These results suggest that the human Fabs selected in this work are a valuable tool for the study of this neoplasia.

  16. Volumetric 3D Display System with Static Screen

    Science.gov (United States)

    Geng, Jason

    2011-01-01

    Current display technology has relied on flat, 2D screens that cannot truly convey the third dimension of visual information: depth. In contrast to conventional visualization that is primarily based on 2D flat screens, the volumetric 3D display possesses a true 3D display volume, and places physically each 3D voxel in displayed 3D images at the true 3D (x,y,z) spatial position. Each voxel, analogous to a pixel in a 2D image, emits light from that position to form a real 3D image in the eyes of the viewers. Such true volumetric 3D display technology provides both physiological (accommodation, convergence, binocular disparity, and motion parallax) and psychological (image size, linear perspective, shading, brightness, etc.) depth cues to human visual systems to help in the perception of 3D objects. In a volumetric 3D display, viewers can watch the displayed 3D images from a completely 360 view without using any special eyewear. The volumetric 3D display techniques may lead to a quantum leap in information display technology and can dramatically change the ways humans interact with computers, which can lead to significant improvements in the efficiency of learning and knowledge management processes. Within a block of glass, a large amount of tiny dots of voxels are created by using a recently available machining technique called laser subsurface engraving (LSE). The LSE is able to produce tiny physical crack points (as small as 0.05 mm in diameter) at any (x,y,z) location within the cube of transparent material. The crack dots, when illuminated by a light source, scatter the light around and form visible voxels within the 3D volume. The locations of these tiny voxels are strategically determined such that each can be illuminated by a light ray from a high-resolution digital mirror device (DMD) light engine. The distribution of these voxels occupies the full display volume within the static 3D glass screen. This design eliminates any moving screen seen in previous

  17. Head Worn Display System for Equivalent Visual Operations

    Science.gov (United States)

    Cupero, Frank; Valimont, Brian; Wise, John; Best. Carl; DeMers, Bob

    2009-01-01

    Head-Worn Displays or so-called, near-to-eye displays have potentially significant advantages in terms of cost, overcoming cockpit space constraints, and for the display of spatially-integrated information. However, many technical issues need to be overcome before these technologies can be successfully introduced into commercial aircraft cockpits. The results of three activities are reported. First, the near-to-eye display design, technological, and human factors issues are described and a literature review is presented. Second, the results of a fixed-base piloted simulation, investigating the impact of near to eye displays on both operational and visual performance is reported. Straight-in approaches were flown in simulated visual and instrument conditions while using either a biocular or a monocular display placed on either the dominant or non-dominant eye. The pilot's flight performance, visual acuity, and ability to detect unsafe conditions on the runway were tested. The data generally supports a monocular design with minimal impact due to eye dominance. Finally, a method for head tracker system latency measurement is developed and used to compare two different devices.

  18. CULTURAL DISPLAY RULES DRIVE EYE GAZE DURING THINKING.

    Science.gov (United States)

    McCarthy, Anjanie; Lee, Kang; Itakura, Shoji; Muir, Darwin W

    2006-11-01

    The authors measured the eye gaze displays of Canadian, Trinidadian, and Japanese participants as they answered questions for which they either knew, or had to derive, the answers. When they knew the answers, Trinidadians maintained the most eye contact, whereas Japanese maintained the least. When thinking about the answers to questions, Canadians and Trinidadians looked up, whereas Japanese looked down. Thus, for humans, gaze displays while thinking are at least in part culturally determined.

  19. A Qualitative Method to Estimate HSI Display Complexity

    International Nuclear Information System (INIS)

    Hugo, Jacques; Gertman, David

    2013-01-01

    There is mounting evidence that complex computer system displays in control rooms contribute to cognitive complexity and, thus, to the probability of human error. Research shows that reaction time increases and response accuracy decreases as the number of elements in the display screen increase. However, in terms of supporting the control room operator, approaches focusing on addressing display complexity solely in terms of information density and its location and patterning, will fall short of delivering a properly designed interface. This paper argues that information complexity and semantic complexity are mandatory components when considering display complexity and that the addition of these concepts assists in understanding and resolving differences between designers and the preferences and performance of operators. This paper concludes that a number of simplified methods, when combined, can be used to estimate the impact that a particular display may have on the operator's ability to perform a function accurately and effectively. We present a mixed qualitative and quantitative approach and a method for complexity estimation

  20. The effect of display movement angle, indicator type and display location on control/display stereotype strength.

    Science.gov (United States)

    Hoffmann, Errol R; Chan, Alan H S

    2017-08-01

    Much research on stereotype strength relating display and control movements for displays moving in the vertical or horizontal directions has been reported. Here we report effects of display movement angle, where the display moves at angles (relative to the vertical) of between 0° and 180°. The experiment used six different controls, four display locations relative to the operator and three types of indicator. Indicator types were included because of the strong effects of the 'scale-side principle' that are variable with display angle. A directional indicator had higher stereotype strength than a neutral indicator, and showed an apparent reversal in control/display stereotype direction beyond an angle of 90°. However, with a neutral indicator this control reversal was not present. Practitioner Summary: The effects of display moving at angles other than the four cardinal directions, types of control, location of display and types of indicator are investigated. Indicator types (directional and neutral) have an effect on stereotype strength and may cause an apparent control reversal with change of display movement angle.

  1. Rapid Isolation of a Single-Chain Antibody against the Cyanobacterial Toxin Microcystin-LR by Phage Display and Its Use in the Immunoaffinity Concentration of Microcystins from Water

    Science.gov (United States)

    McElhiney, Jacqui; Drever, Mathew; Lawton, Linda A.; Porter, Andy J.

    2002-01-01

    A naïve (unimmunized) human semisynthetic phage display library was employed to isolate recombinant antibody fragments against the cyanobacterial hepatotoxin microcystin-LR. Selected antibody scFv genes were cloned into a soluble expression vector and expressed in Escherichia coli for characterization against purified microcystin-LR by competition enzyme-linked immunosorbent assay (ELISA). The most sensitive single-chain antibody (scAb) isolated was capable of detecting microcystin-LR at levels below the World Health Organization limit in drinking water (1 μg liter−1) and cross-reacted with three other purified microcystin variants (microcystin-RR, -LW, and -LF) and the related cyanotoxin nodularin. Extracts of the cyanobacterium Microcystis aeruginosa were assayed by ELISA, and quantifications of microcystins in toxic samples showed good correlation with analysis by high-performance liquid chromatography. Immobilized scAb was also used to prepare immunoaffinity columns, which were assessed for the ability to concentrate microcystin-LR from water for subsequent analysis by high-performance liquid chromatography. Anti-microcystin-LR scAb was immobilized on columns via a hexahistidine tag, ensuring maximum exposure of antigen binding sites, and the performance of the columns was evaluated by directly applying 150 ml of distilled water spiked with 4 μg of purified microcystin-LR. The procedure was simple, and a recovery rate of 94% was achieved following elution in 1 ml of 100% methanol. Large-scale, low-cost production of anti-microcystin-LR scAb in E. coli is an exciting prospect for the development of biosensors and on-line monitoring systems for microcystins and will also facilitate a range of immunoaffinity applications for the cleanup and concentration of these toxins from environmental samples. PMID:12406716

  2. Phage display used for gene cloning of human recombinant antibody against the erythrocyte surface antigen, rhesus D

    DEFF Research Database (Denmark)

    Dziegiel, M; Nielsen, L K; Andersen, P S

    1995-01-01

    A novel phage display system has been developed for PCR amplification and cloning of the Fab fragments of human immunoglobulin genes. Using this system, we have cloned an antibody from a mouse-human hybridoma cell line directed against the erythrocyte antigen rhesus D. Intact erythrocytes were used...... for absorption of the Fab phages. Soluble Fab fragments produced from the cloned material showed identical performance to the parental antibody in agglutination assays. Gel filtration confirmed that the Fab fragment consists of a kappa-Fd heterodimer. The successful use of intact cells for selection of specific...... Fab phages demonstrates that it is possible to by-pass purification of the antigen of interest. Comparison with published germline sequences demonstrated that the immunoglobulin coding regions had the highest homology to the VH 1.9III and V kappa Hum kappa v325 germline genes, respectively....

  3. Chimeric rabbit/human Fab antibodies against the hepatitis Be-antigen and their potential applications in assays, characterization, and therapy.

    Science.gov (United States)

    Zhuang, Xiaolei; Watts, Norman R; Palmer, Ira W; Kaufman, Joshua D; Dearborn, Altaira D; Trenbeath, Joni L; Eren, Elif; Steven, Alasdair C; Rader, Christoph; Wingfield, Paul T

    2017-10-06

    Hepatitis B virus (HBV) infection afflicts millions worldwide, causing cirrhosis and liver cancer. HBV e-antigen (HBeAg), a clinical marker for disease severity, is a soluble variant of the viral capsid protein. HBeAg is not required for viral replication but is implicated in establishing immune tolerance and chronic infection. The structure of recombinant e-antigen (rHBeAg) was recently determined, yet to date, the exact nature and quantitation of HBeAg still remain uncertain. Here, to further characterize HBeAg, we used phage display to produce a panel of chimeric rabbit/human monoclonal antibody fragments (both Fab and scFv) against rHBeAg. Several of the Fab/scFv, expressed in Escherichia coli , had unprecedentedly high binding affinities ( K d ∼10 -12 m) and high specificity. We used Fab/scFv in the context of an enzyme-linked immunosorbent assay (ELISA) for HBeAg quantification, which we compared with commercially available kits and verified with seroconversion panels, the WHO HBeAg standard, rHBeAg, and patient plasma samples. We found that the specificity and sensitivity are superior to those of existing commercial assays. To identify potential fine differences between rHBeAg and HBeAg, we used these Fabs in microscale immunoaffinity chromatography to purify HBeAg from individual patient plasmas. Western blotting and MS results indicated that rHBeAg and HBeAg are essentially structurally identical, although HBeAg from different patients exhibits minor carboxyl-terminal heterogeneity. We discuss several potential applications for the humanized Fab/scFv.

  4. Feasibility Study of Haptic Display for Rotation Tasks of Wrist Work

    OpenAIRE

    曽根, 順治; 岩井, 秀樹; 山田, 勝実; 陳, 軍; 徳山, 喜政; 今野, 晃市; Sone, Junji; Iwai, Hideki; Yamada, Katsumi; Chen, Jun; Tokuyama, Yoshimasa; Konno, Kouichi

    2011-01-01

    We have developed a haptic display for rotational tasks that involve functions of the human wrist. We represent the torque using a motor and a brake. Reference torque curves are obtained by the measuring torque required for each actual task using a torque sensor. The brake represents the stop condition. We have confirmed the effectiveness of the display by comparing the actual tasks with the haptic display experiment.

  5. Real-time Image Generation for Compressive Light Field Displays

    International Nuclear Information System (INIS)

    Wetzstein, G; Lanman, D; Hirsch, M; Raskar, R

    2013-01-01

    With the invention of integral imaging and parallax barriers in the beginning of the 20th century, glasses-free 3D displays have become feasible. Only today—more than a century later—glasses-free 3D displays are finally emerging in the consumer market. The technologies being employed in current-generation devices, however, are fundamentally the same as what was invented 100 years ago. With rapid advances in optical fabrication, digital processing power, and computational perception, a new generation of display technology is emerging: compressive displays exploring the co-design of optical elements and computational processing while taking particular characteristics of the human visual system into account. In this paper, we discuss real-time implementation strategies for emerging compressive light field displays. We consider displays composed of multiple stacked layers of light-attenuating or polarization-rotating layers, such as LCDs. The involved image generation requires iterative tomographic image synthesis. We demonstrate that, for the case of light field display, computed tomographic light field synthesis maps well to operations included in the standard graphics pipeline, facilitating efficient GPU-based implementations with real-time framerates.

  6. Evaluation of technical design of advanced information display

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Woo Chang; Kang, Young Ju; Ji, Jung Hun; Jang, Sung Pil; Jung, Sung Hae [Kumoh National Institute of Technology, Gumi (Korea, Republic of)

    2003-03-15

    The performance of human machine system such as nuclear power plant is highly dependent on the suitability of the interface design of the system. As the computer technology is highly developed, the mental model of computer users including NPP operators has been changed from analogue display type-based stereotype to digitalized one. Therefore, it is necessary and confident to consider the issues to evaluate system suitability of advanced information display on CRT or CBP (Computer Based Procedure). This document is intended for providing an updated and expanded set of user-interface guidelines that meet the needs of designing information display on CRT by finding the generic guidelines involving information display design issues as much as possible. The design Issues and resolutions from the finding may provide the cues for the designers and evaluators of the specific man machine interfaces of digitalized devices.

  7. Evaluation of technical design of advanced information display

    International Nuclear Information System (INIS)

    Cha, Woo Chang; Kang, Young Ju; Ji, Jung Hun; Jang, Sung Pil; Jung, Sung Hae

    2003-03-01

    The performance of human machine system such as nuclear power plant is highly dependent on the suitability of the interface design of the system. As the computer technology is highly developed, the mental model of computer users including NPP operators has been changed from analogue display type-based stereotype to digitalized one. Therefore, it is necessary and confident to consider the issues to evaluate system suitability of advanced information display on CRT or CBP (Computer Based Procedure). This document is intended for providing an updated and expanded set of user-interface guidelines that meet the needs of designing information display on CRT by finding the generic guidelines involving information display design issues as much as possible. The design Issues and resolutions from the finding may provide the cues for the designers and evaluators of the specific man machine interfaces of digitalized devices

  8. Enhancement of antitumor activity of gammaretrovirus carrying IL-12 gene through genetic modification of envelope targeting HER2 receptor: a promising strategy for bladder cancer therapy.

    Science.gov (United States)

    Tsai, Y-S; Shiau, A-L; Chen, Y-F; Tsai, H-T; Tzai, T-S; Wu, C-L

    2010-01-01

    The objective of this study was to develop an HER2-targeted, envelope-modified Moloney murine leukemia virus (MoMLV)-based gammaretroviral vector carrying interleukin (IL)-12 gene for bladder cancer therapy. It displayed a chimeric envelope protein containing a single-chain variable fragment (scFv) antibody to the HER2 receptor and carried the mouse IL-12 gene. The fragment of anti-erbB2scFv was constructed into the proline-rich region of the viral envelope of the packaging vector lacking a transmembrane subunit of the carboxyl terminal region of surface subunit. As compared with envelope-unmodified gammaretroviruses, envelope-modified ones had extended viral tropism to human HER2-expressing bladder cancer cell lines, induced apoptosis, and affected cell cycle progression despite lower viral titers. Moreover, animal studies showed that envelope-modified gammaretroviruses carrying IL-12 gene exerted higher antitumor activity in terms of retarding tumor growth and prolonging the survival of tumor-bearing mice than unmodified ones, which were associated with enhanced tumor cell apoptosis as well as increased intratumoral levels of IL-12, interferon-gamma, IL-1beta, and tumor necrosis factor-alpha proteins. Therefore, the antitumor activity of gammaretroviruses carrying the IL-12 gene was enhanced through genetic modification of the envelope targeting HER2 receptor, which may be a promising strategy for bladder cancer therapy.

  9. Knowledge based development of graphic display systems

    International Nuclear Information System (INIS)

    Woods, D.D.

    1985-01-01

    Most human factors guidelines on computer display design attempt to ensure that human sensory limits are not strained or that users can potentially access data. While this is a necessary and too often an overlooked step in interface design, it does not address issues about how to use computer displays to aid human performance at domain tasks. This challenge to human factors guidance is particularly acute in complex environments such as nuclear power plants where the goal is more than a useable interface system; the interface must support effective human performance at tasks like situation assessment, fault management, problem solving and planning. Studies of human performance in complex domains reveal that human-machine performance failures can often be linked to problems in information handling - data overload, getting lost, keyhole effects, tunnel vision to name but a few. All of these information handling problems represent manifestations of an inability to find, integrate or interpret the ''right'' data at the ''right'' time, i.e., failures where critical information is not detected among the ambient data load, where critical information is not assembled from data distributed over time or over space; and where critical information is not looked for because of misunderstandings or erroneous assumptions (cf., Woods, 1985). Problems of this kind illustrate that the potential to see, read, or access data does not guarantee successful user information extraction. The result is a need for research and guidance on design for enhanced information extraction in addition to design for data availability

  10. 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.

  11. 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.

  12. EAP application to artificial tactile feel display of virtual reality

    Science.gov (United States)

    Konyo, Masashi; Tadokoro, Satoshi; Takamori, Toshi; Oguro, Keisuke

    2001-07-01

    A tactile feel display device for virtual reality was developed using Nafion-Platinum composite type EAP actuator (known as IPMC or ICPF). Conventional tactile displays can hardly express tactile human feeling of the fine touch of the surface of a cloth, because their mechanisms cannot excite minute distributed stimuli on human skin. We propose a new ciliary device using ICPF actuators. The ICPF has sufficient softness, utilizing the passive material property, that complex control is not required. The low drive voltage is safe enough for the touch of fingers. Its simple operation mechanism allows miniaturization for practical equipments. The developed device was designed with a number of cilia consisting of ICPF actuators, where a cilium is 2 mm wide and 5 mm long. An ICPF membrane is cut into pectination, and only the cilium part is plated and has a function of an actuator. An inclined configuration of the cilia produces variety of stimuli to human skin controlling frequencies. We tried to display both pressure and vibration at the same time using modulated low and high frequencies. The result clearly shows that over 80% of the subjects sensed some special tactile feeling. A comparison with real material samples shows that this display can present a subtle distinction of tactile feeling of cloth, especially like a towel and denim.

  13. Energy, mass, model-based displays, and memory recall

    International Nuclear Information System (INIS)

    Beltracchi, L.

    1989-01-01

    The operation of a pressurized water reactor in the context of the conservation laws for energy and mass is discussed. These conservation laws are the basis of the Rankine heat engine cycle. Computer graphic implementation of the heat engine cycle, in terms of temperature-entropy coordinates for water, serves as a model-based display of the plant process. A human user of this display, trained in first principles of the process, may exercise a monitoring strategy based on the conservation laws

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Human Visual Performance and Flat Panel Display Image Quality

    Science.gov (United States)

    1980-07-01

    visible light energy can be described in electro- magnetic energy space as that portion of the electromagnetic wavelength (or frequency) domain to...temporal frequency domain much as one analyzes spatial information in the spatial frequency domain. As the content of a complex but periodic sound ...briefly with the more intepretive aspects of information display, those pertaining to information encoding and the design problems and parame- ters

  16. Experience with model based display for advanced diagnostics and control

    International Nuclear Information System (INIS)

    Staffon, J.D.; Lindsay, R.W.

    1989-01-01

    A full color, model based display system based on the Rankine thermodynamic cycle has been developed for use at the Experimental Breeder Reactor II by plant operators, engineers, and experimenters. The displays generate a real time thermodynamic model of the plant processes on computer screens to provide a direct indication of the plant performance. Operators and others who view the displays are no longer required to mentally ''construct'' a model of the process before acting. The model based display accurately depicts the plant states. It appears to effectively reduce the gulf of evaluation, which should result in a significant reduction in human operator errors if this plant display approach is adopted by the nuclear industry. Preliminary comments from users, including operators, indicate an overwhelming acceptance of the display approach. The displays incorporate alarm functions as well as levels of detail ''paging'' capability. The system is developed on a computer network which allows the easy addition of displays as well as extra computers. Constructing a complete console can be rapid and inexpensive. 1 ref., 2 figs

  17. A Qualitative Method to Estimate HSI Display Complexity

    Energy Technology Data Exchange (ETDEWEB)

    Hugo, Jacques; Gertman, David [Idaho National Laboratory, Idaho (United States)

    2013-04-15

    There is mounting evidence that complex computer system displays in control rooms contribute to cognitive complexity and, thus, to the probability of human error. Research shows that reaction time increases and response accuracy decreases as the number of elements in the display screen increase. However, in terms of supporting the control room operator, approaches focusing on addressing display complexity solely in terms of information density and its location and patterning, will fall short of delivering a properly designed interface. This paper argues that information complexity and semantic complexity are mandatory components when considering display complexity and that the addition of these concepts assists in understanding and resolving differences between designers and the preferences and performance of operators. This paper concludes that a number of simplified methods, when combined, can be used to estimate the impact that a particular display may have on the operator's ability to perform a function accurately and effectively. We present a mixed qualitative and quantitative approach and a method for complexity estimation.

  18. Genes expressed in specific areas of the human fetal cerebral cortex display distinct patterns of evolution.

    Directory of Open Access Journals (Sweden)

    Nelle Lambert

    2011-03-01

    Full Text Available The developmental mechanisms through which the cerebral cortex increased in size and complexity during primate evolution are essentially unknown. To uncover genetic networks active in the developing cerebral cortex, we combined three-dimensional reconstruction of human fetal brains at midgestation and whole genome expression profiling. This novel approach enabled transcriptional characterization of neurons from accurately defined cortical regions containing presumptive Broca and Wernicke language areas, as well as surrounding associative areas. We identified hundreds of genes displaying differential expression between the two regions, but no significant difference in gene expression between left and right hemispheres. Validation by qRTPCR and in situ hybridization confirmed the robustness of our approach and revealed novel patterns of area- and layer-specific expression throughout the developing cortex. Genes differentially expressed between cortical areas were significantly associated with fast-evolving non-coding sequences harboring human-specific substitutions that could lead to divergence in their repertoires of transcription factor binding sites. Strikingly, while some of these sequences were accelerated in the human lineage only, many others were accelerated in chimpanzee and/or mouse lineages, indicating that genes important for cortical development may be particularly prone to changes in transcriptional regulation across mammals. Genes differentially expressed between cortical regions were also enriched for transcriptional targets of FoxP2, a key gene for the acquisition of language abilities in humans. Our findings point to a subset of genes with a unique combination of cortical areal expression and evolutionary patterns, suggesting that they play important roles in the transcriptional network underlying human-specific neural traits.

  19. Design of platform for removing screws from LCD display shields

    Science.gov (United States)

    Tu, Zimei; Qin, Qin; Dou, Jianfang; Zhu, Dongdong

    2017-11-01

    Removing the screws on the sides of a shield is a necessary process in disassembling a computer LCD display. To solve this issue, a platform has been designed for removing the screws on display shields. This platform uses virtual instrument technology with LabVIEW as the development environment to design the mechanical structure with the technologies of motion control, human-computer interaction and target recognition. This platform removes the screws from the sides of the shield of an LCD display mechanically thus to guarantee follow-up separation and recycle.

  20. Function-oriented display system: background and first prototypes

    International Nuclear Information System (INIS)

    Andresen, Gisle; Friberg, Maarten; Teigen, Arild; Pirus, Dominique

    2004-04-01

    The objective of the function-oriented displays and alarm project is to design, implement and evaluate Human System Interfaces (HSI) based on a function-oriented design philosophy. Function-oriented design is an approach for designing HSIs where the plant's functions, identified through a function analysis, are used for determining the content, organisation, and management of displays. The project has used the 'FITNESS approach', originally developed by EDF in France, as a starting point. FITNESS provides an integrated display system consisting of process operating displays, operating procedures, alarms and trend displays - all based on a functional decomposition of the plant. So far, two prototypes have been implemented on the FRESH PWR simulator in HAMMLAB. The first prototype focused on the condensate pumps. Three process operating displays representing functions at different levels of the functional hierarchy were implemented. Computerised startup and shutdown procedures for the condensate pumps function were also implemented. In the second prototype, the scope was increased to cover the main feedwater system. The displays of the first prototype were redesigned and additional displays were created. In conclusion, the first phase of the project has been completed successfully, and we are now ready to enter the second phase. In the second phase, the scope of the prototype will be increased further to include the steam-generators and function-oriented disturbance operating procedures. The prototype will be evaluated in a user test conducted later in 2004. (Author)

  1. Display characterization by eye: contrast ratio and discrimination throughout the grayscale

    Science.gov (United States)

    Gille, Jennifer; Arend, Larry; Larimer, James O.

    2004-06-01

    We have measured the ability of observers to estimate the contrast ratio (maximum white luminance / minimum black or gray) of various displays and to assess luminous discrimination over the tonescale of the display. This was done using only the computer itself and easily-distributed devices such as neutral density filters. The ultimate goal of this work is to see how much of the characterization of a display can be performed by the ordinary user in situ, in a manner that takes advantage of the unique abilities of the human visual system and measures visually important aspects of the display. We discuss the relationship among contrast ratio, tone scale, display transfer function and room lighting. These results may contribute to the development of applications that allow optimization of displays for the situated viewer / display system without instrumentation and without indirect inferences from laboratory to workplace.

  2. Recommended practice for the design of a computer driven Alarm Display Facility for central control rooms of nuclear power generating stations

    International Nuclear Information System (INIS)

    Ben-Yaacov, G.

    1984-01-01

    This paper's objective is to explain the process by which design can prevent human errors in nuclear plant operation. Human factor engineering principles, data, and methods used in the design of computer driven alarm display facilities are discussed. A ''generic'', advanced Alarm Display Facility is described. It considers operator capabilities and limitations in decision-making processes, response dynamics, and human memory limitations. Highlighted are considerations of human factor criteria in the designing and layout of alarm displays. Alarm data sources are described, and their use within the Alarm Display Facility are illustrated

  3. Pixels, people, perception, pet peeves, and possibilities: a look at displays

    Science.gov (United States)

    Task, H. Lee

    2007-04-01

    This year marks the 35 th anniversary of the Visually Coupled Systems symposium held at Brooks Air Force Base, San Antonio, Texas in November of 1972. This paper uses the proceedings of the 1972 VCS symposium as a guide to address several topics associated primarily with helmet-mounted displays, systems integration and the human-machine interface. Specific topics addressed include monocular and binocular helmet-mounted displays (HMDs), visor projection HMDs, color HMDs, system integration with aircraft windscreens, visual interface issues and others. In addition, this paper also addresses a few mysteries and irritations (pet peeves) collected over the past 35+ years of experience in the display and display related areas.

  4. Wearable Laser Pointer Versus Head-mounted Display for Tele-guidance Applications?

    DEFF Research Database (Denmark)

    Jalaliniya, Shahram; Pederson, Thomas; Houben, Steven

    2014-01-01

    Wearable camera and display technology allow remote collaborators to guide activities performed by human agents located elsewhere. This kind of technology augments the range of human perception and actuation. In this paper we quantitatively determine if wearable laser pointers are viable...

  5. Digital Display Integration Project Project Online 2.0

    International Nuclear Information System (INIS)

    Bardsley, J. N.

    1999-01-01

    transfer; and optimizing techniques to reduce communications bandwidth. Additional topics that will be addressed include: obtaining greater color control; minimization of seam widths in tiled displays; and the human factors that impact the efficient use of high resolution displays. The scope of the project will include both direct-view displays, for use by individuals and small groups, and projection systems for conference rooms and auditoriums

  6. Potent anti-leukemia activities of humanized CD19-targeted CAR-T cells in patients with relapsed/refractory acute lymphoblastic leukemia.

    Science.gov (United States)

    Cao, Jiang; Wang, Gang; Cheng, Hai; Wei, Chen; Qi, Kunming; Sang, Wei; Zhenyu, Li; Shi, Ming; Li, Huizhong; Qiao, Jianlin; Pan, Bin; Zhao, Jing; Wu, Qingyun; Zeng, Lingyu; Niu, Mingshan; Jing, Guangjun; Zheng, Junnian; Xu, Kailin

    2018-04-10

    Chimeric antigen receptor T (CAR-T) cell therapy has shown promising results for relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). The immune response induced by murine single-chain variable fragment (scFv) of the CAR may limit CAR-T cell persistence and thus increases the risk of leukemia relapse. In this study, we developed a novel humanized scFv from the murine FMC63 antibody. A total of 18 R/R ALL patients with or without prior murine CD19 CAR-T therapy were treated with humanized CD19-targeted CAR-T cells (hCART19s). After lymphodepletion chemotherapy with cyclophosphamide and fludarabine, the patients received a single dose (1 × 10 6 /kg) of autologous hCART19s infusion. Among the 14 patients without previous CAR-T therapy, 13 (92.9%) achieved complete remission (CR) or CR with incomplete count recovery (CRi) on day 30, whereas 1 of the 3 patients who failed a second murine CAR-T infusion achieved CR after hCART19s infusion. At day 180, the overall and leukemia-free survival rates were 65.8% and 71.4%, respectively. The cumulative incidence of relapse was 22.6%, and the non-relapse mortality rate was 7.1%. During treatment, 13 patients developed grade 1-2 cytokine release syndrome (CRS), 4 patients developed grade 3-5 CRS, and 1 patient experienced reversible neurotoxicity. These results indicated that hCART19s could induce remission in patients with R/R B-ALL, especially in patients who received a reinfusion of murine CAR-T. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  7. Advanced alarm systems: Display and processing issues

    Energy Technology Data Exchange (ETDEWEB)

    O`Hara, J.M. [Brookhaven National Lab., Upton, NY (United States); Wachtel, J.; Perensky, J. [US Nuclear Regulatory Commission, Washington, DC (United States). Office of Nuclear Regulatory Research

    1995-05-01

    This paper describes a research program sponsored by the US Nuclear Regulatory Commission to address the human factors engineering (HFE) deficiencies associated with nuclear power plant alarm systems. The overall objective of the study is to develop HFE review guidance for alarm systems. In support of this objective, human performance issues needing additional research were identified. Among the important issues were alarm processing strategies and alarm display techniques. This paper will discuss these issues and briefly describe our current research plan to address them.

  8. A green-color portable waveguide eyewear display system

    Science.gov (United States)

    Xia, Lingbo; Xu, Ke; Wu, Zhengming; Hu, Yingtian; Li, Zhenzhen; Wang, Yongtian; Liu, Juan

    2013-08-01

    Waveguide display systems are widely used in various display fields, especially in head mounted display. Comparing with the traditional head mounted display system, this device dramatically reduce the size and mass. However, there are still several fatal problems such as high scatting, the cumbersome design and chromatic aberration that should be solved. We designed and fabricated a monochromatic portable eyewear display system consist of a comfortable eyewear device and waveguide system with two holographic gratings located on the substrate symmetrically. We record the gratings on the photopolymer medium with high efficiency and wavelength sensitivity. The light emitting from the micro-display is diffracted by the grating and trapped in the glass substrate by total internal reflection. The relationship between the diffraction efficiency and exposure value is studied and analyzed, and we fabricated the gratings with appropriate diffraction efficiency in a optimization condition. To avoid the disturbance of the stray light, we optimize the waveguide system numerically and perform the optical experiments. With this system, people can both see through the waveguide to obtain the information outside and catch the information from the micro display. After considering the human body engineering and industrial production, we design the structure in a compact and portable way. It has the advantage of small-type configuration and economic acceptable. It is believe that this kind of planar waveguide system is a potentially replaceable choice for the portable devices in future mobile communications.

  9. European display scene

    Science.gov (United States)

    Bartlett, Christopher T.

    2000-08-01

    The manufacture of Flat Panel Displays (FPDs) is dominated by Far Eastern sources, particularly in Active Matrix Liquid Crystal Displays (AMLCD) and Plasma. The United States has a very powerful capability in micro-displays. It is not well known that Europe has a very active research capability which has lead to many innovations in display technology. In addition there is a capability in display manufacturing of organic technologies as well as the licensed build of Japanese or Korean designs. Finally, Europe has a display systems capability in military products which is world class.

  10. Performance Effects of Display Incogruity in a Digital and Analog Clock Reading Task

    Science.gov (United States)

    Comstock, J. Raymond, Jr.; Derks, Peter L.

    2004-01-01

    In an era of increasing automation, it is important to design displays and input devices that minimize human error. In this context, information concerning the human response to the detection of incongruous information is important. Such incongruous information can be operationalized as unexpected (perhaps erroneous) information on which a decision by the human or operation by an automated system is based. In the aviation environment, decision making when faced with inadequate, incomplete, or incongruous information may occur in a failure scenario. An additional challenge facing the human operator in automated environments is maintaining alertness or vigilance. The vigilance issue is of particular concern as a factor that may interact with performance when faced with inadequate, incomplete, or incongruous information. From the literature on eye-scan behavior we know that the time spent looking at a particular display or indicator is a function of the type of information one is trying to discern from the display. For example, quick glances are all it takes for confirming that an indicator is in a normal position or range, whereas a continuous look of several seconds may be required for confirmation that a complex control input is having the desired effect. Important to consider is that while an extended look takes place, visual input from other sources may be missed. Much like an extended look, the interpretation of incongruous information may require extra time. The present experiment was designed to explore the performance consequences of a decision making task when incongruous information was presented. For this experiment a display incongruity was created on a subset of trials of a clock reading laboratory task. Display incongruity was made possible through presentation of 'impossible' times (e.g. 1:65 or 11:90). Subjects made 'same' 'different' decisions and keyboard responses to pairings of Analog-Analog (AA), Digital-Digital (DD), and Analog- Digital (AD

  11. Displays in scintigraphy

    International Nuclear Information System (INIS)

    Todd-Pokropek, A.E.; Pizer, S.M.

    1977-01-01

    Displays have several functions: to transmit images, to permit interaction, to quantitate features and to provide records. The main characteristics of displays used for image transmission are their resolution, dynamic range, signal-to-noise ratio and uniformity. Considerations of visual acuity suggest that the display element size should be much less than the data element size, and in current practice at least 256X256 for a gamma camera image. The dynamic range for image transmission should be such that at least 64 levels of grey (or equivalent) are displayed. Scanner displays are also considered, and in particular, the requirements of a whole-body camera are examined. A number of display systems and devices are presented including a 'new' heated object colour display system. Interaction with displays is considered, including background subtraction, contrast enhancement, position indication and region-of-interest generation. Such systems lead to methods of quantitation, which imply knowledge of the expected distributions. Methods for intercomparing displays are considered. Polaroid displays, which have for so long dominated the field, are in the process of being replaced by stored image displays, now that large cheap memories exist which give an equivalent image quality. The impact of this in nuclear medicine is yet to be seen, but a major effect will be to enable true quantitation. (author)

  12. Investigation of the touch sensitivity of ER fluid based tactile display

    Science.gov (United States)

    Liu, Yanju; Davidson, Rob; Taylor, Paul

    2005-05-01

    A tactile display is programmable device whose controlled surface is intended to be investigated by human touch. It has a great number of potential applications in the field of virtual reality and elsewhere. In this research, a 5x5 touch sensitive tactile display array including electrorheological (ER) fluid has been developed and investigated. Experimental results show that the sensed surface information could be controlled effectively by adjusting the voltage activation pattern imposed on the tactels. In the meantime, it is possible to sense the touching force normal to the display"s surface by monitoring the change of current passing through the ER fluid. These encouraging results are helpful for constructing a new type of tactile display based on ER fluid which can act as both sensor and actuator at the same time.

  13. Monocular display unit for 3D display with correct depth perception

    Science.gov (United States)

    Sakamoto, Kunio; Hosomi, Takashi

    2009-11-01

    A study of virtual-reality system has been popular and its technology has been applied to medical engineering, educational engineering, a CAD/CAM system and so on. The 3D imaging display system has two types in the presentation method; one is a 3-D display system using a special glasses and the other is the monitor system requiring no special glasses. A liquid crystal display (LCD) recently comes into common use. It is possible for this display unit to provide the same size of displaying area as the image screen on the panel. A display system requiring no special glasses is useful for a 3D TV monitor, but this system has demerit such that the size of a monitor restricts the visual field for displaying images. Thus the conventional display can show only one screen, but it is impossible to enlarge the size of a screen, for example twice. To enlarge the display area, the authors have developed an enlarging method of display area using a mirror. Our extension method enables the observers to show the virtual image plane and to enlarge a screen area twice. In the developed display unit, we made use of an image separating technique using polarized glasses, a parallax barrier or a lenticular lens screen for 3D imaging. The mirror can generate the virtual image plane and it enlarges a screen area twice. Meanwhile the 3D display system using special glasses can also display virtual images over a wide area. In this paper, we present a monocular 3D vision system with accommodation mechanism, which is useful function for perceiving depth.

  14. 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.

  15. CD271+ osteosarcoma cells display stem-like properties.

    Directory of Open Access Journals (Sweden)

    Jiguang Tian

    Full Text Available Cancer stem cell (CSC theory has been proposed and verified in many cancers. The existence of osteosarcoma CSCs has been confirmed for many years and multiple surface markers have been employed to identify them. In this study, we identified CD271(+ subpopulation of osteosarcoma displaying stem-like properties. CD271, known as the neural crest nerve growth factor receptor, is the marker of bone marrow mesenchymal stem cells (MSCs and human melanoma-initiating cells. We discovered that CD271 was expressed differentially in diverse types of human osteosarcoma and stabilized cell lines. CD271(+ osteosarcoma cells displayed most of the properties of CSC, such as self-renewal, differentiation, drug resistance and tumorigenicity in vivo. Nanog, Oct3/4, STAT3, DNA-PKcs, Bcl-2 and ABCG2 were more expressed in CD271(+ cells compared with CD271- cells. Our study supported the osteosarcoma CSC hypothesis and, to a certain extent, revealed one of the possible mechanisms involved in maintaining CSCs properties.

  16. 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.

  17. 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.

  18. Detection of Metallothionein in Javanese Medaka (Oryzias javanicus, Using a scFv-Immobilized Protein Chip

    Directory of Open Access Journals (Sweden)

    Euiyeon Lee

    2018-04-01

    Full Text Available Environmental pollution by various industrial chemicals and biological agents poses serious risks to human health. Especially, marine contamination by potentially toxic elements (PTEs has become a global concern in recent years. Many efforts have been undertaken to monitor the PTE contamination of the aquatic environment. However, there are few approaches available to assess the PTE exposure of aquatic organisms. In this research, we developed a strategy to evaluate the heavy metal exposure of marine organisms, by measuring the expression levels of metallothionein protein derived from Oryzias javanicus (OjaMT. OjaMT is a biomarker of heavy metal exposure because the expression level increases upon heavy metal exposure. The developed assay is based on a real-time, label-free surface plasmon resonance (SPR measurement. Anti-OjaMT antibody and anti-OjaMT single-chain fragment of variable region (scFv were used as detection probes. Two types of SPR sensor chips were fabricated, by immobilizing antibody or Cys3-tagged scFv (scFv-Cys3 in a controlled orientation and were tested for in situ label-free OjaMT detection. Compared to the antibody-presenting sensor chips, the scFv-presenting sensor chips showed improved performance, displaying enhanced sensitivity and enabling semi-quantitative detection. The portable SPR system combined with scFv-immobilized sensor chips is expected to provide an excellent point-of-care testing system that can monitor target biomarkers in real time.

  19. 72-directional display having VGA resolution for high-appearance image generation

    Science.gov (United States)

    Takaki, Yasuhiro; Dairiki, Takeshi

    2006-02-01

    The high-density directional display, which was originally developed in order to realize a natural 3D display, is not only a 3D display but also a high-appearance display. The appearances of objects, such as glare and transparency, are the results of the reflection and the refraction of rays. The faithful reproduction of such appearances of objects is impossible using conventional 2D displays because rays diffuse on the display screen. The high-density directional display precisely controls the horizontal ray directions so that it can reproduce the appearances of objects. The fidelity of the reproduction of object appearances depends on the ray angle sampling pitch. The angle sampling pitch is determined by considering the human eye imaging system. In the present study the high-appearance display which has the resolution of 640×400 and emits rays in 72 different horizontal directions with the angle pitch of 0.38° was constructed. Two 72-directional displays were combined, each of which consisted of a high-resolution LCD panel (3,840×2,400) and a slanted lenticular sheet. Two images produced by two displays were superimposed by a half mirror. A slit array was placed at the focal plane of the lenticular sheet for each display to reduce the horizontal image crosstalk in the combined image. The impression analysis shows that the high-appearance display provides higher appearances and presence than the conventional 2D displays do.

  20. Development of human factors experimental evaluation techniques - Human factors design and evaluation of the main control room of atomic power plants using visual display terminals

    Energy Technology Data Exchange (ETDEWEB)

    Han, Sung Ho; Chung, Min Kyun; Choi, Kyung Lim; Song, Young Woong; Eoh, Hong Joon; Lee, In Suk; Kim, Bom Soo; Yeo, Yun Shin; Lee, Haeo Sun [Pohang University of Science and Technology, Pohang (Korea, Republic of)

    1995-07-01

    This study was conducted to build a prototype of the operator interface on a visual display terminal, and to provide a framework for using and applying prototyping techniques. A typical subsystem of an MCR was prototyped and validated by operator testing. Lessons learned during the development as well as prototyping techniques were described in this report for an efficient development. In addition, human factors experimental plans were surveyed and summarized for evaluating new design alternatives as well as the current design of the operator interface. The major results of this study are listed as follow: A method for designing an operator interface prototype on a VDT, A prototype of the operator interface of a typical subsystem, Guidelines for applying prototyping techniques, Characteristics and major considerations of experimental plans, Guidelines for applying prototyping techniques, Characteristics and major considerations of experimental plans, Guidelines for analyzing experimental data, A paradigm for human factors experimentation including experimental designs, procedures, and data analyses. 27 refs., 60 tabs., 47 figs. (author)

  1. CANDU 9 operator plant display system

    International Nuclear Information System (INIS)

    Trueman, R.; Webster, A.; MacBeth, M.J.

    1997-01-01

    To meet evolving client and regulatory needs, AECL has adopted an evolutionary approach to the design of the CANDU 9 control centre. That is, the design incorporates feedback from existing stations, reflects the growing diversity in the roles and responsibilities of the operating staff, and reduces costs associated with plant capital and operations, maintenance and administration (OM and A), through the appropriate introduction of new technologies. Underlying this approach is a refined engineering design process that cost-effectively integrates operational feedback and human factors engineering to define the operating staff information and information presentation requirements. Based on this approach, the CANDU 9 control centre will provide utility operating staff with the means to achieve improved operations and reduced OM and A costs. One of the design features that will contribute to the improved operational capabilities of the control centre is a new Plant Display System (PDS) that is separate from the digital control system. The PDS will be used to implement non-safety panel, and console video display systems within the CANDU 9 main control room (MCR). This paper presents a detailed description of the CANDU 9 Plant Display System and features that provide increased operational capabilities. (author)

  2. Vision and Displays for Military and Security Applications The Advanced Deployable Day/Night Simulation Project

    CERN Document Server

    Niall, Keith K

    2010-01-01

    Vision and Displays for Military and Security Applications presents recent advances in projection technologies and associated simulation technologies for military and security applications. Specifically, this book covers night vision simulation, semi-automated methods in photogrammetry, and the development and evaluation of high-resolution laser projection technologies for simulation. Topics covered include: advances in high-resolution projection, advances in image generation, geographic modeling, and LIDAR imaging, as well as human factors research for daylight simulation and for night vision devices. This title is ideal for optical engineers, simulator users and manufacturers, geomatics specialists, human factors researchers, and for engineers working with high-resolution display systems. It describes leading-edge methods for human factors research, and it describes the manufacture and evaluation of ultra-high resolution displays to provide unprecedented pixel density in visual simulation.

  3. TfR Binding Peptide Screened by Phage Display Technology ...

    African Journals Online (AJOL)

    Purpose: To screen an hTfR affinity peptide and investigate its activity in vitro. Methods: hTfR ... Keywords: Peptide, hTfR, Transferrin receptor, Phage display technology, Enhanced green ..... mediated uptake of peptides that bind the human.

  4. 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.

  5. Illuminant-adaptive color reproduction for mobile display

    Science.gov (United States)

    Kim, Jong-Man; Park, Kee-Hyon; Kwon, Oh-Seol; Cho, Yang-Ho; Ha, Yeong-Ho

    2006-01-01

    This paper proposes an illuminant-adaptive reproduction method using light adaptation and flare conditions for a mobile display. Mobile displays, such as PDAs and cellular phones, are viewed under various lighting conditions. In particular, images displayed in daylight are perceived as quite dark due to the light adaptation of the human visual system, as the luminance of a mobile display is considerably lower than that of an outdoor environment. In addition, flare phenomena decrease the color gamut of a mobile display by increasing the luminance of dark areas and de-saturating the chroma. Therefore, this paper presents an enhancement method composed of lightness enhancement and chroma compensation. First, the ambient light intensity is measured using a lux-sensor, then the flare is calculated based on the reflection ratio of the display device and the ambient light intensity. The relative cone response is nonlinear to the input luminance. This is also changed by the ambient light intensity. Thus, to improve the perceived image, the displayed luminance is enhanced by lightness linearization. In this paper, the image's luminance is transformed by linearization of the response to the input luminance according to the ambient light intensity. Next, the displayed image is compensated according to the physically reduced chroma, resulting from flare phenomena. The reduced chroma value is calculated according to the flare for each intensity. The chroma compensation method to maintain the original image's chroma is applied differently for each hue plane, as the flare affects each hue plane differently. At this time, the enhanced chroma also considers the gamut boundary. Based on experimental observations, the outer luminance-intensity generally ranges from 1,000 lux to 30,000 lux. Thus, in the case of an outdoor environment, i.e. greater than 1,000 lux, this study presents a color reproduction method based on an inverse cone response curve and flare condition. Consequently

  6. Detection and quantification of microcystins (cyanobacterial hepatotoxins) with recombinant antibody fragments isolated from a naïve human phage display library.

    Science.gov (United States)

    McElhiney, J; Lawton, L A; Porter, A J

    2000-12-01

    Single-chain antibody fragments against the cyanobacterial hepatotoxin microcystin-LR were isolated from a naive human phage display library and expressed in Escherichia coli. In competition enzyme-linked immunosorbent assay (ELISA), the most sensitive antibody clone selected from the library detected free microcystin-LR with an IC(50) value of 4 microM. It was found to cross react with three other microcystin variants - microcystin-RR, microcystin-LW and microcystin-LF - and detected microcystins in extracts of the cyanobacterium Microcystis aeruginosa, found to contain the toxins by high-performance liquid chromatography (HPLC). The quantification of microcystins in these extracts by ELISA and HPLC showed good correlation. Although the antibody isolated in this study was considerably less sensitive than the polyclonal and monoclonal antibodies already available for microcystin detection, phage display technology represents a cheaper, more rapid alternative for the production of anti-microcystin antibodies than the methods currently in use.

  7. Design characteristics of safety parameter display system for nuclear power plants

    International Nuclear Information System (INIS)

    Zhang Yuangfang

    1992-02-01

    The design features of safety parameter display system (SPDS) developed by Tsinghua University is introduced. Some new features have been added into the system functions and they are: (1) hierarchical display structure; (2) human factor in the display format design; (3)automatic diagnosis of safety status of nuclear power plant; (4) extension of SPDS use scope; (5) flexible hardware structure. The new approaches in the design are: (1)adopting the international design standards; (2) selecting safety parameters strictly; (3) developing software under multitask operating system; (4) using a nuclear power plant simulator to verify the SPDS design

  8. Survey of standards for electronic image displays

    Science.gov (United States)

    Rowe, William A.

    1996-02-01

    Electronic visual displays have been evolving from the 1960's basis of cathode ray tube (CRT) technology. Now, many other technologies are also available, including both flat panels and projection displays. Standards for these displays are being developed at both the national level and the international levels. Standards activity within the United States is in its infancy and is fragmented according to the inclination of each of the standards developing organizations. The latest round of flat panel display technology was primarily developed in Japan. Initially standards arose from component vendor-to-OEM customer relationships. As a result, Japanese standards for components are the best developed. The Electronics Industries Association of Japan (EIAJ) is providing their standards to the International Electrotechnical Commission (IEC) for adoption. On the international level, professional societies such as the human factors society (hfs) and the International Organization for Standardization (ISO) have completed major standards, hfs developed the first ergonomic standard hfs-100 and the ISO has developed some sections of a broader ergonomic standard ISO 9241. This paper addresses the organization of standards activity. Active organizations and their areas of focus are identified. The major standards that have been completed or are in development are described. Finally, suggestions for improving the this standards activity are proposed.

  9. 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.

  10. 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.

  11. User Evaluation of a Soldier Flexible Display Personal Digital Assistant

    National Research Council Canada - National Science Library

    Sampson, James B; Boynton, Angela C; Mitchell, K. B; Magnifico, Dennis S; DuPont, Frederick J

    2008-01-01

    The U.S. Army Natick Soldier Research, Development and Engineering Center and U.S. Army Research Laboratory, Human Research and Engineering Directorate conducted an evaluation of a Soldier Flexible Display Personal Digital Assistant...

  12. 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.

  13. Invisible Display in Aluminum

    DEFF Research Database (Denmark)

    Prichystal, Jan Phuklin; Hansen, Hans Nørgaard; Bladt, Henrik Henriksen

    2005-01-01

    Bang & Olufsen a/s has been working with ideas for invisible integration of displays in metal surfaces. Invisible integration of information displays traditionally has been possible by placing displays behind transparent or semitransparent materials such as plastic or glass. The wish for an integ......Bang & Olufsen a/s has been working with ideas for invisible integration of displays in metal surfaces. Invisible integration of information displays traditionally has been possible by placing displays behind transparent or semitransparent materials such as plastic or glass. The wish...... for an integrated display in a metal surface is often ruled by design and functionality of a product. The integration of displays in metal surfaces requires metal removal in order to clear the area of the display to some extent. The idea behind an invisible display in Aluminum concerns the processing of a metal...

  14. Targeted DNA vaccines for enhanced induction of idiotype-specific B and T cells

    International Nuclear Information System (INIS)

    Fredriksen, Agnete B.; Sandlie, Inger; Bogen, Bjarne

    2012-01-01

    Background: Idiotypes (Id) are antigenic determinants localized in variable (V) regions of Ig. Id-specific T and B cells (antibodies) play a role in immunotherapy of Id + tumors. However, vaccine strategies that enhance Id-specific responses are needed. Methods: Id + single-chain fragment variable (scFv) from multiple myelomas and B cell lymphomas were prepared in a fusion format that bivalently target surface molecules on antigen-presenting cells (APC). APC-specific targeting units were either scFv from APC-specific mAb (anti-MHC II, anti-CD40) or chemokines (MIP-1α, RANTES). Homodimeric Id-vaccines were injected intramuscularly or intradermally as plasmids in mice, combined with electroporation. Results: (i) Transfected cells secreted plasmid-encoded Id + fusion proteins to extracellular fluid followed by binding of vaccine molecules to APC. (ii) Targeted vaccine molecules increased Id-specific B and T cell responses. (iii) Bivalency and xenogeneic sequences both contributed to enhanced responses. (iv) Targeted Id DNA vaccines induced tumor resistance against challenges with Id + tumors. (v) Human MIP-1α targeting units enhanced Id-specific responses in mice, due to a cross reaction with murine chemokine receptors. Thus, targeted vaccines designed for humans can be quality tested in mice. (vi) Human Id + scFv from four multiple myeloma patients were inserted into the vaccine format and were successfully tested in mice. (vii) Human MIP-1α vaccine proteins enhanced human T cell responses in vitro. (viii) A hypothetical model for how the APC-targeted vaccine molecules enhance Id-specific T and B cells is presented. Conclusion: Targeted DNA Id-vaccines show promising results in preclinical studies, paving the way for testing in patients.

  15. Targeted DNA vaccines for enhanced induction of idiotype-specific B and T cells

    Energy Technology Data Exchange (ETDEWEB)

    Fredriksen, Agnete B.; Sandlie, Inger; Bogen, Bjarne, E-mail: bjarne.bogen@medisin.uio.no [Centre for Immune Regulation, Institute of Immunology, University of Oslo and Oslo University Hospital, Oslo (Norway)

    2012-10-30

    Background: Idiotypes (Id) are antigenic determinants localized in variable (V) regions of Ig. Id-specific T and B cells (antibodies) play a role in immunotherapy of Id{sup +} tumors. However, vaccine strategies that enhance Id-specific responses are needed. Methods: Id{sup +} single-chain fragment variable (scFv) from multiple myelomas and B cell lymphomas were prepared in a fusion format that bivalently target surface molecules on antigen-presenting cells (APC). APC-specific targeting units were either scFv from APC-specific mAb (anti-MHC II, anti-CD40) or chemokines (MIP-1α, RANTES). Homodimeric Id-vaccines were injected intramuscularly or intradermally as plasmids in mice, combined with electroporation. Results: (i) Transfected cells secreted plasmid-encoded Id{sup +} fusion proteins to extracellular fluid followed by binding of vaccine molecules to APC. (ii) Targeted vaccine molecules increased Id-specific B and T cell responses. (iii) Bivalency and xenogeneic sequences both contributed to enhanced responses. (iv) Targeted Id DNA vaccines induced tumor resistance against challenges with Id{sup +} tumors. (v) Human MIP-1α targeting units enhanced Id-specific responses in mice, due to a cross reaction with murine chemokine receptors. Thus, targeted vaccines designed for humans can be quality tested in mice. (vi) Human Id{sup +} scFv from four multiple myeloma patients were inserted into the vaccine format and were successfully tested in mice. (vii) Human MIP-1α vaccine proteins enhanced human T cell responses in vitro. (viii) A hypothetical model for how the APC-targeted vaccine molecules enhance Id-specific T and B cells is presented. Conclusion: Targeted DNA Id-vaccines show promising results in preclinical studies, paving the way for testing in patients.

  16. Coupling Retinal Scanning Displays to the Human Visual System: Visual System Response and Engineering Considerations

    National Research Council Canada - National Science Library

    Turner, Stuart

    2002-01-01

    A retinal scanning display (RSD) is a visual display that presents an image to an observer via a modulated beam of light that is directed through the eye's pupil and rapidly scanned in a raster-like pattern across the retina...

  17. Modeling Power-Constrained Optimal Backlight Dimming for Color Displays

    DEFF Research Database (Denmark)

    Burini, Nino; Nadernejad, Ehsan; Korhonen, Jari

    2013-01-01

    In this paper, we present a framework for modeling color liquid crystal displays (LCDs) having local light-emitting diode (LED) backlight with dimming capability. The proposed framework includes critical aspects like leakage, clipping, light diffusion and human perception of luminance and allows...

  18. T-38 Primary Flight Display Prototyping and HIVE Support Abstract & Summary

    Science.gov (United States)

    Boniface, Andrew

    2015-01-01

    This fall I worked in EV3 within NASA's Johnson Space Center in The HIVE (Human Integrated Vehicles & Environments). The HIVE is responsible for human in the loop testing, getting new technologies in front of astronauts, operators, and users early in the development cycle to make the interfaces more human friendly. Some projects the HIVE is working on includes user interfaces for future spacecraft, wearables to alert astronauts about important information, and test beds to simulate mock missions. During my internship I created a prototype for T-38 aircraft displays using LabVIEW, learned how to use microcontrollers, and helped out with other small tasks in the HIVE. The purpose of developing a prototype for T-38 Displays in LabVIEW is to analyze functions of the display such as navigation in a cost and time effective manner. The LabVIEW prototypes allow Ellington Field AOD to easily make adjustments to the display before hardcoding the final product. LabVIEW was used to create a user interface for simulation almost identical to the real aircraft display. Goals to begin the T-38 PFD (Primary Flight Display) prototype included creating a T-38 PFD hardware display in a software environment, designing navigation for the menu's, incorporating vertical and horizontal navigation bars, and to add a heading bug for compass controls connected to the HSI (Horizontal Situation Indicator). To get started with the project, measurements of the entire display were taken. This enabled an accurate model of the hardware display to be created. Navigation of menu's required some exploration of different buttons on the display. The T-38 simulator and aircraft were used for examining the display. After one piece of the prototype was finished, another trip of to the simulator took place. This was done until all goals for the prototype were complete. Some possible integration ideas for displays in the near future are autopilot selection, touch screen displays, and crew member preferences

  19. Flatbed-type 3D display systems using integral imaging method

    Science.gov (United States)

    Hirayama, Yuzo; Nagatani, Hiroyuki; Saishu, Tatsuo; Fukushima, Rieko; Taira, Kazuki

    2006-10-01

    We have developed prototypes of flatbed-type autostereoscopic display systems using one-dimensional integral imaging method. The integral imaging system reproduces light beams similar of those produced by a real object. Our display architecture is suitable for flatbed configurations because it has a large margin for viewing distance and angle and has continuous motion parallax. We have applied our technology to 15.4-inch displays. We realized horizontal resolution of 480 with 12 parallaxes due to adoption of mosaic pixel arrangement of the display panel. It allows viewers to see high quality autostereoscopic images. Viewing the display from angle allows the viewer to experience 3-D images that stand out several centimeters from the surface of the display. Mixed reality of virtual 3-D objects and real objects are also realized on a flatbed display. In seeking reproduction of natural 3-D images on the flatbed display, we developed proprietary software. The fast playback of the CG movie contents and real-time interaction are realized with the aid of a graphics card. Realization of the safety 3-D images to the human beings is very important. Therefore, we have measured the effects on the visual function and evaluated the biological effects. For example, the accommodation and convergence were measured at the same time. The various biological effects are also measured before and after the task of watching 3-D images. We have found that our displays show better results than those to a conventional stereoscopic display. The new technology opens up new areas of application for 3-D displays, including arcade games, e-learning, simulations of buildings and landscapes, and even 3-D menus in restaurants.

  20. Advanced Colorimetry of Display Systems: Tetra-Chroma3 Display Unit

    Directory of Open Access Journals (Sweden)

    J. Kaiser

    2005-06-01

    Full Text Available High-fidelity color image reproduction is one of the key issues invisual telecommunication systems, for electronic commerce,telemedicine, digital museum and so on. All colorimetric standards ofdisplay systems are up to the present day trichromatic. But, from theshape of a horseshoe-area of all existing colors in the CIE xychromaticity diagram it follows that with three real reproductivelights, the stated area in the CIE xy chromaticity diagram cannot beoverlaid. The expansion of the color gamut of a display device ispossible in a few ways. In this paper, the way of increasing the numberof primaries is studied. The fourth cyan primary is added to threeconventional ones to enlarge the color gamut of reproduction towardscyans and yellow-oranges. The original method of color management forthis new display unit is introduced. In addition, the color gamut ofthe designed additive-based display is successfully compared with thecolor gamut of a modern subtractive-based system. A display with morethan three primary colors is called a multiprimary color display. Thevery advantageous property of such display is the possibility todisplay metameric colors.

  1. Evaluation of viewing experiences induced by a curved three-dimensional display

    Science.gov (United States)

    Mun, Sungchul; Park, Min-Chul; Yano, Sumio

    2015-10-01

    Despite an increased need for three-dimensional (3-D) functionality in curved displays, comparisons pertinent to human factors between curved and flat panel 3-D displays have rarely been tested. This study compared stereoscopic 3-D viewing experiences induced by a curved display with those of a flat panel display by evaluating subjective and objective measures. Twenty-four participants took part in the experiments and viewed 3-D content with two different displays (flat and curved 3-D display) within a counterbalanced and within-subject design. For the 30-min viewing condition, a paired t-test showed significantly reduced P300 amplitudes, which were caused by engagement rather than cognitive fatigue, in the curved 3-D viewing condition compared to the flat 3-D viewing condition at P3 and P4. No significant differences in P300 amplitudes were observed for 60-min viewing. Subjective ratings of realness and engagement were also significantly higher in the curved 3-D viewing condition than in the flat 3-D viewing condition for 30-min viewing. Our findings support that curved 3-D displays can be effective for enhancing engagement among viewers based on specific viewing times and environments.

  2. Up-regulation and subcellular localization of hnRNP A2/B1 in the development of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Cui, Huaqing; Wu, Feng; Sun, Yanling; Fan, Guocai; Wang, Qingming

    2010-01-01

    Hepatocellular carcinoma (HCC) is one of the world's leading causes of death among cancer patients. It is important to find a new biomarker that diagnoses HCC and monitors its treatment. In our previous work, we screened a single-chain antibody (scFv) N14, which could specifically recognize human HepG2 HCC cells but not human non-cancerous liver LO2 cells. However, the antigen it recognized in the cells remained unknown. Recombinant scFv N14 antibody was expressed as an active antibody. Using this antibody with a combination of immunological and proteomic approaches, we identified the antigen of scFv N14 antibody as the heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1). The expression of hnRNP A2/B1 in HCC cells was then investigated by semi-quantitative RT-PCR and immunohistochemistry. We found that the up-regulation of hnRNP A2/B1 was measured at both transcriptional and translational levels in rat HCC cells but not in rat hepatic cells. We also found that in various human hepatic tissues, hnRNP A2/B1 was highly expressed in both human hepatitis virus positive liver tissues and human HCC tissues but not in normal liver tissues. Interestingly, we observed that the localization of hnRNP A2/B1 in HCC cells was altered during the development of HCC. In human hepatitis virus infected tissues hnRNP A2/B1 resides exclusively in the nuclei of hepatocytes. However, when the HCC progressed from a well differentiated to a poorly differentiated stage, hnRNP A2/B1 was increasingly localized in the cytoplasm. In contrast, the HCC tissues with hnRNP A2/B1 highly expressed in the nucleus decreased. This work is the first to show that hnRNP A2/B1 is the antigen specifically recognized by the scFv N14 antibody in HCC cells. The over-expression of hnRNP A2/B1 was confirmed in cultured human and rat HCC cell lines, human virus related hepatitis liver tissues and human HCC tissues. The increased localization of hnRNP A2/B1 in the cytoplasm of HCC cells was revealed

  3. Towards Determination of Visual Requirements for Augmented Reality Displays and Virtual Environments for the Airport Tower

    National Research Council Canada - National Science Library

    2006-01-01

    .... As an example of the type of human performance studies needed to determine the useful specifications of augmented reality displays, an optical see-through display was used in an ATC Tower simulation...

  4. Lambda-Display: A Powerful Tool for Antigen Discovery

    Directory of Open Access Journals (Sweden)

    Nicola Gargano

    2011-04-01

    Full Text Available Since its introduction in 1985, phage display technology has been successfully used in projects aimed at deciphering biological processes and isolating molecules of practical value in several applications. Bacteriophage lambda, representing a classical molecular cloning and expression system has also been exploited for generating large combinatorial libraries of small peptides and protein domains exposed on its capsid. More recently, lambda display has been consistently and successfully employed for domain mapping, antigen discovery and protein interaction studies or, more generally, in functional genomics. We show here the results obtained by the use of large libraries of cDNA and genomic DNA for the molecular dissection of the human B-cell response against complex pathogens, including protozoan parasites, bacteria and viruses. Moreover, by reviewing the experimental work performed in recent investigations we illustrate the potential of lambda display in the diagnostics field and for identifying antigens useful as targets for vaccine development.

  5. Experience in the review of utility control room design review and safety parameter display system programs

    International Nuclear Information System (INIS)

    Moore, V.A.

    1985-01-01

    The Detailed Control Room Design Review (DCRDR) and the Safety Parameter Display System (SPDS) had their origins in the studies and investigations conducted as the result of the TMI-2 accident. The President's Commission (Kemeny Commission) critized NRC for not examining the man-machine interface, over-emphasizing equipment, ignoring human beings, and tolerating outdated technology in control rooms. The Commission's Special Inquiry Group (Rogovin Report) recommended greater application of human factors engineering including better instrumentation displays and improved control room design. The NRC Lessons Learned Task Force concluded that licensees should review and improve control rooms using NRC Human engineering guidelines, and install safety parameter display systems (then called the safety staff vector). The TMI Action Plan Item I.D.1 and I.D.2 were based on these recommendations

  6. Vision Algorithms Catch Defects in Screen Displays

    Science.gov (United States)

    2014-01-01

    Andrew Watson, a senior scientist at Ames Research Center, developed a tool called the Spatial Standard Observer (SSO), which models human vision for use in robotic applications. Redmond, Washington-based Radiant Zemax LLC licensed the technology from NASA and combined it with its imaging colorimeter system, creating a powerful tool that high-volume manufacturers of flat-panel displays use to catch defects in screens.

  7. Microlaser-based displays

    Science.gov (United States)

    Bergstedt, Robert; Fink, Charles G.; Flint, Graham W.; Hargis, David E.; Peppler, Philipp W.

    1997-07-01

    Laser Power Corporation has developed a new type of projection display, based upon microlaser technology and a novel scan architecture, which provides the foundation for bright, extremely high resolution images. A review of projection technologies is presented along with the limitations of each and the difficulties they experience in trying to generate high resolution imagery. The design of the microlaser based projector is discussed along with the advantage of this technology. High power red, green, and blue microlasers have been designed and developed specifically for use in projection displays. These sources, in combination with high resolution, high contrast modulator, produce a 24 bit color gamut, capable of supporting the full range of real world colors. The new scan architecture, which reduces the modulation rate and scan speeds required, is described. This scan architecture, along with the inherent brightness of the laser provides the fundamentals necessary to produce a 5120 by 4096 resolution display. The brightness and color uniformity of the display is excellent, allowing for tiling of the displays with far fewer artifacts than those in a traditionally tiled display. Applications for the display include simulators, command and control centers, and electronic cinema.

  8. An anti-tumor protein produced by Trichinella spiralis and identified by screening a T7 phage display library, induces apoptosis in human hepatoma H7402 cells

    Science.gov (United States)

    Trichinella spiralis infection confers effective resistance to tumor cell expansion. In this study, a T7 phage cDNA display library was constructed to express genes encoded by T. spiralis. Organic phase multi-cell screening was used to sort through candidate proteins in a transfected human chronic m...

  9. Handbook of display technology

    CERN Document Server

    Castellano, Joseph A

    1992-01-01

    This book presents a comprehensive review of technical and commercial aspects of display technology. It provides design engineers with the information needed to select proper technology for new products. The book focuses on flat, thin displays such as light-emitting diodes, plasma display panels, and liquid crystal displays, but it also includes material on cathode ray tubes. Displays include a large number of products from televisions, auto dashboards, radios, and household appliances, to gasoline pumps, heart monitors, microwave ovens, and more.For more information on display tech

  10. SureTrak Probability of Impact Display

    Science.gov (United States)

    Elliott, John

    2012-01-01

    The SureTrak Probability of Impact Display software was developed for use during rocket launch operations. The software displays probability of impact information for each ship near the hazardous area during the time immediately preceding the launch of an unguided vehicle. Wallops range safety officers need to be sure that the risk to humans is below a certain threshold during each use of the Wallops Flight Facility Launch Range. Under the variable conditions that can exist at launch time, the decision to launch must be made in a timely manner to ensure a successful mission while not exceeding those risk criteria. Range safety officers need a tool that can give them the needed probability of impact information quickly, and in a format that is clearly understandable. This application is meant to fill that need. The software is a reuse of part of software developed for an earlier project: Ship Surveillance Software System (S4). The S4 project was written in C++ using Microsoft Visual Studio 6. The data structures and dialog templates from it were copied into a new application that calls the implementation of the algorithms from S4 and displays the results as needed. In the S4 software, the list of ships in the area was received from one local radar interface and from operators who entered the ship information manually. The SureTrak Probability of Impact Display application receives ship data from two local radars as well as the SureTrak system, eliminating the need for manual data entry.

  11. Engineering bacterial surface displayed human norovirus capsid proteins: A novel system to explore interaction between norovirus and ligands

    Directory of Open Access Journals (Sweden)

    Mengya eNiu

    2015-12-01

    Full Text Available Human noroviruses (HuNoVs are major contributors to acute nonbacterial gastroenteritis outbreaks. Many aspects of HuNoVs are poorly understood due to both the current inability to culture HuNoVs, and the lack of efficient small animal models. Surrogates for HuNoVs, such as recombinant viral like particles (VLPs expressed in eukaryotic system or P particles expressed in prokaryotic system, have been used for studies in immunology and interaction between the virus and its receptors. However, it is difficult to use VLPs or P particles to collect or isolate potential ligands binding to these recombinant capsid proteins. In this study, a new strategy was used to collect HuNoVs binding ligands through the use of ice nucleation protein (INP to display recombinant capsid proteins of HuNoVs on bacterial surfaces. The viral protein-ligand complex could be easily separated by a low speed centrifugation step. This system was also used to explore interaction between recombinant capsid proteins of HuNoVs and their receptors. In this system, the VP1 capsid encoding gene (ORF2 and the protruding domain (P domain encoding gene (3’ terminal fragment of ORF2 of HuNoVs GI.1 and GII.4 were fused with 5’ terminal fragment of ice nucleation protein encoding gene (inaQn. The results demonstrated that the recombinant VP1 and P domains of HuNoVs were expressed and anchored on the surface of Escherichia coli BL21 cells after the bacteria were transformed with the corresponding plasmids. Both cell surface displayed VP1 and P domains could be recognized by HuNoVs specific antibodies and interact with the viral histo-blood group antigens receptors. In both cases, displayed P domains had better binding abilities than VP1. This new strategy of using displayed HuNoVs capsid proteins on the bacterial surface could be utilized to separate HuNoVs binding components from complex samples, to investigate interaction between the virus and its receptors, as well as to develop an

  12. Liquid crystal display

    International Nuclear Information System (INIS)

    Takami, K.

    1981-01-01

    An improved liquid crystal display device is described which can display letters, numerals and other necessary patterns in the night time using a minimized amount of radioactive material. To achieve this a self-luminous light source is placed in a limited region corresponding to a specific display area. (U.K.)

  13. INFORMATION DISPLAY: CONSIDERATIONS FOR DESIGNING COMPUTER-BASED DISPLAY SYSTEMS

    International Nuclear Information System (INIS)

    O'HARA, J.M.; PIRUS, D.; BELTRATCCHI, L.

    2004-01-01

    This paper discussed the presentation of information in computer-based control rooms. Issues associated with the typical displays currently in use are discussed. It is concluded that these displays should be augmented with new displays designed to better meet the information needs of plant personnel and to minimize the need for interface management tasks (the activities personnel have to do to access and organize the information they need). Several approaches to information design are discussed, specifically addressing: (1) monitoring, detection, and situation assessment; (2) routine task performance; and (3) teamwork, crew coordination, collaborative work

  14. The psychology of computer displays in the modern mission control center

    Science.gov (United States)

    Granaas, Michael M.; Rhea, Donald C.

    1988-01-01

    Work at NASA's Western Aeronautical Test Range (WATR) has demonstrated the need for increased consideration of psychological factors in the design of computer displays for the WATR mission control center. These factors include color perception, memory load, and cognitive processing abilities. A review of relevant work in the human factors psychology area is provided to demonstrate the need for this awareness. The information provided should be relevant in control room settings where computerized displays are being used.

  15. Flight Deck Display Technologies for 4DT and Surface Equivalent Visual Operations

    Science.gov (United States)

    Prinzel, Lawrence J., III; Jones, Denis R.; Shelton, Kevin J.; Arthur, Jarvis J., III; Bailey, Randall E.; Allamandola, Angela S.; Foyle, David C.; Hooey, Becky L.

    2009-01-01

    NASA research is focused on flight deck display technologies that may significantly enhance situation awareness, enable new operating concepts, and reduce the potential for incidents/accidents for terminal area and surface operations. The display technologies include surface map, head-up, and head-worn displays; 4DT guidance algorithms; synthetic and enhanced vision technologies; and terminal maneuvering area traffic conflict detection and alerting systems. This work is critical to ensure that the flight deck interface technologies and the role of the human participants can support the full realization of the Next Generation Air Transportation System (NextGen) and its novel operating concepts.

  16. 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

  17. Internal epithelia in Drosophila display rudimentary competence to form cytoplasmic networks of transgenic human vimentin.

    Science.gov (United States)

    Gullmets, Josef; Torvaldson, Elin; Lindqvist, Julia; Imanishi, Susumu Y; Taimen, Pekka; Meinander, Annika; Eriksson, John E

    2017-12-01

    Cytoplasmic intermediate filaments (cIFs) are found in all eumetazoans, except arthropods. To investigate the compatibility of cIFs in arthropods, we expressed human vimentin (hVim), a cIF with filament-forming capacity in vertebrate cells and tissues, transgenically in Drosophila Transgenic hVim could be recovered from whole-fly lysates by using a standard procedure for intermediate filament (IF) extraction. When this procedure was used to test for the possible presence of IF-like proteins in flies, only lamins and tropomyosin were observed in IF-enriched extracts, thereby providing biochemical reinforcement to the paradigm that arthropods lack cIFs. In Drosophila , transgenic hVim was unable to form filament networks in S2 cells and mesenchymal tissues; however, cage-like vimentin structures could be observed around the nuclei in internal epithelia, which suggests that Drosophila retains selective competence for filament formation. Taken together, our results imply that although the filament network formation competence is partially lost in Drosophila , a rudimentary filament network formation ability remains in epithelial cells. As a result of the observed selective competence for cIF assembly in Drosophila , we hypothesize that internal epithelial cIFs were the last cIFs to disappear from arthropods.-Gullmets, J., Torvaldson, E., Lindqvist, J., Imanishi, S. Y., Taimen, P., Meinander, A., Eriksson, J. E. Internal epithelia in Drosophila display rudimentary competence to form cytoplasmic networks of transgenic human vimentin. © FASEB.

  18. Combining Phage and Yeast Cell Surface Antibody Display to Identify Novel Cell Type-Selective Internalizing Human Monoclonal Antibodies.

    Science.gov (United States)

    Bidlingmaier, Scott; Su, Yang; Liu, Bin

    2015-01-01

    Using phage antibody display, large libraries can be generated and screened to identify monoclonal antibodies with affinity for target antigens. However, while library size and diversity is an advantage of the phage display method, there is limited ability to quantitatively enrich for specific binding properties such as affinity. One way of overcoming this limitation is to combine the scale of phage display selections with the flexibility and quantitativeness of FACS-based yeast surface display selections. In this chapter we describe protocols for generating yeast surface antibody display libraries using phage antibody display selection outputs as starting material and FACS-based enrichment of target antigen-binding clones from these libraries. These methods should be widely applicable for the identification of monoclonal antibodies with specific binding properties.

  19. Advances in phage display technology for drug discovery.

    Science.gov (United States)

    Omidfar, Kobra; Daneshpour, Maryam

    2015-06-01

    Over the past decade, several library-based methods have been developed to discover ligands with strong binding affinities for their targets. These methods mimic the natural evolution for screening and identifying ligand-target interactions with specific functional properties. Phage display technology is a well-established method that has been applied to many technological challenges including novel drug discovery. This review describes the recent advances in the use of phage display technology for discovering novel bioactive compounds. Furthermore, it discusses the application of this technology to produce proteins and peptides as well as minimize the use of antibodies, such as antigen-binding fragment, single-chain fragment variable or single-domain antibody fragments like VHHs. Advances in screening, manufacturing and humanization technologies demonstrate that phage display derived products can play a significant role in the diagnosis and treatment of disease. The effects of this technology are inevitable in the development pipeline for bringing therapeutics into the market, and this number is expected to rise significantly in the future as new advances continue to take place in display methods. Furthermore, a widespread application of this methodology is predicted in different medical technological areas, including biosensing, monitoring, molecular imaging, gene therapy, vaccine development and nanotechnology.

  20. Liquid Crystal Airborne Display

    Science.gov (United States)

    1977-08-01

    Cum.nings, J. P., et al., Properties and Limitations oe Liquid Crystals for Aircraft Displays, Honeywell Corporate Researc ."I Center, Final Report HR-72...basic module could be used to build displays for both the commercial and military! 157- marhecs, and so would establi sh a broad and sizable market ... market for the display becomes a reality; therein lies, f TABLE 16 THE COURSE OF FUTURE DISPLAY DEVELOPMENT Today 1976-77 1980 1985 Display Size 2" 1 3.2

  1. Integrated color face graphs for plant accident display

    International Nuclear Information System (INIS)

    Hara, Fumio

    1987-01-01

    This paper presents an integrated man-machine interface that uses cartoon-like colored graphs in the form of faces, that, through different facial expressions, display a plant condition. This is done by drawing the face on a CRT by nonlinearly transforming 31 variables and coloring the face. This integrated color graphics technique is applied to display the progess of events in the Three Mile Island nuclear power plant accident. Human visual perceptive characteristics are investigated in relation to the perception of the plant accident process, the naturality in face color change, and the consistency between facial expressions and colors. This paper concludes that colors used in an integrated color face graphs must be completely consistent with emotional feelings perceived from the colors. (author)

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

    Directory of Open Access Journals (Sweden)

    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.

  3. JAVA Stereo Display Toolkit

    Science.gov (United States)

    Edmonds, Karina

    2008-01-01

    This toolkit provides a common interface for displaying graphical user interface (GUI) components in stereo using either specialized stereo display hardware (e.g., liquid crystal shutter or polarized glasses) or anaglyph display (red/blue glasses) on standard workstation displays. An application using this toolkit will work without modification in either environment, allowing stereo software to reach a wider audience without sacrificing high-quality display on dedicated hardware. The toolkit is written in Java for use with the Swing GUI Toolkit and has cross-platform compatibility. It hooks into the graphics system, allowing any standard Swing component to be displayed in stereo. It uses the OpenGL graphics library to control the stereo hardware and to perform the rendering. It also supports anaglyph and special stereo hardware using the same API (application-program interface), and has the ability to simulate color stereo in anaglyph mode by combining the red band of the left image with the green/blue bands of the right image. This is a low-level toolkit that accomplishes simply the display of components (including the JadeDisplay image display component). It does not include higher-level functions such as disparity adjustment, 3D cursor, or overlays all of which can be built using this toolkit.

  4. A novel active heads-up display for driver assistance.

    Science.gov (United States)

    Doshi, Anup; Cheng, Shinko Yuanhsien; Trivedi, Mohan Manubhai

    2009-02-01

    In this paper, we introduce a novel laser-based wide-area heads-up windshield display which is capable of actively interfacing with a human as part of a driver assistance system. The dynamic active display (DAD) is a unique prototype interface that presents safety-critical visual icons to the driver in a manner that minimizes the deviation of his or her gaze direction without adding to unnecessary visual clutter. As part of an automotive safety system, the DAD presents alerts in the field of view of the driver only if necessary, which is based upon the state and pose of the driver, vehicle, and environment. This paper examines the effectiveness of DAD through a comprehensive comparative experimental evaluation of a speed compliance driver assistance system, which is implemented on a vehicular test bed. Three different types of display protocols for assisting a driver to comply with speed limits are tested on actual roadways, and these are compared with a conventional dashboard display. Given the inclination, drivers who are given an overspeed warning alert reduced the time required to slow down to the speed limit by 38% (p system.

  5. An evaluation of software tools for the design and development of cockpit displays

    Science.gov (United States)

    Ellis, Thomas D., Jr.

    1993-01-01

    The use of all-glass cockpits at the NASA Langley Research Center (LaRC) simulation facility has changed the means of design, development, and maintenance of instrument displays. The human-machine interface has evolved from a physical hardware device to a software-generated electronic display system. This has subsequently caused an increased workload at the facility. As computer processing power increases and the glass cockpit becomes predominant in facilities, software tools used in the design and development of cockpit displays are becoming both feasible and necessary for a more productive simulation environment. This paper defines LaRC requirements of a display software development tool and compares two available applications against these requirements. As a part of the software engineering process, these tools reduce development time, provide a common platform for display development, and produce exceptional real-time results.

  6. Latest development of display technologies

    International Nuclear Information System (INIS)

    Gao Hong-Yue; Yao Qiu-Xiang; Liu Pan; Zheng Zhi-Qiang; Liu Ji-Cheng; Zheng Hua-Dong; Zeng Chao; Yu Ying-Jie; Sun Tao; Zeng Zhen-Xiang

    2016-01-01

    In this review we will focus on recent progress in the field of two-dimensional (2D) and three-dimensional (3D) display technologies. We present the current display materials and their applications, including organic light-emitting diodes (OLEDs), flexible OLEDs quantum dot light emitting diodes (QLEDs), active-matrix organic light emitting diodes (AMOLEDs), electronic paper (E-paper), curved displays, stereoscopic 3D displays, volumetric 3D displays, light field 3D displays, and holographic 3D displays. Conventional 2D display devices, such as liquid crystal devices (LCDs) often result in ambiguity in high-dimensional data images because of lacking true depth information. This review thus provides a detailed description of 3D display technologies. (topical review)

  7. 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.

  8. Displays and simulators

    Science.gov (United States)

    Mohon, N.

    A 'simulator' is defined as a machine which imitates the behavior of a real system in a very precise manner. The major components of a simulator and their interaction are outlined in brief form, taking into account the major components of an aircraft flight simulator. Particular attention is given to the visual display portion of the simulator, the basic components of the display, their interactions, and their characteristics. Real image displays are considered along with virtual image displays, and image generators. Attention is given to an advanced simulator for pilot training, a holographic pancake window, a scan laser image generator, the construction of an infrared target simulator, and the Apollo Command Module Simulator.

  9. Touch displays: the effects of palm rejection technology on productivity, comfort, biomechanics and positioning.

    Science.gov (United States)

    Camilleri, Matt J; Malige, Ajith; Fujimoto, Jeffrey; Rempel, David M

    2013-01-01

    Direct touch displays can improve the human-computer experience and productivity; however, the higher hand locations may increase shoulder fatigue. Palm rejection (PR) technology may reduce shoulder loads by allowing the palms to rest on the display and increase productivity by registering the touched content and fingertips through the palms rather than shoulders. The effects of PR were evaluated by having participants perform touch tasks while posture and reaction force on the display were measured. Enabling PR, during which the subjects could place the palms on the display (but were not required to), resulted in increased wrist extension, force applied to the display and productivity, and less discomfort, but had no effect on the self-selected positioning of the display. Participants did not deliberately place their palms on the display; therefore, there was no reduction in shoulder load and the increased productivity was not due to improved hand registration. The increased productivity may have been due to reduced interruptions from palm contacts or reduced motor control demands.

  10. Next Generation Flight Displays Using HTML5

    Science.gov (United States)

    Greenwood, Brian

    2016-01-01

    The Human Integrated Vehicles and Environments (HIVE) lab at Johnson Space Center (JSC) is focused on bringing together inter-disciplinary talent to design and integrate innovative human interface technologies for next generation manned spacecraft. As part of this objective, my summer internship project centered on an ongoing investigation in to building flight displays using the HTML5 standard. Specifically, the goals of my project were to build and demo "flight-like" crew and wearable displays as well as create a webserver for live systems being developed by the Advanced Exploration Systems (AES) program. In parallel to my project, a LabVIEW application, called a display server, was created by the HIVE that uses an XTCE (XML (Extensible Markup Language) Telemetry and Command Exchange) parser and CCSDS (Consultative Committee for Space Data System) space packet decoder to translate telemetry items sent by the CFS (Core Flight Software) over User Datagram Protocol (UDP). It was the webserver's job to receive these UDP messages and send them to the displays. To accomplish this functionality, I utilized Node.js and the accompanying Express framework. On the display side, I was responsible for creating the power system (AMPS) displays. I did this by using HTML5, CSS and JavaScript to create web pages that could update and change dynamically based on the data they received from the webserver. At this point, I have not started on the commanding, being able to send back to the CFS, portion of the displays but hope to have this functionality working by the completion of my internship. I also created a way to test the webserver's functionality without the display server by making a JavaScript application that read in a comma-separate values (CSV) file and converted it to XML which was then sent over UDP. One of the major requirements of my project was to build everything using as little preexisting code as possible, which I accomplished by only using a handful of Java

  11. Displays enabling mobile multimedia

    Science.gov (United States)

    Kimmel, Jyrki

    2007-02-01

    With the rapid advances in telecommunications networks, mobile multimedia delivery to handsets is now a reality. While a truly immersive multimedia experience is still far ahead in the mobile world, significant advances have been made in the constituent audio-visual technologies to make this become possible. One of the critical components in multimedia delivery is the mobile handset display. While such alternatives as headset-style near-to-eye displays, autostereoscopic displays, mini-projectors, and roll-out flexible displays can deliver either a larger virtual screen size than the pocketable dimensions of the mobile device can offer, or an added degree of immersion by adding the illusion of the third dimension in the viewing experience, there are still challenges in the full deployment of such displays in real-life mobile communication terminals. Meanwhile, direct-view display technologies have developed steadily, and can provide a development platform for an even better viewing experience for multimedia in the near future. The paper presents an overview of the mobile display technology space with an emphasis on the advances and potential in developing direct-view displays further to meet the goal of enabling multimedia in the mobile domain.

  12. Impact of Advanced Alarm Systems and Information Displays on Human Reliability in the Digital Control Room of Nuclear Power Plants

    International Nuclear Information System (INIS)

    Kim, Jong Hyun; Dang, Vinh N

    2011-01-01

    This paper discusses the potential impacts of two advanced features of digital control rooms, alarm systems and information display systems, on the Human Reliability Analysis (HRA) in nuclear power plants. Although the features of digital control rooms have already been implemented in new or upgraded nuclear power plants, HRAs have so far not taken much credit for these features. In this circumstance, this paper aims at examining the potential effects of these features on human performance and discussing how these effects can be addressed with existing HRA methods. A conclusion derivable from past experimental studies is that those features are supportive in the severe conditions such as complex scenarios and knowledge-based works. However, in the less complex scenarios and rule-based work, they may have no difference with or sometimes negative impacts on operator performance. The discussion about the impact on the HRA is provided on the basis on the THERP method

  13. On Integrity of Flexible Displays

    Science.gov (United States)

    Bouten, Piet C. P.

    Nowadays two display types are dominant in the display market: the bulky cathode ray tube (CRT) and liquid crystal displays (LCD). Both types use glass as substrate material. The LCD display is the dominant player for mobile applications, in for instance mobile phones and portable computers. In the development of displays and their applications a clear interest exists to replace the rigid rectangular display cells by free-shaped, curved or even roll-up cells. These types of applications require flexible displays.

  14. Book Display as Adult Service

    Directory of Open Access Journals (Sweden)

    Matthew S. Moore

    1997-03-01

    Full Text Available 無Book display as an adult service is defined as choosing and positioning adult books from the collection to increase their circulation. The author contrasts bookstore arrangement for sales versus library arrangement for access. The paper considers the library-as-a-whole as a display, examines the right size for an in-library display, and discusses mass displays, end-caps, on-shelf displays, and the Tiffany approach. The author proposes that an effective display depends on an imaginative, unifying theme, and that book displays are part of the joy of libraries.

  15. Children's Control/Display Stereotypes.

    Science.gov (United States)

    Hoffmann, Errol R; Chan, Alan H S; Tai, Judy P C

    2018-06-01

    Objective The aim of this study was to determine control/display stereotypes for children of a range of ages and development of these stereotypes with age. Background Little is known about control/display stereotypes for children of different ages and the way in which these stereotypes develop with age. This study is part of a program to determine the need to design differentially for these age groups. Method We tested four groups of children with various tasks (age groups 5 to 7, 8 to 10, 11 to 13, 14 to 16), with about 30 in each group. Examples of common tasks were opening a bottle, turning on taps, and allocating numbers to keypads. More complex tasks involved rotating a control to move a display in a requested direction. Results Tasks with which different age groups were familiar showed no effect of age group. Different control/display arrangements generally showed an increase in stereotype strength with age, with dependence on the form of the control/display arrangement. Two-dimensional arrangements, with the control on the same plane as the display, had higher stereotype strength than three-dimensional arrangements for all age groups, suggesting an effect of familiarity with controls and displays with increasing age. Conclusion Children's control/display stereotypes do not differ greatly from those of adults, and hence, design for children older than 5 years of age, for control/display stereotypes, can be the same as that for adult populations. Application When designing devices for children, the relationship between controls and displays can be as for adult populations, for which there are considerable experimental data.

  16. Optical Addressing of Multi-Colour Photochromic Material Mixture for Volumetric Display

    Science.gov (United States)

    Hirayama, Ryuji; Shiraki, Atsushi; Naruse, Makoto; Nakamura, Shinichiro; Nakayama, Hirotaka; Kakue, Takashi; Shimobaba, Tomoyoshi; Ito, Tomoyoshi

    2016-08-01

    This is the first study to demonstrate that colour transformations in the volume of a photochromic material (PM) are induced at the intersections of two control light channels, one controlling PM colouration and the other controlling decolouration. Thus, PM colouration is induced by position selectivity, and therefore, a dynamic volumetric display may be realised using these two control lights. Moreover, a mixture of multiple PM types with different absorption properties exhibits different colours depending on the control light spectrum. Particularly, the spectrum management of the control light allows colour-selective colouration besides position selectivity. Therefore, a PM-based, full-colour volumetric display is realised. We experimentally construct a mixture of two PM types and validate the operating principles of such a volumetric display system. Our system is constructed simply by mixing multiple PM types; therefore, the display hardware structure is extremely simple, and the minimum size of a volume element can be as small as the size of a molecule. Volumetric displays can provide natural three-dimensional (3D) perception; therefore, the potential uses of our system include high-definition 3D visualisation for medical applications, architectural design, human-computer interactions, advertising, and entertainment.

  17. Display of adenoregulin with a novel Pichia pastoris cell surface display system.

    Science.gov (United States)

    Ren, Ren; Jiang, Zhengbing; Liu, Meiyun; Tao, Xinyi; Ma, Yushu; Wei, Dongzhi

    2007-02-01

    Two Pichia pastoris cell surface display vectors were constructed. The vectors consisted of the flocculation functional domain of Flo1p with its own secretion signal sequence or the alpha-factor secretion signal sequence, a polyhistidine (6xHis) tag for detection, an enterokinase recognition site, and the insertion sites for target proteins. Adenoregulin (ADR) is a 33-amino-acid antimicrobial peptide isolated from Phyllomedusa bicolor skin. The ADR was expressed and displayed on the Pichia pastoris KM71 cell surface with the system reported. The displayed recombinant ADR fusion protein was detected by fluorescence microscopy and confocal laser scanning microscopy (CLSM). The antimicrobial activity of the recombinant adenoregulin was detected after proteolytic cleavage of the fusion protein on cell surface. The validity of the Pichia pastoris cell surface display vectors was proved by the displayed ADR.

  18. How Does Abundant Display Space Support Data Analysis?

    DEFF Research Database (Denmark)

    Knudsen, Søren

    This thesis explores information visualizations on large, high-resolution touch displays for analysis of massive amounts of data. The ever increasing rate at which data is collected about everything from peoples’ health, over organisations expenditures, to scientific experiments, necessitates new...... or about the benefits they might bring. The present thesis draws on the fields of human-computer interaction (HCI) and information visualization (InfoVis) to answer these questions....

  19. Flat panel display - Impurity doping technology for flat panel displays

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Toshiharu [Advanced Technology Planning, Sumitomo Eaton Nova Corporation, SBS Tower 9F, 10-1, Yoga 4-chome, Setagaya-ku, 158-0097 Tokyo (Japan)]. E-mail: suzuki_tsh@senova.co.jp

    2005-08-01

    Features of the flat panel displays (FPDs) such as liquid crystal display (LCD) and organic light emitting diode (OLED) display, etc. using low temperature poly-Si (LTPS) thin film transistors (TFTs) are briefly reviewed comparing with other FPDs. The requirements for fabricating TFTs used for high performance FPDs and system on glass (SoG) are addressed. This paper focuses on the impurity doping technology, which is one of the key technologies together with crystallization by laser annealing, formation of high quality gate insulator and gate-insulator/poly-Si interface. The issues to be solved in impurity doping technology for state of the art and future TFTs are clarified.

  20. Flat panel display - Impurity doping technology for flat panel displays

    International Nuclear Information System (INIS)

    Suzuki, Toshiharu

    2005-01-01

    Features of the flat panel displays (FPDs) such as liquid crystal display (LCD) and organic light emitting diode (OLED) display, etc. using low temperature poly-Si (LTPS) thin film transistors (TFTs) are briefly reviewed comparing with other FPDs. The requirements for fabricating TFTs used for high performance FPDs and system on glass (SoG) are addressed. This paper focuses on the impurity doping technology, which is one of the key technologies together with crystallization by laser annealing, formation of high quality gate insulator and gate-insulator/poly-Si interface. The issues to be solved in impurity doping technology for state of the art and future TFTs are clarified

  1. Development of scanning holographic display using MEMS SLM

    Science.gov (United States)

    Takaki, Yasuhiro

    2016-10-01

    Holography is an ideal three-dimensional (3D) display technique, because it produces 3D images that naturally satisfy human 3D perception including physiological and psychological factors. However, its electronic implementation is quite challenging because ultra-high resolution is required for display devices to provide sufficient screen size and viewing zone. We have developed holographic display techniques to enlarge the screen size and the viewing zone by use of microelectromechanical systems spatial light modulators (MEMS-SLMs). Because MEMS-SLMs can generate hologram patterns at a high frame rate, the time-multiplexing technique is utilized to virtually increase the resolution. Three kinds of scanning systems have been combined with MEMS-SLMs; the screen scanning system, the viewing-zone scanning system, and the 360-degree scanning system. The screen scanning system reduces the hologram size to enlarge the viewing zone and the reduced hologram patterns are scanned on the screen to increase the screen size: the color display system with a screen size of 6.2 in. and a viewing zone angle of 11° was demonstrated. The viewing-zone scanning system increases the screen size and the reduced viewing zone is scanned to enlarge the viewing zone: a screen size of 2.0 in. and a viewing zone angle of 40° were achieved. The two-channel system increased the screen size to 7.4 in. The 360-degree scanning increases the screen size and the reduced viewing zone is scanned circularly: the display system having a flat screen with a diameter of 100 mm was demonstrated, which generates 3D images viewed from any direction around the flat screen.

  2. Polymer Dispersed Liquid Crystal Displays

    Science.gov (United States)

    Doane, J. William

    The following sections are included: * INTRODUCTION AND HISTORICAL DEVELOPMENT * PDLC MATERIALS PREPARATION * Polymerization induced phase separation (PIPS) * Thermally induced phase separation (TIPS) * Solvent induced phase separation (SIPS) * Encapsulation (NCAP) * RESPONSE VOLTAGE * Dielectric and resistive effects * Radial configuration * Bipolar configuration * Other director configurations * RESPONSE TIME * DISPLAY CONTRAST * Light scattering and index matching * Incorporation of dyes * Contrast measurements * PDLC DISPLAY DEVICES AND INNOVATIONS * Reflective direct view displays * Large-scale, flexible displays * Switchable windows * Projection displays * High definition spatial light modulator * Haze-free PDLC shutters: wide angle view displays * ENVIRONMENTAL STABILITY * ACKNOWLEDGEMENTS * REFERENCES

  3. Information rich display design

    International Nuclear Information System (INIS)

    Welch, Robin; Braseth, Alf Ove; Veland, Oeystein

    2004-01-01

    This paper presents the concept Information Rich Displays. The purpose of Information Rich Displays (IRDs) is to condensate prevailing information in process displays in such a way that each display format (picture) contains more relevant information for the user. Compared to traditional process control displays, this new concept allows the operator to attain key information at a glance and at the same time allows for improved monitoring of larger portions of the process. This again allows for reduced navigation between both process and trend displays and ease the cognitive demand on the operator. This concept has been created while working on designing display prototypes for the offshore petroleum production facilities of tomorrow. Offshore installations basically consist of wells, separation trains (where oil, gas and water are separated from each other), an oil tax measurement system (where oil quality is measured and the pressure increased to allow for export), gas compression (compression of gas for export) and utility systems (water treatment, chemical systems etc.). This means that an offshore control room operator has to deal with a complex process that comprises several functionally different systems. The need for a new approach to offshore display format design is in particular based on shortcomings in today's designs related to the keyhole effect, where the display format only reveals a fraction of the whole process. Furthermore, the upcoming introduction of larger off- and on-shore operation centres will increase the size and complexity of the operators' work domain. In the light of the increased demands on the operator, the proposed IRDs aim to counter the negative effects this may have on the workload. In this work we have attempted to classify the wide range of different roles an operator can have in different situations. The information content and amount being presented to the operator in a display should be viewed in context of the roles the

  4. Usability and Effectiveness of Advanced General Aviation Cockpit Displays for Instrument Flight Procedures

    National Research Council Canada - National Science Library

    Williams, Kevin

    2003-01-01

    .... The study was designed to identify human factors that should be considered during the deployment of this technology to the entire general aviation community and in the development of future displays...

  5. Display of nuclear medicine imaging studies

    International Nuclear Information System (INIS)

    Singh, B.; Kataria, S.K.; Samuel, A.M.

    2002-08-01

    Nuclear medicine imaging studies involve evaluation of a large amount of image data. Digital signal processing techniques have introduced processing algorithms that increase the information content of the display. Nuclear medicine imaging studies require interactive selection of suitable form of display and pre-display processing. Static imaging study requires pre-display processing to detect focal defects. Point operations (histogram modification) along with zoom and capability to display more than one image in one screen is essential. This album mode of display is also applicable to dynamic, MUGA and SPECT data. Isometric display or 3-D graph of the image data is helpful in some cases e.g. point spread function, flood field data. Cine display is used on a sequence of images e.g. dynamic, MUGA and SPECT imaging studies -to assess the spatial movement of tracer with time. Following methods are used at the investigator's discretion for inspection of the 3-D object. 1) Display of orthogonal projections, 2) Display of album of user selected coronal/ sagital/ transverse orthogonal slices, 3) Display of three orthogonal slices through user selected point, 4) Display of a set of orthogonal slices generated in the user-selected volume, 5) Generation and display of 3-D shaded surface. 6) Generation of volume data and display along with the 3-D shaded surface, 7) Side by side display orthogonal slices of two 3-D objects. Displaying a set of two-dimensional slices of a 3-D reconstructed object through shows all the defects but lacks the 3-D perspective. Display of shaded surface lacks the ability to show the embedded defects. Volume display -combining the 3-D surface and gray level volume data is perhaps the best form of display. This report describes these forms of display along with the theory. (author)

  6. Antibodies against Venom of the Snake Deinagkistrodon acutus.

    Science.gov (United States)

    Lee, Chi-Hsin; Lee, Yu-Ching; Liang, Meng-Huei; Leu, Sy-Jye; Lin, Liang-Tzung; Chiang, Jen-Ron; Yang, Yi-Yuan

    2016-01-01

    Snake venom protein from Deinagkistrodon acutus (DA protein), one of the major venomous species in Taiwan, causes hemorrhagic symptoms that can lead to death. Although horse-derived antivenin is a major treatment, relatively strong and detrimental side effects are seen occasionally. In our study, yolk immunoglobulin (IgY) was purified from eggs, and DA protein was recognized using Western blotting and an enzyme-linked immunosorbent assay (ELISA), similar to therapeutic horse antivenin. The ELISA also indicated that specific IgY antibodies were elicited after the fifth booster, plateaued, and lasted for at least 3 months. To generate monoclonal single-chain variable fragment (scFv) antibodies, we used phage display technology to construct two libraries with short or long linkers, containing 6.24 × 10(8) and 5.28 × 10(8) transformants, respectively. After four rounds of biopanning, the eluted phage titer increased, and the phage-based ELISA indicated that the specific clones were enriched. Nucleotide sequences of 30 individual clones expressing scFv were analyzed and classified into four groups that all specifically recognized the DA venom protein. Furthermore, based on mass spectrometry, the scFv-bound protein was deduced to be snake venom metalloproteinase proteins. Most importantly, both IgY and mixed scFv inhibited the lethal effect in mice injected with the minimum lethal dosage of the DA protein. We suggest that together, these antibodies could be applied to the development of diagnostic agents or treatments for snakebite envenomation in the future. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  7. Automatic adjustment of display window (gray-level condition) for MR images using neural networks

    International Nuclear Information System (INIS)

    Ohhashi, Akinami; Nambu, Kyojiro.

    1992-01-01

    We have developed a system to automatically adjust the display window width and level (WWL) for MR images using neural networks. There were three main points in the development of our system as follows: 1) We defined an index for the clarity of a displayed image, and called 'EW'. EW is a quantitative measure of the clarity of an image displayed in a certain WWL, and can be derived from the difference between gray-level with the WWL adjusted by a human expert and with a certain WWL. 2) We extracted a group of six features from a gray-level histogram of a displayed image. We designed two neural networks which are able to learn the relationship between these features and the desired output (teaching signal), 'EQ', which is normalized to 0 to 1.0 from EW. Two neural networks were used to share the patterns to be learned; one learns a variety of patterns with less accuracy, and the other learns similar patterns with accuracy. Learning was performed using a back-propagation method. As a result, the neural networks after learning are able to provide a quantitative measure, 'Q', of the clarity of images displayed in the designated WWL. 3) Using the 'Hill climbing' method, we have been able to determine the best possible WWL for a displaying image. We have tested this technique for MR brain images. The results show that this system can adjust WWL comparable to that adjusted by a human expert for the majority of test images. The neural network is effective for the automatic adjustment of the display window for MR images. We are now studying the application of this method to MR images of another regions. (author)

  8. A history and overview of the safety parameter display system concept

    International Nuclear Information System (INIS)

    Joyce, J.P.; Lapinsky, G.W.

    1983-01-01

    Inquiries into the accident at the Three Mile Island Nuclear Power Plant Unit 2, on March 28, 1979 brought to public attention the need to improve operators' capabilities to interact with the systems under their control. Recommendations ran the full gamut of human/machine interaction, from improvements in training and procedures to improvements in control and display hardware in the control room. This presentation briefly traces the history and development of a display concept that evolved in the post-TMI era, the Safety Parameter Display System or SPDS. The SPDS is intended to function as a detection aid for control room operators, providing an integrated overview of significant plant parameters. The purpose of this report is to describe the general concept of SPDS, its history, and its current regulatory status. A review of NRC guidance documents is included, as well as a discussion of NRC requirements placed on the SPDS. The presentation concludes with an outline of the NRC staff review process for safety parameter display systems and a synopsis of the results of generic SPDS reviews performed thus far

  9. Display technologies for augmented reality

    Science.gov (United States)

    Lee, Byoungho; Lee, Seungjae; Jang, Changwon; Hong, Jong-Young; Li, Gang

    2018-02-01

    With the virtue of rapid progress in optics, sensors, and computer science, we are witnessing that commercial products or prototypes for augmented reality (AR) are penetrating into the consumer markets. AR is spotlighted as expected to provide much more immersive and realistic experience than ordinary displays. However, there are several barriers to be overcome for successful commercialization of AR. Here, we explore challenging and important topics for AR such as image combiners, enhancement of display performance, and focus cue reproduction. Image combiners are essential to integrate virtual images with real-world. Display performance (e.g. field of view and resolution) is important for more immersive experience and focus cue reproduction may mitigate visual fatigue caused by vergence-accommodation conflict. We also demonstrate emerging technologies to overcome these issues: index-matched anisotropic crystal lens (IMACL), retinal projection displays, and 3D display with focus cues. For image combiners, a novel optical element called IMACL provides relatively wide field of view. Retinal projection displays may enhance field of view and resolution of AR displays. Focus cues could be reconstructed via multi-layer displays and holographic displays. Experimental results of our prototypes are explained.

  10. Next generation smart window display using transparent organic display and light blocking screen.

    Science.gov (United States)

    Kim, Gyeong Woo; Lampande, Raju; Choe, Dong Cheol; Ko, Ik Jang; Park, Jin Hwan; Pode, Ramchandra; Kwon, Jang Hyuk

    2018-04-02

    Transparent organic light emitting diodes (TOLED) have widespread applications in the next-generation display devices particularly in the large size transparent window and interactive displays. Herein, we report high performance and stable attractive smart window displays using facile process. Advanced smart window display is realized by integrating the high performance light blocking screen and highly transparent white OLED panel. The full smart window display reveals a maximum transmittance as high as 64.2% at the wavelength of 600 nm and extremely good along with tunable ambient contrast ratio (171.94:1) compared to that of normal TOLED (4.54:1). Furthermore, the performance decisive light blocking screen has demonstrated an excellent optical and electrical characteristics such as i) high transmittance (85.56% at 562nm) at light-penetrating state, ii) superior absorbance (2.30 at 562nm) in light interrupting mode, iii) high optical contrast (85.50 at 562 nm), iv) high optical stability for more than 25,000 cycle of driving, v) fast switching time of 1.9 sec, and vi) low driving voltage of 1.7 V. The experimental results of smart window display are also validated using optical simulation. The proposed smart window display technology allows us to adjust the intensity of daylight entering the system quickly and conveniently.

  11. Visual merchandising window display

    Directory of Open Access Journals (Sweden)

    Opris (Cas. Stanila M.

    2013-12-01

    Full Text Available Window display plays a major part in the selling strategies; it does not only include the simple display of goods, nowadays it is a form of art, also having the purpose of sustaining the brand image. This article wants to reveal the tools that are essential in creating a fabulous window display. Being a window designer is not an easy job, you have to always think ahead trends, to have a sense of colour, to know how to use light to attract customers in the store after only one glance at the window. The big store window displays are theatre scenes: with expensive backgrounds, special effects and high fashion mannequins. The final role of the displays is to convince customers to enter the store and trigger the purchasing act which is the final goal of the retail activity.

  12. NASA UAS Integration into the NAS Project Detect and Avoid Display Evaluations

    Science.gov (United States)

    Shively, Jay

    2016-01-01

    As part of the Air Force - NASA Bi-Annual Research Council Meeting, slides will be presented on phase 1 Detect and Avoid (DAA) display evaluations. A series of iterative human-in-the-loops (HITL) experiments were conducted with different display configurations to objectively measure pilot performance on maintaining well clear. To date, four simulations and two mini-HITLs have been conducted. Data from these experiments have been incorporated into a revised alerting structure and included in the RTCA SC 228 Phase 1 Minimum Operational Performance Standards (MOPS) proposal. Plans for phase 2 are briefly discussed.

  13. Three-dimensional display of the heart, aorta, lungs, and airway using CT

    International Nuclear Information System (INIS)

    Fram, E.K.; Godwin, J.D.; Putman, C.E.

    1982-01-01

    In previous studies of human anatomy, three-dimensional display of CT data has required laborious manual boundary tracking, except for high-contrast structures such as the spine. Automated boundary tracking techniques have been extended so that they can function well for both high-contrast and soft-tissue interfaces. These methods have been applied to the in vivo study of human lungs, heart, aorta, and larynx in this paper

  14. 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

  15. Display systems for NPP control

    International Nuclear Information System (INIS)

    Rozov, S.S.

    1988-01-01

    Main trends in development of display systems used as the means for image displaying in NPP control systems are considered. It is shown that colour display devices appear to be the most universal means for concentrated data presentation. Along with digital means the display systems provide for high-speed response, sufficient for operative control of executive mechanisms. A conclusion is drawn that further development of display systems will move towards creation of large colour fields (on reflection base or with multicolour gas-discharge elements)

  16. Towards Determination of Visual Requirements for Augmented Reality Displays and Virtual Environments for the Airport Tower

    Science.gov (United States)

    Ellis, Stephen R.

    2006-01-01

    The visual requirements for augmented reality or virtual environments displays that might be used in real or virtual towers are reviewed with respect to similar displays already used in aircraft. As an example of the type of human performance studies needed to determine the useful specifications of augmented reality displays, an optical see-through display was used in an ATC Tower simulation. Three different binocular fields of view (14deg, 28deg, and 47deg) were examined to determine their effect on subjects ability to detect aircraft maneuvering and landing. The results suggest that binocular fields of view much greater than 47deg are unlikely to dramatically improve search performance and that partial binocular overlap is a feasible display technique for augmented reality Tower applications.

  17. Intracellular scFvs against the viral E6 oncoprotein provoke apoptosis in human papillomavirus-positive cancer cells

    International Nuclear Information System (INIS)

    Lagrange, Magali; Boulade-Ladame, Charlotte; Mailly, Laurent; Weiss, Etienne; Orfanoudakis, Georges; Deryckere, Francois

    2007-01-01

    The E6 protein of human papillomavirus type 16 (16E6) is involved in the tumorigenesis of human cervical cells by targeting numerous cellular proteins. We have designed a strategy for neutralizing 16E6 based on the intracellular expression of single-chain Fv antibodies (scFvs) specific to 16E6. Recombinant adenovirus vectors were constructed to allow expression of two 16E6-binding scFvs and one 16E6-non-binding scFv in HPV16-positive and -negative cells. Expression of the scFvs provoked two types of effects: (i) inhibition of proliferation of all cell lines tested, this aspecific toxicity being likely due to the aggregation of unfolded scFvs; and (ii) apoptosis observed only in HPV16-positive cervical cancer cell lines after expression of 16E6-binding scFvs, this specific effect being proportional to the intracellular solubility of the scFvs. These data demonstrate the feasibility of intracellular immunization with anti-16E6 scFvs and highlight the importance of the solubility of the intracellular antibodies

  18. Design and Characterization of a Human Monoclonal Antibody that Modulates Mutant Connexin 26 Hemichannels Implicated in Deafness and Skin Disorders

    Directory of Open Access Journals (Sweden)

    Liang Xu

    2017-09-01

    Full Text Available Background: Mutations leading to changes in properties, regulation, or expression of connexin-made channels have been implicated in 28 distinct human hereditary diseases. Eight of these result from variants of connexin 26 (Cx26, a protein critically involved in cell-cell signaling in the inner ear and skin. Lack of non-toxic drugs with defined mechanisms of action poses a serious obstacle to therapeutic interventions for diseases caused by mutant connexins. In particular, molecules that specifically modulate connexin hemichannel function without affecting gap junction channels are considered of primary importance for the study of connexin hemichannel role in physiological as well as pathological conditions. Monoclonal antibodies developed in the last three decades have become the most important class of therapeutic biologicals. Recombinant methods permit rapid selection and improvement of monoclonal antibodies from libraries with large diversity.Methods: By screening a combinatorial library of human single-chain fragment variable (scFv antibodies expressed in phage, we identified a candidate that binds an extracellular epitope of Cx26. We characterized antibody action using a variety of biochemical and biophysical assays in HeLa cells, organotypic cultures of mouse cochlea and human keratinocyte-derived cells.Results: We determined that the antibody is a remarkably efficient, non-toxic, and completely reversible inhibitor of hemichannels formed by connexin 26 and does not affect direct cell-cell communication via gap junction channels. Importantly, we also demonstrate that the antibody efficiently inhibits hyperative mutant Cx26 hemichannels implicated in autosomal dominant non-syndromic hearing impairment accompanied by keratitis and hystrix-like ichthyosis-deafness (KID/HID syndrome. We solved the crystal structure of the antibody, identified residues that are critical for binding and used molecular dynamics to uncover its mechanism of action

  19. Directional backlight liquid crystal autostereoscopic display: technical challenges, research progress, and prospect (Conference Presentation)

    Science.gov (United States)

    Fan, Hang; Li, Kunyang; Zhou, Yangui; Liang, Haowen; Wang, Jiahui; Zhou, Jianying

    2016-09-01

    Recent upsurge on virtual and augmented realities (VR and AR) has re-ignited the interest to the immerse display technology. The VR/AR technology based on stereoscopic display is believed in its early stage as glasses-free, or autostereoscopic display, will be ultimately adopted for the viewing convenience, visual comfort and for the multi-viewer purposes. On the other hand, autostereoscopic display has not yet received positive market response for the past years neither with stereoscopic displays using shutter or polarized glasses. We shall present the analysis on the real-world applications, rigid user demand, the drawbacks to the existing barrier- and lenticular lens-based LCD autostereoscopy. We shall emphasize the emerging autostereoscopic display, and notably on directional backlight LCD technology using a hybrid spatial- and temporal-control scenario. We report the numerical simulation of a display system using Monte-Carlo ray-tracing method with the human retina as the real image receiver. The system performance is optimized using newly developed figure of merit for system design. The reduced crosstalk in an autostereoscopic system, the enhanced display quality, including the high resolution received by the retina, the display homogeneity without Moiré- and defect-pattern, will be highlighted. Recent research progress including a novel scheme for diffraction-free backlight illumination, the expanded viewing zone for autostereoscopic display, and the novel Fresnel lens array to achieve a near perfect display in 2D/3D mode will be introduced. The experimental demonstration will be presented to the autostereoscopic display with the highest resolution, low crosstalk, Moiré- and defect- pattern free.

  20. Soft tissue segmentation and 3D display from computerized tomography and magnetic resonance imaging

    International Nuclear Information System (INIS)

    Fan, R.T.; Trivedi, S.S.; Fellingham, L.L.; Gamboa-Aldeco, A.; Hedgcock, M.W.

    1987-01-01

    Volume calculation and 3D display of human anatomy facilitate a physician's diagnosis, treatment, and evaluation. Accurate segmentation of soft tissue structures is a prerequisite for such volume calculations and 3D displays, but segmentation by hand-outlining structures is often tedious and time-consuming. In this paper, methods based on analysis of statistics of image gray level are applied to segmentation of soft tissue in medical images, with the goal of making segmentation automatic or semi-automatic. The resulting segmented images, volume calculations, and 3D displays are analyzed and compared with results based on physician-drawn outlines as well as actual volume measurements

  1. Large-screen display industry: market and technology trends for direct view and projection displays

    Science.gov (United States)

    Castellano, Joseph A.; Mentley, David E.

    1996-03-01

    Large screen information displays are defined as dynamic electronic displays that can be viewed by more than one person and are at least 2-feet wide. These large area displays for public viewing provide convenience, entertainment, security, and efficiency to the viewers. There are numerous uses for large screen information displays including those in advertising, transportation, traffic control, conference room presentations, computer aided design, banking, and military command/control. A noticeable characteristic of the large screen display market is the interchangeability of display types. For any given application, the user can usually choose from at least three alternative technologies, and sometimes from many more. Some display types have features that make them suitable for specific applications due to temperature, brightness, power consumption, or other such characteristic. The overall worldwide unit consumption of large screen information displays of all types and for all applications (excluding consumer TV) will increase from 401,109 units in 1995 to 655,797 units in 2002. On a unit consumption basis, applications in business and education represent the largest share of unit consumption over this time period; in 1995, this application represented 69.7% of the total. The market (value of shipments) will grow from DOL3.1 billion in 1995 to DOL3.9 billion in 2002. The market will be dominated by front LCD projectors and LCD overhead projector plates.

  2. Identification of human candidate genes for male infertility by digital differential display.

    Science.gov (United States)

    Olesen, C; Hansen, C; Bendsen, E; Byskov, A G; Schwinger, E; Lopez-Pajares, I; Jensen, P K; Kristoffersson, U; Schubert, R; Van Assche, E; Wahlstroem, J; Lespinasse, J; Tommerup, N

    2001-01-01

    Evidence for the importance of genetic factors in male fertility is accumulating. In the literature and the Mendelian Cytogenetics Network database, 265 cases of infertile males with balanced reciprocal translocations have been described. The candidacy for infertility of 14 testis-expressed transcripts (TETs) were examined by comparing their chromosomal mapping position to the position of balanced reciprocal translocation breakpoints found in the 265 infertile males. The 14 TETs were selected by using digital differential display (electronic subtraction) to search for apparently testis-specific transcripts in the TIGR database. The testis specificity of the 14 TETs was further examined by reverse transcription-polymerase chain reaction (RT-PCR) on adult and fetal tissues showing that four TETs (TET1 to TET4) were testis-expressed only, six TETs (TET5 to TET10) appeared to be differentially expressed and the remaining four TETs (TET11 to TET14) were ubiquitously expressed. Interestingly, the two tesis expressed-only transcripts, TET1 and TET2, mapped to chromosomal regions where seven and six translocation breakpoints have been reported in infertile males respectively. Furthermore, one ubiquitously, but predominantly testis-expressed, transcript, TET11, mapped to 1p32-33, where 13 translocation breakpoints have been found in infertile males. Interestingly, the mouse mutation, skeletal fusions with sterility, sks, maps to the syntenic region in the mouse genome. Another transcript, TET7, was the human homologue of rat Tpx-1, which functions in the specific interaction of spermatogenic cells with Sertoli cells. TPX-1 maps to 6p21 where three cases of chromosomal breakpoints in infertile males have been reported. Finally, TET8 was a novel transcript which in the fetal stage is testis-specific, but in the adult is expressed in multiple tissues, including testis. We named this novel transcript fetal and adult testis-expressed transcript (FATE).

  3. A virtual image chain for perceived image quality of medical display

    Science.gov (United States)

    Marchessoux, Cédric; Jung, Jürgen

    2006-03-01

    This paper describes a virtual image chain for medical display (project VICTOR: granted in the 5th framework program by European commission). The chain starts from raw data of an image digitizer (CR, DR) or synthetic patterns and covers image enhancement (MUSICA by Agfa) and both display possibilities, hardcopy (film on viewing box) and softcopy (monitor). Key feature of the chain is a complete image wise approach. A first prototype is implemented in an object-oriented software platform. The display chain consists of several modules. Raw images are either taken from scanners (CR-DR) or from a pattern generator, in which characteristics of DR- CR systems are introduced by their MTF and their dose-dependent Poisson noise. The image undergoes image enhancement and comes to display. For soft display, color and monochrome monitors are used in the simulation. The image is down-sampled. The non-linear response of a color monitor is taken into account by the GOG or S-curve model, whereas the Standard Gray-Scale-Display-Function (DICOM) is used for monochrome display. The MTF of the monitor is applied on the image in intensity levels. For hardcopy display, the combination of film, printer, lightbox and viewing condition is modeled. The image is up-sampled and the DICOM-GSDF or a Kanamori Look-Up-Table is applied. An anisotropic model for the MTF of the printer is applied on the image in intensity levels. The density-dependent color (XYZ) of the hardcopy film is introduced by Look-Up-tables. Finally a Human Visual System Model is applied to the intensity images (XYZ in terms of cd/m2) in order to eliminate nonvisible differences. Comparison leads to visible differences, which are quantified by higher order image quality metrics. A specific image viewer is used for the visualization of the intensity image and the visual difference maps.

  4. Human detection and discrimination of tactile repeatability, mechanical backlash, and temporal delay in a combined tactile-kinesthetic haptic display system.

    Science.gov (United States)

    Doxon, Andrew J; Johnson, David E; Tan, Hong Z; Provancher, William R

    2013-01-01

    Many of the devices used in haptics research are over-engineered for the task and are designed with capabilities that go far beyond human perception levels. Designing devices that more closely match the limits of human perception will make them smaller, less expensive, and more useful. However, many device-centric perception thresholds have yet to be evaluated. To this end, three experiments were conducted, using one degree-of-freedom contact location feedback device in combination with a kinesthetic display, to provide a more explicit set of specifications for similar tactile-kinesthetic haptic devices. The first of these experiments evaluated the ability of humans to repeatedly localize tactile cues across the fingerpad. Subjects could localize cues to within 1.3 mm and showed bias toward the center of the fingerpad. The second experiment evaluated the minimum perceptible difference of backlash at the tactile element. Subjects were able to discriminate device backlash in excess of 0.46 mm on low-curvature models and 0.93 mm on high-curvature models. The last experiment evaluated the minimum perceptible difference of system delay between user action and device reaction. Subjects were able to discriminate delays in excess of 61 ms. The results from these studies can serve as the maximum (i.e., most demanding) device specifications for most tactile-kinesthetic haptic systems.

  5. Scalable Resolution Display Walls

    KAUST Repository

    Leigh, Jason; Johnson, Andrew; Renambot, Luc; Peterka, Tom; Jeong, Byungil; Sandin, Daniel J.; Talandis, Jonas; Jagodic, Ratko; Nam, Sungwon; Hur, Hyejung; Sun, Yiwen

    2013-01-01

    This article will describe the progress since 2000 on research and development in 2-D and 3-D scalable resolution display walls that are built from tiling individual lower resolution flat panel displays. The article will describe approaches and trends in display hardware construction, middleware architecture, and user-interaction design. The article will also highlight examples of use cases and the benefits the technology has brought to their respective disciplines. © 1963-2012 IEEE.

  6. X-Windows Widget for Image Display

    Science.gov (United States)

    Deen, Robert G.

    2011-01-01

    XvicImage is a high-performance XWindows (Motif-compliant) user interface widget for displaying images. It handles all aspects of low-level image display. The fully Motif-compliant image display widget handles the following tasks: (1) Image display, including dithering as needed (2) Zoom (3) Pan (4) Stretch (contrast enhancement, via lookup table) (5) Display of single-band or color data (6) Display of non-byte data (ints, floats) (7) Pseudocolor display (8) Full overlay support (drawing graphics on image) (9) Mouse-based panning (10) Cursor handling, shaping, and planting (disconnecting cursor from mouse) (11) Support for all user interaction events (passed to application) (12) Background loading and display of images (doesn't freeze the GUI) (13) Tiling of images.

  7. Study on the visibility of an electroluminescent display for automobiles; Jidoshayo EL display no shininsei

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, N; Harada, M; Idogaki, T [Denso Corp., Aichi (Japan)

    1997-10-01

    This report explores the visibility of an Electroluminescent (EL) display for automotive use. Displays for automobiles are exposed to the direct rays of the sun and forced to operate in wide temperature range. Therefore, luminous flux density by the lighting on EL display panel and operating environment temperature must be considered for the visibility evaluation. Sensory evaluation on the visibility and physical measurements such as contrast, chromaticity difference in accordance with the viewing angle change indicate that the visibility of the EL display for automobiles is advantageous over other displays. 6 refs., 11 figs., 1 tab.

  8. Laser illuminated flat panel display

    Energy Technology Data Exchange (ETDEWEB)

    Veligdan, J.T.

    1995-12-31

    A 10 inch laser illuminated flat panel Planar Optic Display (POD) screen has been constructed and tested. This POD screen technology is an entirely new concept in display technology. Although the initial display is flat and made of glass, this technology lends itself to applications where a plastic display might be wrapped around the viewer. The display screen is comprised of hundreds of planar optical waveguides where each glass waveguide represents a vertical line of resolution. A black cladding layer, having a lower index of refraction, is placed between each waveguide layer. Since the cladding makes the screen surface black, the contrast is high. The prototype display is 9 inches wide by 5 inches high and approximately I inch thick. A 3 milliwatt HeNe laser is used as the illumination source and a vector scanning technique is employed.

  9. Prediction of HDR quality by combining perceptually transformed display measurements with machine learning

    Science.gov (United States)

    Choudhury, Anustup; Farrell, Suzanne; Atkins, Robin; Daly, Scott

    2017-09-01

    We present an approach to predict overall HDR display quality as a function of key HDR display parameters. We first performed subjective experiments on a high quality HDR display that explored five key HDR display parameters: maximum luminance, minimum luminance, color gamut, bit-depth and local contrast. Subjects rated overall quality for different combinations of these display parameters. We explored two models | a physical model solely based on physically measured display characteristics and a perceptual model that transforms physical parameters using human vision system models. For the perceptual model, we use a family of metrics based on a recently published color volume model (ICT-CP), which consists of the PQ luminance non-linearity (ST2084) and LMS-based opponent color, as well as an estimate of the display point spread function. To predict overall visual quality, we apply linear regression and machine learning techniques such as Multilayer Perceptron, RBF and SVM networks. We use RMSE and Pearson/Spearman correlation coefficients to quantify performance. We found that the perceptual model is better at predicting subjective quality than the physical model and that SVM is better at prediction than linear regression. The significance and contribution of each display parameter was investigated. In addition, we found that combined parameters such as contrast do not improve prediction. Traditional perceptual models were also evaluated and we found that models based on the PQ non-linearity performed better.

  10. Peptides of the constant region of antibodies display fungicidal activity.

    Directory of Open Access Journals (Sweden)

    Luciano Polonelli

    Full Text Available Synthetic peptides with sequences identical to fragments of the constant region of different classes (IgG, IgM, IgA of antibodies (Fc-peptides exerted a fungicidal activity in vitro against pathogenic yeasts, such as Candida albicans, Candida glabrata, Cryptococcus neoformans, and Malassezia furfur, including caspofungin and triazole resistant strains. Alanine-substituted derivatives of fungicidal Fc-peptides, tested to evaluate the critical role of each residue, displayed unaltered, increased or decreased candidacidal activity in vitro. An Fc-peptide, included in all human IgGs, displayed a therapeutic effect against experimental mucosal and systemic candidiasis in mouse models. It is intriguing to hypothesize that some Fc-peptides may influence the antifungal immune response and constitute the basis for devising new antifungal agents.

  11. Peptides of the Constant Region of Antibodies Display Fungicidal Activity

    Science.gov (United States)

    Polonelli, Luciano; Ciociola, Tecla; Magliani, Walter; Zanello, Pier Paolo; D'Adda, Tiziana; Galati, Serena; De Bernardis, Flavia; Arancia, Silvia; Gabrielli, Elena; Pericolini, Eva; Vecchiarelli, Anna; Arruda, Denise C.; Pinto, Marcia R.; Travassos, Luiz R.; Pertinhez, Thelma A.; Spisni, Alberto; Conti, Stefania

    2012-01-01

    Synthetic peptides with sequences identical to fragments of the constant region of different classes (IgG, IgM, IgA) of antibodies (Fc-peptides) exerted a fungicidal activity in vitro against pathogenic yeasts, such as Candida albicans, Candida glabrata, Cryptococcus neoformans, and Malassezia furfur, including caspofungin and triazole resistant strains. Alanine-substituted derivatives of fungicidal Fc-peptides, tested to evaluate the critical role of each residue, displayed unaltered, increased or decreased candidacidal activity in vitro. An Fc-peptide, included in all human IgGs, displayed a therapeutic effect against experimental mucosal and systemic candidiasis in mouse models. It is intriguing to hypothesize that some Fc-peptides may influence the antifungal immune response and constitute the basis for devising new antifungal agents. PMID:22470523

  12. Design and Evaluation of a Thermal Tactile Display for Colour Rendering

    Directory of Open Access Journals (Sweden)

    Zhen Jia

    2015-11-01

    Full Text Available This paper proposes a novel method of manipulating both thermal change rate and thermal intensity to convey colour information by using a thermal tactile display. The colour-space transformation from {red, green, blue} to {hue, saturation, intensity} is introduced, and the mapping between colour and temperature is established based on warm and cold colours. Considering the lower resolution of the tactile channel, six limited stimulation levels are generated to represent colours. Based on the semi-infinite body model, the thermal response within the skin for each stimulation form is investigated. The Peltier element of the display is designed to convey different thermal stimuli to the human finger. Two experiments are performed to evaluate the performance of the display: colour identification and discrimination. Experimental results indicate that there is a response bias among the perceived colours for the traditional method of only employing thermal intensity, but there is no response bias for the proposed method; subjects’ mean recognition accuracy with the proposed method is significantly higher than that gained using the traditional method. Furthermore, colour information of the captured images can be reliably discriminated by using this devised thermal tactile display.

  13. System analysis of formation and perception processes of three-dimensional images in volumetric displays

    Science.gov (United States)

    Bolshakov, Alexander; Sgibnev, Arthur

    2018-03-01

    One of the promising devices is currently a volumetric display. Volumetric displays capable to visualize complex three-dimensional information as nearly as possible to its natural – volume form without the use of special glasses. The invention and implementation of volumetric display technology will expand opportunities of information visualization in various spheres of human activity. The article attempts to structure and describe the interrelation of the essential characteristics of objects in the area of volumetric visualization. Also there is proposed a method of calculation of estimate total number of voxels perceived by observers during the 3D demonstration, generated using a volumetric display with a rotating screen. In the future, it is planned to expand the described technique and implement a system for estimation the quality of generated images, depending on the types of biplanes and their initial characteristics.

  14. OLED displays and lighting

    CERN Document Server

    Koden, Mitsuhiro

    2017-01-01

    Organic light-emitting diodes (OLEDs) have emerged as the leading technology for the new display and lighting market. OLEDs are solid-state devices composed of thin films of organic molecules that create light with the application of electricity. OLEDs can provide brighter, crisper displays on electronic devices and use less power than conventional light-emitting diodes (LEDs) or liquid crystal displays (LCDs) used today. This book covers both the fundamentals and practical applications of flat and flexible OLEDs.

  15. Human engineering evaluation of Hamaoka No. 3 advanced control room CRT display system

    International Nuclear Information System (INIS)

    Okajima, Hiroyuki; Ito, Takahiko; Noguchi, Yoshihiro; Kabasawa, Yoshihiko

    1985-01-01

    As the central control board of Hamaoka No. 3 plant, a new type control board was adopted for the purpose of powerfully supporting the general judgement function of operators by processing enormous plant data in the normal operation and at the time of an accident with a computer, and displaying the results on CRT screens in the summarized form. Recently, the evaluation of this new control board was carried out by ergonomical techniques, and it was confirmed that the initial objective has been attained. Besides, the criteria for the ergonomical evaluation of central control boards mainly for CRT display were determined, and the contents of design were able to be systematically evaluated and verified. As the ergonomical design of the central control board, the easy distinction of the function of switches, the easy confirmation of system constitution by mimics, the use of CRTs, the easy identification of operation pilot lamps, alarms, instruments and so on were considered. The central control board consists of the main control board, auxiliary control boards and vertical boards, and 12 CRTs are installed. (Kako, I.)

  16. Stereotype for direction-of-movement of the controls associated with some displays

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyun Chul; Lee, Jung Woon; Lee, Yong Hee; Oh, Un Seok; Cha, Woo Chang

    2002-05-01

    The human factor design guideline which has been developed for Ulchin Nuclear Units 3 and 4, HF010, refers mainly to NUREG-0700 which was based on American operators' behaviors. It is very important to develop the design guidelines which can be applicable for Korean operators for the purpose of designing the Korean Standard Nuclear Power plant more safely. The objective of this project is to provide the standards, guidelines and bases applicable for HF010 through the within-subject experiment for obtaining Korean operators' population stereotype for direction-of-movement of the KSNP controls associated with the displays. The scope and contents of this project includes the taxonomy of displays/controls types in KSNP MCR, development of the facilitating system for stereotype experiment, survey of the researches on display compatibility and experiment for obtaining population stereotype of control movement.

  17. Stereotype for direction-of-movement of the controls associated with some displays

    International Nuclear Information System (INIS)

    Lee, Hyun Chul; Lee, Jung Woon; Lee, Yong Hee; Oh, Un Seok; Cha, Woo Chang

    2002-05-01

    The human factor design guideline which has been developed for Ulchin Nuclear Units 3 and 4, HF010, refers mainly to NUREG-0700 which was based on American operators' behaviors. It is very important to develop the design guidelines which can be applicable for Korean operators for the purpose of designing the Korean Standard Nuclear Power plant more safely. The objective of this project is to provide the standards, guidelines and bases applicable for HF010 through the within-subject experiment for obtaining Korean operators' population stereotype for direction-of-movement of the KSNP controls associated with the displays. The scope and contents of this project includes the taxonomy of displays/controls types in KSNP MCR, development of the facilitating system for stereotype experiment, survey of the researches on display compatibility and experiment for obtaining population stereotype of control movement

  18. Dichroic Liquid Crystal Displays

    Science.gov (United States)

    Bahadur, Birendra

    The following sections are included: * INTRODUCTION * DICHROIC DYES * Chemical Structure * Chemical and Photochemical Stability * THEORETICAL MODELLING * DEFECTS CAUSED BY PROLONGED LIGHT IRRADIATION * CHEMICAL STRUCTURE AND PHOTOSTABILITY * OTHER PARAMETERS AFFECTING PHOTOSTABILITY * CELL PREPARATION * DICHROIC PARAMETERS AND THEIR MEASUREMENTS * Order Parameter and Dichroic Ratio Of Dyes * Absorbance, Order Parameter and Dichroic Ratio Measurements * IMPACT OF DYE STRUCTURE AND LIQUID CRYSTAL HOST ON PHYSICAL PROPERTIES OF A DICHROIC MIXTURE * Order Parameter and Dichroic Ratio * EFFECT OF LENGTH OF DICHROIC DYES ON THE ORDER PARAMETER * EFFECT OF THE BREADTH OF DYE ON THE ORDER PARAMETER * EFFECT OF THE HOST ON THE ORDER PARAMETER * TEMPERATURE VARIATION OF THE ORDER PARAMETER OF DYES IN A LIQUID CRYSTAL HOST * IMPACT OF DYE CONCENTRATION ON THE ORDER PARAMETER * Temperature Range * Viscosity * Dielectric Constant and Anisotropy * Refractive Indices and Birefringence * solubility43,153-156 * Absorption Wavelength and Auxochromic Groups * Molecular Engineering of Dichroic Dyes * OPTICAL, ELECTRO-OPTICAL AND LIFE PARAMETERS * Colour And CIE Colour space120,160-166 * CIE 1931 COLOUR SPACE * CIE 1976 CHROMATICITY DIAGRAM * CIE UNIFORM COLOUR SPACES & COLOUR DIFFERENCE FORMULAE120,160-166 * Electro-Optical Parameters120 * LUMINANCE * CONTRAST AND CONTRAST RATIO * SWITCHING SPEED * Life Parameters and Failure Modes * DICHROIC MIXTURE FORMULATION * Monochrome Mixture * Black Mixture * ACHROMATIC BLACK MIXTURE FOR HEILMEIER DISPLAYS * Effect of Illuminant on Display Colour * Colour of the Field-On State * Effect of Dye Linewidth * Optimum Centroid Wavelengths * Effect of Dye Concentration * Mixture Formulation Using More Than Three Dyes * ACHROMATIC MIXTURE FOR WHITE-TAYLOR TYPE DISPLAYS * HEILMEIER DISPLAYS * Theoretical Modelling * Threshold Characteristic * Effects of Dye Concentration on Electro-optical Parameters * Effect of Cholesteric Doping * Effect of Alignment

  19. 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.

  20. Web data display system based on data segment technology of MDSplus

    International Nuclear Information System (INIS)

    Liu Rui; Zhang Ming; Wen Chuqiao; Zheng Wei; Zhuang Ge; Yu Kexun

    2014-01-01

    Long pulse operation is the main character of advanced Tokamak, so the technology of data storage and human-data interaction are vital for dealing with the large data generated in long pulse experiment. The Web data display system was designed. The system is based on the ASP. NET architecture, and it reads segmented-record data from MDSplus database by segmented-record technology and displays the data on Web page by using NI Measurement Studio control library. With the segmented-record technology, long pulse data could be divided into many small units, data segments. Users can read the certain data segments from the long pulse data according to their special needs. Also, the system develops an efficient strategy for reading segmented record data, showing the waveforms required by users accurately and quickly. The data display Web system was tested on J-TEXT Tokamak, and was proved to be reliable and efficient to achieve the initial design goal. (authors)

  1. Trastuzumab-binding peptide display by Tobacco mosaic virus

    International Nuclear Information System (INIS)

    Frolova, Olga Y.; Petrunia, Igor V.; Komarova, Tatiana V.; Kosorukov, Vyacheslav S.; Sheval, Eugene V.; Gleba, Yuri Y.; Dorokhov, Yuri L.

    2010-01-01

    Human epidermal growth factor receptor-2 (HER2/neu) is a target for the humanized monoclonal antibody trastuzumab. Recently, trastuzumab-binding peptides (TBP) of HER2/neu that inhibit proliferation of breast cancer cells were identified. We have now studied conditions of efficient assembly in vivo of Tobacco mosaic virus (TMV)-based particles displaying TBP on its surface. The system is based on an Agrobacterium-mediated co-delivery of binary vectors encoding TMV RNA and coat protein (CP) with TBP in its C-terminal extension into plant leaves. We show how the fusion of amino acid substituted TBP (sTBP) to CP via a flexible peptide linker can improve the manufacturability of recombinant TMV (rTMV). We also reveal that rTMV particles with exposed sTBP retained trastuzumab-binding capacity but lost an anti-HER2/neu immunogenic scaffold function. Mouse antibodies against rTMV did not recognize HER2/neu on surface of human SK-BR-3 cells.

  2. Technical and radiological image quality comparison of different liquid crystal displays for radiology

    Directory of Open Access Journals (Sweden)

    Dams FE

    2014-10-01

    Full Text Available Francina EM Dams,2 KY Esther Leung,1 Pieter HM van der Valk,2 Marc CJM Kock,2 Jeroen Bosman,1 Sjoerd P Niehof1 1Medical Physics and Technology, 2Department of Radiology, Albert Schweitzer Hospital, Dordrecht, The Netherlands Background: To inform cost-effective decisions in purchasing new medical liquid crystal displays, we compared the image quality in displays made by three manufacturers. Methods: We recruited 19 radiologists and residents to compare the image quality of four liquid crystal displays, including 3-megapixel Barco®, Eizo®, and NEC® displays and a 6-megapixel Barco display. The evaluators were blinded to the manufacturers' names. Technical assessments were based on acceptance criteria and test patterns proposed by the American Association of Physicists in Medicine. Radiological assessments were performed on images from the American Association of Physicists in Medicine Task Group 18. They included X-ray images of the thorax, knee, and breast, a computed tomographic image of the thorax, and a magnetic resonance image of the brain. Image quality was scored on an analog scale (range 0–10. Statistical analysis was performed with repeated-measures analysis of variance. Results: The Barco 3-megapixel display passed all acceptance criteria. The Eizo and NEC displays passed the acceptance criteria, except for the darkest pixel value in the grayscale display function. The Barco 6-megapixel display failed criteria for the maximum luminance response and the veiling glare. Mean radiological assessment scores were 7.8±1.1 (Barco 3-megapixel, 7.8±1.2 (Eizo, 8.1±1.0 (NEC, and 8.1±1.0 (Barco 6-megapixel. No significant differences were found between displays. Conclusion: According to the tested criteria, all the displays had comparable image quality; however, there was a three-fold difference in price between the most and least expensive displays. Keywords: data display, humans, radiographic image enhancement, user-computer interface

  3. Prazosin Displays Anticancer Activity against Human Prostate Cancers: Targeting DNA, Cell Cycle

    Directory of Open Access Journals (Sweden)

    Ssu-Chia Lin

    2007-10-01

    Full Text Available Quinazoline-based α1,-adrenoceptor antagonists, in particular doxazosin, terazosin, are suggested to display antineoplastic activity against prostate cancers. However, there are few studies elucidating the effect of prazosin. In this study, prazosin displayed antiproliferative activity superior to that of other α1-blockers, including doxazosin, terazosin, tamsulosin, phentolamine. Prazosin induced G2 checkpoint arrest, subsequent apoptosis in prostate cancer PC-3, DU-145, LNCaP cells. In p53-null PC-3 cells, prazosin induced an increase in DNA str, breaks, ATM/ATR checkpoint pathways, leading to the activation of downstream signaling cascades, including Cdc25c phosphorylation at Ser216, nuclear export of Cdc25c, cyclin-dependent kinase (Cdk 1 phosphorylation at Tyr15. The data, together with sustained elevated cyclin A levels (other than cyclin B1 levels, suggested that Cdki activity was inactivated by prazosin. Moreover, prazosin triggered mitochondria-mediated, caspaseexecuted apoptotic pathways in PC-3 cells. The oral administration of prazosin significantly reduced tumor mass in PC-3-derived cancer xenografts in nude mice. In summary, we suggest that prazosin is a potential antitumor agent that induces cell apoptosis through the induction of DNA damage stress, leading to Cdki inactivation, G2 checkpoint arrest. Subsequently, mitochondriamediated caspase cascades are triggered to induce apoptosis in PC-3 cells.

  4. Crosstalk evaluation in stereoscopic displays

    NARCIS (Netherlands)

    Wang, L.; Teunissen, C.; Tu, Yan; Chen, Li; Zhang, P.; Zhang, T.; Heynderickx, I.E.J.

    2011-01-01

    Substantial progress in liquid-crystal display and polarization film technology has enabled several types of stereoscopic displays. Despite all progress, some image distortions still exist in these 3-D displays, of which interocular crosstalk - light leakage of the image for one eye to the other eye

  5. Consortium for military LCD display procurement

    Science.gov (United States)

    Echols, Gregg

    2002-08-01

    International Display Consortium (IDC) is the joining together of display companies to combined their buying power and obtained favorable terms with a major LCD manufacturer. Consolidating the buying power and grouping the demand enables the rugged display industry of avionics, ground vehicles, and ship based display manufacturers to have unencumbered access to high performance AMLCDs while greatly reducing risk and lowering cost. With an unrestricted supply of AMLCD displays, the consortium members have total control of their risk, cost, deliveries and added value partners. Every display manufacturer desires a very close relationship with a display vender. With IDC each consortium member achieves a close relationship. Consortium members enjoy cost effective access to high performance, industry standard sized LCD panels, and modified commercial displays with 100 degree C clearing points and portrait configurations. Consortium members also enjoy proposal support, technical support and long-term support.

  6. Liquid crystal true 3D displays for augmented reality applications

    Science.gov (United States)

    Li, Yan; Liu, Shuxin; Zhou, Pengcheng; Chen, Quanming; Su, Yikai

    2018-02-01

    Augmented reality (AR) technology, which integrates virtual computer-generated information into the real world scene, is believed to be the next-generation human-machine interface. However, most AR products adopt stereoscopic 3D display technique, which causes the accommodation-vergence conflict. To solve this problem, we have proposed two approaches. The first is a multi-planar volumetric display using fast switching polymer-stabilized liquid crystal (PSLC) films. By rapidly switching the films between scattering and transparent states while synchronizing with a high-speed projector, the 2D slices of a 3D volume could be displayed in time sequence. We delved into the research on developing high-performance PSLC films in both normal mode and reverse mode; moreover, we also realized the demonstration of four-depth AR images with correct accommodation cues. For the second approach, we realized a holographic AR display using digital blazed gratings and a 4f system to eliminate zero-order and higher-order noise. With a 4k liquid crystal on silicon device, we achieved a field of view (FOV) of 32 deg. Moreover, we designed a compact waveguidebased holographic 3D display. In the design, there are two holographic optical elements (HOEs), each of which functions as a diffractive grating and a Fresnel lens. Because of the grating effect, holographic 3D image light is coupled into and decoupled out of the waveguide by modifying incident angles. Because of the lens effect, the collimated zero order light is focused at a point, and got filtered out. The optical power of the second HOE also helps enlarge FOV.

  7. Hemifacial Display of Emotion in the Resting State

    Directory of Open Access Journals (Sweden)

    M. K. Mandal

    1992-01-01

    Full Text Available The human face at rest displays distinguishable asymmetries with some lateralization of emotion or expression. The asymmetrical nature of the resting face was examined by preparing hemifacial composites, left–left, right–right, along with normal facial orientation. The left side and right side composites were constructed by using the lateral half of one side of the face and its mirror-reversal. The left side facial composites were found to be more emotional than the right side or normal facial orientations of neutral expressions.

  8. Super high precision 200 ppi liquid crystal display series; Chokoseido 200 ppi ekisho display series

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-03-01

    In mobile equipment, in demand is a high precision liquid crystal display (LCD) having the power of expression equivalent to printed materials like magazines because of the necessity of displaying a large amount of information on a easily potable small screen. In addition, with the spread and high-quality image of digital still cameras, it is strongly desired to display photographed digital image data in high quality. Toshiba Corp., by low temperature polysilicone (p-Si) technology, commercialized the liquid crystal display series of 200 ppi (pixels per inch) precision dealing with the rise of the high-precision high-image quality LCD market. The super high precision of 200 ppi enables the display of smooth beautiful animation comparable to printed sheets of magazines and photographs. The display series are suitable for the display of various information services such as electronic books and electronic photo-viewers including internet. The screen sizes lined up are No. 4 type VGA (640x480 pixels) of a small pocket notebook size and No. 6.3 type XGA (1,024x768 pixels) of a paperback size, with a larger screen to be furthered. (translated by NEDO)

  9. A Compressive Superresolution Display

    KAUST Repository

    Heide, Felix; Gregson, James; Wetzstein, Gordon; Raskar, Ramesh; Heidrich, Wolfgang

    2014-01-01

    In this paper, we introduce a new compressive display architecture for superresolution image presentation that exploits co-design of the optical device configuration and compressive computation. Our display allows for superresolution, HDR, or glasses-free 3D presentation.

  10. A Compressive Superresolution Display

    KAUST Repository

    Heide, Felix

    2014-06-22

    In this paper, we introduce a new compressive display architecture for superresolution image presentation that exploits co-design of the optical device configuration and compressive computation. Our display allows for superresolution, HDR, or glasses-free 3D presentation.

  11. Stereoscopic display in a slot machine

    Science.gov (United States)

    Laakso, M.

    2012-03-01

    This paper reports the results of a user trial with a slot machine equipped with a stereoscopic display. The main research question was to find out what kind of added value does stereoscopic 3D (S-3D) bring to slot games? After a thorough literature survey, a novel gaming platform was designed and implemented. Existing multi-game slot machine "Nova" was converted to "3DNova" by replacing the monitor with an S-3D display and converting six original games to S-3D format. To evaluate the system, several 3DNova machines were put available for players for four months. Both qualitative and quantitative analysis was carried out from statistical values, questionnaires and observations. According to the results, people find the S-3D concept interesting but the technology is not optimal yet. Young adults and adults were fascinated by the system, older people were more cautious. Especially the need to wear stereoscopic glasses provide a challenge; ultimate system would probably use autostereoscopic technology. Also the games should be designed to utilize its full power. The main contributions of this paper are lessons learned from creating an S-3D slot machine platform and novel information about human factors related to stereoscopic slot machine gaming.

  12. Human engineering

    International Nuclear Information System (INIS)

    Yang, Seong Hwan; Park, Bum; Gang, Yeong Sik; Gal, Won Mo; Baek, Seung Ryeol; Choe, Jeong Hwa; Kim, Dae Sung

    2006-07-01

    This book mentions human engineering, which deals with introduction of human engineering, Man-Machine system like system design, and analysis and evaluation of Man-Machine system, data processing and data input, display, system control of man, human mistake and reliability, human measurement and design of working place, human working, hand tool and manual material handling, condition of working circumstance, working management, working analysis, motion analysis working measurement, and working improvement and design in human engineering.

  13. JTEC panel on display technologies in Japan

    Science.gov (United States)

    Tannas, Lawrence E., Jr.; Glenn, William E.; Credelle, Thomas; Doane, J. William; Firester, Arthur H.; Thompson, Malcolm

    1992-01-01

    This report is one in a series of reports that describes research and development efforts in Japan in the area of display technologies. The following are included in this report: flat panel displays (technical findings, liquid crystal display development and production, large flat panel displays (FPD's), electroluminescent displays and plasma panels, infrastructure in Japan's FPD industry, market and projected sales, and new a-Si active matrix liquid crystal display (AMLCD) factory); materials for flat panel displays (liquid crystal materials, and light-emissive display materials); manufacturing and infrastructure of active matrix liquid crystal displays (manufacturing logistics and equipment); passive matrix liquid crystal displays (LCD basics, twisted nematics LCD's, supertwisted nematic LCD's, ferroelectric LCD's, and a comparison of passive matrix LCD technology); active matrix technology (basic active matrix technology, investment environment, amorphous silicon, polysilicon, and commercial products and prototypes); and projection displays (comparison of Japanese and U.S. display research, and technical evaluation of work).

  14. Australian Children's Understanding of Display Rules

    Science.gov (United States)

    Choy, Grace

    2009-01-01

    Cultural display rules govern the manifestation of emotional expressions. In compliance with display rules, the facial expressions displayed (i.e. apparent emotion) may be incongruent with the emotion experienced (i.e. real emotion). This study investigates Australian Caucasian children's understanding of display rules. A sample of 80 four year…

  15. The case for transparent depth display

    NARCIS (Netherlands)

    Kooi, F.L.

    2003-01-01

    Purpose: The continuing developments in display technology have resulted in the ability to present increasing amounts of data on computer displays. One of the coming break-throughs is generally believed to be the introduction of '3-D displays': displays with a true sense of depth. Though these types

  16. Nonlinear mapping of the luminance in dual-layer high dynamic range displays

    Science.gov (United States)

    Guarnieri, Gabriele; Ramponi, Giovanni; Bonfiglio, Silvio; Albani, Luigi

    2009-02-01

    It has long been known that the human visual system (HVS) has a nonlinear response to luminance. This nonlinearity can be quantified using the concept of just noticeable difference (JND), which represents the minimum amplitude of a specified test pattern an average observer can discern from a uniform background. The JND depends on the background luminance following a threshold versus intensity (TVI) function. It is possible to define a curve which maps physical luminances into a perceptually linearized domain. This mapping can be used to optimize a digital encoding, by minimizing the visibility of quantization noise. It is also commonly used in medical applications to display images adapting to the characteristics of the display device. High dynamic range (HDR) displays, which are beginning to appear on the market, can display luminance levels outside the range in which most standard mapping curves are defined. In particular, dual-layer LCD displays are able to extend the gamut of luminance offered by conventional liquid crystals towards the black region; in such areas suitable and HVS-compliant luminance transformations need to be determined. In this paper we propose a method, which is primarily targeted to the extension of the DICOM curve used in medical imaging, but also has a more general application. The method can be modified in order to compensate for the ambient light, which can be significantly greater than the black level of an HDR display and consequently reduce the visibility of the details in dark areas.

  17. New ultraportable display technology and applications

    Science.gov (United States)

    Alvelda, Phillip; Lewis, Nancy D.

    1998-08-01

    MicroDisplay devices are based on a combination of technologies rooted in the extreme integration capability of conventionally fabricated CMOS active-matrix liquid crystal display substrates. Customized diffraction grating and optical distortion correction technology for lens-system compensation allow the elimination of many lenses and systems-level components. The MicroDisplay Corporation's miniature integrated information display technology is rapidly leading to many new defense and commercial applications. There are no moving parts in MicroDisplay substrates, and the fabrication of the color generating gratings, already part of the CMOS circuit fabrication process, is effectively cost and manufacturing process-free. The entire suite of the MicroDisplay Corporation's technologies was devised to create a line of application- specific integrated circuit single-chip display systems with integrated computing, memory, and communication circuitry. Next-generation portable communication, computer, and consumer electronic devices such as truly portable monitor and TV projectors, eyeglass and head mounted displays, pagers and Personal Communication Services hand-sets, and wristwatch-mounted video phones are among the may target commercial markets for MicroDisplay technology. Defense applications range from Maintenance and Repair support, to night-vision systems, to portable projectors for mobile command and control centers.

  18. Bibliographic Displays in OPACs and Web Catalogs: How Well Do They Comply with Display Guidelines?

    Science.gov (United States)

    Cherry, Joan M.

    1998-01-01

    Evaluation of data from assessments of full bibliographic displays in academic library OPACs (online public access catalogs) and World Wide Web catalogs against a checklist of desirable features found that OPAC displays scored 58% and Web displays scored 60%. Discusses weaknesses, focusing on those found in the majority of the displays…

  19. A nanobody:GFP bacterial platform that enables functional enzyme display and easy quantification of display capacity

    DEFF Research Database (Denmark)

    Wendel, Sofie; Christian Fischer, Emil; Martinez, Virginia

    2016-01-01

    Background: Bacterial surface display is an attractive technique for the production of cell-anchored, functional proteins and engineering of whole-cell catalysts. Although various outer membrane proteins have been used for surface display, an easy and versatile high-throughput-compatible assay...... to displaying the nanobody alone. We used flow cytometry to analyse display capability on single-cell versus population level and found that the signal peptide of the anchor has great effect on display efficiency.Conclusions: We have developed an inexpensive and easy read-out assay for surface display using...... nanobody: GFP interactions. The assay is compatible with the most common fluorescence detection methods, including multi-well plate whole-cell fluorescence detection, SDS-PAGE in-gel fluorescence, microscopy and flow cytometry. We anticipate that the platform will facilitate future in-depth studies...

  20. 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

  1. Human fibroblasts display a differential focal adhesion phenotype relative to chimpanzee.

    Science.gov (United States)

    Advani, Alexander S; Chen, Annie Y; Babbitt, Courtney C

    2016-01-01

    There are a number of documented differences between humans and our closest relatives in responses to wound healing and in disease susceptibilities, suggesting a differential cellular response to certain environmental factors. In this study, we sought to look at a specific cell type, fibroblasts, to examine differences in cellular adhesion between humans and chimpanzees in visualized cells and in gene expression. We have found significant differences in the number of focal adhesions between primary human and chimpanzee fibroblasts. Additionally, we see that adhesion related gene ontology categories are some of the most differentially expressed between human and chimpanzee in normal fibroblast cells. These results suggest that human and chimpanzee fibroblasts may have somewhat different adhesive properties, which could play a role in differential disease phenotypes and responses to external factors. © The Author(s) 2016. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

  2. Minimalism context-aware displays.

    Science.gov (United States)

    Cai, Yang

    2004-12-01

    Despite the rapid development of cyber technologies, today we still have very limited attention and communication bandwidth to process the increasing information flow. The goal of the study is to develop a context-aware filter to match the information load with particular needs and capacities. The functions include bandwidth-resolution trade-off and user context modeling. From the empirical lab studies, it is found that the resolution of images can be reduced in order of magnitude if the viewer knows that he/she is looking for particular features. The adaptive display queue is optimized with real-time operational conditions and user's inquiry history. Instead of measuring operator's behavior directly, ubiquitous computing models are developed to anticipate user's behavior from the operational environment data. A case study of the video stream monitoring for transit security is discussed in the paper. In addition, the author addresses the future direction of coherent human-machine vision systems.

  3. Reconfigurable Full-Page Braille Displays

    Science.gov (United States)

    Garner, H. Douglas

    1994-01-01

    Electrically actuated braille display cells of proposed type arrayed together to form full-page braille displays. Like other braille display cells, these provide changeable patterns of bumps driven by digitally recorded text stored on magnetic tapes or in solid-state electronic memories. Proposed cells contain electrorheological fluid. Viscosity of such fluid increases in strong electrostatic field.

  4. Display-management system for MFTF

    International Nuclear Information System (INIS)

    Nelson, D.O.

    1981-01-01

    The Mirror Fusion Test Facility (MFTF) is controlled by 65 local control microcomputers which are supervised by a local network of nine 32-bit minicomputers. Associated with seven of the nine computers are state-of-the-art graphics devices, each with extensive local processing capability. These devices provide the means for an operator to interact with the control software running on the minicomputers. It is critical that the information the operator views accurately reflects the current state of the experiment. This information is integrated into dynamically changing pictures called displays. The primary organizational component of the display system is the software-addressable segment. The segments created by the display creation software are managed by display managers associated with each graphics device. Each display manager uses sophisticated storage management mechanisms to keep the proper segments resident in the local graphics device storage

  5. Integrated Display and Environmental Awareness System - System Architecture Definition

    Science.gov (United States)

    Doule, Ondrej; Miranda, David; Hochstadt, Jake

    2017-01-01

    The Integrated Display and Environmental Awareness System (IDEAS) is an interdisciplinary team project focusing on the development of a wearable computer and Head Mounted Display (HMD) based on Commercial-Off-The-Shelf (COTS) components for the specific application and needs of NASA technicians, engineers and astronauts. Wearable computers are on the verge of utilization trials in daily life as well as industrial environments. The first civil and COTS wearable head mounted display systems were introduced just a few years ago and they probed not only technology readiness in terms of performance, endurance, miniaturization, operability and usefulness but also maturity of practice in perspective of a socio-technical context. Although the main technical hurdles such as mass and power were addressed as improvements on the technical side, the usefulness, practicality and social acceptance were often noted on the side of a broad variety of humans' operations. In other words, although the technology made a giant leap, its use and efficiency still looks for the sweet spot. The first IDEAS project started in January 2015 and was concluded in January 2017. The project identified current COTS systems' capability at minimum cost and maximum applicability and brought about important strategic concepts that will serve further IDEAS-like system development.

  6. Data display with the Q system

    International Nuclear Information System (INIS)

    Oothoudt, M.A.

    1979-01-01

    The Q data-acquisition system for PDP-11 mini-computers at the Clinton P. Anderson Meson Physics Facility (LAMPF) provides experimenters with basic tools for on-line data display. Tasks are available to plot one- and two-parameter histograms on Tektronix 4000 series storage-tube terminals. The histograms to be displayed and the display format may be selected with simple keyboard commands. A task is also available to create and display live two-parameter scatter plots for any acquired or calculated quantities. Other tasks in the system manage the display data base, list display parameters and histogram contents on hardcopy devices, and save core histograms on disk or tape for off-line analysis. 8 figures

  7. A nanobody:GFP bacterial platform that enables functional enzyme display and easy quantification of display capacity.

    Science.gov (United States)

    Wendel, Sofie; Fischer, Emil C; Martínez, Virginia; Seppälä, Susanna; Nørholm, Morten H H

    2016-05-03

    Bacterial surface display is an attractive technique for the production of cell-anchored, functional proteins and engineering of whole-cell catalysts. Although various outer membrane proteins have been used for surface display, an easy and versatile high-throughput-compatible assay for evaluating and developing surface display systems is missing. Using a single domain antibody (also called nanobody) with high affinity for green fluorescent protein (GFP), we constructed a system that allows for fast, fluorescence-based detection of displayed proteins. The outer membrane hybrid protein LppOmpA and the autotransporter C-IgAP exposed the nanobody on the surface of Escherichia coli with very different efficiency. Both anchors were capable of functionally displaying the enzyme Chitinase A as a fusion with the nanobody, and this considerably increased expression levels compared to displaying the nanobody alone. We used flow cytometry to analyse display capability on single-cell versus population level and found that the signal peptide of the anchor has great effect on display efficiency. We have developed an inexpensive and easy read-out assay for surface display using nanobody:GFP interactions. The assay is compatible with the most common fluorescence detection methods, including multi-well plate whole-cell fluorescence detection, SDS-PAGE in-gel fluorescence, microscopy and flow cytometry. We anticipate that the platform will facilitate future in-depth studies on the mechanism of protein transport to the surface of living cells, as well as the optimisation of applications in industrial biotech.

  8. Conceptual Design of Industrial Process Displays

    DEFF Research Database (Denmark)

    Pedersen, C.R.; Lind, Morten

    1999-01-01

    discusses aspects of process display design taking into account both the designer's and the operator's points of view. Three aspects are emphasized: the operator tasks, the display content and the display form. The distinction between these three aspects is the basis for proposing an outline for a display......Today, process displays used in industry are often designed on the basis of piping and instrumentation diagrams without any method of ensuring that the needs of the operators are fulfilled. Therefore, a method for a systematic approach to the design of process displays is needed. This paper...... by a simple example from a plant with batch processes. Later the method is applied to develop a supervisory display for a condenser system in a nuclear power plant. The differences between the continuous plant domain of power production and the batch processes from the example are analysed and broad...

  9. Improvements in data display

    International Nuclear Information System (INIS)

    Ellis, G.W.

    1979-01-01

    An analog signal processor is described in this patent for connecting a source of analog signals to a cathode ray tube display in order to extend the dynamic range of the display. This has important applications in the field of computerised X-ray tomography since significant medical information, such as tumours in soft tissue, is often represented by minimal level changes in image density. Cathode ray tube displays are limited to approximately 15 intensity levels. Thus if both strong and weak absorption of the X-rays occurs, the dynamic range of the transmitted signals will be too large to permit small variations to be examined directly on a cathode ray display. Present tomographic image reconstruction methods are capable of quantising X-ray absorption density measurements into 256 or more distinct levels and a description is given of the electronics which enables the upper and lower range of intensity levels to be independently set and continuously varied. (UK)

  10. Comparison of helmet-mounted display designs in support of wayfinding

    Science.gov (United States)

    Kumagai, Jason K.; Massel, Lisa; Tack, David; Bossi, Linda

    2003-09-01

    The Canadian Soldier Information Requirements Technology Demonstration (SIREQ TD) soldier modernization research and development program has conducted experiments to help determine the types and amount of information needed to support wayfinding across a range of terrain environments, the most effective display modality for providing the information (visual, auditory or tactile) that will minimize conflict with other infantry tasks, and to optimize interface design. In this study, seven different visual helmet-mounted display (HMD) designs were developed based on soldier feedback from previous studies. The displays and an in-service compass condition were contrasted to investigate how the visual HMD interfaces influenced navigation performance. Displays varied with respect to their information content, frame of reference, point of view, and display features. Twelve male infantry soldiers used all eight experimental conditions to locate bearings to waypoints. From a constant location, participants were required to face waypoints presented at offset bearings of 25, 65, and 120 degrees. Performance measures included time to identify waypoints, accuracy, and head misdirection errors. Subjective measures of performance included ratings of ease of use, acceptance for land navigation, and mental demand. Comments were collected to identify likes, dislikes and possible improvements required for HMDs. Results underlined the potential performance enhancement of GPS-based navigation with HMDs, the requirement for explicit directional information, the desirability of both analog and digital information, the performance benefits of an egocentric frame of reference, the merit of a forward field of view, and the desirability of a guide to help landmark. Implications for the information requirements and human factors design of HMDs for land-based navigational tasks are discussed.

  11. Helmet-Mounted Display Design Guide

    Science.gov (United States)

    1997-11-03

    on openStack create menu "CSHMD" set the menuitems of "CSHMD" to "(Main Menu; References;-; Definitions;Display Criteria;Display Formats;Display Modes...34Macintosh" then put ":" into dirSep else put "V’ into dirSep put stackPathO&"Resource"&dirSep into gResPath put 0 into gXRef end openStack on

  12. Ruggedized Full-Color Flexible OLED Display

    National Research Council Canada - National Science Library

    Hack, Michael

    2003-01-01

    .... The team comprised Universal Display Corporation, Princeton University, the University of Southern California, Penn State University, L3 Displays and Vitex Systems, and was led by Universal Display Corporation (PI: Michael Hack...

  13. Combat vehicle crew helmet-mounted display: next generation high-resolution head-mounted display

    Science.gov (United States)

    Nelson, Scott A.

    1994-06-01

    The Combat Vehicle Crew Head-Mounted Display (CVC HMD) program is an ARPA-funded, US Army Natick Research, Development, and Engineering Center monitored effort to develop a high resolution, flat panel HMD for the M1 A2 Abrams main battle tank. CVC HMD is part of the ARPA High Definition Systems (HDS) thrust to develop and integrate small (24 micrometers square pels), high resolution (1280 X 1024 X 6-bit grey scale at 60 frame/sec) active matrix electroluminescent (AMEL) and active matrix liquid crystal displays (AMLCD) for head mounted and projection applications. The Honeywell designed CVC HMD is a next generation head-mounted display system that includes advanced flat panel image sources, advanced digital display driver electronics, high speed (> 1 Gbps) digital interconnect electronics, and light weight, high performance optical and mechanical designs. The resulting dramatic improvements in size, weight, power, and cost have already led to program spin offs for both military and commercial applications.

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

    Science.gov (United States)

    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.

  15. Basics of Antibody Phage Display Technology.

    Science.gov (United States)

    Ledsgaard, Line; Kilstrup, Mogens; Karatt-Vellatt, Aneesh; McCafferty, John; Laustsen, Andreas H

    2018-06-09

    Antibody discovery has become increasingly important in almost all areas of modern medicine. Different antibody discovery approaches exist, but one that has gained increasing interest in the field of toxinology and antivenom research is phage display technology. In this review, the lifecycle of the M13 phage and the basics of phage display technology are presented together with important factors influencing the success rates of phage display experiments. Moreover, the pros and cons of different antigen display methods and the use of naïve versus immunized phage display antibody libraries is discussed, and selected examples from the field of antivenom research are highlighted. This review thus provides in-depth knowledge on the principles and use of phage display technology with a special focus on discovery of antibodies that target animal toxins.

  16. Ergonomic evaluation of CRT display in new control panels for nuclear power stations

    International Nuclear Information System (INIS)

    Kabazawa, Yoshihiko

    1983-01-01

    New control panels are to support powerfully the synthetic judgement function of operators by processing enormous plant data in the normal operation and at the time of accidents in nuclear power stations, and displaying the results in collective and ordered form on CRTs. This time, by carrying out the evaluation of new control panels using human engineering method, it was able to be confirmed that the new control panels have achieved the initial objectives, and to determine the criteria for the ergonomic evaluation of central control panels mainly with CRT display. Besides, it is considered that the application to wide range can be expected for this evaluation, not only to the CRT display system of the new control panels for nuclear power stations but also to other CRT images, therefore, the outline is reported. Chubu Electric Power Co., Inc. plans to adopt the new control panels with CRT display effectively utilizing process computers hereafter. It is necessary to give sufficient consideration to the method of using CRT images, the kinds of displayed images, colors and the form and arrangement of letters and symbols. 12 CRTs are used for the new control panel. The results are reflected to the control panel for Hamaoka No.3 plant. (Kako, I.)

  17. Advanced integrated real-time clinical displays.

    Science.gov (United States)

    Kruger, Grant H; Tremper, Kevin K

    2011-09-01

    Intelligent medical displays have the potential to improve patient outcomes by integrating multiple physiologic signals, exhibiting high sensitivity and specificity, and reducing information overload for physicians. Research findings have suggested that information overload and distractions caused by patient care activities and alarms generated by multiple monitors in acute care situations, such as the operating room and the intensive care unit, may produce situations that negatively impact the outcomes of patients under anesthesia. This can be attributed to shortcomings of human-in-the-loop monitoring and the poor specificity of existing physiologic alarms. Modern artificial intelligence techniques (ie, intelligent software agents) are demonstrating the potential to meet the challenges of next-generation patient monitoring and alerting. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Understanding the exposure-time effect on speckle contrast measurements for laser displays

    Science.gov (United States)

    Suzuki, Koji; Kubota, Shigeo

    2018-02-01

    To evaluate the influence of exposure time on speckle noise for laser displays, speckle contrast measurement method was developed observable at a human eye response time using a high-sensitivity camera which has a signal multiplying function. The nonlinearity of camera light sensitivity was calibrated to measure accurate speckle contrasts, and the measuring lower limit noise of speckle contrast was improved by applying spatial-frequency low pass filter to the captured images. Three commercially available laser displays were measured over a wide range of exposure times from tens of milliseconds to several seconds without adjusting the brightness of laser displays. The speckle contrast of raster-scanned mobile projector without any speckle-reduction device was nearly constant over various exposure times. On the contrary to this, in full-frame projection type laser displays equipped with a temporally-averaging speckle-reduction device, some of their speckle contrasts close to the lower limits noise were slightly increased at the shorter exposure time due to the noise. As a result, the exposure-time effect of speckle contrast could not be observed in our measurements, although it is more reasonable to think that the speckle contrasts of laser displays, which are equipped with the temporally-averaging speckle-reduction device, are dependent on the exposure time. This discrepancy may be attributed to the underestimation of temporal averaging factor. We expected that this method is useful for evaluating various laser displays and clarify the relationship between the speckle noise and the exposure time for a further verification of speckle reduction.

  19. Resolution and noise measurements of five CRT and LCD medical displays

    International Nuclear Information System (INIS)

    Saunders, Robert S. Jr.; Samei, Ehsan

    2006-01-01

    The performance of soft-copy displays plays a significant role in the overall image quality of a digital radiographic system. In this work, we discuss methods to characterize the resolution and noise of both cathode ray tube (CRT) and liquid crystal display (LCD) devices. We measured the image quality of five different commercial display devices, representing both CRT and LCD technologies, using a high-quality charge-coupled device (CCD) camera. The modulation transfer function (MTF) was calculated using the line technique, correcting for the MTF of the CCD camera and the display pixel size. The normalized noise power spectrum (NPS) was computed from two-dimensional Fourier analysis of uniform images. To separate the effects of pixel structure from interpixel luminance variations, we created structure-free images by eliminating the pixel structures of the display device. The NPS was then computed from these structure-free images to isolate interpixel luminance variations. We found that the MTF of LCDs remained close to the theoretical limit dictated by their inherent pixel size (0.85±0.08 at Nyquist frequency), in contrast to the MTF for the two CRT displays, which dropped to 0.15±0.08 at the Nyquist frequency. However, the NPS of LCDs showed significant peaks due to the subpixel structure, while the NPS of CRT displays exhibited a nearly flat power spectrum. After removing the pixel structure, the structured noise peaks for LCDs were eliminated and the overall noise magnitude was significantly reduced. The average total noise-to-signal ratio for CRT displays was 6.55%±0.59%, of which 6.03%±0.24% was due to interpixel luminance variations, while LCD displays had total noise to signal ratios of 46.1%±5.1% of which 1.50%±0.41% were due to interpixel luminance variations. Depending on the extent of the blurring and prewhitening processes of the human visual system, the magnitude of the display noise (including pixel structure) potentially perceived by the

  20. Three-dimensional hologram display system

    Science.gov (United States)

    Mintz, Frederick (Inventor); Chao, Tien-Hsin (Inventor); Bryant, Nevin (Inventor); Tsou, Peter (Inventor)

    2009-01-01

    The present invention relates to a three-dimensional (3D) hologram display system. The 3D hologram display system includes a projector device for projecting an image upon a display medium to form a 3D hologram. The 3D hologram is formed such that a viewer can view the holographic image from multiple angles up to 360 degrees. Multiple display media are described, namely a spinning diffusive screen, a circular diffuser screen, and an aerogel. The spinning diffusive screen utilizes spatial light modulators to control the image such that the 3D image is displayed on the rotating screen in a time-multiplexing manner. The circular diffuser screen includes multiple, simultaneously-operated projectors to project the image onto the circular diffuser screen from a plurality of locations, thereby forming the 3D image. The aerogel can use the projection device described as applicable to either the spinning diffusive screen or the circular diffuser screen.

  1. 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

  2. Draft revision of human factors guideline HF-010

    International Nuclear Information System (INIS)

    Lee, Hyun Chul; Lee, Yong Hee; Oh, In Seok; Lee, Jung Woon; Cha, Woo Chang; Lee, Dhong Ha

    2003-05-01

    The Application of Human Factors to the design of Man-Machine Interfaces System(MMIS) in the nuclear power plant is essential to the safety and productivity of the nuclear power plants, human factors standards and guidelines as well as human factors analysis methods and experiments are weightily used to the design application. A Korean engineering company has developed a human factors engineering guideline, so-call HF-010, and has used it for human factors design, however the revision of HF-010 is necessary owing to lack of the contents related to the advanced MMI(Man-Machine Interfaces). As the results of the reviews of HF-010, it is found out that the revision of Section 9. Computer Displays of HF-010 is urgent, thus the revision was drafted on the basis of integrated human factors design guidelines for VDT, human factors design guidelines for PMAS SPADES display, human factors design guidelines for PMAS alarm display, and human factors design guidelines for electronic displays developed by the surveillance and operation support project of KOICS. The draft revision of HF-010 Section 9 proposed in this report can be utilized for the human factors design of the advanced MMI, and the high practical usability of the draft can be kept up through the continuous revision according to the advancement of digital technology

  3. Display rules versus display autonomy: emotion regulation, emotional exhaustion, and task performance in a call center simulation.

    Science.gov (United States)

    Goldberg, Lori Sideman; Grandey, Alicia A

    2007-07-01

    "Service with a smile" is satisfying for the customer, but such display rules may be costly to the employee and the organization. Most previous research on such costs has used self-reported and cross-sectional designs. The authors use an experimental approach to test tenets of resource depletion theories; specifically, whether the self-regulation of emotions required by display rules depletes energy and attentional resources during a service encounter. Using a call center simulation with three "customer" interactions, the authors found that participants given positive display rules (e.g., be enthusiastic and hide frustration) reported more postsimulation exhaustion and made more errors on the order form compared to those with display autonomy. Customer hostility during one of the calls also increased exhaustion overall and the number of errors during that specific call, though proposed interactions with display rules were not supported. Surface-level emotion regulation, but not deep-level, was the mechanism for the energy depletion effect of display rules, while display rules had a direct effect on performance decrements. Theoretical and practical implications for display rules as part of job requirements are discussed. Copyright 2007 APA

  4. A polymorphic variant in the human electron transfer flavoprotein alpha-chain (alpha-T171) displays decreased thermal stability and is overrepresented in very-long-chain acyl-CoA dehydrogenase-deficient patients with mild childhood presentation

    DEFF Research Database (Denmark)

    Bross, P; Pedersen, P; Nyholm, M

    1999-01-01

    The consequences of two amino acid polymorphisms of human electron transfer flavoprotein (alpha-T/I171 in the alpha-subunit and beta-M/T154 in the beta-subunit) on the thermal stability of the enzyme are described. The alpha-T171 variant displayed a significantly decreased thermal stability, wher....... This is compatible with a negative modulating effect of the less-stable alpha-T171 ETF variant in this group of VLCAD patients that harbor missense mutations in at least one allele and therefore potentially display residual levels of VLCAD enzyme activity. Udgivelsesdato: 1999-Jun...

  5. Paediatric dose display

    International Nuclear Information System (INIS)

    Griffin, D.W.; Derges, S.; Hesslewood, S.

    1984-01-01

    A compact, inexpensive unit, based on an 8085 microprocessor, has been designed for calculating doses of intravenous radioactive injections for children. It has been used successfully for over a year. The dose is calculated from the body surface area and the result displayed in MBq. The operator can obtain the required dose on a twelve character alphanumeric display by entering the age of the patient and the adult dose using a hexadecimal keyboard. Circuit description, memory map and input/output, and firmware are dealt with. (U.K.)

  6. Development of anti-infectives using phage display: biological agents against bacteria, viruses, and parasites.

    Science.gov (United States)

    Huang, Johnny X; Bishop-Hurley, Sharon L; Cooper, Matthew A

    2012-09-01

    The vast majority of anti-infective therapeutics on the market or in development are small molecules; however, there is now a nascent pipeline of biological agents in development. Until recently, phage display technologies were used mainly to produce monoclonal antibodies (MAbs) targeted against cancer or inflammatory disease targets. Patent disputes impeded broad use of these methods and contributed to the dearth of candidates in the clinic during the 1990s. Today, however, phage display is recognized as a powerful tool for selecting novel peptides and antibodies that can bind to a wide range of antigens, ranging from whole cells to proteins and lipid targets. In this review, we highlight research that exploits phage display technology as a means of discovering novel therapeutics against infectious diseases, with a focus on antimicrobial peptides and antibodies in clinical or preclinical development. We discuss the different strategies and methods used to derive, select, and develop anti-infectives from phage display libraries and then highlight case studies of drug candidates in the process of development and commercialization. Advances in screening, manufacturing, and humanization technologies now mean that phage display can make a significant contribution in the fight against clinically important pathogens.

  7. Scaling Robotic Displays: Displays and Techniques for Dismounted Movement with Robots

    Science.gov (United States)

    2010-04-01

    you are performing the low crawl 4.25 5.00 Drive the robot while you are negotiating the hill 6.00 5.00 Drive the robot while you are climbing the... stairs 4.67 5.00 Drive the robot while you are walking 5.70 5.27 HMD It was fairly doable. 1 When you’re looking through the lens, it’s not...Scaling Robotic Displays: Displays and Techniques for Dismounted Movement with Robots by Elizabeth S. Redden, Rodger A. Pettitt

  8. Diethylene glycol monoethyl ether (Transcutol) displays antiproliferative properties alone and in combination with xanthines.

    Science.gov (United States)

    Levi-Schaffer, F; Dayan, N; Touitou, E

    1996-01-01

    In the present study we have investigated the effects of diethylene glycol monoethyl ether (Transcutol) in combination with theophylline, caffeine and dyphylline and alone on 3T3 mouse fibroblast proliferation. These three xanthines (1-0.01 mM) inhibited fibroblast proliferation by themselves. Enhancement of the effect was detected by addition of 1 and 0.1 mM Transcutol. Transcutol alone also displayed a dose-dependent inhibition (2-0.01 mM) of both 3T3 and human normal and psoriatic fibroblasts, although normal human fibroblasts were the least sensitive to Transcutol antiproliferative activity. Transcutol was assessed for its antiproliferative effects on YAC lymphoma and P-815 mastocytoma human cell lines. Transcutol inhibited cell proliferation of both these cell lines, being more effective towards P-815 mastocytoma (at 2 mM it displayed 3.95-fold vs. 2.4-fold inhibition towards YAC lymphoma). In conclusion, we have shown that Transcutol has antiproliferative effects on 3T3 murine, human normal and psoriatic fibroblasts and tumour cell lines. In addition it enhances xanthine antiproliferative effects on 3T3 fibroblasts. Therefore it might be a useful topical drug alone or in combination with xanthines in the treatment of skin hyperproliferative disorders.

  9. Liquid crystal displays with plastic substrates

    Science.gov (United States)

    Lueder, Ernst H.

    1998-04-01

    Plastic substrates for the cells of displays exhibit only 1/6 of the weight of glass substrates; they are virtually unbreakable; their flexibility allows the designer to give them a shape suppressing reflections, to realize a display board on a curved surface or meeting the requirements for an appealing styling; displays with plastics are thinner which provides a wider viewing angle. These features render them attractive for displays in portable systems such as mobile phones, pagers, smart cards, personal digital assistants (PDAs) and portable computers. Reflective displays are especially attractive as they don't need a back light. The most important requirements are the protection of plastics against gas permeation and chemical agents, the prevention of layers on plastics to crack or peel off when the plastic is bent and the development of low temperature thin film processes because the plastics, as a rule, only tolerate temperatures below 150 degrees Celsius. Bistable reflective FLC- and PSCT-displays with plastic substrates will be introduced. Special sputtered SiO2-orientation layers preserve the displayed information even if pressure or torsion is applied. MIM-addressed PDLC-displays require additional Al- or Ti-layers which provide the necessary ductility. Sputtered or PECVD-generated TFTs can be fabricated on plastics at temperatures below 150 degrees Celsius.

  10. Perceived Intensity of Emotional Point-Light Displays Is Reduced in Subjects with ASD

    Science.gov (United States)

    Krüger, Britta; Kaletsch, Morten; Pilgramm, Sebastian; Schwippert, Sven-Sören; Hennig, Jürgen; Stark, Rudolf; Lis, Stefanie; Gallhofer, Bernd; Sammer, Gebhard; Zentgraf, Karen; Munzert, Jörn

    2018-01-01

    One major characteristic of autism spectrum disorder (ASD) is problems with social interaction and communication. The present study explored ASD-related alterations in perceiving emotions expressed via body movements. 16 participants with ASD and 16 healthy controls observed video scenes of human interactions conveyed by point-light displays. They…

  11. Plant state display device

    International Nuclear Information System (INIS)

    Kadota, Kazuo; Ito, Toshiichiro.

    1994-01-01

    The device of the present invention conducts information processing suitable for a man to solve a problem in a plant such as a nuclear power plant incorporating a great amount of information, where safety is required and provides information to an operator. Namely, theories and rules with respect to the flow and balanced state of materials and energy upon plant start-up, and a vapor cycle of operation fluids are symbolized and displayed on the display screen of the device. Then, the display of the plant information suitable to the information processing for a man to dissolve problems is provided. Accordingly, a mechanism for analyzing a purpose of the plant is made more definite, thereby enabling to prevent an erroneous judgement of an operator and occurrence of plant troubles. In addition, a simular effect can also be expected when the theories and rules with respect to the flow and the balanced state of materials and energy and thermohydrodynamic behavior of the operation fluids in a state of after-heat removing operation during shutdown of the plant are symbolized and displayed. (I.S.)

  12. Using Auditory Cues to Perceptually Extract Visual Data in Collaborative, Immersive Big-Data Display Systems

    Science.gov (United States)

    Lee, Wendy

    The advent of multisensory display systems, such as virtual and augmented reality, has fostered a new relationship between humans and space. Not only can these systems mimic real-world environments, they have the ability to create a new space typology made solely of data. In these spaces, two-dimensional information is displayed in three dimensions, requiring human senses to be used to understand virtual, attention-based elements. Studies in the field of big data have predominately focused on visual representations and extractions of information with little focus on sounds. The goal of this research is to evaluate the most efficient methods of perceptually extracting visual data using auditory stimuli in immersive environments. Using Rensselaer's CRAIVE-Lab, a virtual reality space with 360-degree panorama visuals and an array of 128 loudspeakers, participants were asked questions based on complex visual displays using a variety of auditory cues ranging from sine tones to camera shutter sounds. Analysis of the speed and accuracy of participant responses revealed that auditory cues that were more favorable for localization and were positively perceived were best for data extraction and could help create more user-friendly systems in the future.

  13. Challenges in Optimizing a Prostate Carcinoma Binding Peptide, Identified through the Phage Display Technology

    Directory of Open Access Journals (Sweden)

    Jürgen Debus

    2011-02-01

    Full Text Available The transfer of peptides identified through the phage display technology to clinical applications is difficult. Major drawbacks are the metabolic degradation and label instability. The aim of our work is the optimization of DUP-1, a peptide which was identified by phage display to specifically target human prostate carcinoma. To investigate the influence of chelate conjugation, DOTA was coupled to DUP-1 and labeling was performed with 111In. To improve serum stability cyclization of DUP-1 and targeted D-amino acid substitution were carried out. Alanine scanning was performed for identification of the binding site and based on the results peptide fragments were chemically synthesized. The properties of modified ligands were investigated in in vitro binding and competition assays. In vivo biodistribution studies were carried out in mice, carrying human prostate tumors subcutaneously. DOTA conjugation resulted in different cellular binding kinetics, rapid in vivo renal clearance and increased tumor-to-organ ratios. Cyclization and D-amino acid substitution increased the metabolic stability but led to binding affinity decrease. Fragment investigation indicated that the sequence NRAQDY might be significant for target-binding. Our results demonstrate challenges in optimizing peptides, identified through phage display libraries, and show that careful investigation of modified derivatives is necessary in order to improve their characteristics.

  14. A Study on Large Display Panel Design for the Countermeasures against Team Errors within the Main Control Room of APR-1400

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sa Kil; Lee, Yong Hee [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-10-15

    The personal aspect of human errors has been mainly overcome by virtue of the education and training. However, in the system aspect, the education and training system needs to be reconsidered for more effective reduction of human errors affected from various systems hazards. Traditionally the education and training systems are mainly not focused on team skills such as communication, situational awareness, and coordination, etc. but individual knowledge, skill, and attitude. However, the team factor is one of the crucial issues to reduce the human errors in most industries. In this study, we identify the emerging types of team errors, especially, in digitalized control room of nuclear power plants such as the APR-1400 main control room. Most works in nuclear industry are to be performed by a team of more than two persons. Even though the individual errors can be detected and recovered by the qualified others and/or the well trained team, it is rather seldom that the errors by team could be easily detected and properly recovered by the team itself. Note that the team is defined as two or more people who are appropriately interacting with each other, and the team is a dependent aggregate, which accomplishes a valuable goal. Team error is one of the typical organizational errors that may occur during performing operations in nuclear power plants. The large display panel is a representative feature of digitalized control room. As a group-view display, the large display panel provides plant overview to the operators. However, in terms of team performance and team errors, the large display panel is on a discussion board still because the large display panel was designed just a concept of passive display. In this study, we will propose revised large display panel which is integrated with several alternative interfaces against feasible team errors.

  15. A Study on Large Display Panel Design for the Countermeasures against Team Errors within the Main Control Room of APR-1400

    International Nuclear Information System (INIS)

    Kim, Sa Kil; Lee, Yong Hee

    2015-01-01

    The personal aspect of human errors has been mainly overcome by virtue of the education and training. However, in the system aspect, the education and training system needs to be reconsidered for more effective reduction of human errors affected from various systems hazards. Traditionally the education and training systems are mainly not focused on team skills such as communication, situational awareness, and coordination, etc. but individual knowledge, skill, and attitude. However, the team factor is one of the crucial issues to reduce the human errors in most industries. In this study, we identify the emerging types of team errors, especially, in digitalized control room of nuclear power plants such as the APR-1400 main control room. Most works in nuclear industry are to be performed by a team of more than two persons. Even though the individual errors can be detected and recovered by the qualified others and/or the well trained team, it is rather seldom that the errors by team could be easily detected and properly recovered by the team itself. Note that the team is defined as two or more people who are appropriately interacting with each other, and the team is a dependent aggregate, which accomplishes a valuable goal. Team error is one of the typical organizational errors that may occur during performing operations in nuclear power plants. The large display panel is a representative feature of digitalized control room. As a group-view display, the large display panel provides plant overview to the operators. However, in terms of team performance and team errors, the large display panel is on a discussion board still because the large display panel was designed just a concept of passive display. In this study, we will propose revised large display panel which is integrated with several alternative interfaces against feasible team errors

  16. Three-dimensional Imaging, Visualization, and Display

    CERN Document Server

    Javidi, Bahram; Son, Jung-Young

    2009-01-01

    Three-Dimensional Imaging, Visualization, and Display describes recent developments, as well as the prospects and challenges facing 3D imaging, visualization, and display systems and devices. With the rapid advances in electronics, hardware, and software, 3D imaging techniques can now be implemented with commercially available components and can be used for many applications. This volume discusses the state-of-the-art in 3D display and visualization technologies, including binocular, multi-view, holographic, and image reproduction and capture techniques. It also covers 3D optical systems, 3D display instruments, 3D imaging applications, and details several attractive methods for producing 3D moving pictures. This book integrates the background material with new advances and applications in the field, and the available online supplement will include full color videos of 3D display systems. Three-Dimensional Imaging, Visualization, and Display is suitable for electrical engineers, computer scientists, optical e...

  17. Human-machine interface upgrade

    International Nuclear Information System (INIS)

    Kropik, M.; Matejka, K.; Sklenka, L.; Chab, V.

    2002-01-01

    The article describes a new human-machine interface that was installed at the VR-1 training reactor. The human-machine interface upgrade was completed in the summer 2001. The interface was designed with respect to functional, ergonomic and aesthetic requirements. The interface is based on a personal computer equipped with two displays. One display enables alphanumeric communication between the reactor operator and the nuclear reactor I and C. The second display is a graphical one. It presents the status of the reactor, principal parameters (as power, period), control rods positions, course of the reactor power. Furthermore, it is possible to set parameters, to show the active core configuration, to perform reactivity calculations, etc. The software for the new human-machine interface was produced with the InTouch developing tool of the Wonder-Ware Company. It is possible to switch the language of the interface between Czech and English because of many foreign students and visitors to the reactor. Microcomputer based communication units with proper software were developed to connect the new human-machine interface with the present reactor I and C. The new human-machine interface at the VR-1 training reactor improves the comfort and safety of the reactor utilisation, facilitates experiments and training, and provides better support for foreign visitors. (orig.)

  18. SNS online display technologies for EPICS

    International Nuclear Information System (INIS)

    Kasemir, K.U.; Chen, X.; Purcell, J.; Danilova, E.

    2012-01-01

    The ubiquitousness of web clients from personal computers to cell phones results in a growing demand for web-based access to control system data. At the Oak Ridge National Laboratory Spallation Neutron Source (SNS) we have investigated different technical approaches to provide read access to data in the Experimental Physics and Industrial Control System (EPICS) for a wide variety of web client devices. The core web technology, HTTP, is less than ideal for online control system displays. Appropriate use of Ajax, especially the Long Poll paradigm, can alleviate fundamental HTTP limitations. The SNS Status web uses basic Ajax technology to generate generic displays for a wide audience. The Dashboard uses Long Poll and more client-side Java-Script to offer more customization and faster updates for users that need specialized displays. The Web OPI uses RAP for web access to any BOY display, offering utmost flexibility because users can create their own BOY displays in CSS. These three approaches complement each other. Users can access generic status displays with zero effort, invest time in creating their fully customized displays for the Web OPI, or use the Dashboard as an intermediate solution

  19. Dyes for displays

    Science.gov (United States)

    Claussen, U.

    1984-01-01

    The improvement of contrast and visibility of LCD by two different means was undertaken. The two methods are: (1) development of fluorescent dyes to increase the visibility of fluorescent activated displays (FLAD); and (2) development of dichroic dyes to increase the contrast of displays. This work was done in close cooperation with the electronic industry, where the newly synthesized dyes were tested. The targets for the chemical synthesis were selected with the help of computer model calculations. A marketable range of dyes was developed. Since the interest of the electronic industries concerning FLAD was low, the investigations were stopped. Dichroic dyes, especially black mixtures with good light fastness, order parameter, and solubility in nematic phases were developed. The application of these dyes is restricted to indoor use because of an increase of viscosity below -10 C. Applications on a technical scale, e.g., for the automotive industry, will be possible if the displays work at temperatures down to -40 C. This problem requires a complex optimization of the dye/nematic phase system.

  20. Flat panel planar optic display

    Energy Technology Data Exchange (ETDEWEB)

    Veligdan, J.T. [Brookhaven National Lab., Upton, NY (United States). Dept. of Advanced Technology

    1994-11-01

    A prototype 10 inch flat panel Planar Optic Display, (POD), screen has been constructed and tested. This display screen is comprised of hundreds of planar optic class sheets bonded together with a cladding layer between each sheet where each glass sheet represents a vertical line of resolution. The display is 9 inches wide by 5 inches high and approximately 1 inch thick. A 3 milliwatt HeNe laser is used as the illumination source and a vector scanning technique is employed.

  1. Performance of NCAP projection displays

    Science.gov (United States)

    Jones, Philip J.; Tomita, Akira; Wartenberg, Mark

    1991-08-01

    Prototypes of projection displays based on dispersions of liquid crystal in polymer matrices are beginning to appear. The principle of operation depends on electrically switchable light scattering. They are potentially much brighter than current cathode ray tube (CRT) or twisted nematic liquid crystal (TN LC) cell based displays. Comparisons of efficacy and efficiency show this. The contrast and brightness of such displays depend on a combination of the f- number of the projection system and the scattering characteristics of the light valve. Simplified equations can be derived to show these effects. The degree of scattering of current NCAP formulations is sufficient to produce good contrast projection displays, at convenient voltages, that are around three times brighter than TN LC projectors because of the lack of polarizers in the former.

  2. Compressive multi-mode superresolution display

    KAUST Repository

    Heide, Felix

    2014-01-01

    Compressive displays are an emerging technology exploring the co-design of new optical device configurations and compressive computation. Previously, research has shown how to improve the dynamic range of displays and facilitate high-quality light field or glasses-free 3D image synthesis. In this paper, we introduce a new multi-mode compressive display architecture that supports switching between 3D and high dynamic range (HDR) modes as well as a new super-resolution mode. The proposed hardware consists of readily-available components and is driven by a novel splitting algorithm that computes the pixel states from a target high-resolution image. In effect, the display pixels present a compressed representation of the target image that is perceived as a single, high resolution image. © 2014 Optical Society of America.

  3. Color dependence with horizontal-viewing angle and colorimetric characterization of two displays using different backlighting

    Science.gov (United States)

    Castro, José J.; Pozo, Antonio M.; Rubiño, Manuel

    2013-11-01

    In this work we studied the color dependence with a horizontal-viewing angle and colorimetric characterization of two liquid-crystal displays (LCD) using two different backlighting: Cold Cathode Fluorescent Lamps (CCFLs) and light-emitting diodes (LEDs). The LCDs studied had identical resolution, size, and technology (TFT - thin film transistor). The colorimetric measurements were made with the spectroradiometer SpectraScan PR-650 following the procedure recommended in the European guideline EN 61747-6. For each display, we measured at the centre of the screen the chromaticity coordinates at horizontal viewing angles of 0, 20, 40, 60 and 80 degrees for the achromatic (A), red (R), green (G) and blue (B) channels. Results showed a greater color-gamut area for the display with LED backlight, compared with the CCFL backlight, showing a greater range of colors perceptible by human vision. This color-gamut area diminished with viewing angle for both displays. Higher differences between trends for viewing angles were observed in the LED-backlight, especially for the R- and G-channels, demonstrating a higher variability of the chromaticity coordinates with viewing angle. The best additivity was reached by the LED-backlight display (a lower error percentage). LED-backlight display provided better color performance of visualization.

  4. Nuclear image display controller

    International Nuclear Information System (INIS)

    Roth, D.A.

    1985-01-01

    In a nuclear imaging system the digitized x and y coordinates of gamma ray photon emission events address memory locations corresponding to the coordinates. The respective locations are incremented each time they are addressed so at the end of a selected time or event count period the locations contain digital values or raw data corresponding to the intensity of pixels comprising an image frame. The raw data for a frame is coupled to one input of an arithmetic logic unit (ALU) whose output is coupled to a display controller memory. The output of the controller memory is coupled to another ALU input with a feedback bus and is also coupled to a further signal processing circuit which includes means for converting processed data to analog video signals for television display. The ALU is selectively controlled to let raw image data pass through to the display controllor memory or alternately to add (or subtract) raw data for the last image frame developed to the raw data for preceding frames held in the display controller to thereby produce the visual effect on the television screen of an isotope flowing through anatomy

  5. Dimensions of Situatedness for Digital Public Displays

    Directory of Open Access Journals (Sweden)

    Rui José

    2014-01-01

    Full Text Available Public displays are often strongly situated signs deeply embedded in their physical, social, and cultural setting. Understanding how the display is coupled with on-going situations, its level of situatedness, provides a key element for the interpretation of the displays themselves but is also an element for the interpretation of place, its situated practices, and its social context. Most digital displays, however, do not achieve the same sense of situatedness that seems so natural in their nondigital counterparts. This paper investigates people’s perception of situatedness when considering the connection between public displays and their context. We have collected over 300 photos of displays and conducted a set of analysis tasks involving focus groups and structured interviews with 15 participants. The contribution is a consolidated list of situatedness dimensions that should provide a valuable resource for reasoning about situatedness in digital displays and informing the design and development of display systems.

  6. On-line data display

    Science.gov (United States)

    Lang, Sherman Y. T.; Brooks, Martin; Gauthier, Marc; Wein, Marceli

    1993-05-01

    A data display system for embedded realtime systems has been developed for use as an operator's user interface and debugging tool. The motivation for development of the On-Line Data Display (ODD) have come from several sources. In particular the design reflects the needs of researchers developing an experimental mobile robot within our laboratory. A proliferation of specialized user interfaces revealed a need for a flexible communications and graphical data display system. At the same time the system had to be readily extensible for arbitrary graphical display formats which would be required for data visualization needs of the researchers. The system defines a communication protocol transmitting 'datagrams' between tasks executing on the realtime system and virtual devices displaying the data in a meaningful way on a graphical workstation. The communication protocol multiplexes logical channels on a single data stream. The current implementation consists of a server for the Harmony realtime operating system and an application written for the Macintosh computer. Flexibility requirements resulted in a highly modular server design, and a layered modular object- oriented design for the Macintosh part of the system. Users assign data types to specific channels at run time. Then devices are instantiated by the user and connected to channels to receive datagrams. The current suite of device types do not provide enough functionality for most users' specialized needs. Instead the system design allows the creation of new device types with modest programming effort. The protocol, design and use of the system are discussed.

  7. Flexible displays, rigid designs?

    DEFF Research Database (Denmark)

    Hornbæk, Kasper

    2015-01-01

    Rapid technological progress has enabled a wide range of flexible displays for computing devices, but the user experience--which we're only beginning to understand--will be the key driver for successful designs.......Rapid technological progress has enabled a wide range of flexible displays for computing devices, but the user experience--which we're only beginning to understand--will be the key driver for successful designs....

  8. Microencapsulated Electrophoretic Films for Electronic Paper Displays

    Science.gov (United States)

    Amundson, Karl

    2003-03-01

    Despite the dominance of liquid crystal displays, they do not perform some functions very well. While backlit liquid crystal displays can offer excellent color performance, they wash out in bright lighting and suffer from high power consumption. Reflective liquid crystal displays have limited brightness, making these devices challenging to read for long periods of time. Flexible liquid crystal displays are difficult to manufacture and keep stable. All of these attributes (long battery lifetime, bright reflective appearance, compatibility with flexible substrates) are traits that would be found in an ideal electronic paper display - an updateable substitute for paper that could be employed in electronic books, newspapers, and other applications. I will discuss technologies that are being developed for electronic-paper-like displays, and especially on particle-based technologies. A microencapsulated electrophoretic display technology is being developed at the E Ink corporation. This display film offers offer high brightness and an ink-on-paper appearance, compatibility with flexible substrates, and image stability that can lead to very low power consumption. I will present some of the physical and chemical challenges associated with making display films with high performance.

  9. Human Renal Normal, Tumoral, and Cancer Stem Cells Express Membrane-Bound Interleukin-15 Isoforms Displaying Different Functions

    Directory of Open Access Journals (Sweden)

    Sandy Azzi

    2015-06-01

    Full Text Available Intrarenal interleukin-15 (IL-15 participates to renal pathophysiology, but the role of its different membrane-bound isoforms remains to be elucidated. In this study, we reassess the biology of membrane-bound IL-15 (mb-IL-15 isoforms by comparing primary cultures of human renal proximal tubular epithelial cells (RPTEC to peritumoral (ptumTEC, tumoral (RCC, and cancer stem cells (CSC/CD105+. RPTEC express a 14 to 16 kDa mb-IL-15, whose existence has been assumed but never formally demonstrated and likely represents the isoform anchored at the cell membrane through the IL-15 receptor α (IL-15Rα chain, because it is sensitive to acidic treatment and is not competent to deliver a reverse signal. By contrast, ptumTEC, RCC, and CSC express a novel N-hyperglycosylated, short-lived transmembrane mb-IL-15 (tmb-IL-15 isoform around 27 kDa, resistant to acidic shock, delivering a reverse signal in response to its soluble receptor (sIL-15Rα. This reverse signal triggers the down-regulation of the tumor suppressor gene E-cadherin in ptumTEC and RCC but not in CSC/CD105+, where it promotes survival. Indeed, through the AKT pathway, tmb-IL-15 protects CSC/CD105+ from non-programmed cell death induced by serum starvation. Finally, both mb-IL-15 and tmb-IL-15 are sensitive to metalloproteases, and the cleaved tmb-IL-15 (25 kDa displays a powerful anti-apoptotic effect on human hematopoietic cells. Overall, our data indicate that both mb-IL-15 and tmb-IL-15 isoforms play a complex role in renal pathophysiology downregulating E-cadherin and favoring cell survival. Moreover, “apparently normal” ptumTEC cells, sharing different properties with RCC, could contribute to organize an enlarged peritumoral “preneoplastic” environment committed to favor tumor progression.

  10. Revisiting the debate on the relationship between display rules and performance: considering the explicitness of display rules.

    Science.gov (United States)

    Christoforou, Paraskevi S; Ashforth, Blake E

    2015-01-01

    We argue that the strength with which the organization communicates expectations regarding the appropriate emotional expression toward customers (i.e., explicitness of display rules) has an inverted U-shaped relationship with service delivery behaviors, customer satisfaction, and sales performance. Further, we argue that service organizations need a particular blend of explicitness of display rules and role discretion for the purpose of optimizing sales performance. As hypothesized, findings from 2 samples of salespeople suggest that either high or low explicitness of display rules impedes service delivery behaviors and sales performance, which peaks at moderate explicitness of display rules and high role discretion. The findings also suggest that the explicitness of display rules has a positive relationship with customer satisfaction. (c) 2015 APA, all rights reserved.

  11. Growth, development, reproduction, physiological and behavioural studies on living organisms, human adults and children exposed to radiation from video displays

    International Nuclear Information System (INIS)

    Laverdure, A.M.; Surbeck, J.; North, M.O.; Tritto, J.

    2001-01-01

    Various living organisms, human workers and children were tested for any biological action resulting from exposure to radiation from video display terminals (VDTs). VDTs were powered by a 50-Hz alternating voltage of 220 V. Measured electric and magnetic fields were 13 V/M and 50 nT, respectively. Living organisms were maintained under their normal breeding conditions and control values were obtained before switching on the VDT. Various effects related to the irradiation time were demonstrated, i.e. growth delay in algae and Drosophila, a body weight deficiency in rats, abnormal peaks of mortality in Daphnia and Drosophila, teratological effects in chick embryos and behavioural disturbances in rats. The embryonic and neonatal periods showed a high sensitivity to the VDT radiation. In humans, after 4 h of working in front of a VDT screen, an increase in tiredness and a decrease in the resistance of the immune system were observed in workers. In prepubertal children, 20 min of exposure were sufficient to induce neuropsychological disturbances; pre-pubertal young people appear to be particularly sensitive to the effect of the radiation. In human testicular biopsies cultured in vitro for 24 h in front of a VDT screen, mitotic and meiotic disturbances, the appearance of degeneration in some aspects of the cells and significant disorganisation of the seminiferous tubules were demonstrated and related to modification of the metabolism of the sample. An experimental apparatus has been developed and tested that aims to prevent the harm from VDT radiation. Known commercially as the 'emf-Bioshield', it ensures effective protection against harmful biological effects of VDT radiation. (author)

  12. Choosing colors for map display icons using models of visual search.

    Science.gov (United States)

    Shive, Joshua; Francis, Gregory

    2013-04-01

    We show how to choose colors for icons on maps to minimize search time using predictions of a model of visual search. The model analyzes digital images of a search target (an icon on a map) and a search display (the map containing the icon) and predicts search time as a function of target-distractor color distinctiveness and target eccentricity. We parameterized the model using data from a visual search task and performed a series of optimization tasks to test the model's ability to choose colors for icons to minimize search time across icons. Map display designs made by this procedure were tested experimentally. In a follow-up experiment, we examined the model's flexibility to assign colors in novel search situations. The model fits human performance, performs well on the optimization tasks, and can choose colors for icons on maps with novel stimuli to minimize search time without requiring additional model parameter fitting. Models of visual search can suggest color choices that produce search time reductions for display icons. Designers should consider constructing visual search models as a low-cost method of evaluating color assignments.

  13. Software for Minsk-32 display station

    International Nuclear Information System (INIS)

    Belyaeva, L.M.; Gangrskaya, O.G.; Manno, I.; Fefilov, B.V.; Ehsenski, J.

    1976-01-01

    The mathematical provision is described of the Minsk-32 display station. Described is the application of editing program DOSE, assembler translator SLANG and program display-focal. Program DOSE permits to edit the texts with the aid of a rester display on Minsk-32 magnetic tape. The program system permits to use a disk monitor system

  14. Distributed rendering for multiview parallax displays

    Science.gov (United States)

    Annen, T.; Matusik, W.; Pfister, H.; Seidel, H.-P.; Zwicker, M.

    2006-02-01

    3D display technology holds great promise for the future of television, virtual reality, entertainment, and visualization. Multiview parallax displays deliver stereoscopic views without glasses to arbitrary positions within the viewing zone. These systems must include a high-performance and scalable 3D rendering subsystem in order to generate multiple views at real-time frame rates. This paper describes a distributed rendering system for large-scale multiview parallax displays built with a network of PCs, commodity graphics accelerators, multiple projectors, and multiview screens. The main challenge is to render various perspective views of the scene and assign rendering tasks effectively. In this paper we investigate two different approaches: Optical multiplexing for lenticular screens and software multiplexing for parallax-barrier displays. We describe the construction of large-scale multi-projector 3D display systems using lenticular and parallax-barrier technology. We have developed different distributed rendering algorithms using the Chromium stream-processing framework and evaluate the trade-offs and performance bottlenecks. Our results show that Chromium is well suited for interactive rendering on multiview parallax displays.

  15. Human isolates of Salmonella enterica serovar Typhimurium from Taiwan displayed significantly higher levels of antimicrobial resistance than those from Denmark.

    Science.gov (United States)

    Torpdahl, Mia; Lauderdale, Tsai-Ling; Liang, Shiu-Yun; Li, Ishien; Wei, Sung-Hsi; Chiou, Chien-Shun

    2013-02-01

    Salmonella enterica serovar Typhimurium is a major zoonotic pathogen with a high prevalence of antimicrobial resistance. This pathogen can disseminate across borders and spread far distances via the food trade and international travel. In this study, we compared the genotypes and antimicrobial resistance of 378 S. Typhimurium isolates collected in Taiwan and Denmark between 2009 and 2010. Genotyping revealed that many S. Typhimurium strains were concurrently circulating in Taiwan, Denmark and other countries in 2009 and 2010. When compared to the isolates collected from Denmark, the isolates from Taiwan displayed a significantly higher level of resistance to 11 of the 12 tested antimicrobials. Seven genetic clusters (A-G) were designated for the isolates. A high percentage of the isolates in genetic clusters C, F and G were multidrug-resistant. Of the isolates in cluster C, 79.2% were ASSuT-resistant, characterized by resistance to ampicillin, streptomycin, sulfamethoxazole, and tetracycline. In cluster F, 84.1% of the isolates were ACSSuT-resistant (resistant to ASSuT and chloramphenicol). Cluster G was unique to Taiwan and characterized in most isolates by the absence of three VNTRs (ST20, ST30 and STTR6) as well as a variety of multidrug resistance profiles. This cluster exhibited very high to extremely high levels of resistance to several first-line drugs, and among the seven clusters, it displayed the highest levels of resistance to cefotaxime and ceftazidime, ciprofloxacin and gentamicin. The high prevalence of antimicrobial resistance in S. Typhimurium from Taiwan highlights the necessity to strictly regulate the use of antimicrobials in the agriculture and human health care sectors. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Content dependent selection of image enhancement parameters for mobile displays

    Science.gov (United States)

    Lee, Yoon-Gyoo; Kang, Yoo-Jin; Kim, Han-Eol; Kim, Ka-Hee; Kim, Choon-Woo

    2011-01-01

    Mobile devices such as cellular phones and portable multimedia player with capability of playing terrestrial digital multimedia broadcasting (T-DMB) contents have been introduced into consumer market. In this paper, content dependent image quality enhancement method for sharpness and colorfulness and noise reduction is presented to improve perceived image quality on mobile displays. Human visual experiments are performed to analyze viewers' preference. Relationship between the objective measures and the optimal values of image control parameters are modeled by simple lookup tables based on the results of human visual experiments. Content dependent values of image control parameters are determined based on the calculated measures and predetermined lookup tables. Experimental results indicate that dynamic selection of image control parameters yields better image quality.

  17. Spielräume schulischer Displays

    Directory of Open Access Journals (Sweden)

    Antje Lehn

    2014-03-01

    Full Text Available Antje Lehn zeigt in ihrem Beitrag, wie durch einen erweiterten Display-Begriff in der Schulklasse durch konkrete Projekte Frontalunterricht unterwandert und das Klassenzimmer zu einem ergebnisoffenen Handlungsraum umgestaltet werden kann. Auch Decken, Spiegel, Tische und Spinde sind Displays ...

  18. Performance evaluation of a kinesthetic-tactual display

    Science.gov (United States)

    Jagacinski, R. J.; Flach, J. M.; Gilson, R. D.; Dunn, R. S.

    1982-01-01

    Simulator studies demonstrated the feasibility of using kinesthetic-tactual (KT) displays for providing collective and cyclic command information, and suggested that KT displays may increase pilot workload capability. A dual-axis laboratory tracking task suggested that beyond reduction in visual scanning, there may be additional sensory or cognitive benefits to the use of multiple sensory modalities. Single-axis laboratory tracking tasks revealed performance with a quickened KT display to be equivalent to performance with a quickened visual display for a low frequency sum-of-sinewaves input. In contrast, an unquickened KT display was inferior to an unquickened visual display. Full scale simulator studies and/or inflight testing are recommended to determine the generality of these results.

  19. CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor Growth.

    Science.gov (United States)

    Golubovskaya, Vita; Berahovich, Robert; Zhou, Hua; Xu, Shirley; Harto, Hizkia; Li, Le; Chao, Cheng-Chi; Mao, Mike Ming; Wu, Lijun

    2017-10-21

    CD47 is a glycoprotein of the immunoglobulin superfamily that is often overexpressed in different types of hematological and solid cancer tumors and plays important role in blocking phagocytosis, increased tumor survival, metastasis and angiogenesis. In the present report, we designed CAR (chimeric antigen receptor)-T cells that bind CD47 antigen. We used ScFv (single chain variable fragment) from mouse CD47 antibody to generate CD47-CAR-T cells for targeting different cancer cell lines. CD47-CAR-T cells effectively killed ovarian, pancreatic and other cancer cells and produced high level of cytokines that correlated with expression of CD47 antigen. In addition, CD47-CAR-T cells significantly blocked BxPC3 pancreatic xenograft tumor growth after intratumoral injection into NSG mice. Moreover, we humanized mouse CD47 ScFv and showed that it effectively bound CD47 antigen. The humanized CD47-CAR-T cells also specifically killed ovarian, pancreatic, and cervical cancer cell lines and produced IL-2 that correlated with expression of CD47. Thus, CD47-CAR-T cells can be used as a novel cellular therapeutic agent for treating different types of cancer.

  20. Exploring interaction with 3D volumetric displays

    Science.gov (United States)

    Grossman, Tovi; Wigdor, Daniel; Balakrishnan, Ravin

    2005-03-01

    Volumetric displays generate true volumetric 3D images by actually illuminating points in 3D space. As a result, viewing their contents is similar to viewing physical objects in the real world. These displays provide a 360 degree field of view, and do not require the user to wear hardware such as shutter glasses or head-trackers. These properties make them a promising alternative to traditional display systems for viewing imagery in 3D. Because these displays have only recently been made available commercially (e.g., www.actuality-systems.com), their current use tends to be limited to non-interactive output-only display devices. To take full advantage of the unique features of these displays, however, it would be desirable if the 3D data being displayed could be directly interacted with and manipulated. We investigate interaction techniques for volumetric display interfaces, through the development of an interactive 3D geometric model building application. While this application area itself presents many interesting challenges, our focus is on the interaction techniques that are likely generalizable to interactive applications for other domains. We explore a very direct style of interaction where the user interacts with the virtual data using direct finger manipulations on and around the enclosure surrounding the displayed 3D volumetric image.

  1. Species-Dependent Functionality of the Human Cytolytic Fusion Proteins Granzyme B-H22(scFv and H22(scFv-Angiogenin in Macrophages

    Directory of Open Access Journals (Sweden)

    Theo Thepen

    2013-01-01

    Full Text Available Human cytolytic fusion proteins (hCFPs are comprised of a specific cell-surface-binding moiety and an effector molecule of human origin. In contrast to common immunotoxins, including bacterial or plant toxins, they are considered not to be immunogenic. Two examples for human pro-apoptotic effector proteins are the serine protease Granzyme B and the RNase Angiogenin. Pre-clinical testing of functionality in in vitro and in vivo studies is essential for therapeutics. Establishing relevant animal models that have predictive value for therapeutic success is a great challenge in biomedical research. In this study, we investigated the species-dependent cytotoxic activity of two hCFPs prior to their application in a murine inflammation model. We found that in vitro and ex vivo either hCFP was able to kill human cells only, leaving murine cells unaffected. In contrast, no species-dependency was found for the bacterial Pseudomonas exotoxin A based immunotoxin H22(scFv-ETA’. This species-dependent functioning has to be carefully considered when performing pre-clinical studies in animal models.

  2. Beyond advertising : large displays for supporting people’s needs and activities in public space

    NARCIS (Netherlands)

    Kanis, Marije; Groen, Maarten; Meys, Wouter; Slakhorst, Wout; Veenstra, Mettina

    2011-01-01

    This paper explores how displays can be used to support human needs and activities in public spaces rather than be employed for commercial purposes only. Based on our analysis of screen usage around the world, eight different categories of usage are described and motivated. For the purpose of

  3. Solution-processed single-wall carbon nanotube transistor arrays for wearable display backplanes

    Directory of Open Access Journals (Sweden)

    Byeong-Cheol Kang

    2018-01-01

    Full Text Available In this paper, we demonstrate solution-processed single-wall carbon nanotube thin-film transistor (SWCNT-TFT arrays with polymeric gate dielectrics on the polymeric substrates for wearable display backplanes, which can be directly attached to the human body. The optimized SWCNT-TFTs without any buffer layer on flexible substrates exhibit a linear field-effect mobility of 1.5cm2/V-s and a threshold voltage of around 0V. The statistical plot of the key device metrics extracted from 35 SWCNT-TFTs which were fabricated in different batches at different times conclusively support that we successfully demonstrated high-performance solution-processed SWCNT-TFT arrays which demand excellent uniformity in the device performance. We also investigate the operational stability of wearable SWCNT-TFT arrays against an applied strain of up to 40%, which is the essential for a harsh degree of strain on human body. We believe that the demonstration of flexible SWCNT-TFT arrays which were fabricated by all solution-process except the deposition of metal electrodes at process temperature below 130oC can open up new routes for wearable display backplanes.

  4. Refreshing Refreshable Braille Displays.

    Science.gov (United States)

    Russomanno, Alexander; O'Modhrain, Sile; Gillespie, R Brent; Rodger, Matthew W M

    2015-01-01

    The increased access to books afforded to blind people via e-publishing has given them long-sought independence for both recreational and educational reading. In most cases, blind readers access materials using speech output. For some content such as highly technical texts, music, and graphics, speech is not an appropriate access modality as it does not promote deep understanding. Therefore blind braille readers often prefer electronic braille displays. But, these are prohibitively expensive. The search is on, therefore, for a low-cost refreshable display that would go beyond current technologies and deliver graphical content as well as text. And many solutions have been proposed, some of which reduce costs by restricting the number of characters that can be displayed, even down to a single braille cell. In this paper, we demonstrate that restricting tactile cues during braille reading leads to poorer performance in a letter recognition task. In particular, we show that lack of sliding contact between the fingertip and the braille reading surface results in more errors and that the number of errors increases as a function of presentation speed. These findings suggest that single cell displays which do not incorporate sliding contact are likely to be less effective for braille reading.

  5. Dual-functioning peptides discovered by phage display increase the magnitude and specificity of BMSC attachment to mineralized biomaterials.

    Science.gov (United States)

    Ramaraju, Harsha; Miller, Sharon J; Kohn, David H

    2017-07-01

    Design of biomaterials for cell-based therapies requires presentation of specific physical and chemical cues to cells, analogous to cues provided by native extracellular matrices (ECM). We previously identified a peptide sequence with high affinity towards apatite (VTKHLNQISQSY, VTK) using phage display. The aims of this study were to identify a human MSC-specific peptide sequence through phage display, combine it with the apatite-specific sequence, and verify the specificity of the combined dual-functioning peptide to both apatite and human bone marrow stromal cells. In this study, a combinatorial phage display identified the cell binding sequence (DPIYALSWSGMA, DPI) which was combined with the mineral binding sequence to generate the dual peptide DPI-VTK. DPI-VTK demonstrated significantly greater binding affinity (1/K D ) to apatite surfaces compared to VTK, phosphorylated VTK (VTK phos ), DPI-VTK phos , RGD-VTK, and peptide-free apatite surfaces (p biomaterial surfaces and subsequently increase cell proliferation and differentiation. These new peptides expand biomaterial design methodology for cell-based regeneration of bone defects. This strategy of combining cell and material binding phage display derived peptides is broadly applicable to a variety of systems requiring targeted adhesion of specific cell populations, and may be generalized to the engineering of any adhesion surface. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Gamma camera display system

    International Nuclear Information System (INIS)

    Stout, K.J.

    1976-01-01

    A gamma camera having an array of photomultipliers coupled via pulse shaping circuitry and a resistor weighting circuit to a display for forming an image of a radioactive subject is described. A linearizing circuit is coupled to the weighting circuit, the linearizing circuit including a nonlinear feedback circuit with diode coupling to the weighting circuit for linearizing the correspondence between points of the display and points of the subject. 4 Claims, 5 Drawing Figures

  7. Software for graphic display systems

    International Nuclear Information System (INIS)

    Karlov, A.A.

    1978-01-01

    In this paper some aspects of graphic display systems are discussed. The design of a display subroutine library is described, with an example, and graphic dialogue software is considered primarily from the point of view of the programmer who uses a high-level language. (Auth.)

  8. Information Display: Considerations for Designing Modern Computer-Based Display Systems

    International Nuclear Information System (INIS)

    O'Hara, J.; Pirus, D.; Beltracchi, L.

    2003-01-01

    OAK- B135 To help nuclear utilities and suppliers design and implement plant information management systems and displays that provide accurate and timely information and require minimal navigation and interface management

  9. Yeast surface display platform for rapid discovery of conformationally selective nanobodies

    DEFF Research Database (Denmark)

    McMahon, Conor; Baier, Alexander S.; Pascolutti, Roberta

    2018-01-01

    this problem, we report a fully in vitro platform for nanobody discovery based on yeast surface display. We provide a blueprint for identifying nanobodies, demonstrate the utility of the library by crystallizing a nanobody with its antigen, and most importantly, we utilize the platform to discover...... conformationally selective nanobodies to two distinct human GPCRs. To facilitate broad deployment of this platform, the library and associated protocols are freely available for nonprofit research....

  10. Construction of a recombinant single chain antibody recognizing nonreducing terminal mannose residues applicable to immunohistochemistry.

    Science.gov (United States)

    Yuasa, Noriyuki; Iida, Noriko; Sakaue, Hiroyuki; Zhang, Wei; Wilczynski, Sharon; Fujita-Yamaguchi, Yoko

    2007-10-01

    We recently reported characterization of 25 clones isolated from a phage library displaying human scFvs using a neoglycolipid Man3-DPPE, which was synthesized from mannotriose (Man3) and dipalmitoylphosphatidylethanolamine (DPPE). Of those, 5A3 scFv was successfully expressed and purified as a humanized scFv-Fc form (Sakai et al., Biochemistry 46:253, 2007, Zhang et al. ibid 263). To carry out immunohistochemistry (IHC) in human tissues, a HA tag sequence was introduced to the 5A3 scFv-Fc gene and the resulting construct was transfected to murine myeloma NS0 cells. The 5A3 scFv-Fc protein expressed was affinity-purified. Sodium dodecyl sulfate polyacrylamide gel electrophoresis under nonreducing and reducing conditions and enzyme-linked immunosorbent assay confirmed that 5A3 scFv-Fc protein is dimeric and retained the ability to recognize nonreducing terminal mannose residues. IHC staining of non-neoplastic tissues by this recombinant antibody revealed that no immunoreactivity was detectable in most of 16 tissues examined. Exceptions were found in IHC staining of kidney and pancreas, which demonstrated clear staining of proximal tubules and islet of Langerhans, respectively. These results demonstrated that nonreducing terminal mannose residues are not usually present under normal physiological conditions. This study thus provided a potentially useful tool for examination of the nonreducing terminal mannose residues, which may become exposed under certain pathophysiologycal conditions.

  11. Development of advanced direct perception displays for nuclear power plants to enhance monitoring, control and fault management

    International Nuclear Information System (INIS)

    Jones, B.; Shaheen, S.; Moray, N.; Sanderson, P.; Reising, D.V.

    1993-01-01

    With recent theoretical and empirical research in basic and applied psychology, human factors, and engineering, it is now sufficient to define an integrated approach to the deign of advanced displays for present and future nuclear power plants. Traditionally, the conventional displays have shown operators the individual variables on gauges, meters, strip charts, etc. This design approach requires the operators to mentally integrate the separately displayed variables and determine the implications for the plant state. This traditional approach has been known as the single-sensor-single-indicator display design and it places an intolerable amount of mental workload on operators during transients and abnormal conditions. This report discusses a new alternative approach which is the use of direct perception interfaces. Direct perception a interfaces display the underlying physical and system constraints of the situation in a directly perceptual way, such that the viewer need not reason about what is seen to identify system states, but can identify the state of the system perceptually. It is expected that displays which show the dynamics of fundamental physical laws should better support operator decisions and diagnoses of plant states. The purpose of this research project is to develop a suite of direct perception displays for PWR nuclear power plant operations

  12. Refreshable Braille displays using EAP actuators

    Science.gov (United States)

    Bar-Cohen, Yoseph

    2010-04-01

    Refreshable Braille can help visually impaired persons benefit from the growing advances in computer technology. The development of such displays in a full screen form is a great challenge due to the need to pack many actuators in small area without interferences. In recent years, various displays using actuators such as piezoelectric stacks have become available in commercial form but most of them are limited to one line Braille code. Researchers in the field of electroactive polymers (EAP) investigated methods of using these materials to form full screen displays. This manuscript reviews the state of the art of producing refreshable Braille displays using EAP-based actuators.

  13. Refreshable Braille Displays Using EAP Actuators

    Science.gov (United States)

    Bar-Cohen, Yoseph

    2010-01-01

    Refreshable Braille can help visually impaired persons benefit from the growing advances in computer technology. The development of such displays in a full screen form is a great challenge due to the need to pack many actuators in small area without interferences. In recent years, various displays using actuators such as piezoelectric stacks have become available in commercial form but most of them are limited to one line Braille code. Researchers in the field of electroactive polymers (EAP) investigated methods of using these materials to form full screen displays. This manuscript reviews the state of the art of producing refreshable Braille displays using EAP-based actuators..

  14. The development of human factors technologies -The development of human factors experimental evaluation techniques-

    International Nuclear Information System (INIS)

    Shim, Bong Sik; Oh, In Suk; Cha, Kyung Hoh; Lee, Hyun Chul

    1995-07-01

    In this year, we studied the followings: 1) Development of operator mental workload evaluation techniques, 2) Development of a prototype for preliminary human factors experiment, 3) Suitability test of information display on a large scale display panel, 4) Development of guidelines for VDU-based control room design, 5) Development of integrated test facility (ITF). 6) Establishment of an eye tracking system, and we got the following results: 1) Mental workload evaluation techniques for MMI evaluation, 2) PROTOPEX (PROTOtype for preliminary human factors experiment) for preliminary human factors experiments, 3) Usage methods of APTEA (Analysis-Prototyping-Training-Experiment-Analysis) experiment design, 4) Design guidelines for human factors verification, 5) Detail design requirements and development plan of ITF, 6) Eye movement measurement system. 38 figs, 20 tabs, 54 refs. (Author)

  15. System Would Generate Virtual Heads-Up Display

    Science.gov (United States)

    Lambert, James L.

    1994-01-01

    Proposed helmet-mounted electronic display system superimposes full-color alphanumerical and/or graphical information onto observer's visual field. Displayed information projected directly onto observer's retinas, giving observer illusion of full-size computer display in foreground or background. Display stereoscopic, holographic, or in form of virtual image. Used by pilots to view navigational information while looking outside or at instruments, by security officers to view information about critical facilities while looking at visitors, or possibly even stock-exchange facilities to view desktop monitors and overhead displays simultaneously. System includes acousto-optical tunable filter (AOTF), which acts as both spectral filter and spatial light modulator.

  16. Manufacturing considerations for AMLCD cockpit displays

    Science.gov (United States)

    Luo, Fang-Chen

    1995-06-01

    AMLCD cockpit displays need to meet more stringent requirements compared with AMLCD commercial displays in areas such as environmental conditions, optical performance and device reliability. Special considerations are required for the manufacturing of AMLCD cockpit displays in each process step to address these issues. Some examples are: UV stable polarizers, wide-temperature LC material, strong LC glue seal, ESS test system, gray scale voltage EEPROM, etc.

  17. Designing low cost LED display for the billboard

    Science.gov (United States)

    Hong, Yi-Jian; Uang, Chii-Maw; Wang, Ping-Chieh; Ho, Zu-Sheng

    2011-10-01

    With quickly advance of the computer, microelectronics and photonics technologies, LED display panel becomes a new electronic advertising media. It can be used to show any information whatever characters or graphics. Most LED display panels are built of many Light-Emitting Diodes arranged in a matrix form. The display has many advantages such as low power, low cost, long life and high definition. Because the display panel is asked to show rich color, the LED display panel's driving system becomes very complex. The design methodology of LED display panel's driver becomes more and more important to meet the market requirements. Cost is always the most important issue in public market domain. In this paper, we report a design methodology of LED display panel's driver based on the microprocessor control unit (MCU) system and LED display controller IC, HT1632C, to control three colors, RGB, color LED display panel and the modular panel size is 24*16 in matrix form. The HT1632C is a memory mapping LED display controller, it can be used on many applications, such as digital clock, thermometer, counter, voltmeter or other instrumentation readouts. Three pieces of HT1632C are used to drive a 24*16 RGB LED display panel, in our design case. Each HT163C chip is used to control one of the R, G and B color. As the drive mode is driven in DC mode, the RGB display panel can create and totally of seven colors under the control of MCU. The MCU generates the control signal to drive HT1632C. In this study, the software design methodology is adopted with dynamic display principle. When the scan frequency is 60Hz, LED display panel will get the clear picture and be able to display seven colors.

  18. [Application of the grayscale standard display function to general purpose liquid-crystal display monitors for clinical use].

    Science.gov (United States)

    Tanaka, Nobukazu; Naka, Kentaro; Sueoka, Masaki; Higashida, Yoshiharu; Morishita, Junji

    2010-01-20

    Interpretations of medical images have been shifting to soft-copy readings with liquid-crystal display (LCD) monitors. The display function of the medical-grade LCD monitor for soft-copy readings is recommended to calibrate the grayscale standard display function (GSDF) in accordance with the guidelines of Japan and other countries. In this study, the luminance and display function of five models of eight general purpose LCD monitors were measured to gain an understanding of their characteristics. Moreover, the display function (gamma 2.2 or gamma 1.8) of general purpose LCD monitors was converted to GSDF through the use of a look-up table, and the detectability of a simulated lung nodule in the chest x-ray image was examined. As a result, the maximum luminance, contrast ratio, and luminance uniformity of general purpose LCD monitors, except for one model of two LCD monitors, met the management grade 1 standard in the guideline JESRA X-0093-2005. In addition, the detectability of simulated lung nodule in the mediastinal space was obviously improved by converting the display function of a general purpose LCD monitor into GSDF.

  19. Displaying Sensed Tactile Cues with a Fingertip Haptic Device.

    Science.gov (United States)

    Pacchierotti, Claudio; Prattichizzo, Domenico; Kuchenbecker, Katherine J

    2015-01-01

    Telerobotic systems enable humans to explore and manipulate remote environments for applications such as surgery and disaster response, but few such systems provide the operator with cutaneous feedback. This article presents a novel approach to remote cutaneous interaction; our method is compatible with any fingertip tactile sensor and any mechanical tactile display device, and it does not require a position/force or skin deformation model. Instead, it directly maps the sensed stimuli to the best possible input commands for the device's motors using a data set recorded with the tactile sensor inside the device. As a proof of concept, we considered a haptic system composed of a BioTac tactile sensor, in charge of measuring contact deformations, and a custom 3-DoF cutaneous device with a flat contact platform, in charge of applying deformations to the user's fingertip. To validate the proposed approach and discover its inherent tradeoffs, we carried out two remote tactile interaction experiments. The first one evaluated the error between the tactile sensations registered by the BioTac in a remote environment and the sensations created by the cutaneous device for six representative tactile interactions and 27 variations of the display algorithm. The normalized average errors in the best condition were 3.0 percent of the BioTac's full 12-bit scale. The second experiment evaluated human subjects' experiences for the same six remote interactions and eight algorithm variations. The average subjective rating for the best algorithm variation was 8.2 out of 10, where 10 is best.

  20. Insight into the potential for DNA idiotypic fusion vaccines designed for patients by analysing xenogeneic anti-idiotypic antibody responses

    Science.gov (United States)

    Forconi, Francesco; King, Catherine A; Sahota, Surinder S; Kennaway, Christopher K; Russell, Nigel H; Stevenson, Freda K

    2002-01-01

    DNA vaccines induce immune responses against encoded proteins, and have clear potential for cancer vaccines. For B-cell tumours, idiotypic (Id) immunoglobulin encoded by the variable region genes provides a target antigen. When assembled as single chain Fv (scFv), and fused to an immunoenhancing sequence from tetanus toxin (TT), DNA fusion vaccines induce anti-Id antibodies. In lymphoma models, these antibodies have a critical role in mediating protection. For application to patients with lymphoma, two questions arise: first, whether pre-existing antibody against TT affects induction of anti-scFv antibodies; second, whether individual human scFv fusion sequences are able to fold consistently to generate antibodies able to recognize private conformational Id determinants expressed by tumour cells. Using xenogeneic vaccination with scFv sequences from four patients, we have shown that pre-existing anti-TT immunity slows, but does not prevent, anti-Id antibody responses. To determine folding, we have monitored the ability of nine DNAscFv–FrC patients' vaccines to induce xenogeneic anti-Id antibodies. Antibodies were induced in all cases, and were strikingly specific for each patient's immunoglobulin with little cross-reactivity between patients, even when similar VH or VL genes were involved. Blocking experiments with human serum confirmed reactivity against private determinants in 26–97% of total antibody. Both immunoglobulin G1 (IgG1) and IgG2a subclasses were present at 1·3 : 1–15 : 1 consistent with a T helper 2-dominated response. Xenogeneic vaccination provides a simple route for testing individual patients' DNAscFv–FrC fusion vaccines, and offers a strategy for production of anti-Id antibodies. The findings underpin the approach of DNA idiotypic fusion vaccination for patients with B-cell tumours. PMID:12225361

  1. Generating Animated Displays of Spacecraft Orbits

    Science.gov (United States)

    Candey, Robert M.; Chimiak, Reine A.; Harris, Bernard T.

    2005-01-01

    Tool for Interactive Plotting, Sonification, and 3D Orbit Display (TIPSOD) is a computer program for generating interactive, animated, four-dimensional (space and time) displays of spacecraft orbits. TIPSOD utilizes the programming interface of the Satellite Situation Center Web (SSCWeb) services to communicate with the SSC logic and database by use of the open protocols of the Internet. TIPSOD is implemented in Java 3D and effects an extension of the preexisting SSCWeb two-dimensional static graphical displays of orbits. Orbits can be displayed in any or all of the following seven reference systems: true-of-date (an inertial system), J2000 (another inertial system), geographic, geomagnetic, geocentric solar ecliptic, geocentric solar magnetospheric, and solar magnetic. In addition to orbits, TIPSOD computes and displays Sibeck's magnetopause and Fairfield's bow-shock surfaces. TIPSOD can be used by the scientific community as a means of projection or interpretation. It also has potential as an educational tool.

  2. Integrated application of human factors to a power plant control room information system

    International Nuclear Information System (INIS)

    Fish, H.C. Jr.; Gutierrez, R.

    1988-01-01

    The human factors plan was developed as a methodology to apply human factors from the conceptual design of the EPIC system to the functional verification conducted at the plant. An integral part of the Human Factors Plan was the Functional Verification Plan. Developed in parallel, this second plan and its resultant programs verified functional appropriateness of the SPDS display, NSSS displays, EOP displays, man-machine interfaces (MMI), and workstation designs. The functional verification process was performed at the hardware/software developer's factory and at the JAFNPP, following installation of the EPIC system. Because the EPIC system replaces existing control room equipment, it is important that human factors be applied in a systematic manner consistent with other control room displays and controls. To ensure that this goal was met, a human factors plan was developed

  3. IMDISP - INTERACTIVE IMAGE DISPLAY PROGRAM

    Science.gov (United States)

    Martin, M. D.

    1994-01-01

    The Interactive Image Display Program (IMDISP) is an interactive image display utility for the IBM Personal Computer (PC, XT and AT) and compatibles. Until recently, efforts to utilize small computer systems for display and analysis of scientific data have been hampered by the lack of sufficient data storage capacity to accomodate large image arrays. Most planetary images, for example, require nearly a megabyte of storage. The recent development of the "CDROM" (Compact Disk Read-Only Memory) storage technology makes possible the storage of up to 680 megabytes of data on a single 4.72-inch disk. IMDISP was developed for use with the CDROM storage system which is currently being evaluated by the Planetary Data System. The latest disks to be produced by the Planetary Data System are a set of three disks containing all of the images of Uranus acquired by the Voyager spacecraft. The images are in both compressed and uncompressed format. IMDISP can read the uncompressed images directly, but special software is provided to decompress the compressed images, which can not be processed directly. IMDISP can also display images stored on floppy or hard disks. A digital image is a picture converted to numerical form so that it can be stored and used in a computer. The image is divided into a matrix of small regions called picture elements, or pixels. The rows and columns of pixels are called "lines" and "samples", respectively. Each pixel has a numerical value, or DN (data number) value, quantifying the darkness or brightness of the image at that spot. In total, each pixel has an address (line number, sample number) and a DN value, which is all that the computer needs for processing. DISPLAY commands allow the IMDISP user to display all or part of an image at various positions on the display screen. The user may also zoom in and out from a point on the image defined by the cursor, and may pan around the image. To enable more or all of the original image to be displayed on the

  4. Oil defect detection of electrowetting display

    Science.gov (United States)

    Chiang, Hou-Chi; Tsai, Yu-Hsiang; Yan, Yung-Jhe; Huang, Ting-Wei; Mang, Ou-Yang

    2015-08-01

    In recent years, transparent display is an emerging topic in display technologies. Apply in many fields just like mobile device, shopping or advertising window, and etc. Electrowetting Display (EWD) is one kind of potential transparent display technology advantages of high transmittance, fast response time, high contrast and rich color with pigment based oil system. In mass production process of Electrowetting Display, oil defects should be found by Automated Optical Inspection (AOI) detection system. It is useful in determination of panel defects for quality control. According to the research of our group, we proposed a mechanism of AOI detection system detecting the different kinds of oil defects. This mechanism can detect different kinds of oil defect caused by oil overflow or material deteriorated after oil coating or driving. We had experiment our mechanism with a 6-inch Electrowetting Display panel from ITRI, using an Epson V750 scanner with 1200 dpi resolution. Two AOI algorithms were developed, which were high speed method and high precision method. In high precision method, oil jumping or non-recovered can be detected successfully. This mechanism of AOI detection system can be used to evaluate the oil uniformity in EWD panel process. In the future, our AOI detection system can be used in quality control of panel manufacturing for mass production.

  5. You Be the Judge: Display.

    Science.gov (United States)

    Koeninger, Jimmy G.

    The instructional package was developed to provide the distributive education teacher-coordinator with visual materials that can be used to supplement existing textbook offerings in the area of display (visual merchandising). Designed for use with 35mm slides of retail store displays, the package allows the student to view the slides of displays…

  6. Psychophysical analysis of monitor display functions affecting observer diagnostic performance of CT image on liquid crystal display monitors

    International Nuclear Information System (INIS)

    Yamaguchi, M.; Fujita, H.; Asai, Y.; Uemura, M.; Ookura, Y.; Matsumoto, M.; Johkoh, T.

    2005-01-01

    The aim of the present study was to propose suitable display functions for CT image representation on liquid crystal display (LCD) monitors by analyzing the characteristics of the monitor's typical display functions using psychophysical analysis. The luminance of the LCD monitor was adjusted to a maximum of 275 cd/m 2 and 480 cd/m 2 . Three types of postcalibrated display functions (i.e., GSDF, CIELAB, and Exponential γ 2.2) were evaluated. Luminance calculation of a new grayscale test pattern (NGTP) was done for the conversion of the digital driving level (DDL) into the CT value. The psychophysical gradient δ of display functions for the CT value was evaluated and compared via statistical analysis. The δ value of GSDF and CIE decreased exponentially; however, the δ value of Exponential γ 2.2 showed a convex curve with a peak at a specific point. There was a statistically significant difference among the δ values of the three types of display functions on the 480 cd/m 2 maximum via Kruskal Wallis test (P<0.001). The GSDF was suitable for observation of abdominal and lung CT images; however, the display function combined the Exponential γ 2.2 and the GSDF functions and was ideal for observation of brain CT images by psychophysical analysis. (orig.)

  7. Method for control-room display design

    International Nuclear Information System (INIS)

    Montmayeul, R.

    1988-01-01

    This document describes a method for control-room displays design. It can be used either for isolated display to add to an existing system either for the design of a full system of operator aids. The method is a top-down design with steps of possible iteration. The emphasis is put on display design rather than on system design; system aspects are just mentioned. Advantages of using a method are described [fr

  8. Statistical Arbitrage Mining for Display Advertising

    OpenAIRE

    Zhang, Weinan; Wang, Jun

    2015-01-01

    We study and formulate arbitrage in display advertising. Real-Time Bidding (RTB) mimics stock spot exchanges and utilises computers to algorithmically buy display ads per impression via a real-time auction. Despite the new automation, the ad markets are still informationally inefficient due to the heavily fragmented marketplaces. Two display impressions with similar or identical effectiveness (e.g., measured by conversion or click-through rates for a targeted audience) may sell for quite diff...

  9. Frequency of Gingival Display During Smiling and Comparison of Biometric Measurements in Subjects with and without Gingival Display

    International Nuclear Information System (INIS)

    Khan, F.; Abbas, M.

    2014-01-01

    Objective: To determine the frequency of gingival display during smiling and to compare biometric measurements in subjects with and without gingival display. Study Design: Cross-sectional study. Place and Duration of Study: Department of Prosthodontics, Dr. Ishrat-ul-Ibad Khan Institute of Oral Health Sciences, Dow University of Health Sciences, Karachi, from October 2012 to March 2013. Methodology: A total of 275 subjects (121 men and 154 women) were included in this study. The age of the participants ranged between 21 and 65 years. Measurements were carried out using digital caliper. For each participants, the gingival display was judged as either visible or not. The amounts of horizontal and vertical overlap of anterior teeth were measured using a digital caliper. Gender differences in these parameters and the relationship between subjects showing gingival display when smiling and the two intraoral dental biometric measurements were determined. Statistical analyses of data were performed using SPSS version 17.0 software. The mean scores for gender were calculated and a Student's t-test was used to identify significant differences between both groups. Significant level was set to 0.05. Results: A relatively small percentage of the subjects (37.8%) displayed gingiva when smiling. More women significantly displayed gingiva when smiling than men, with a 2:1 female: male ratio. Women had significantly (p=0.001) more horizontal overlap (3.34 +- 1.45 mm) than men (2.90 +- 1.44 mm), although no significant gender difference were found in vertical overlap. Subjects with gingival display had significantly (p < 0.05) more horizontal (3.49 +- 1.36 mm) and vertical (3.26 +- 1.47 mm) overlap of anterior teeth compared to those who did not display gingiva when smiling. Conclusion: Significantly more women displayed gingiva in smiling. Women had significantly more horizontal overlap than men. No gender differences were recorded between vertical overlap. Subjects who displayed

  10. Demonstration of Vibrational Braille Code Display Using Large Displacement Micro-Electro-Mechanical Systems Actuators

    Science.gov (United States)

    Watanabe, Junpei; Ishikawa, Hiroaki; Arouette, Xavier; Matsumoto, Yasuaki; Miki, Norihisa

    2012-06-01

    In this paper, we present a vibrational Braille code display with large-displacement micro-electro-mechanical systems (MEMS) actuator arrays. Tactile receptors are more sensitive to vibrational stimuli than to static ones. Therefore, when each cell of the Braille code vibrates at optimal frequencies, subjects can recognize the codes more efficiently. We fabricated a vibrational Braille code display that used actuators consisting of piezoelectric actuators and a hydraulic displacement amplification mechanism (HDAM) as cells. The HDAM that encapsulated incompressible liquids in microchambers with two flexible polymer membranes could amplify the displacement of the MEMS actuator. We investigated the voltage required for subjects to recognize Braille codes when each cell, i.e., the large-displacement MEMS actuator, vibrated at various frequencies. Lower voltages were required at vibration frequencies higher than 50 Hz than at vibration frequencies lower than 50 Hz, which verified that the proposed vibrational Braille code display is efficient by successfully exploiting the characteristics of human tactile receptors.

  11. 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.

  12. Real-time acquisition and display of flow contrast using speckle variance optical coherence tomography in a graphics processing unit.

    Science.gov (United States)

    Xu, Jing; Wong, Kevin; Jian, Yifan; Sarunic, Marinko V

    2014-02-01

    In this report, we describe a graphics processing unit (GPU)-accelerated processing platform for real-time acquisition and display of flow contrast images with Fourier domain optical coherence tomography (FDOCT) in mouse and human eyes in vivo. Motion contrast from blood flow is processed using the speckle variance OCT (svOCT) technique, which relies on the acquisition of multiple B-scan frames at the same location and tracking the change of the speckle pattern. Real-time mouse and human retinal imaging using two different custom-built OCT systems with processing and display performed on GPU are presented with an in-depth analysis of performance metrics. The display output included structural OCT data, en face projections of the intensity data, and the svOCT en face projections of retinal microvasculature; these results compare projections with and without speckle variance in the different retinal layers to reveal significant contrast improvements. As a demonstration, videos of real-time svOCT for in vivo human and mouse retinal imaging are included in our results. The capability of performing real-time svOCT imaging of the retinal vasculature may be a useful tool in a clinical environment for monitoring disease-related pathological changes in the microcirculation such as diabetic retinopathy.

  13. Three-dimensional volumetric display by inclined-plane scanning

    Science.gov (United States)

    Miyazaki, Daisuke; Eto, Takuma; Nishimura, Yasuhiro; Matsushita, Kenji

    2003-05-01

    A volumetric display system based on three-dimensional (3-D) scanning that uses an inclined two-dimensional (2-D) image is described. In the volumetric display system a 2-D display unit is placed obliquely in an imaging system into which a rotating mirror is inserted. When the mirror is rotated, the inclined 2-D image is moved laterally. A locus of the moving image can be observed by persistence of vision as a result of the high-speed rotation of the mirror. Inclined cross-sectional images of an object are displayed on the display unit in accordance with the position of the image plane to observe a 3-D image of the object by persistence of vision. Three-dimensional images formed by this display system satisfy all the criteria for stereoscopic vision. We constructed the volumetric display systems using a galvanometer mirror and a vector-scan display unit. In addition, we constructed a real-time 3-D measurement system based on a light section method. Measured 3-D images can be reconstructed in the 3-D display system in real time.

  14. Displays: Entering a New Dimension

    Science.gov (United States)

    Starkman, Neal

    2007-01-01

    As display technologies prepare to welcome 3-D, the 21st-century classroom will soon bear little resemblance to anything students and teachers have ever seen. In this article, the author presents the latest innovations in the world of digital display technology. These include: (1) Touchlight, an interactive touch screen program that takes a normal…

  15. Crystal ball single event display

    International Nuclear Information System (INIS)

    Grosnick, D.; Gibson, A.; Allgower, C.; Alyea, J.; Argonne National Lab., IL

    1997-01-01

    The Single Event Display (SED) is a routine that is designed to provide information graphically about a triggered event within the Crystal Ball. The SED is written entirely in FORTRAN and uses the CERN-based HICZ graphing package. The primary display shows the amount of energy deposited in each of the NaI crystals on a Mercator-like projection of the crystals. Ten different shades and colors correspond to varying amounts of energy deposited within a crystal. Information about energy clusters is displayed on the crystal map by outlining in red the thirteen (or twelve) crystals contained within a cluster and assigning each cluster a number. Additional information about energy clusters is provided in a series of boxes containing useful data about the energy distribution among the crystals within the cluster. Other information shown on the event display include the event trigger type and data about π o 's and η's formed from pairs of clusters as found by the analyzer. A description of the major features is given, along with some information on how to install the SED into the analyzer

  16. Synthetic vision display evaluation studies

    Science.gov (United States)

    Regal, David M.; Whittington, David H.

    1994-01-01

    The goal of this research was to help us understand the display requirements for a synthetic vision system for the High Speed Civil Transport (HSCT). Four experiments were conducted to examine the effects of different levels of perceptual cue complexity in displays used by pilots in a flare and landing task. Increased levels of texture mapping of terrain and runway produced mixed results, including harder but shorter landings and a lower flare initiation altitude. Under higher workload conditions, increased texture resulted in an improvement in performance. An increase in familiar size cues did not result in improved performance. Only a small difference was found between displays using two patterns of high resolution texture mapping. The effects of increased perceptual cue complexity on performance was not as strong as would be predicted from the pilot's subjective reports or from related literature. A description of the role of a synthetic vision system in the High Speed Civil Transport is provide along with a literature review covering applied research related to perceptual cue usage in aircraft displays.

  17. New human machine interface for VR-1 training reactor

    International Nuclear Information System (INIS)

    Kropik, M.; Matejka, K.; Sklenka, L.; Chab, V.

    2002-01-01

    The contribution describes a new human machine interface that was installed at the VR-1 training reactor. The human machine interface update was completed in the summer 2001. The human machine interface enables to operate the training reactor. The interface was designed with respect to functional, ergonomic and aesthetic requirements. The interface is based on a personal computer equipped with two displays. One display enables alphanumeric communication between a reactor operator and the control and safety system of the nuclear reactor. Messages appear from the control system, the operator can write commands and send them there. The second display is a graphical one. It is possible to represent there the status of the reactor, principle parameters (as power, period), control rods' positions, the course of the reactor power. Furthermore, it is possible to set parameters, to show the active core configuration, to perform reactivity calculations, etc. The software for the new human machine interface was produced in the InTouch developing environment of the WonderWare Company. It is possible to switch the language of the interface between Czech and English because of many foreign students and visitors at the reactor. The former operator's desk was completely removed and superseded with a new one. Besides of the computer and the two displays, there are control buttons, indicators and individual numerical displays of instrumentation there. Utilised components guarantee high quality of the new equipment. Microcomputer based communication units with proper software were developed to connect the contemporary control and safety system with the personal computer of the human machine interface and the individual displays. New human machine interface at the VR-1 training reactor improves the safety and comfort of the reactor utilisation, facilitates experiments and training, and provides better support of foreign visitors.(author)

  18. Volumetric, dashboard-mounted augmented display

    Science.gov (United States)

    Kessler, David; Grabowski, Christopher

    2017-11-01

    The optical design of a compact volumetric display for drivers is presented. The system displays a true volume image with realistic physical depth cues, such as focal accommodation, parallax and convergence. A large eyebox is achieved with a pupil expander. The windshield is used as the augmented reality combiner. A freeform windshield corrector is placed at the dashboard.

  19. Flexible Bistable Cholesteric Reflective Displays

    Science.gov (United States)

    Yang, Deng-Ke

    2006-03-01

    Cholesteric liquid crystals (ChLCs) exhibit two stable states at zero field condition-the reflecting planar state and the nonreflecting focal conic state. ChLCs are an excellent candidate for inexpensive and rugged electronic books and papers. This paper will review the display cell structure,materials and drive schemes for flexible bistable cholesteric (Ch) reflective displays.

  20. Multivalent display of the antimicrobial peptides BP100 and BP143

    Directory of Open Access Journals (Sweden)

    Imma Güell

    2012-12-01

    Full Text Available Carbohydrates are considered as promising templates for the display of multiple copies of antimicrobial peptides. Herein, we describe the design and synthesis of chimeric structures containing two or four copies of the antimicrobial peptides KKLFKKILKYL-NH2 (BP100 and KKLfKKILKYL-NH2 (BP143 attached to the carbohydrate template cyclodithioerythritol (cDTE or α-D-galactopyranoside (Galp. The synthesis involved the preparation of the corresponding peptide aldehyde followed by coupling to an aminooxy-functionalized carbohydrate template. After purification, the multivalent display systems were obtained in high purities (90–98% and in good yields (42–64%. These compounds were tested against plant and human pathogenic bacteria and screened for their cytotoxicity on eukaryotic cells. They showed lower MIC values than the parent peptides against the bacteria analyzed. In particular, the carbopeptides derived from cDTE and Galp, which contained two or four copies of BP100, respectively, were 2- to 8-fold more active than the monomeric peptide against the phytopathogenic bacteria. These results suggest that preassembling antimicrobial peptides to multimeric structures is not always associated with a significant improvement of the activity. In contrast, the carbopeptides synthesized were active against human red blood cells pointing out that peptide preassembly is critical for the hemolytic activity. Notably, peptide preassembly resulted in an enhanced bactericidal effect.

  1. Antecedents and consequences of emotional display rule perceptions.

    Science.gov (United States)

    Diefendorff, James M; Richard, Erin M

    2003-04-01

    Central to all theories of emotional labor is the idea that individuals follow emotional display rules that specify the appropriate expression of emotions on the job. This investigation examined antecedents and consequences of emotional display rule perceptions. Full-time working adults (N = 152) from a variety of occupations provided self-report data, and supervisors and coworkers completed measures pertaining to the focal employees. Results using structural equation modeling revealed that job-based interpersonal requirements, supervisor display rule perceptions, and employee extraversion and neuroticism were predictive of employee display rule perceptions. Employee display rule perceptions, in turn, were related to self-reported job satisfaction and coworker ratings of employees' emotional displays on the job. Finally, neuroticism had direct negative relationships with job satisfaction and coworker ratings of employees' emotional displays.

  2. New portable FELIX 3D display

    Science.gov (United States)

    Langhans, Knut; Bezecny, Daniel; Homann, Dennis; Bahr, Detlef; Vogt, Carsten; Blohm, Christian; Scharschmidt, Karl-Heinz

    1998-04-01

    An improved generation of our 'FELIX 3D Display' is presented. This system is compact, light, modular and easy to transport. The created volumetric images consist of many voxels, which are generated in a half-sphere display volume. In that way a spatial object can be displayed occupying a physical space with height, width and depth. The new FELIX generation uses a screen rotating with 20 revolutions per second. This target screen is mounted by an easy to change mechanism making it possible to use appropriate screens for the specific purpose of the display. An acousto-optic deflection unit with an integrated small diode pumped laser draws the images on the spinning screen. Images can consist of up to 10,000 voxels at a refresh rate of 20 Hz. Currently two different hardware systems are investigated. The first one is based on a standard PCMCIA digital/analog converter card as an interface and is controlled by a notebook. The developed software is provided with a graphical user interface enabling several animation features. The second, new prototype is designed to display images created by standard CAD applications. It includes the development of a new high speed hardware interface suitable for state-of-the- art fast and high resolution scanning devices, which require high data rates. A true 3D volume display as described will complement the broad range of 3D visualization tools, such as volume rendering packages, stereoscopic and virtual reality techniques, which have become widely available in recent years. Potential applications for the FELIX 3D display include imaging in the field so fair traffic control, medical imaging, computer aided design, science as well as entertainment.

  3. Characterization of a pneumatic balloon actuator for use in refreshable Braille displays.

    Science.gov (United States)

    Fan, Richard E; Feinman, Adam M; Wottawa, Christopher; King, Chih-Hung; Franco, Miguel L; Dutson, Erik P; Grundfest, Warren S; Culjat, Martin O

    2009-01-01

    Many existing refreshable Braille display technologies are costly or lack robust performance. A process has been developed to fabricate consistent and reliable pneumatic balloon actuators at low material cost, using a novel manufacturing process. This technique has been adapted for use in refreshable Braille displays that feature low power consumption, ease of manufacture and small form factor. A prototype refreshable cell, conforming to American Braille standards, was developed and tested. The cell was fabricated from molded PDMS to form balloon actuators with a spin-coated silicone film, and fast pneumatic driving elements and an electronic control system were developed to drive the Braille dots. Perceptual testing was performed to determine the feasibility of the approach using a single blind human subject. The subject was able to detect randomized Braille letters rapidly generated by the actuator with 100% character detection accuracy.

  4. Evaluation of tactual displays for flight control

    Science.gov (United States)

    Levison, W. H.; Tanner, R. B.; Triggs, T. J.

    1973-01-01

    Manual tracking experiments were conducted to determine the suitability of tactual displays for presenting flight-control information in multitask situations. Although tracking error scores are considerably greater than scores obtained with a continuous visual display, preliminary results indicate that inter-task interference effects are substantially less with the tactual display in situations that impose high visual scanning workloads. The single-task performance degradation found with the tactual display appears to be a result of the coding scheme rather than the use of the tactual sensory mode per se. Analysis with the state-variable pilot/vehicle model shows that reliable predictions of tracking errors can be obtained for wide-band tracking systems once the pilot-related model parameters have been adjusted to reflect the pilot-display interaction.

  5. Real time speech formant analyzer and display

    Science.gov (United States)

    Holland, George E.; Struve, Walter S.; Homer, John F.

    1987-01-01

    A speech analyzer for interpretation of sound includes a sound input which converts the sound into a signal representing the sound. The signal is passed through a plurality of frequency pass filters to derive a plurality of frequency formants. These formants are converted to voltage signals by frequency-to-voltage converters and then are prepared for visual display in continuous real time. Parameters from the inputted sound are also derived and displayed. The display may then be interpreted by the user. The preferred embodiment includes a microprocessor which is interfaced with a television set for displaying of the sound formants. The microprocessor software enables the sound analyzer to present a variety of display modes for interpretive and therapeutic used by the user.

  6. Transparent 3D display for augmented reality

    Science.gov (United States)

    Lee, Byoungho; Hong, Jisoo

    2012-11-01

    Two types of transparent three-dimensional display systems applicable for the augmented reality are demonstrated. One of them is a head-mounted-display-type implementation which utilizes the principle of the system adopting the concave floating lens to the virtual mode integral imaging. Such configuration has an advantage in that the threedimensional image can be displayed at sufficiently far distance resolving the accommodation conflict with the real world scene. Incorporating the convex half mirror, which shows a partial transparency, instead of the concave floating lens, makes it possible to implement the transparent three-dimensional display system. The other type is the projection-type implementation, which is more appropriate for the general use than the head-mounted-display-type implementation. Its imaging principle is based on the well-known reflection-type integral imaging. We realize the feature of transparent display by imposing the partial transparency to the array of concave mirror which is used for the screen of reflection-type integral imaging. Two types of configurations, relying on incoherent and coherent light sources, are both possible. For the incoherent configuration, we introduce the concave half mirror array, whereas the coherent one adopts the holographic optical element which replicates the functionality of the lenslet array. Though the projection-type implementation is beneficial than the head-mounted-display in principle, the present status of the technical advance of the spatial light modulator still does not provide the satisfactory visual quality of the displayed three-dimensional image. Hence we expect that the head-mounted-display-type and projection-type implementations will come up in the market in sequence.

  7. New developments in flexible cholesteric liquid crystal displays

    Science.gov (United States)

    Schneider, Tod; Davis, Donald J.; Franklin, Sean; Venkataraman, Nithya; McDaniel, Diaz; Nicholson, Forrest; Montbach, Erica; Khan, Asad; Doane, J. William

    2007-02-01

    Flexible Cholesteric liquid crystal displays have been rapidly maturing into a strong contender in the flexible display market. Encapsulation of the Cholesteric liquid crystal permits the use of flexible plastic substrates and roll-to-roll production. Recent advances include ultra-thin displays, laser-cut segmented displays of variable geometry, and smart card applications. Exciting technologies such as simultaneous laser-edge sealing and singulation enable high volume production, excellent quality control and non-traditional display geometries and formats.

  8. 27 CFR 6.35 - Renting display space.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Renting display space. 6.35 Section 6.35 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... Renting display space. The renting of display space by an industry member at a retail establishment...

  9. 27 CFR 6.56 - Renting display space.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Renting display space. 6.56 Section 6.56 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... Distribution Service § 6.56 Renting display space. A promotion whereby an industry member rents display space...

  10. 14 CFR 255.4 - Display of information.

    Science.gov (United States)

    2010-01-01

    ... REGULATIONS AIRLINE COMPUTER RESERVATIONS SYSTEMS § 255.4 Display of information. (a) All systems shall provide at least one integrated display that includes the schedules, fares, rules, and availability of all... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Display of information. 255.4 Section 255.4...

  11. Novel microscope-integrated stereoscopic heads-up display for intrasurgical optical coherence tomography

    Science.gov (United States)

    Shen, Liangbo; Carrasco-Zevallos, Oscar; Keller, Brenton; Viehland, Christian; Waterman, Gar; Hahn, Paul S.; Kuo, Anthony N.; Toth, Cynthia A.; Izatt, Joseph A.

    2016-01-01

    Intra-operative optical coherence tomography (OCT) requires a display technology which allows surgeons to visualize OCT data without disrupting surgery. Previous research and commercial intrasurgical OCT systems have integrated heads-up display (HUD) systems into surgical microscopes to provide monoscopic viewing of OCT data through one microscope ocular. To take full advantage of our previously reported real-time volumetric microscope-integrated OCT (4D MIOCT) system, we describe a stereoscopic HUD which projects a stereo pair of OCT volume renderings into both oculars simultaneously. The stereoscopic HUD uses a novel optical design employing spatial multiplexing to project dual OCT volume renderings utilizing a single micro-display. The optical performance of the surgical microscope with the HUD was quantitatively characterized and the addition of the HUD was found not to substantially effect the resolution, field of view, or pincushion distortion of the operating microscope. In a pilot depth perception subject study, five ophthalmic surgeons completed a pre-set dexterity task with 50.0% (SD = 37.3%) higher success rate and in 35.0% (SD = 24.8%) less time on average with stereoscopic OCT vision compared to monoscopic OCT vision. Preliminary experience using the HUD in 40 vitreo-retinal human surgeries by five ophthalmic surgeons is reported, in which all surgeons reported that the HUD did not alter their normal view of surgery and that live surgical maneuvers were readily visible in displayed stereoscopic OCT volumes. PMID:27231616

  12. Novel microscope-integrated stereoscopic heads-up display for intrasurgical optical coherence tomography.

    Science.gov (United States)

    Shen, Liangbo; Carrasco-Zevallos, Oscar; Keller, Brenton; Viehland, Christian; Waterman, Gar; Hahn, Paul S; Kuo, Anthony N; Toth, Cynthia A; Izatt, Joseph A

    2016-05-01

    Intra-operative optical coherence tomography (OCT) requires a display technology which allows surgeons to visualize OCT data without disrupting surgery. Previous research and commercial intrasurgical OCT systems have integrated heads-up display (HUD) systems into surgical microscopes to provide monoscopic viewing of OCT data through one microscope ocular. To take full advantage of our previously reported real-time volumetric microscope-integrated OCT (4D MIOCT) system, we describe a stereoscopic HUD which projects a stereo pair of OCT volume renderings into both oculars simultaneously. The stereoscopic HUD uses a novel optical design employing spatial multiplexing to project dual OCT volume renderings utilizing a single micro-display. The optical performance of the surgical microscope with the HUD was quantitatively characterized and the addition of the HUD was found not to substantially effect the resolution, field of view, or pincushion distortion of the operating microscope. In a pilot depth perception subject study, five ophthalmic surgeons completed a pre-set dexterity task with 50.0% (SD = 37.3%) higher success rate and in 35.0% (SD = 24.8%) less time on average with stereoscopic OCT vision compared to monoscopic OCT vision. Preliminary experience using the HUD in 40 vitreo-retinal human surgeries by five ophthalmic surgeons is reported, in which all surgeons reported that the HUD did not alter their normal view of surgery and that live surgical maneuvers were readily visible in displayed stereoscopic OCT volumes.

  13. Stability-Diversity Tradeoffs Impose Fundamental Constraints on Selection of Synthetic Human VH/VL Single-Domain Antibodies from In Vitro Display Libraries.

    Science.gov (United States)

    Henry, Kevin A; Kim, Dae Young; Kandalaft, Hiba; Lowden, Michael J; Yang, Qingling; Schrag, Joseph D; Hussack, Greg; MacKenzie, C Roger; Tanha, Jamshid

    2017-01-01

    Human autonomous V H /V L single-domain antibodies (sdAbs) are attractive therapeutic molecules, but often suffer from suboptimal stability, solubility and affinity for cognate antigens. Mos