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Sample records for heat-induced epitope retrieval

  1. A single simple procedure for dewaxing, hydration and heat-induced epitope retrieval (HIER) for immunohistochemistry in formalin fixed paraffin-embedded tissue

    DEFF Research Database (Denmark)

    Paulsen, I M S; Dimke, H; Frische, S

    2015-01-01

    Heat-induced epitope retrieval (HIER) is widely used for immunohistochemistry on formalin fixed paraffin-embedded tissue and includes temperatures well above the melting point of paraffin. We therefore tested whether traditional xylene-based removal of paraffin is required on sections from paraff...... of dewaxing in xylene. In conclusion, the HIER procedure described and tested can be used as a single procedure enabling dewaxing, hydration and epitope retrieval for immunohistochemistry in formalin fixed paraffin-embedded tissue....

  2. A single simple procedure for dewaxing, hydration and heat-induced epitope retrieval (HIER for immunohistochemistry in formalin fixed paraffin-embedded tissue

    Directory of Open Access Journals (Sweden)

    I.M.S. Paulsen

    2015-11-01

    Full Text Available Heat-induced epitope retrieval (HIER is widely used for immunohistochemistry on formalin fixed paraffin-embedded tissue and includes temperatures well above the melting point of paraffin. We therefore tested whether traditional xylene-based removal of paraffin is required on sections from paraffin-embedded tissue, when HIER is performed by vigorous boiling in 10 mM Tris/0.5 mM EGTA-buffer (pH=9. Immunohistochemical results using HIER with or without prior dewaxing in xylene were evaluated using 7 primary antibodies targeting proteins located in the cytosol, intracellular vesicles and plasma membrane. No effect of omitting prior dewaxing was observed on staining pattern. Semiquantitative analysis did not show HIER to influence the intensity of labelling consistently. Consequently, quantification of immune labelling intensity using fluorescent secondary antibodies was performed at 5 dilutions of primary antibody with and without prior dewaxing in xylene. No effect of omitting prior dewaxing on signal intensity was detectable indicating similar immunoreactivity in dewaxed and non-dewaxed sections. The intensity of staining the nucleus with the DNA-stain ToPro3 was similarly unaffected by omission of dewaxing in xylene. In conclusion, the HIER procedure described and tested can be used as a single procedure enabling dewaxing, hydration and epitope retrieval for immunohistochemistry in formalin fixed paraffin-embedded tissue.

  3. Microbiota epitope similarity either dampens or enhances the immunogenicity of disease-associated antigenic epitopes.

    Directory of Open Access Journals (Sweden)

    Sebastian Carrasco Pro

    Full Text Available The microbiome influences adaptive immunity and molecular mimicry influences T cell reactivity. Here, we evaluated whether the sequence similarity of various antigens to the microbiota dampens or increases immunogenicity of T cell epitopes. Sets of epitopes and control sequences derived from 38 antigenic categories (infectious pathogens, allergens, autoantigens were retrieved from the Immune Epitope Database (IEDB. Their similarity to microbiome sequences was calculated using the BLOSUM62 matrix. We found that sequence similarity was associated with either dampened (tolerogenic; e.g. most allergens or increased (inflammatory; e.g. Dengue and West Nile viruses likelihood of a peptide being immunogenic as a function of epitope source category. Ten-fold cross-validation and validation using sets of manually curated epitopes and non-epitopes derived from allergens were used to confirm these initial observations. Furthermore, the genus from which the microbiome homologous sequences were derived influenced whether a tolerogenic versus inflammatory modulatory effect was observed, with Fusobacterium most associated with inflammatory influences and Bacteroides most associated with tolerogenic influences. We validated these effects using PBMCs stimulated with various sets of microbiome peptides. "Tolerogenic" microbiome peptides elicited IL-10 production, "inflammatory" peptides elicited mixed IL-10/IFNγ production, while microbiome epitopes homologous to self were completely unreactive for both cytokines. We also tested the sequence similarity of cockroach epitopes to specific microbiome sequences derived from households of cockroach allergic individuals and non-allergic controls. Microbiomes from cockroach allergic households were less likely to contain sequences homologous to previously defined cockroach allergens. These results are compatible with the hypothesis that microbiome sequences may contribute to the tolerization of T cells for allergen

  4. Furan: A critical heat induced dietary contaminant

    DEFF Research Database (Denmark)

    Mariotti, María S.; Granby, Kit; Rozowski, Jaime

    2013-01-01

    The presence of furan in a broad range of heat processed foods (0-6000 μg kg-1) has received considerable attention due to the fact that this heat induced contaminant is considered as a "possible carcinogenic compound to humans". Since a genotoxic mode of action could be associated with furan...... of some critical factors such as heating conditions, pH and matrix microstructure are discussed in order to propose some potential methodologies for furan mitigation in a wide range of heated foods. © 2013 The Royal Society of Chemistry....

  5. Epitope prediction methods

    DEFF Research Database (Denmark)

    Karosiene, Edita

    Analysis. The chapter provides detailed explanations on how to use different methods for T cell epitope discovery research, explaining how input should be given as well as how to interpret the output. In the last chapter, I present the results of a bioinformatics analysis of epitopes from the yellow fever...... peptide-MHC interactions. Furthermore, using yellow fever virus epitopes, we demonstrated the power of the %Rank score when compared with the binding affinity score of MHC prediction methods, suggesting that this score should be considered to be used for selecting potential T cell epitopes. In summary...... immune responses. Therefore, it is of great importance to be able to identify peptides that bind to MHC molecules, in order to understand the nature of immune responses and discover T cell epitopes useful for designing new vaccines and immunotherapies. MHC molecules in humans, referred to as human...

  6. Concept of heat-induced inkless eco-printing.

    Science.gov (United States)

    Chen, Jinxiang; Wang, Yong; Xie, Juan; Meng, Chuang; Wu, Gang; Zu, Qiao

    2012-07-01

    Existing laser and inkjet printers often produce adverse effects on human health, the recycling of printing paper and the environment. Therefore, this paper examines the thermogravimetry curves for printer paper, analyzes the discoloration of paper using heat-induction, and investigates the relationship between paper discoloration and the heat-inducing temperature. The mechanism of heat-induced printing is analyzed initially, and its feasibility is determined by a comparative analysis of heat-induced (laser ablation) printing and commercial printing. The innovative concept of heat-induced inkless eco-printing is proposed, in which the required text or graphics are formed on the printing paper via yellowing and blackening produced by thermal energy. This process does not require ink during the printing process; thus, it completely eliminates the aforementioned health and environmental issues. This research also contributes to related interdisciplinary research in biology, laser technology, photochemistry, nano-science, paper manufacturing and color science. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Heat-induced alterations in the cell nucleus

    International Nuclear Information System (INIS)

    Kampinga, H.H.

    1989-01-01

    Hyperthermia may kill eukaryotic cells and may also enhance the radiosensitivity of those cells that survive the heat treatment. Clinically, the possible use of hyperthermia as an adjuvant in the radiotherapeutic treatment of cancer needs the understanding of mechanisms that underlay heat-induced cell death and radiosensitization. By in vitro heating of established human (HeLaS3) and rodent (Ehrlich Ascites Tumor and LM fibroblast) cell lines, both killing and radiosensitization were investigated. (author). 1067 refs.; 76 figs.; 19 tabs

  8. Chlorophyll loss associated with heat-induced senescence in bentgrass.

    Science.gov (United States)

    Jespersen, David; Zhang, Jing; Huang, Bingru

    2016-08-01

    Heat stress-induced leaf senescence is characterized by the loss of chlorophyll from leaf tissues. The objectives of this study were to examine genetic variations in the level of heat-induced leaf senescence in hybrids of colonial (Agrostis capillaris)×creeping bentgrass (Agrostis stolonifera) contrasting in heat tolerance, and determine whether loss of leaf chlorophyll during heat-induced leaf senescence was due to suppressed chlorophyll synthesis and/or accelerated chlorophyll degradation in the cool-season perennial grass species. Plants of two hybrid backcross genotypes ('ColxCB169' and 'ColxCB190') were exposed to heat stress (38/33°C, day/night) for 28 d in growth chambers. The analysis of turf quality, membrane stability, photochemical efficiency, and chlorophyll content demonstrated significant variations in the level of leaf senescence induced by heat stress between the two genotypes, with ColXCB169 exhibiting a lesser degree of decline in chlorophyll content, photochemical efficiency and membrane stability than ColXCB190. The assays of enzymatic activity or gene expression of several major chlorophyll-synthesizing (porphobilinogen deaminase, Mg-chelatase, protochlorophyllide-reductase) and chlorophyll-degrading enzymes (chlorophyllase, pheophytinase, and chlorophyll-degrading peroxidase) indicated heat-induced decline in leaf chlorophyll content was mainly due to accelerated chlorophyll degradation, as manifested by increased gene expression levels of chlorophyllase and pheophytinase, and the activity of pheophytinase (PPH), while chlorophyll-synthesizing genes and enzymatic activities were not differentially altered by heat stress in the two genotypes. The analysis of heat-induced leaf senescence of pph mutants of Arabidopsis further confirmed that PPH could be one enzymes that plays key roles in regulating heat-accelerated chlorophyll degradation. Further research on enzymes responsible in part for the loss of chlorophyll during heat-induced

  9. Immune epitope database analysis resource

    DEFF Research Database (Denmark)

    Kim, Yohan; Ponomarenko, Julia; Zhu, Zhanyang

    2012-01-01

    The immune epitope database analysis resource (IEDB-AR: http://tools.iedb.org) is a collection of tools for prediction and analysis of molecular targets of T- and B-cell immune responses (i.e. epitopes). Since its last publication in the NAR webserver issue in 2008, a new generation of peptide......, and the homology mapping tool was updated to enable mapping of discontinuous epitopes onto 3D structures. Furthermore, to serve a wider range of users, the number of ways in which IEDB-AR can be accessed has been expanded. Specifically, the predictive tools can be programmatically accessed using a web interface...

  10. Immune Epitope Database and Analysis Resource (IEDB)

    Data.gov (United States)

    U.S. Department of Health & Human Services — This repository contains antibody/B cell and T cell epitope information and epitope prediction and analysis tools for use by the research community worldwide. Immune...

  11. The Immune Epitope Database 2.0

    DEFF Research Database (Denmark)

    Hoof, Ilka; Vita, R; Zarebski, L

    2010-01-01

    The Immune Epitope Database (IEDB, www.iedb.org) provides a catalog of experimentally characterized B and T cell epitopes, as well as data on Major Histocompatibility Complex (MHC) binding and MHC ligand elution experiments. The database represents the molecular structures recognized by adaptive...... immune receptors and the experimental contexts in which these molecules were determined to be immune epitopes. Epitopes recognized in humans, nonhuman primates, rodents, pigs, cats and all other tested species are included. Both positive and negative experimental results are captured. Over the course...

  12. Epitope discovery with phylogenetic hidden Markov models.

    LENUS (Irish Health Repository)

    Lacerda, Miguel

    2010-05-01

    Existing methods for the prediction of immunologically active T-cell epitopes are based on the amino acid sequence or structure of pathogen proteins. Additional information regarding the locations of epitopes may be acquired by considering the evolution of viruses in hosts with different immune backgrounds. In particular, immune-dependent evolutionary patterns at sites within or near T-cell epitopes can be used to enhance epitope identification. We have developed a mutation-selection model of T-cell epitope evolution that allows the human leukocyte antigen (HLA) genotype of the host to influence the evolutionary process. This is one of the first examples of the incorporation of environmental parameters into a phylogenetic model and has many other potential applications where the selection pressures exerted on an organism can be related directly to environmental factors. We combine this novel evolutionary model with a hidden Markov model to identify contiguous amino acid positions that appear to evolve under immune pressure in the presence of specific host immune alleles and that therefore represent potential epitopes. This phylogenetic hidden Markov model provides a rigorous probabilistic framework that can be combined with sequence or structural information to improve epitope prediction. As a demonstration, we apply the model to a data set of HIV-1 protein-coding sequences and host HLA genotypes.

  13. Sex specific effects of heat induced hormesis in Hsf-deficient Drosophila melanogaster

    DEFF Research Database (Denmark)

    Sørensen, J G; Kristensen, Torsten Nygård; Kristensen, K V

    2007-01-01

    In insects mild heat stress early in life has been reported to increase life span and heat resistance later in life, a phenomenon termed hormesis. Here, we test if the induction of the heat shock response by mild heat stress is mediating hormesis in longevity and heat resistance at older age...... line, seemingly mediated by the production of heat shock proteins (Hsps). The results indicate that heat inducible Hsps are important for heat induced hormesis in longevity and heat stress resistance. However, the results also suggest that other processes are involved and that different mechanisms...... might have marked sex specific impact...

  14. Automatic Generation of Validated Specific Epitope Sets

    Directory of Open Access Journals (Sweden)

    Sebastian Carrasco Pro

    2015-01-01

    Full Text Available Accurate measurement of B and T cell responses is a valuable tool to study autoimmunity, allergies, immunity to pathogens, and host-pathogen interactions and assist in the design and evaluation of T cell vaccines and immunotherapies. In this context, it is desirable to elucidate a method to select validated reference sets of epitopes to allow detection of T and B cells. However, the ever-growing information contained in the Immune Epitope Database (IEDB and the differences in quality and subjects studied between epitope assays make this task complicated. In this study, we develop a novel method to automatically select reference epitope sets according to a categorization system employed by the IEDB. From the sets generated, three epitope sets (EBV, mycobacteria and dengue were experimentally validated by detection of T cell reactivity ex vivo from human donors. Furthermore, a web application that will potentially be implemented in the IEDB was created to allow users the capacity to generate customized epitope sets.

  15. Epitope mapping: the first step in developing epitope-based vaccines.

    Science.gov (United States)

    Gershoni, Jonathan M; Roitburd-Berman, Anna; Siman-Tov, Dror D; Tarnovitski Freund, Natalia; Weiss, Yael

    2007-01-01

    Antibodies are an effective line of defense in preventing infectious diseases. Highly potent neutralizing antibodies can intercept a virus before it attaches to its target cell and, thus, inactivate it. This ability is based on the antibodies' specific recognition of epitopes, the sites of the antigen to which antibodies bind. Thus, understanding the antibody/epitope interaction provides a basis for the rational design of preventive vaccines. It is assumed that immunization with the precise epitope, corresponding to an effective neutralizing antibody, would elicit the generation of similarly potent antibodies in the vaccinee. Such a vaccine would be a 'B-cell epitope-based vaccine', the implementation of which requires the ability to backtrack from a desired antibody to its corresponding epitope. In this article we discuss a range of methods that enable epitope discovery based on a specific antibody. Such a reversed immunological approach is the first step in the rational design of an epitope-based vaccine. Undoubtedly, the gold standard for epitope definition is x-ray analyses of crystals of antigen:antibody complexes. This method provides atomic resolution of the epitope; however, it is not readily applicable to many antigens and antibodies, and requires a very high degree of sophistication and expertise. Most other methods rely on the ability to monitor the binding of the antibody to antigen fragments or mutated variations. In mutagenesis of the antigen, loss of binding due to point modification of an amino acid residue is often considered an indication of an epitope component. In addition, computational combinatorial methods for epitope mapping are also useful. These methods rely on the ability of the antibody of interest to affinity isolate specific short peptides from combinatorial phage display peptide libraries. The peptides are then regarded as leads for the definition of the epitope corresponding to the antibody used to screen the peptide library. For

  16. Heat shock transcription factors regulate heat induced cell death in a ...

    Indian Academy of Sciences (India)

    2007-03-29

    Mar 29, 2007 ... Heat shock transcription factors regulate heat induced cell death in a rat ... the synthesis of heat shock proteins (Hsps) which is strictly regulated by ... The lack of Hsp synthesis in these cells was due to a failure in HSF1 DNA ...

  17. Heat-induced whey protein isolate fibrils: Conversion, hydrolysis, and disulphide bond formation

    NARCIS (Netherlands)

    Bolder, S.G.; Vasbinder, A.; Sagis, L.M.C.; Linden, van der E.

    2007-01-01

    Fibril formation of individual pure whey proteins and whey protein isolate (WPI) was studied. The heat-induced conversion of WPI monomers into fibrils at pH 2 and low ionic strength increased with heating time and protein concentration. Previous studies, using a precipitation method, size-exclusion

  18. CELLS OVEREXPRESSING HSP27 SHOW ACCELERATED RECOVERY FROM HEAT-INDUCED NUCLEAR-PROTEIN AGGREGATION

    NARCIS (Netherlands)

    KAMPINGA, HH; BRUNSTING, JF; STEGE, GJJ; KONINGS, AWT; LANDRY, J

    1994-01-01

    Protein denaturation/aggregation upon cell exposure to heat shock is a likely cause of cell death. in the nucleus, protein aggregation has often been correlated to inhibition of nuclear located processes and heat-induced cell killing. in Chinese hamster 023 cells made thermotolerant by a prior

  19. Palm kernel cake extract exerts hepatoprotective activity in heat-induced oxidative stress in chicken hepatocytes.

    Science.gov (United States)

    Oskoueian, Ehsan; Abdullah, Norhani; Idrus, Zulkifli; Ebrahimi, Mahdi; Goh, Yong Meng; Shakeri, Majid; Oskoueian, Armin

    2014-10-02

    Palm kernel cake (PKC), the most abundant by-product of oil palm industry is believed to contain bioactive compounds with hepatoprotective potential. These compounds may serve as hepatoprotective agents which could help the poultry industry to alleviate adverse effects of heat stress on liver function in chickens. This study was performed to evaluate the hepatoprotective potential of PKC extract in heat-induced oxidative stress in chicken hepatocytes. The nature of the active metabolites and elucidation of the possible mechanism involved were also investigated. The PKC extract possessed free radical scavenging activity with values significantly (p < 0.05) lower than silymarin as the reference antioxidant. Heat-induced oxidative stress in chicken hepatocyte impaired the total protein, lipid peroxidation and antioxidant enzymes activity significantly (p < 0.05). Treatment of heat-induced hepatocytes with PKC extract (125 μg/ml) and silymarin as positive control increased these values significantly (p < 0.05). The real time PCR and western blot analyses revealed the significant (p < 0.05) up-regulation of oxidative stress biomarkers including TNF-like, IFN-γ and IL-1β genes; NF-κB, COX-2, iNOS and Hsp70 proteins expression upon heat stress in chicken hepatocytes. The PKC extract and silymarin were able to alleviate the expression of all of these biomarkers in heat-induced chicken hepatocytes. The gas chromatography-mass spectrometry analysis of PKC extract showed the presence of fatty acids, phenolic compounds, sugar derivatives and other organic compounds such as furfural which could be responsible for the observed hepatoprotective activity. Palm kernel cake extract could be a potential agent to protect hepatocytes function under heat induced oxidative stress.

  20. Resistance mutations and CTL epitopes in archived HIV-1 DNA of patients on antiviral treatment: toward a new concept of vaccine.

    Directory of Open Access Journals (Sweden)

    Jennifer Papuchon

    Full Text Available Eleven patients responding successfully to first-line antiretroviral therapy (ART were investigated for proviral drug resistance mutations (DRMs in RT by ultra-deep pyrosequencing (UDPS. After molecular typing of the class I alleles A and B, the CTL epitopes in the Gag, Nef and Pol regions of the provirus were sequenced and compared to the reference HXB2 HIV-1 epitopes. They were then matched with the HLA alleles with determination of theoretical affinity (TA. For 3 patients, the results could be compared with an RNA sample of the circulating virus at initiation of therapy. Five out of 11 patients exhibited DRMs by UDPS. The issue is whether a therapeutic switch is relevant in these patients by taking into account the identity of the archived resistance mutations. When the archived CTL epitopes were determined on the basis of the HLA alleles, different patterns were observed. Some epitopes were identical to those reported for the reference with the same TA, while others were mutated with a decrease in TA. In 2 cases, an epitope was observed as a combination of subpopulations at entry and was retrieved as a single population with lower TA at success. With regard to immunological stimulation and given the variability of the archived CTL epitopes, we propose a new concept of curative vaccine based on identification of HIV-1 CTL epitopes after prior sequencing of proviral DNA and matching with HLA class I alleles.

  1. Localization of immunodominant linear B-cell epitopes of Vibrio ...

    African Journals Online (AJOL)

    AJL

    2012-05-01

    May 1, 2012 ... In order to locate the epitopes of OmpU protein, epitope prediction was performed ... enzyme linked immunosorbent assay; OmpU, outer membrane protein U .... recombinant plasmids were extracted and identified by PCR,.

  2. Catalase epitopes vaccine design for Helicobacter pylori: A ...

    African Journals Online (AJOL)

    Jane

    2011-08-15

    Aug 15, 2011 ... colored region and P1 anchor or the starting residue of each ..... score of MVNKDVKQTT; * 1, MVNKDVKQTT is a composition of two epitopes: MVNKDVKQT and .... Therapeutic efficacy of a multi-epitope vaccine against.

  3. Foreign Body Retrieval

    Medline Plus

    Full Text Available ... Physician Resources Professions Site Index A-Z Foreign Body Retrieval Foreign body retrieval is the removal of ... foreign body detection and removal? What is Foreign Body Retrieval? Foreign body retrieval involves the removal of ...

  4. DRREP: deep ridge regressed epitope predictor.

    Science.gov (United States)

    Sher, Gene; Zhi, Degui; Zhang, Shaojie

    2017-10-03

    The ability to predict epitopes plays an enormous role in vaccine development in terms of our ability to zero in on where to do a more thorough in-vivo analysis of the protein in question. Though for the past decade there have been numerous advancements and improvements in epitope prediction, on average the best benchmark prediction accuracies are still only around 60%. New machine learning algorithms have arisen within the domain of deep learning, text mining, and convolutional networks. This paper presents a novel analytically trained and string kernel using deep neural network, which is tailored for continuous epitope prediction, called: Deep Ridge Regressed Epitope Predictor (DRREP). DRREP was tested on long protein sequences from the following datasets: SARS, Pellequer, HIV, AntiJen, and SEQ194. DRREP was compared to numerous state of the art epitope predictors, including the most recently published predictors called LBtope and DMNLBE. Using area under ROC curve (AUC), DRREP achieved a performance improvement over the best performing predictors on SARS (13.7%), HIV (8.9%), Pellequer (1.5%), and SEQ194 (3.1%), with its performance being matched only on the AntiJen dataset, by the LBtope predictor, where both DRREP and LBtope achieved an AUC of 0.702. DRREP is an analytically trained deep neural network, thus capable of learning in a single step through regression. By combining the features of deep learning, string kernels, and convolutional networks, the system is able to perform residue-by-residue prediction of continues epitopes with higher accuracy than the current state of the art predictors.

  5. Image retrieval

    DEFF Research Database (Denmark)

    Ørnager, Susanne

    1997-01-01

    The paper touches upon indexing and retrieval for effective searches of digitized images. Different conceptions of what subject indexing means are described as a basis for defining an operational subject indexing strategy for images. The methodology is based on the art historian Erwin Panofsky......), special knowledge about image codes, and special knowledge about history of ideas. The semiologist Roland Barthes has established a semiology for pictorial expressions based on advertising photos. Barthes uses the concepts denotation/connotation where denotations can be explained as the sober expression...

  6. Testosterone Depletion by Castration May Protect Mice from Heat-Induced Multiple Organ Damage and Lethality

    Directory of Open Access Journals (Sweden)

    Ruei-Tang Cheng

    2010-01-01

    Full Text Available When the vehicle-treated, sham-operated mice underwent heat stress, the fraction survival and core temperature at +4 h of body heating were found to be 5 of 15 and 34.4∘C±0.3∘C, respectively. Castration 2 weeks before the start of heat stress decreased the plasma levels of testosterone almost to zero, protected the mice from heat-induced death (fraction survival, 13/15 and reduced the hypothermia (core temperature, 37.3∘C. The beneficial effects of castration in ameliorating lethality and hypothermia can be significantly reduced by testosterone replacement. Heat-induced apoptosis, as indicated by terminal deoxynucleotidyl- transferase- mediatedαUDP-biotin nick end-labeling staining, were significantly prevented by castration. In addition, heat-induced neuronal damage, as indicated by cell shrinkage and pyknosis of nucleus, to the hypothalamus was also castration-prevented. Again, the beneficial effects of castration in reducing neuronal damage to the hypothalamus as well as apoptosis in multiple organs during heatstroke, were significantly reversed by testosterone replacement. The data indicate that testosterone depletion by castration may protect mice from heatstroke-induced multiple organ damage and lethality.

  7. Localization of immunodominant linear B-cell epitopes of Vibrio ...

    African Journals Online (AJOL)

    Outer membrane protein U (OmpU), an adhesion protein of Vibrio mimicus, is a good antigen, but its epitopes are still unclear. In order to locate the epitopes of OmpU protein, epitope prediction was performed using the amino acid sequence of OmpU protein of V. mimicus HX4 strain that was isolated from the diseased ...

  8. Viral O-GalNAc peptide epitopes

    DEFF Research Database (Denmark)

    Olofsson, Sigvard; Blixt, Klas Ola; Bergström, Tomas

    2016-01-01

    Viral envelope glycoproteins are major targets for antibodies that bind to and inactivate viral particles. The capacity of a viral vaccine to induce virus-neutralizing antibodies is often used as a marker for vaccine efficacy. Yet the number of known neutralization target epitopes is restricted o...

  9. Detailing Radio Frequency Heating Induced by Coronary Stents: A 7.0 Tesla Magnetic Resonance Study

    Science.gov (United States)

    Santoro, Davide; Winter, Lukas; Müller, Alexander; Vogt, Julia; Renz, Wolfgang; Özerdem, Celal; Grässl, Andreas; Tkachenko, Valeriy; Schulz-Menger, Jeanette; Niendorf, Thoralf

    2012-01-01

    The sensitivity gain of ultrahigh field Magnetic Resonance (UHF-MR) holds the promise to enhance spatial and temporal resolution. Such improvements could be beneficial for cardiovascular MR. However, intracoronary stents used for treatment of coronary artery disease are currently considered to be contra-indications for UHF-MR. The antenna effect induced by a stent together with RF wavelength shortening could increase local radiofrequency (RF) power deposition at 7.0 T and bears the potential to induce local heating, which might cause tissue damage. Realizing these constraints, this work examines RF heating effects of stents using electro-magnetic field (EMF) simulations and phantoms with properties that mimic myocardium. For this purpose, RF power deposition that exceeds the clinical limits was induced by a dedicated birdcage coil. Fiber optic probes and MR thermometry were applied for temperature monitoring using agarose phantoms containing copper tubes or coronary stents. The results demonstrate an agreement between RF heating induced temperature changes derived from EMF simulations versus MR thermometry. The birdcage coil tailored for RF heating was capable of irradiating power exceeding the specific-absorption rate (SAR) limits defined by the IEC guidelines by a factor of three. This setup afforded RF induced temperature changes up to +27 K in a reference phantom. The maximum extra temperature increase, induced by a copper tube or a coronary stent was less than 3 K. The coronary stents examined showed an RF heating behavior similar to a copper tube. Our results suggest that, if IEC guidelines for local/global SAR are followed, the extra RF heating induced in myocardial tissue by stents may not be significant versus the baseline heating induced by the energy deposited by a tailored cardiac transmit RF coil at 7.0 T, and may be smaller if not insignificant than the extra RF heating observed under the circumstances used in this study. PMID:23185498

  10. Detailing radio frequency heating induced by coronary stents: a 7.0 Tesla magnetic resonance study.

    Directory of Open Access Journals (Sweden)

    Davide Santoro

    Full Text Available The sensitivity gain of ultrahigh field Magnetic Resonance (UHF-MR holds the promise to enhance spatial and temporal resolution. Such improvements could be beneficial for cardiovascular MR. However, intracoronary stents used for treatment of coronary artery disease are currently considered to be contra-indications for UHF-MR. The antenna effect induced by a stent together with RF wavelength shortening could increase local radiofrequency (RF power deposition at 7.0 T and bears the potential to induce local heating, which might cause tissue damage. Realizing these constraints, this work examines RF heating effects of stents using electro-magnetic field (EMF simulations and phantoms with properties that mimic myocardium. For this purpose, RF power deposition that exceeds the clinical limits was induced by a dedicated birdcage coil. Fiber optic probes and MR thermometry were applied for temperature monitoring using agarose phantoms containing copper tubes or coronary stents. The results demonstrate an agreement between RF heating induced temperature changes derived from EMF simulations versus MR thermometry. The birdcage coil tailored for RF heating was capable of irradiating power exceeding the specific-absorption rate (SAR limits defined by the IEC guidelines by a factor of three. This setup afforded RF induced temperature changes up to +27 K in a reference phantom. The maximum extra temperature increase, induced by a copper tube or a coronary stent was less than 3 K. The coronary stents examined showed an RF heating behavior similar to a copper tube. Our results suggest that, if IEC guidelines for local/global SAR are followed, the extra RF heating induced in myocardial tissue by stents may not be significant versus the baseline heating induced by the energy deposited by a tailored cardiac transmit RF coil at 7.0 T, and may be smaller if not insignificant than the extra RF heating observed under the circumstances used in this study.

  11. Kinetics of heat-induced color change of a tuna-vegetable mixture

    OpenAIRE

    Scherer, Erika; Sandoval, Aleida J; Barreiro, José A

    2009-01-01

    Heat induced color change kinetics in a tuna-vegetable mixture was evaluated by measuring color parameter "L" (Hunter-Lab) and 5-hydroxi-methyl-furfural (5-HMF) accumulation. For this purpose small reusable stainless steel TDT cans were used and the kinetic studies performed in a temperature range characteristic of thermal processing of low acid canned foods (110-125°C). The color parameter L was better described by a pseudo zero order while a pseudo first order reaction was found for 5-HMF a...

  12. High-Throughput Tools for Characterization of Antibody Epitopes

    DEFF Research Database (Denmark)

    Christiansen, Anders

    mapping. In Chapter 1, it was examined whether combining phage display, a traditional epitope mapping approach, with HTS would improve the method. The developed approach was successfully used to map Ara h 1 epitopes in sera from patients with peanut allergy. Notably, the sera represented difficult...... proliferation advantages. Finally, in Chapter 4, a different emerging technology, next-generation peptide microarrays, was applied for epitope mapping of major peanut allergens using sera from allergic patients. New developments in the peptide microarray have enabled a greatly increased throughput....... In this study, these improvements were utilized to characterize epitopes at high resolution, i.e. determine the importance of each residue for antibody binding, for all major peanut allergens. Epitope reactivity among patients often converged on known epitope hotspots, however the binding patterns were somewhat...

  13. Proof of principle for epitope-focused vaccine design

    Science.gov (United States)

    Correia, Bruno E.; Bates, John T.; Loomis, Rebecca J.; Baneyx, Gretchen; Carrico, Chris; Jardine, Joseph G.; Rupert, Peter; Correnti, Colin; Kalyuzhniy, Oleksandr; Vittal, Vinayak; Connell, Mary J.; Stevens, Eric; Schroeter, Alexandria; Chen, Man; MacPherson, Skye; Serra, Andreia M.; Adachi, Yumiko; Holmes, Margaret A.; Li, Yuxing; Klevit, Rachel E.; Graham, Barney S.; Wyatt, Richard T.; Baker, David; Strong, Roland K.; Crowe, James E.; Johnson, Philip R.; Schief, William R.

    2014-03-01

    Vaccines prevent infectious disease largely by inducing protective neutralizing antibodies against vulnerable epitopes. Several major pathogens have resisted traditional vaccine development, although vulnerable epitopes targeted by neutralizing antibodies have been identified for several such cases. Hence, new vaccine design methods to induce epitope-specific neutralizing antibodies are needed. Here we show, with a neutralization epitope from respiratory syncytial virus, that computational protein design can generate small, thermally and conformationally stable protein scaffolds that accurately mimic the viral epitope structure and induce potent neutralizing antibodies. These scaffolds represent promising leads for the research and development of a human respiratory syncytial virus vaccine needed to protect infants, young children and the elderly. More generally, the results provide proof of principle for epitope-focused and scaffold-based vaccine design, and encourage the evaluation and further development of these strategies for a variety of other vaccine targets, including antigenically highly variable pathogens such as human immunodeficiency virus and influenza.

  14. Comparison of two mathematical models for describing heat-induced cell killing

    International Nuclear Information System (INIS)

    Roti Roti, J.L.; Henle, K.J.

    1980-01-01

    A computer-based minimization algorithm is utilized to obtain the optimum fits of two models to hyperthermic cell killing data. The models chosen are the multitarget, single-hit equation, which is in general use, and the linear-quadratic equation, which has been applied to cell killing by ionizing irradiation but not to heat-induced cell killing. The linear-quadratic equation fits hyperthermic cell killing data as well as the multitarget, single-hit equation. Both parameters of the linear-quadratic equation obey the Arrhenius law, whereas only one of the two parameters of the multitarget, single-hit equation obeys the Arrhenius law. Thus the linear-quadratic function can completely define cell killing as a function of both time and temperature. In addition, the linear-quadratic model will provide a simplified approach to the study of the synergism between heat and X irradiation

  15. High epitope expression levels increase competition between T cells.

    Directory of Open Access Journals (Sweden)

    Almut Scherer

    2006-08-01

    Full Text Available Both theoretical predictions and experimental findings suggest that T cell populations can compete with each other. There is some debate on whether T cells compete for aspecific stimuli, such as access to the surface on antigen-presenting cells (APCs or for specific stimuli, such as their cognate epitope ligand. We have developed an individual-based computer simulation model to study T cell competition. Our model shows that the expression level of foreign epitopes per APC determines whether T cell competition is mainly for specific or aspecific stimuli. Under low epitope expression, competition is mainly for the specific epitope stimuli, and, hence, different epitope-specific T cell populations coexist readily. However, if epitope expression levels are high, aspecific competition becomes more important. Such between-specificity competition can lead to competitive exclusion between different epitope-specific T cell populations. Our model allows us to delineate the circumstances that facilitate coexistence of T cells of different epitope specificity. Understanding mechanisms of T cell coexistence has important practical implications for immune therapies that require a broad immune response.

  16. Bioinformatics Tools for the Prediction of T-Cell Epitopes

    DEFF Research Database (Denmark)

    Andreatta, Massimo; Nielsen, Morten

    2018-01-01

    T-cell responses are activated by specific peptides, called epitopes, presented on the cell surface by MHC molecules. Binding of peptides to the MHC is the most selective step in T-cell antigen presentation and therefore an essential factor in the selection of potential epitopes. Several in-vitro...

  17. A xylogalacturonan epitope is specifically associated with plant cell detachment

    DEFF Research Database (Denmark)

    Willats, William George Tycho; McCartney, L.; Steele-King, C.G.

    2004-01-01

    A monoclonal antibody (LM8) was generated with specificity for xyloglacturonan (XGA) isolated from pea (Pisum sativum L.) testae. Characterization of the LM8 epitope indicates that it is a region of XGA that is highly substituted with xylose. Immunocytochemical analysis indicates that this epitop...

  18. Confirmation of antibodies against L-tryptophan-like epitope in ...

    African Journals Online (AJOL)

    Confirmation of antibodies against L-tryptophan-like epitope in human African trypanosomosis serological diagnostic. ... number of patients in Congo. A diagnostic test based on this synthetic epitope, especially in combination with other tests, might improve the HAT diagnostic test in field conditions. Key words: Tryptophan ...

  19. Immune epitope database analysis resource (IEDB-AR)

    DEFF Research Database (Denmark)

    Zhang, Qing; Wang, Peng; Kim, Yohan

    2008-01-01

    We present a new release of the immune epitope database analysis resource (IEDB-AR, http://tools.immuneepitope.org), a repository of web-based tools for the prediction and analysis of immune epitopes. New functionalities have been added to most of the previously implemented tools, and a total...

  20. BepiPred-2.0: improving sequence-based B-cell epitope prediction using conformational epitopes

    DEFF Research Database (Denmark)

    Jespersen, Martin Closter; Peters, Bjoern; Nielsen, Morten

    2017-01-01

    Antibodies have become an indispensable tool for many biotechnological and clinical applications. They bind their molecular target (antigen) by recognizing a portion of its structure (epitope) in a highly specific manner. The ability to predict epitopes from antigen sequences alone is a complex t...

  1. Spectroscopic analysis of the role of extractives on heat-induced discoloration of black locust (Robinia pseudoacacia)

    Science.gov (United States)

    Yao Chen; Yongming Fan; Jianmin Gao; Mandla A. Tshabalala; Nicole M. Stark

    2012-01-01

    To investigate the role of extractives on heat-induced discoloration of wood, samples of black locust (Robinia pseudoacacia) wood flour were extracted with various solvents prior to heat-treatment. Analysis of their color parameters and chromophoric structures showed that the chroma value of the unextracted sample decreased while that of the...

  2. Connectionist Interaction Information Retrieval.

    Science.gov (United States)

    Dominich, Sandor

    2003-01-01

    Discussion of connectionist views for adaptive clustering in information retrieval focuses on a connectionist clustering technique and activation spreading-based information retrieval model using the interaction information retrieval method. Presents theoretical as well as simulation results as regards computational complexity and includes…

  3. Rapid insight into heating-induced phase transformations in the solid state of the calcium salt of atorvastatin using multivariate data analysis

    DEFF Research Database (Denmark)

    Christensen, Niels Peter Aae; Van Eerdenbrugh, Bernard; Kwok, Kaho

    2013-01-01

    To investigate the heating-induced dehydration and melting behavior of the trihydrate phase of the calcium salt of atorvastatin.......To investigate the heating-induced dehydration and melting behavior of the trihydrate phase of the calcium salt of atorvastatin....

  4. Prediction of antigenic epitopes on protein surfaces by consensus scoring

    Directory of Open Access Journals (Sweden)

    Zhang Chi

    2009-09-01

    Full Text Available Abstract Background Prediction of antigenic epitopes on protein surfaces is important for vaccine design. Most existing epitope prediction methods focus on protein sequences to predict continuous epitopes linear in sequence. Only a few structure-based epitope prediction algorithms are available and they have not yet shown satisfying performance. Results We present a new antigen Epitope Prediction method, which uses ConsEnsus Scoring (EPCES from six different scoring functions - residue epitope propensity, conservation score, side-chain energy score, contact number, surface planarity score, and secondary structure composition. Applied to unbounded antigen structures from an independent test set, EPCES was able to predict antigenic eptitopes with 47.8% sensitivity, 69.5% specificity and an AUC value of 0.632. The performance of the method is statistically similar to other published methods. The AUC value of EPCES is slightly higher compared to the best results of existing algorithms by about 0.034. Conclusion Our work shows consensus scoring of multiple features has a better performance than any single term. The successful prediction is also due to the new score of residue epitope propensity based on atomic solvent accessibility.

  5. The kinetics of removal of heat-induced excess nuclear protein

    International Nuclear Information System (INIS)

    Roti, J.L.R.; Uygur, N.; Higashikubo, R.

    1984-01-01

    To investigate the role of protein content, temperature and heating time in the removal of heat-induced excess protein associated with the isolated nucleus, the kinetics of protein removal was monitored for 6 to 8 hours following exposure to 7 hyperthermic protocols. Four of these (47 0 C-7.5 min., 46 0 C-15 min., 45 0 C-30 min., and 44 0 C-60 min.) resulted in a nuclear protein content approximately twice that of nuclei from unheated cells (2.05 +- .14) following heat exposure. Three protocols (45 0 C-15 min., 44 0 C-30 min. and 43 0 C-60 min.) resulted in a nuclear protein content approximately 1.6 times normal (1.63 +- .12). If nuclear protein content were the only determinant in the recovery rate, then the same half time for nuclear protein removal would be expected within each group of protocols. Rate constants for nuclear protein removal were obtained by regression analysis. The half-time for nuclear protein removal increased with decreasing temperature and increasing heating time for the same nuclear protein content. This result suggests that the heating time and temperature are more of a determinant in the removal kinetics than protein content alone. Extended kinetics of recovery (to 36 hours) showed incomplete recovery and a secondary increase in protein associated with the isolated nucleus. These results were due to cell-cycle rearrangement (G/sub 2/ block) and unbalanced growth

  6. Formation of tRNA granules in the nucleus of heat-induced human cells

    International Nuclear Information System (INIS)

    Miyagawa, Ryu; Mizuno, Rie; Watanabe, Kazunori; Ijiri, Kenichi

    2012-01-01

    Highlights: ► tRNAs are tranlocated into the nucleus in heat-induced HeLa cells. ► tRNAs form the unique granules in the nucleus. ► tRNA ganules overlap with nuclear stress granules. -- Abstract: The stress response, which can trigger various physiological phenomena, is important for living organisms. For instance, a number of stress-induced granules such as P-body and stress granule have been identified. These granules are formed in the cytoplasm under stress conditions and are associated with translational inhibition and mRNA decay. In the nucleus, there is a focus named nuclear stress body (nSB) that distinguishes these structures from cytoplasmic stress granules. Many splicing factors and long non-coding RNA species localize in nSBs as a result of stress. Indeed, tRNAs respond to several kinds of stress such as heat, oxidation or starvation. Although nuclear accumulation of tRNAs occurs in starved Saccharomyces cerevisiae, this phenomenon is not found in mammalian cells. We observed that initiator tRNA Met (Meti) is actively translocated into the nucleus of human cells under heat stress. During this study, we identified unique granules of Meti that overlapped with nSBs. Similarly, elongator tRNA Met was translocated into the nucleus and formed granules during heat stress. Formation of tRNA granules is closely related to the translocation ratio. Then, all tRNAs may form the specific granules.

  7. Insights into the Molecular Events That Regulate Heat-Induced Chilling Tolerance in Citrus Fruits.

    Science.gov (United States)

    Lafuente, María T; Establés-Ortíz, Beatriz; González-Candelas, Luis

    2017-01-01

    Low non-freezing temperature may cause chilling injury (CI), which is responsible for external quality deterioration in many chilling-sensitive horticultural crops. Exposure of chilling-sensitive citrus cultivars to non-lethal high-temperature conditioning may increase their chilling tolerance. Very little information is available about the molecular events involved in such tolerance. In this work, the molecular events associated with the low temperature tolerance induced by heating Fortune mandarin, which is very sensitive to chilling, for 3 days at 37°C prior to cold storage is presented. A transcriptomic analysis reveals that heat-conditioning has an important impact favoring the repression of genes in cold-stored fruit, and that long-term heat-induced chilling tolerance is an active process that requires activation of transcription factors involved in transcription initiation and of the WRKY family. The analysis also shows that chilling favors degradation processes, which affect lipids and proteins, and that the protective effect of the heat-conditioning treatment is more likely to be related to the repression of the genes involved in lipid degradation than to the modification of fatty acids unsaturation, which affects membrane permeability. Another major factor associated with the beneficial effect of the heat treatment on reducing CI is the regulation of stress-related proteins. Many of the genes that encoded such proteins are involved in secondary metabolism and in oxidative stress-related processes.

  8. Heat-induced accumulation and futile cycling of trehalose in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Hottiger, T.; Schmutz, P.; Wiemken, A.

    1987-01-01

    Heat shock resulted in rapid accumulation of large amounts of trehalose in Saccharomyces cerevisiae. In cultures growing exponentially on glucose, the trehalose content of the cells increased from 0.01 to 1 g/g of protein within 1 h after the incubation temperature was shifted from 27 to 40 0 C. When the temperature was readjusted to 27 0 C, the accumulated trehalose was rapidly degraded. In parallel, the activity of the trehalose-phosphate synthase, the key enzyme of trehalose biosynthesis, increased about six fold during the heat shock and declined to normal level after readjustment of the temperature. Surprisingly, the activity of neutral trehalase, the key enzyme of trehalose degradation, also increased about threefold during the heat shock and remained almost constant during recovery of the cells at 27 0 C. In pulse-labeling experiments with [ 14 C] glucose, trehalose was found to be turned over rapidly in heat-shocked cells, indicating that both anabolic and catabolic enzymes of trehalose metabolism were active in vivo. Possible functions of the heat-induced accumulation of trehalose and its rapid turnover in an apparently futile cycle during heat shock are discussed

  9. Transient, heat-induced thermal resistance in the small intestine of mouse

    International Nuclear Information System (INIS)

    Hume, S.P.; Marigold, J.C.L.

    1980-01-01

    Heat-induced thermal resistance has been investigated in mouse jejunum by assaying crypt survival 24 h after treatment. Hyperthermia was achieved by immersing an exteriorized loop of intestine in a bath of Krebs-Ringer solution. Two approaches have been used. In the first, thermal survival curves were obtained following single hyperthermal treatments at temperatures in the range 42 to 44 0 C. Transient thermal resistance, inducted by a plateau in the crypt survival curve, developed during heating at temperatures around 42.5 0 C after 60 to 80 min. In the second series of experiments, a priming heat treatment (40.0, 41.0, 41.5, or 42.0 0 C for 60 min) was followed at varying intervals by a test treatment at 43.0 0 C. A transient resistance to the second treatment was induced, the extent and time of development being dependent upon the priming treatment. Crypt survival curves for thermally resistant intestine showed an increase in thermal D 0 and a decrease in n compared with curves from previously unheated intestine

  10. Heat-induced-radiolabeling and click chemistry: A powerful combination for generating multifunctional nanomaterials.

    Directory of Open Access Journals (Sweden)

    Hushan Yuan

    Full Text Available A key advantage of nanomaterials for biomedical applications is their ability to feature multiple small reporter groups (multimodality, or combinations of reporter groups and therapeutic agents (multifunctionality, while being targeted to cell surface receptors. Here a facile combination of techniques for the syntheses of multimodal, targeted nanoparticles (NPs is presented, whereby heat-induced-radiolabeling (HIR labels NPs with radiometals and so-called click chemistry is used to attach bioactive groups to the NP surface. Click-reactive alkyne or azide groups were first attached to the nonradioactive clinical Feraheme (FH NPs. Resulting "Alkyne-FH" and "Azide-FH" intermediates, like the parent NP, tolerated 89Zr labeling by the HIR method previously described. Subsequently, biomolecules were quickly conjugated to the radioactive NPs by either copper-catalyzed or copper-free click reactions with high efficiency. Synthesis of the Alkyne-FH or Azide-FH intermediates, followed by HIR and then by click reactions for biomolecule attachment, provides a simple and potentially general path for the synthesis of multimodal, multifunctional, and targeted NPs for biomedical applications.

  11. Insights into the Molecular Events That Regulate Heat-Induced Chilling Tolerance in Citrus Fruits

    Directory of Open Access Journals (Sweden)

    María T. Lafuente

    2017-06-01

    Full Text Available Low non-freezing temperature may cause chilling injury (CI, which is responsible for external quality deterioration in many chilling-sensitive horticultural crops. Exposure of chilling-sensitive citrus cultivars to non-lethal high-temperature conditioning may increase their chilling tolerance. Very little information is available about the molecular events involved in such tolerance. In this work, the molecular events associated with the low temperature tolerance induced by heating Fortune mandarin, which is very sensitive to chilling, for 3 days at 37°C prior to cold storage is presented. A transcriptomic analysis reveals that heat-conditioning has an important impact favoring the repression of genes in cold-stored fruit, and that long-term heat-induced chilling tolerance is an active process that requires activation of transcription factors involved in transcription initiation and of the WRKY family. The analysis also shows that chilling favors degradation processes, which affect lipids and proteins, and that the protective effect of the heat-conditioning treatment is more likely to be related to the repression of the genes involved in lipid degradation than to the modification of fatty acids unsaturation, which affects membrane permeability. Another major factor associated with the beneficial effect of the heat treatment on reducing CI is the regulation of stress-related proteins. Many of the genes that encoded such proteins are involved in secondary metabolism and in oxidative stress-related processes.

  12. heat-induced biological changes as heat tolerance indices related to growth performance in buffaloes

    International Nuclear Information System (INIS)

    Kaldes, M.Z.N.

    2004-01-01

    the main objective of this study was to predict new heat tolerance indices related to hot summer growth performance, depending on heat - induced changes in some physiological and biochemical parameters of young water buffalo calves. the present study was carried out on 8 egyptian male buffalo calves of 6 months old and 106.8 kg mean body weight (B W), and on the same animals of 12 months old and 179.5 kg mean B W. the animals were maintained in a climatic chamber of the egyptian atomic energy authority. the animals were maintained in metabolic cages inside a climatic chamber for 3 weeks under mild climate (20-24 c and 50-60% Rh, equivalent to 62-72 THI) for 6 hours daily as adjustment period,followed by 5 and 7 days in the 6- and 12-month old calves, respectively at the same climatic conditions as a control period.this was followed by 6 hours of acute heat exposure period (33-43 c and 40-60% Rh, equivalent to 85-93 Thi), then by chronic heat exposure period of the same climatic conditions for 5 and 7 days in the 6- and 12- month old calves, respectively.Rectal temperature (RT) and respiration rate (RR) were estimated daily, whereas BW was estimated at the beginning and the end of each exposure period

  13. Heat-induced electron emission in paraelectric phase of triglycine sulfate heated with great rate

    CERN Document Server

    Sidorkin, A A; Rogazinskaya, O V; Milovidova, S D

    2002-01-01

    One recorded experimentally heat-induced electron emission in ferroelectric triglycine sulfate (TGS) crystal within temperature range exceeding the Curie point by 10-15 K. One studied cases of q = dT/dt various rates of linear heating of specimens of TGS nominally pure crystal and TGS crystal with chromium impurity. Increase of heating rate is shown to result in increase of emission current density within the whole investigated range of temperatures. Temperature of emission occurrence depends on q rate negligibly. At the same time, temperature of emission disappearance monotonically increases with q growth. At q below 1 K/min it is localized below the Curie point. At q = 4-5 K/min the mentioned temperature reaches 60-65 deg C. In TGS crystal with chromium impurity the temperature of emission occurrence is close to the case of pure TGS. In this case, the range of emission drawing in paraphase here is by about 2 times narrower in contrast to the case of pure TGS heated with the same rate

  14. Expitope: a web server for epitope expression.

    Science.gov (United States)

    Haase, Kerstin; Raffegerst, Silke; Schendel, Dolores J; Frishman, Dmitrij

    2015-06-01

    Adoptive T cell therapies based on introduction of new T cell receptors (TCRs) into patient recipient T cells is a promising new treatment for various kinds of cancers. A major challenge, however, is the choice of target antigens. If an engineered TCR can cross-react with self-antigens in healthy tissue, the side-effects can be devastating. We present the first web server for assessing epitope sharing when designing new potential lead targets. We enable the users to find all known proteins containing their peptide of interest. The web server returns not only exact matches, but also approximate ones, allowing a number of mismatches of the users choice. For the identified candidate proteins the expression values in various healthy tissues, representing all vital human organs, are extracted from RNA Sequencing (RNA-Seq) data as well as from some cancer tissues as control. All results are returned to the user sorted by a score, which is calculated using well-established methods and tools for immunological predictions. It depends on the probability that the epitope is created by proteasomal cleavage and its affinities to the transporter associated with antigen processing and the major histocompatibility complex class I alleles. With this framework, we hope to provide a helpful tool to exclude potential cross-reactivity in the early stage of TCR selection for use in design of adoptive T cell immunotherapy. The Expitope web server can be accessed via http://webclu.bio.wzw.tum.de/expitope. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Public epitopes and the antigenic structure of the HLA molecules.

    Science.gov (United States)

    Rodey, G E; Fuller, T C

    1987-01-01

    Simplified procedures for determining amino acid sequences in proteins and nucleotide sequences in DNA have rapidly expanded the number of MHC molecules for which primary amino acid structure is known. These molecules will be especially valuable as tools to study the structure-function relationships of globular proteins because of the extensive polymorphism of genes coding the MHC genes products. The general three-dimensional structure of class I MHC molecules was recently deduced, but the more subtle topographical microconformations are still undefined. Definition and topographical mapping of epitopes, defined by serological or cellular immune effector products, will be critical probes for these three-dimensional studies. Comparative studies of amino acid sequences among various MHC and molecules have revealed distinct regions of hypervariability in the alpha-1 and -2 domains of class I heavy chains and the alpha-1 and beta-1 domains of most class II molecules. Mutant MHC molecules that differ from each other by no more than one to three amino acids can have structural changes which may result in a loss of the private epitopes that defined the allelic gene product. On the basis of these studies, the private epitopes are thought to be determined by one or more of the hypervariable regions. Similar studies of the relationships between specific regions of the molecule and public epitopes are not fully explored. Because public epitopes are partially conserved structures, one might expect that their structure is not principally determined by hypervariable region. In fact, however, some public epitopes, such as A2/B17 and BW4/Bw6, do map to diversity regions. Epitope mapping as a means of identifying specific topographic sites and relating these sites to specific functional regions of the molecule will be difficult unless the epitopes themselves are better defined. Thus, the capacity to distinguish spatially distinct public epitopes from cross-reactive homologous

  16. Design and characterization of epitope-scaffold immunogens that present the motavizumab epitope from respiratory syncytial virus.

    Science.gov (United States)

    McLellan, Jason S; Correia, Bruno E; Chen, Man; Yang, Yongping; Graham, Barney S; Schief, William R; Kwong, Peter D

    2011-06-24

    Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, but an effective vaccine has not yet been developed. An ideal vaccine would elicit protective antibodies while avoiding virus-specific T-cell responses, which have been implicated in vaccine-enhanced disease with previous RSV vaccines. We propose that heterologous proteins designed to present RSV-neutralizing antibody epitopes and to elicit cognate antibodies have the potential to fulfill these vaccine requirements, as they can be fashioned to be free of viral T-cell epitopes. Here we present the design and characterization of three epitope-scaffolds that present the epitope of motavizumab, a potent neutralizing antibody that binds to a helix-loop-helix motif in the RSV fusion glycoprotein. Two of the epitope-scaffolds could be purified, and one epitope-scaffold based on a Staphylococcus aureus protein A domain bound motavizumab with kinetic and thermodynamic properties consistent with the free epitope-scaffold being stabilized in a conformation that closely resembled the motavizumab-bound state. This epitope-scaffold was well folded as assessed by circular dichroism and isothermal titration calorimetry, and its crystal structure (determined in complex with motavizumab to 1.9 Å resolution) was similar to the computationally designed model, with all hydrogen-bond interactions critical for binding to motavizumab preserved. Immunization of mice with this epitope-scaffold failed to elicit neutralizing antibodies but did elicit sera with F binding activity. The elicitation of F binding antibodies suggests that some of the design criteria for eliciting protective antibodies without virus-specific T-cell responses are being met, but additional optimization of these novel immunogens is required. Published by Elsevier Ltd.

  17. High-throughput epitope identification for snakebite antivenom

    DEFF Research Database (Denmark)

    Engmark, Mikael; De Masi, Federico; Laustsen, Andreas Hougaard

    Insight into the epitopic recognition pattern for polyclonal antivenoms is a strong tool for accurate prediction of antivenom cross-reactivity and provides a basis for design of novel antivenoms. In this work, a high-throughput approach was applied to characterize linear epitopes in 966 individua...... toxins from pit vipers (Crotalidae) using the ICP Crotalidae antivenom. Due to an abundance of snake venom metalloproteinases and phospholipase A2s in the venoms used for production of the investigated antivenom, this study focuses on these toxin families.......Insight into the epitopic recognition pattern for polyclonal antivenoms is a strong tool for accurate prediction of antivenom cross-reactivity and provides a basis for design of novel antivenoms. In this work, a high-throughput approach was applied to characterize linear epitopes in 966 individual...

  18. An assessment on epitope prediction methods for protozoa genomes

    Directory of Open Access Journals (Sweden)

    Resende Daniela M

    2012-11-01

    Full Text Available Abstract Background Epitope prediction using computational methods represents one of the most promising approaches to vaccine development. Reduction of time, cost, and the availability of completely sequenced genomes are key points and highly motivating regarding the use of reverse vaccinology. Parasites of genus Leishmania are widely spread and they are the etiologic agents of leishmaniasis. Currently, there is no efficient vaccine against this pathogen and the drug treatment is highly toxic. The lack of sufficiently large datasets of experimentally validated parasites epitopes represents a serious limitation, especially for trypanomatids genomes. In this work we highlight the predictive performances of several algorithms that were evaluated through the development of a MySQL database built with the purpose of: a evaluating individual algorithms prediction performances and their combination for CD8+ T cell epitopes, B-cell epitopes and subcellular localization by means of AUC (Area Under Curve performance and a threshold dependent method that employs a confusion matrix; b integrating data from experimentally validated and in silico predicted epitopes; and c integrating the subcellular localization predictions and experimental data. NetCTL, NetMHC, BepiPred, BCPred12, and AAP12 algorithms were used for in silico epitope prediction and WoLF PSORT, Sigcleave and TargetP for in silico subcellular localization prediction against trypanosomatid genomes. Results A database-driven epitope prediction method was developed with built-in functions that were capable of: a removing experimental data redundancy; b parsing algorithms predictions and storage experimental validated and predict data; and c evaluating algorithm performances. Results show that a better performance is achieved when the combined prediction is considered. This is particularly true for B cell epitope predictors, where the combined prediction of AAP12 and BCPred12 reached an AUC value

  19. Heat induced fracturing of rock in an existing uniaxial stress field

    International Nuclear Information System (INIS)

    Mathis, J.; Stephansson, O.; Bjarnason, B.; Hakami, H.; Herdocia, A.; Mattila, U.; Singh, U.

    1986-01-01

    This study was initiated under the premise that it may be possible to determine the state of stress in the earth's crust by heat induced fracturing of the rock surrounding a borehole. The theory involved is superficially simple, involving the superposition of the stress field around a borehole due to the existing virgin stresses and the uniform stress field of thermally loaded rock as induced by a heater. Since the heat stress field is uniform, varying only in magnitude and gradient as a function of heater input, fracturing should be controlled by the non-uniform virgin stress field. To determine if the method was, in fact, feasible, a series of laboratory test were conducted. These tests consisted of physically loading center drilled cubes of rock, 0.3 m on a side, uniaxially from 0 to 25 MPa. The blocks were then thermally loaded with a nominally rated 3.7 kW heater until failure occurred. Results from these laboratory tests were then compared to analytical studies of the problem, i.e., finite element and discrete theoretical analysis. Overall, results were such that the method is likely eliminated as a stress measurement technique. The immediate development of a thermal compressive zone on the borehole wall overlaps the tensile zone created by the uniaxial stress field, forcing the failure is thus controlled largely by the power input of the heater, being retarded by the small compressive stresses genrated by the uniaxial stress field. This small retardation effect is of such low magnitude that the retardation effect is of such low magnitude that the fracture time is relatively insensitive to the local virgin stress field. (authors)

  20. Formation of tRNA granules in the nucleus of heat-induced human cells

    Energy Technology Data Exchange (ETDEWEB)

    Miyagawa, Ryu [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Department of Biological Science, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8654 (Japan); Mizuno, Rie [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Watanabe, Kazunori, E-mail: watanabe@ric.u-tokyo.ac.jp [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Ijiri, Kenichi [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Department of Biological Science, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8654 (Japan)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer tRNAs are tranlocated into the nucleus in heat-induced HeLa cells. Black-Right-Pointing-Pointer tRNAs form the unique granules in the nucleus. Black-Right-Pointing-Pointer tRNA ganules overlap with nuclear stress granules. -- Abstract: The stress response, which can trigger various physiological phenomena, is important for living organisms. For instance, a number of stress-induced granules such as P-body and stress granule have been identified. These granules are formed in the cytoplasm under stress conditions and are associated with translational inhibition and mRNA decay. In the nucleus, there is a focus named nuclear stress body (nSB) that distinguishes these structures from cytoplasmic stress granules. Many splicing factors and long non-coding RNA species localize in nSBs as a result of stress. Indeed, tRNAs respond to several kinds of stress such as heat, oxidation or starvation. Although nuclear accumulation of tRNAs occurs in starved Saccharomyces cerevisiae, this phenomenon is not found in mammalian cells. We observed that initiator tRNA{sup Met} (Meti) is actively translocated into the nucleus of human cells under heat stress. During this study, we identified unique granules of Meti that overlapped with nSBs. Similarly, elongator tRNA{sup Met} was translocated into the nucleus and formed granules during heat stress. Formation of tRNA granules is closely related to the translocation ratio. Then, all tRNAs may form the specific granules.

  1. Heat-induced changes to lipid molecular structure in Vimy flaxseed: Spectral intensity and molecular clustering

    Science.gov (United States)

    Yu, Peiqiang; Damiran, Daalkhaijav

    2011-06-01

    Autoclaving was used to manipulate nutrient utilization and availability. The objectives of this study were to characterize any changes of the functional groups mainly associated with lipid structure in flaxseed ( Linum usitatissimum, cv. Vimy), that occurred on a molecular level during the treatment process using infrared Fourier transform molecular spectroscopy. The parameters included lipid CH 3 asymmetric (ca. 2959 cm -1), CH 2 asymmetric (ca. 2928 cm -1), CH 3 symmetric (ca. 2871 cm -1) and CH 2 symmetric (ca. 2954 cm -1) functional groups, lipid carbonyl C dbnd O ester group (ca. 1745 cm -1), lipid unsaturation group (CH attached to C dbnd C) (ca. 3010 cm -1) as well as their ratios. Hierarchical cluster analysis (CLA) and principal components analysis (PCA) were conducted to identify molecular spectral differences. Flaxseed samples were kept raw for the control or autoclaved in batches at 120 °C for 20, 40 or 60 min for treatments 1, 2 and 3, respectively. Molecular spectral analysis of lipid functional group ratios showed a significant decrease ( P 0.05) on lipid carbonyl C dbnd O ester group and lipid unsaturation group (CH attached to C dbnd C) (with average spectral peak area intensities of 138.3 and 68.8 IR intensity units, respectively). Multivariate molecular spectral analyses, CLA and PCA, were unable to make distinctions between the different treatment original spectra at the CH 3 and CH 2 asymmetric and symmetric region (ca. 2988-2790 cm -1). The results indicated that autoclaving had an impact to the mid-infrared molecular spectrum of flaxseed to identify heat-induced changes in lipid conformation. A future study is needed to quantify the relationship between lipid molecular structure changes and functionality/availability.

  2. Pressure effects on the structure, kinetic, and thermodynamic properties of heat-induced aggregation of protein studied by FT-IR spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Taniguchi, Y [Applied Chemistry Department, Ritsumeikan University, Kusatsu, Shiga 525-8577 (Japan); Okuno, A [Research Department 3, Central Research, Bridgestone Co. Kodaira, Tokyo 187-8531 (Japan); Kato, M, E-mail: taniguti@sk.ritsumei.ac.j [Pharmaceutical Sciences Department, Ritsumeikan University, Kusatsu, Shiga 525-8577 (Japan)

    2010-03-01

    Pressure can retrain the heat-induced aggregation and dissociate the heat-induced aggregates. We observed the aggregation-preventing pressure effect and the aggregates-dissociating pressure effect to characterize the heat-induced aggregation of equine serum albumin (ESA) by FT-IR spectroscopy. The results suggest the {alpha}-helical structure collapses at the beginning of heat-induced aggregation through the swollen structure, and then the rearrangement of structure to the intermolecular {beta}-sheet takes place through partially unfolded structure. We determined the activation volume for the heat-induced aggregation ({Delta}V'' = +93 ml/mol) and the partial molar volume difference between native state and heat-induced aggregates ({Delta}V=+32 ml/mol). This positive partial molar volume difference suggests that the heat-induced aggregates have larger internal voids than the native structure. Moreover, the positive volume change implies that the formation of the intermolecular {beta}-sheet is unfavorable under high pressure.

  3. Computational elucidation of potential antigenic CTL epitopes in Ebola virus.

    Science.gov (United States)

    Dikhit, Manas R; Kumar, Santosh; Vijaymahantesh; Sahoo, Bikash R; Mansuri, Rani; Amit, Ajay; Yousuf Ansari, Md; Sahoo, Ganesh C; Bimal, Sanjiva; Das, Pradeep

    2015-12-01

    Cell-mediated immunity is important for the control of Ebola virus infection. We hypothesized that those HLA A0201 and HLA B40 restricted epitopes derived from Ebola virus proteins, would mount a good antigenic response. Here we employed an immunoinformatics approach to identify specific 9mer amino acid which may be capable of inducing a robust cell-mediated immune response in humans. We identified a set of 28 epitopes that had no homologs in humans. Specifically, the epitopes derived from NP, RdRp, GP and VP40 share population coverage of 93.40%, 84.15%, 74.94% and 77.12%, respectively. Based on the other HLA binding specificity and population coverage, seven novel promiscuous epitopes were identified. These 7 promiscuous epitopes from NP, RdRp and GP were found to have world-wide population coverage of more than 95% indicating their potential significance as useful candidates for vaccine design. Epitope conservancy analysis also suggested that most of the peptides are highly conserved (100%) in other virulent Ebola strain (Mayinga-76, Kikwit-95 and Makona-G3816- 2014) and can therefore be further investigated for their immunological relevance and usefulness as vaccine candidates. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Application of X-ray phase-contrast tomography in quantative studies of heat induced structural changes in meat

    DEFF Research Database (Denmark)

    Miklos, R.; Nielsen, M. S.; Einarsdottir, Hildur

    2013-01-01

    X-ray computed tomography is increasingly used in the studies of food structure. This paper describes the perspectives of use of phase contrast computed tomography in studies of heat induced structural changes in meat. From the data it was possible to obtain reconstructed images of the sample...... structure for visualization and qualitative studies of the sample structure. Further data segmentation allowed structural changes to be quantified....

  5. Laparoscopic specimen retrieval bags.

    Science.gov (United States)

    Smorgick, Noam

    2014-10-01

    Specimen retrieval bags have long been used in laparoscopic gynecologic surgery for contained removal of adnexal cysts and masses. More recently, the concerns regarding spread of malignant cells during mechanical morcellation of myoma have led to an additional use of specimen retrieval bags for contained "in-bag" morcellation. This review will discuss the indications for use retrieval bags in gynecologic endoscopy, and describe the different specimen bags available to date.

  6. Effects of rare sugar d-allulose on heat-induced gelation of surimi prepared from marine fish.

    Science.gov (United States)

    Ogawa, Masahiro; Inoue, Masaki; Hayakawa, Shigeru; O'Charoen, Siwaporn; Ogawa, Makiko

    2017-11-01

    d-Allulose (Alu), the C3-epimer of d-fructose, is a non-caloric sweetener (0.39 kcal g -1 ) with a suppressive effect on postprandial blood glucose elevation. The aim of this study was to investigate the effects of Alu used as a sweetener and gel improver instead of sucrose on heat-induced gelation of surimi. The puncture test of a heat-induced surimi gel showed that with 50 g kg -1 Alu the gel had 15% and 6% higher gel strength than the corresponding gel with sucrose (Suc) and with sorbitol (Sor), respectively. In addition, Alu-gel had 26% and 25% higher water-holding capacity (WHC) than Suc- and Sor-gel. Heating of myofibrillar protein with Alu, unlike Suc and Sor, facilitated the formation of both disulfide and non-disulfide crosslinks that might be associated with the mechanical properties and WHC of Alu-gel. Alu improves the mechanical properties and WHC of the heat-induced surimi gel. Furthermore, Alu is low in calories compared with Suc (4.0 kcal g -1 ) and Sor (3.0 kcal g -1 ). Thus Alu will be an alternative of Suc or Sor for developing surimi-based products with health benefits. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  7. Effect of heat-induced pain stimuli on pulse transit time and pulse wave amplitude in healthy volunteers.

    Science.gov (United States)

    van Velzen, Marit H N; Loeve, Arjo J; Kortekaas, Minke C; Niehof, Sjoerd P; Mik, Egbert G; Stolker, Robert J

    2016-01-01

    Pain is commonly assessed subjectively by interpretations of patient behaviour and/or reports from patients. When this is impossible the availability of a quantitative objective pain assessment tool based on objective physiological parameters would greatly benefit clinical practice and research beside the standard self-report tests. Vasoconstriction is one of the physiological responses to pain. The aim of this study was to investigate whether pulse transit time (PTT) and pulse wave amplitude (PWA) decrease in response to this vasoconstriction when caused by heat-induced pain. The PTT and PWA were measured in healthy volunteers, on both index fingers using photoplethysmography and electrocardiography. Each subject received 3 heat-induced pain stimuli using a Temperature-Sensory Analyzer thermode block to apply a controlled, increasing temperature from 32.0 °C to 50.0 °C to the skin. After reaching 50.0 °C, the thermode was immediately cooled down to 32.0 °C. The study population was divided into 2 groups with a time-interval between the stimuli 20s or 60s. The results showed a significant (p  Heat-induced pain causes a decrease of PTT and PWA. Consequently, it is expected that, in the future, PTT and PWA may be applied as objective indicators of pain, either beside the standard self-report test, or when self-report testing is impossible.

  8. Private information retrieval

    CERN Document Server

    Yi, Xun; Bertino, Elisa

    2013-01-01

    This book deals with Private Information Retrieval (PIR), a technique allowing a user to retrieve an element from a server in possession of a database without revealing to the server which element is retrieved. PIR has been widely applied to protect the privacy of the user in querying a service provider on the Internet. For example, by PIR, one can query a location-based service provider about the nearest car park without revealing his location to the server.The first PIR approach was introduced by Chor, Goldreich, Kushilevitz and Sudan in 1995 in a multi-server setting, where the user retriev

  9. Identification, characterization, and synthesis of peptide epitopes and a recombinant six-epitope protein for Trichomonas vaginalis serodiagnosis

    Directory of Open Access Journals (Sweden)

    Alderete JF

    2013-08-01

    Full Text Available J F Alderete, Calvin J NeaceSchool of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USAAbstract: There is a need for a rapid, accurate serodiagnostic test useful for both women and men infected by Trichomonas vaginalis, which causes the number one sexually transmitted infection (STI. Women and men exposed to T. vaginalis make serum antibody to fructose-1,6-bisphosphate aldolase (ALD, α-enolase (ENO, and glyceraldehyde-3-phosphate dehydrogenase (GAP. We identified, by epitope mapping, the common and distinct epitopes of each protein detected by the sera of women patients with trichomonosis and by the sera of men highly seropositive to the immunogenic protein α-actinin (positive control sera. We analyzed the amino acid sequences to determine the extent of identity of the epitopes of each protein with other proteins in the databanks. This approach identified epitopes unique to T. vaginalis, indicating these peptide-epitopes as possible targets for a serodiagnostic test. Individual or combinations of 15-mer peptide epitopes with low to no identity with other proteins were reactive with positive control sera from both women and men but were unreactive with negative control sera. These analyses permitted the synthesis of a recombinant His6 fusion protein of 111 amino acids with an Mr of ~13.4 kDa, which consisted of 15-mer peptides of two distinct epitopes each for ALD, ENO, and GAP. This recombinant protein was purified by affinity chromatography. This composite protein was detected by enzyme-linked immunosorbent assay (ELISA, dot blots, and immunoblots, using positive control sera from women and men. These data indicate that it is possible to identify epitopes and that either singly, in combination, or as a composite protein represent targets for a point-of-care serodiagnostic test for T. vaginalis.Keywords: diagnostics, point-of-care, targets, trichomonosis

  10. RETRIEVAL EVENTS EVALUATION

    International Nuclear Information System (INIS)

    Wilson, T.

    1999-01-01

    The purpose of this analysis is to evaluate impacts to the retrieval concept presented in the Design Analysis ''Retrieval Equipment and Strategy'' (Reference 6), from abnormal events based on Design Basis Events (DBE) and Beyond Design Basis Events (BDBE) as defined in two recent analyses: (1) DBE/Scenario Analysis for Preclosure Repository Subsurface Facilities (Reference 4); and (2) Preliminary Preclosure Design Basis Event Calculations for the Monitored Geologic Repository (Reference 5) The objective of this task is to determine what impacts the DBEs and BDBEs have on the equipment developed for retrieval. The analysis lists potential impacts and recommends changes to be analyzed in subsequent design analyses for developed equipment, or recommend where additional equipment may be needed, to allow retrieval to be performed in all DBE or BDBE situations. This analysis supports License Application design and therefore complies with the requirements of Systems Description Document input criteria comparison as presented in Section 7, Conclusions. In addition, the analysis discusses the impacts associated with not using concrete inverts in the emplacement drifts. The ''Retrieval Equipment and Strategy'' analysis was based on a concrete invert configuration in the emplacement drift. The scope of the analysis, as presented in ''Development Plan for Retrieval Events Evaluation'' (Reference 3) includes evaluation and criteria of the following: Impacts to retrieval from the emplacement drift based on DBE/BDBEs, and changes to the invert configuration for the preclosure period. Impacts to retrieval from the main drifts based on DBE/BDBEs for the preclosure period

  11. Retrieval from semantic memory.

    NARCIS (Netherlands)

    Noordman-Vonk, Wietske

    1977-01-01

    The present study has been concerned with the retrieval of semantic information. Retrieving semantic information is a fundamental process in almost any kind of cognitive behavior. The introduction presented the main experimental paradigms and results found in the literature on semantic memory as

  12. HEAT INDUCIBLE EXPRESSION OF ANTIFREEZE PROTEIN GENES FROM THE BEETLES Tenebrio molitor AND Microdera punctipennis.

    Science.gov (United States)

    Li, Jieqiong; Ma, Wenjing; Ma, Ji

    2016-01-01

    Antifreeze proteins (AFPs) play important roles in protecting poikilothermic organisms from cold damage. The expression of AFP genes (afps) is induced by low temperature. However, it is reported that heat can influence the expression of afps in the desert beetle Microdera punctipennis. To further detect whether heat also induce the expression of afps in other insects, and to determine the expression profiling of insect afps at different temperatures. The expression of antifreeze protein genes in the two beetles, Microdera punctipennis and Tenebrio molitor that have quite different living environment, under different temperatures were studied by using real-time quantitative PCR. Mild low temperatures (5~15 degree C), high temperature (38~47 degree C for M. punctipennis, or 37~42 degree C for T. molitor) and temperature difference (10~30 degree C) all stimulated strongly to the expression of AFP genes (Mpafps) in M. punctipennis which lives in the wild filed in desert. The mRNA level of Mpafps after M. punctipennis were exposed to these temperatures for 1h~5h was at least 30-fold of the control at 25 degree C. For T. molitor which is breeding in door with wheat bran all these temperatures stimulated significantly to the expression of Tmafps, while the extent and degree of the temperature stimulation on Tmafps expression were much lower than on Mpafps. After T. molitor were exposed to 5 degree C and 15 degree C for 1h~5h, the mRNA level of Tmafps was over 6-fold and 45-fold of the control at 25 degree C. High temperature (37~42 degree C) for 1h~3h treatments increased Tmafps mRNA level 4.8-fold of the control. Temperature difference of 10 degree C was effective in stimulating Tmafps expression. The expression of insect antifreeze protein genes both in M. punctipennis and T. molitor was induced by heat, suggesting that this phenomenon may be common in insects; the extent and degree of the influence differ in species that have different living conditions. The heat

  13. Tempo enhances heat-induced apoptosis by mitochondrial targeting of Bax

    International Nuclear Information System (INIS)

    Zhao, Q.-L.; Fujiwara, Y.; Kondo, T.

    2003-01-01

    A stable membrane-permeable nitroxide, Tempo, exerts an SOD-like antioxidant activity against ROS. Reportedly, Tempo inhibits ROS-induced thymocyte apoptosis, while 10 mM Tempo activates JNK1 to induce apoptosis in breast cancer cells. We have observed that nontoxic 5 mM Tempo enhances suboptimal hyperthermia (44 deg C/10 min)-induced apoptosis in U937 cells. Here we report the enhancing mechanism, focusing on activation and targeting of Bax to mitochondria and cytochrome c release. Methods: U937 cells were treated with either Tempo (5 mM, 37 deg C/10 min), heating (44 deg C/10 min), or Tempo-plus-heating, washed and incubated for various times up to 6 h, until assessing apoptosis, mitochondrial potential (ΔΨ>), and amount of superoxide by flow cytometry using Annexin V-FITC/PI, TMRM, and dihydroethidium, respectively. Bax, Bcl-2 and Bcl-XL, and cytochrome c were detected by western blotting, activated Bax was by immunoprecipitation, and ATP was by a luciferase assay. Bax targeting to and cytochrome c release from mitochorndria were also detected immunocytochemically under fluorescent microscopy. Results and Discussion: Treatment of U937 cells with 5 mM Tempo for 10 min at 37 deg C or suboptimal heating (44 deg C/ 10 min) alone did not induce apoptosis. The combined treatment with 5 mM Tempo and 44 deg C for 10 min dramatically induced ∼90% apoptosis in 6 h, as did the 44 deg C/30 min heating. During the enhanced apoptosis, cytochrome c release progressed. Although signals of Bcl-2, Bcl-XL and Bax in cell lysates were not altered, Bax was specifically activated and translocated to mitochondria after the combined treatment. Further, loss of ΔΨ>and decreases in superoxide and ATP progressed after the combined treatment, suggesting that the treatment may disturb mitochondrial electron transport. Thus, Tempo sensitizes the heat-induced apoptosis through (1) targeting of Bax to mitochondria and releasing cytochrome c, and (2) mitochondrial dysfunction

  14. HIV-1 subtype A gag variability and epitope evolution.

    Science.gov (United States)

    Abidi, Syed Hani; Kalish, Marcia L; Abbas, Farhat; Rowland-Jones, Sarah; Ali, Syed

    2014-01-01

    The aim of this study was to examine the course of time-dependent evolution of HIV-1 subtype A on a global level, especially with respect to the dynamics of immunogenic HIV gag epitopes. We used a total of 1,893 HIV-1 subtype A gag sequences representing a timeline from 1985 through 2010, and 19 different countries in Africa, Europe and Asia. The phylogenetic relationship of subtype A gag and its epidemic dynamics was analysed through a Maximum Likelihood tree and Bayesian Skyline plot, genomic variability was measured in terms of G → A substitutions and Shannon entropy, and the time-dependent evolution of HIV subtype A gag epitopes was examined. Finally, to confirm observations on globally reported HIV subtype A sequences, we analysed the gag epitope data from our Kenyan, Pakistani, and Afghan cohorts, where both cohort-specific gene epitope variability and HLA restriction profiles of gag epitopes were examined. The most recent common ancestor of the HIV subtype A epidemic was estimated to be 1956 ± 1. A period of exponential growth began about 1980 and lasted for approximately 7 years, stabilized for 15 years, declined for 2-3 years, then stabilized again from about 2004. During the course of evolution, a gradual increase in genomic variability was observed that peaked in 2005-2010. We observed that the number of point mutations and novel epitopes in gag also peaked concurrently during 2005-2010. It appears that as the HIV subtype A epidemic spread globally, changing population immunogenetic pressures may have played a role in steering immune-evolution of this subtype in new directions. This trend is apparent in the genomic variability and epitope diversity of HIV-1 subtype A gag sequences.

  15. HIV-1 subtype A gag variability and epitope evolution.

    Directory of Open Access Journals (Sweden)

    Syed Hani Abidi

    Full Text Available OBJECTIVE: The aim of this study was to examine the course of time-dependent evolution of HIV-1 subtype A on a global level, especially with respect to the dynamics of immunogenic HIV gag epitopes. METHODS: We used a total of 1,893 HIV-1 subtype A gag sequences representing a timeline from 1985 through 2010, and 19 different countries in Africa, Europe and Asia. The phylogenetic relationship of subtype A gag and its epidemic dynamics was analysed through a Maximum Likelihood tree and Bayesian Skyline plot, genomic variability was measured in terms of G → A substitutions and Shannon entropy, and the time-dependent evolution of HIV subtype A gag epitopes was examined. Finally, to confirm observations on globally reported HIV subtype A sequences, we analysed the gag epitope data from our Kenyan, Pakistani, and Afghan cohorts, where both cohort-specific gene epitope variability and HLA restriction profiles of gag epitopes were examined. RESULTS: The most recent common ancestor of the HIV subtype A epidemic was estimated to be 1956 ± 1. A period of exponential growth began about 1980 and lasted for approximately 7 years, stabilized for 15 years, declined for 2-3 years, then stabilized again from about 2004. During the course of evolution, a gradual increase in genomic variability was observed that peaked in 2005-2010. We observed that the number of point mutations and novel epitopes in gag also peaked concurrently during 2005-2010. CONCLUSION: It appears that as the HIV subtype A epidemic spread globally, changing population immunogenetic pressures may have played a role in steering immune-evolution of this subtype in new directions. This trend is apparent in the genomic variability and epitope diversity of HIV-1 subtype A gag sequences.

  16. Enterovirus 71 viral capsid protein linear epitopes: Identification and characterization

    Directory of Open Access Journals (Sweden)

    Gao Fan

    2012-01-01

    Full Text Available Abstract Background To characterize the human humoral immune response against enterovirus 71 (EV71 infection and map human epitopes on the viral capsid proteins. Methods A series of 256 peptides spanning the capsid proteins (VP1, VP2, VP3 of BJ08 strain (genomic C4 were synthesized. An indirect enzyme-linked immunosorbent assay (ELISA was carried out to detect anti-EV71 IgM and IgG in sera of infected children in acute or recovery phase. The partially overlapped peptides contained 12 amino acids and were coated in the plate as antigen (0.1 μg/μl. Sera from rabbits immunized with inactivated BJ08 virus were also used to screen the peptide panel. Results A total of 10 human anti-EV71 IgM epitopes (vp1-14 in VP1; vp2-6, 21, 40 and 50 in VP2 and vp3-10, 12, 15, 24 and 75 in VP3 were identified in acute phase sera. In contrast, only one anti-EV71 IgG epitope in VP1 (vp1-15 was identified in sera of recovery stage. Four rabbit anti-EV71 IgG epitopes (vp1-14, 31, 54 and 71 were identified and mapped to VP1. Conclusion These data suggested that human IgM epitopes were mainly mapped to VP2 and VP3 with multi-epitope responses occurred at acute infection, while the only IgG epitope located on protein VP1 was activated in recovery phase sera. The dynamic changes of humoral immune response at different stages of infection may have public health significance in evaluation of EV71 vaccine immunogenicity and the clinical application of diagnostic reagents.

  17. Confirmation of a new conserved linear epitope of Lyssavirus nucleoprotein.

    Science.gov (United States)

    Xinjun, Lv; Xuejun, Ma; Lihua, Wang; Hao, Li; Xinxin, Shen; Pengcheng, Yu; Qing, Tang; Guodong, Liang

    2012-05-01

    Bioinformatics analysis was used to predict potential epitopes of Lyssavirus nucleoprotein and highlighted some distinct differences in the quantity and localization of the epitopes disclosed by epitope analysis of monoclonal antibodies against Lyssavirus nucleoprotein. Bioinformatics analysis showed that the domain containing residues 152-164 of Lyssavirus nucleoprotein was a conserved linear epitope that had not been reported previously. Immunization of two rabbits with the corresponding synthetic peptide conjugated to the Keyhole Limpe hemocyanin (KLH) macromolecule resulted in a titer of anti-peptide antibody above 1:200,000 in rabbit sera as detected by indirect enzyme-linked immunosorbent assay (ELISA). Western blot analysis demonstrated that the anti-peptide antibody recognized denatured Lyssavirus nucleoprotein in sodium dodecylsulfonate-polyacrylate gel electrophoresis (SDS-PAGE). Affinity chromatography purification and FITC-labeling of the anti-peptide antibody in rabbit sera was performed. FITC-labeled anti-peptide antibody could recognize Lyssavirus nucleoprotein in BSR cells and canine brain tissues even at a 1:200 dilution. Residues 152-164 of Lyssavirus nucleoprotein were verified as a conserved linear epitope in Lyssavirus. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. High Throughput T Epitope Mapping and Vaccine Development

    Directory of Open Access Journals (Sweden)

    Giuseppina Li Pira

    2010-01-01

    Full Text Available Mapping of antigenic peptide sequences from proteins of relevant pathogens recognized by T helper (Th and by cytolytic T lymphocytes (CTL is crucial for vaccine development. In fact, mapping of T-cell epitopes provides useful information for the design of peptide-based vaccines and of peptide libraries to monitor specific cellular immunity in protected individuals, patients and vaccinees. Nevertheless, epitope mapping is a challenging task. In fact, large panels of overlapping peptides need to be tested with lymphocytes to identify the sequences that induce a T-cell response. Since numerous peptide panels from antigenic proteins are to be screened, lymphocytes available from human subjects are a limiting factor. To overcome this limitation, high throughput (HTP approaches based on miniaturization and automation of T-cell assays are needed. Here we consider the most recent applications of the HTP approach to T epitope mapping. The alternative or complementary use of in silico prediction and experimental epitope definition is discussed in the context of the recent literature. The currently used methods are described with special reference to the possibility of applying the HTP concept to make epitope mapping an easier procedure in terms of time, workload, reagents, cells and overall cost.

  19. Retrieval options study

    Energy Technology Data Exchange (ETDEWEB)

    1980-03-01

    This Retrieval Options Study is part of the systems analysis activities of the Office of Nuclear Waste Isolation to develop the scientific and technological bases for radioactive waste repositories in various geologic media. The study considers two waste forms, high level waste and spent fuel, and defines various classes of waste retrieval and recovery. A methodology and data base are developed which allow the relative evaluation of retrieval and recovery costs and the following technical criteria: safety; technical feasibility; ease of retrieval; probable intact retrieval time; safeguards; monitoring; criticality; and licensability. A total of 505 repository options are defined and the cost and technical criteria evaluated utilizing a combination of facts and engineering judgments. The repositories evaluated are selected combinations of the following parameters: Geologic Media (salt, granite, basalt, shale); Retrieval Time after Emplacement (5 and 25 years); Emplacement Design (nominal hole, large hole, carbon steel canister, corrosion resistant canister, backfill in hole, nominal sleeves, thick wall sleeves); Emplacement Configuration (single vertical, multiple vertical, single horizontal, multiple horizontal, vaults; Thermal Considerations; (normal design, reduced density, once-through ventilation, recirculated ventilation); Room Backfill; (none, run-of-mine, early, 5 year delay, 25 year delay, decommissioned); and Rate of Retrieval; (same as emplacement, variably slower depending on repository/canister condition).

  20. Retrieval options study

    International Nuclear Information System (INIS)

    1980-03-01

    This Retrieval Options Study is part of the systems analysis activities of the Office of Nuclear Waste Isolation to develop the scientific and technological bases for radioactive waste repositories in various geologic media. The study considers two waste forms, high level waste and spent fuel, and defines various classes of waste retrieval and recovery. A methodology and data base are developed which allow the relative evaluation of retrieval and recovery costs and the following technical criteria: safety; technical feasibility; ease of retrieval; probable intact retrieval time; safeguards; monitoring; criticality; and licensability. A total of 505 repository options are defined and the cost and technical criteria evaluated utilizing a combination of facts and engineering judgments. The repositories evaluated are selected combinations of the following parameters: Geologic Media (salt, granite, basalt, shale); Retrieval Time after Emplacement (5 and 25 years); Emplacement Design (nominal hole, large hole, carbon steel canister, corrosion resistant canister, backfill in hole, nominal sleeves, thick wall sleeves); Emplacement Configuration (single vertical, multiple vertical, single horizontal, multiple horizontal, vaults; Thermal Considerations; (normal design, reduced density, once-through ventilation, recirculated ventilation); Room Backfill; (none, run-of-mine, early, 5 year delay, 25 year delay, decommissioned); and Rate of Retrieval;

  1. Topological Aspects of Information Retrieval.

    Science.gov (United States)

    Egghe, Leo; Rousseau, Ronald

    1998-01-01

    Discusses topological aspects of theoretical information retrieval, including retrieval topology; similarity topology; pseudo-metric topology; document spaces as topological spaces; Boolean information retrieval as a subsystem of any topological system; and proofs of theorems. (LRW)

  2. Epitope Mapping of Monoclonal Antibody PMab-48 Against Dog Podoplanin.

    Science.gov (United States)

    Yamada, Shinji; Kaneko, Mika K; Itai, Shunsuke; Chang, Yao-Wen; Nakamura, Takuro; Yanaka, Miyuki; Ogasawara, Satoshi; Murata, Takeshi; Uchida, Hiroaki; Tahara, Hideaki; Harada, Hiroyuki; Kato, Yukinari

    2018-04-02

    Podoplanin (PDPN), a type I transmembrane sialoglycoprotein, is expressed on normal renal podocytes, pulmonary type I alveolar cells, and lymphatic endothelial cells. Increased expression of PDPN in cancers is associated with poor prognosis and hematogenous metastasis through interactions with C-type lectin-like receptor 2 (CLEC-2) on platelets. We previously reported a novel PMab-48 antibody, which is an anti-dog PDPN (dPDPN) monoclonal antibody (mAb) recognizing PDPN expressed in lymphatic endothelial cells. However, the binding epitope of PMab-48 is yet to be clarified. In this study, an enzyme-linked immunosorbent assay and flow cytometry were used to investigate epitopes of PMab-48. The results revealed that the critical epitope of PMab-48 comprises Asp29, Asp30, Ile31, Ile32, and Pro33 of dPDPN.

  3. Antibody specific epitope prediction-emergence of a new paradigm.

    Science.gov (United States)

    Sela-Culang, Inbal; Ofran, Yanay; Peters, Bjoern

    2015-04-01

    The development of accurate tools for predicting B-cell epitopes is important but difficult. Traditional methods have examined which regions in an antigen are likely binding sites of an antibody. However, it is becoming increasingly clear that most antigen surface residues will be able to bind one or more of the myriad of possible antibodies. In recent years, new approaches have emerged for predicting an epitope for a specific antibody, utilizing information encoded in antibody sequence or structure. Applying such antibody-specific predictions to groups of antibodies in combination with easily obtainable experimental data improves the performance of epitope predictions. We expect that further advances of such tools will be possible with the integration of immunoglobulin repertoire sequencing data. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Epitope Mapping of Monoclonal Antibody PMab-38 Against Dog Podoplanin.

    Science.gov (United States)

    Chang, Yao-Wen; Yamada, Shinji; Kaneko, Mika K; Kato, Yukinari

    2017-12-01

    Podoplanin (PDPN), a type I transmembrane sialoglycoprotein, is extensively expressed by normal lymphatic endothelial cells, renal podocytes, and pulmonary type I alveolar cells. Nevertheless, increased expression of PDPN in malignant tumors not only associates with poor prognosis but also facilitates hematogenous metastasis through interaction with C-type lectin-like receptor-2 presented on platelets, followed by PDPN-mediated platelet activation. We previously reported a novel PMab-38 antibody, an anti-dog PDPN (dPDPN) monoclonal antibody, which specifically recognizes PDPN in squamous cell carcinomas melanomas and cancer-associated fibroblasts in canine cancer tissues. However, the specific binding with the epitope of PMab-38 remains undefined. In this study, flow cytometry was utilized to investigate the epitope of PMab-38, which was determined using a series of deletion or point mutants of dPDPN. The results revealed that the critical epitope of PMab-38 is Tyr67 and Glu68 of dPDPN.

  5. Novel X-ray phase-contrast tomography method for quantitative studies of heat induced structural changes in meat

    DEFF Research Database (Denmark)

    Miklos, Rikke; Nielsen, Mikkel Schou; Einarsdottir, Hildur

    2014-01-01

    The objective of this study was to evaluate the use of X-ray phase-contrast tomography combined with 3D image segmentation to investigate the heat induced structural changes in meat. The measurements were performed at the Swiss synchrotron radiation light source using a grating interferometric...... and separated into a water phase and a gel phase formed by the sarcoplasmic proteins in the exudate. The results show that X-ray phase contrast tomography offers unique possibilities in studies both the meat structure and the different meat component such as water, fat, connective tissue and myofibrils...

  6. Neutralization epitopes on HIV pseudotyped with HTLV-I: Conservation of carbohydrate Epitopes

    DEFF Research Database (Denmark)

    Sørensen, A M; Nielsen, C; Arendrup, M

    1994-01-01

    One mechanism for expanding the cellular tropism of human immunodeficiency virus (HIV) in vitro is through formation of phenotypically mixed particles (pseudotypes) with human T lymphotropic virus type I (HTLV-I). In this study we found that pseudotypes allow penetration of HIV particles into CD4......-negative cells, previously nonsusceptible to HIV infection. The infection of CD4-negative cells with pseudotypes could be blocked with anti-HTLV-I serum but failed to be significantly inhibited with anti-HIV serum or a V3-neutralizing anti-gp120 monoclonal antibody. This may represent a possibility...... by cell-free pseudotypes in CD4-negative cells. We suggest that although viral cofactors might expand the tropism of HIV in vivo, HIV and HTLV-I seem to induce common carbohydrate neutralization epitopes....

  7. Neutralization epitopes on HIV pseudotyped with HTLV-I: conservation of carbohydrate epitopes

    DEFF Research Database (Denmark)

    Sørensen, A M; Nielsen, C; Arendrup, M

    1994-01-01

    One mechanism for expanding the cellular tropism of human immunodeficiency virus (HIV) in vitro is through formation of phenotypically mixed particles (pseudotypes) with human T lymphotropic virus type I (HTLV-I). In this study we found that pseudotypes allow penetration of HIV particles into CD4......-negative cells, previously nonsusceptible to HIV infection. The infection of CD4-negative cells with pseudotypes could be blocked with anti-HTLV-I serum but failed to be significantly inhibited with anti-HIV serum or a V3-neutralizing anti-gp120 monoclonal antibody. This may represent a possibility...... by cell-free pseudotypes in CD4-negative cells. We suggest that although viral cofactors might expand the tropism of HIV in vivo, HIV and HTLV-I seem to induce common carbohydrate neutralization epitopes....

  8. Information retrieval system

    Science.gov (United States)

    Berg, R. F.; Holcomb, J. E.; Kelroy, E. A.; Levine, D. A.; Mee, C., III

    1970-01-01

    Generalized information storage and retrieval system capable of generating and maintaining a file, gathering statistics, sorting output, and generating final reports for output is reviewed. File generation and file maintenance programs written for the system are general purpose routines.

  9. RETRIEVAL EQUIPMENT DESCRIPTIONS

    International Nuclear Information System (INIS)

    J. Steinhoff

    1997-01-01

    The objective and the scope of this document are to list and briefly describe the major mobile equipment necessary for waste package (WP) retrieval from the proposed subsurface nuclear waste repository at Yucca Mountain. Primary performance characteristics and some specialized design features of the equipment are explained and summarized in the individual subsections of this document. There are no quality assurance requirements or QA controls in this document. Retrieval under normal conditions is accomplished with the same fleet of equipment as is used for emplacement. Descriptions of equipment used for retrieval under normal conditions is found in Emplacement Equipment Descriptions, DI: BCAF00000-01717-5705-00002 (a document in progress). Equipment used for retrieval under abnormal conditions is addressed in this document and consists of the following: (1) Inclined Plane Hauler; (2) Bottom Lift Transporter; (3) Load Haul Dump (LHD) Loader; (4) Heavy Duty Forklift for Emplacement Drifts; (5) Covered Shuttle Car; (6) Multipurpose Vehicle; and (7) Scaler

  10. Foreign Body Retrieval

    Medline Plus

    Full Text Available ... object is solid or filled with fluid). In medicine, ultrasound is used to detect changes in appearance, ... Anesthesia Safety X-ray, Interventional Radiology and Nuclear Medicine Radiation Safety Videos related to Foreign Body Retrieval ...

  11. Foreign Body Retrieval

    Medline Plus

    Full Text Available ... tissues. top of page What are some common uses of the procedure? Foreign body retrieval is used ... bones also may be difficult to visualize. Additional evaluation is required when the suspected foreign body is ...

  12. Changing Information Retrieval Behaviours

    DEFF Research Database (Denmark)

    Constantiou, Ioanna D.; Lehrer, Christiane; Hess, Thomas

    2014-01-01

    on the continuance of LBS use and indicate changes in individuals' information retrieval behaviours in everyday life. In particular, the distinct value dimension of LBS in specific contexts of use changes individuals' behaviours towards accessing location-related information....

  13. Retrieve An Image

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Retrieve An Image. “A building”. “Box-shaped”. “Brown Color”. “Foreshortened view”. OR. Why not specify a similar looking picture? -- Main Motivation!

  14. Foreign Body Retrieval

    Medline Plus

    Full Text Available ... related to Foreign Body Retrieval Sponsored by Please note RadiologyInfo.org is not a medical facility. Please ... is further reviewed by committees from the American College of Radiology (ACR) and the Radiological Society of ...

  15. Foreign Body Retrieval

    Medline Plus

    Full Text Available ... tissues. top of page What are some common uses of the procedure? Foreign body retrieval is used ... community, you can search the ACR-accredited facilities database . This website does not provide cost information. The ...

  16. Prediction of residues in discontinuous B-cell epitopes using protein 3D structures

    DEFF Research Database (Denmark)

    Andersen, P.H.; Nielsen, Morten; Lund, Ole

    2006-01-01

    . We show that the new structure-based method has a better performance for predicting residues of discontinuous epitopes than methods based solely on sequence information, and that it can successfully predict epitope residues that have been identified by different techniques. DiscoTope detects 15...... experimental epitope mapping in both rational vaccine design and development of diagnostic tools, and may lead to more efficient epitope identification....

  17. Rotation Invariant Color Retrieval

    OpenAIRE

    Swapna Borde; Udhav Bhosle

    2013-01-01

    The new technique for image retrieval using the color features extracted from images based on LogHistogram is proposed. The proposed technique is compared with Global color histogram and histogram ofcorners .It has been observed that number of histogram bins used for retrieval comparison of proposedtechnique (Log Histogram)is less as compared to Global Color Histogram and Histogram of corners. Theexperimental results on a database of 792 images with 11 classes indicate that proposed method (L...

  18. File list: Oth.Gon.05.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Gon.05.Epitope_tags.AllCell mm9 TFs and others Epitope tags Gonad SRX153152,SRX...153153,SRX153151 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Gon.05.Epitope_tags.AllCell.bed ...

  19. File list: Oth.Liv.10.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: Oth.Emb.05.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.05.Epitope_tags.AllCell mm9 TFs and others Epitope tags Embryo SRX663359,SR...SRX967653,SRX139878 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.05.Epitope_tags.AllCell.bed ...

  1. File list: Oth.NoD.10.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.NoD.10.Epitope_tags.AllCell sacCer3 TFs and others Epitope tags No description ...http://dbarchive.biosciencedbc.jp/kyushu-u/sacCer3/assembled/Oth.NoD.10.Epitope_tags.AllCell.bed ...

  2. File list: Oth.CeL.50.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  3. File list: Oth.Liv.50.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  4. File list: Oth.Adl.50.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Adl.50.Epitope_tags.AllCell dm3 TFs and others Epitope tags Adult SRX181419,SRX...ttp://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Oth.Adl.50.Epitope_tags.AllCell.bed ...

  5. File list: Oth.Prs.50.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Prs.50.Epitope_tags.AllCell hg19 TFs and others Epitope tags Prostate SRX084527...,SRX084528,SRX084524 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Prs.50.Epitope_tags.AllCell.bed ...

  6. File list: Oth.Utr.05.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Utr.05.Epitope_tags.AllCell hg19 TFs and others Epitope tags Uterus SRX248763,S...,SRX735140,SRX735139,SRX210703,SRX210702,SRX095386,SRX968127 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Utr.05.Epitope_tags.AllCell.bed ...

  7. File list: Oth.Myo.50.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  8. File list: Oth.Utr.50.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: Oth.Neu.10.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Neu.10.Epitope_tags.AllCell hg19 TFs and others Epitope tags Neural SRX367452,S...RX367451 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Neu.10.Epitope_tags.AllCell.bed ...

  10. File list: Oth.NoD.10.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.NoD.10.Epitope_tags.AllCell hg19 TFs and others Epitope tags No description htt...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.NoD.10.Epitope_tags.AllCell.bed ...

  11. File list: Oth.Myo.20.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Myo.20.Epitope_tags.AllCell hg19 TFs and others Epitope tags Muscle SRX1470542,...SRX1470544 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Myo.20.Epitope_tags.AllCell.bed ...

  12. File list: Oth.NoD.50.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.NoD.50.Epitope_tags.AllCell hg19 TFs and others Epitope tags No description htt...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.NoD.50.Epitope_tags.AllCell.bed ...

  13. File list: Oth.Epd.05.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Epd.05.Epitope_tags.AllCell hg19 TFs and others Epitope tags Epidermis SRX51236...8,SRX512367,SRX718420,SRX512372,SRX512366,SRX512373,SRX807621,SRX807620 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Epd.05.Epitope_tags.AllCell.bed ...

  14. File list: Oth.Adl.20.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Adl.20.Epitope_tags.AllCell dm3 TFs and others Epitope tags Adult SRX181427,SRX...ttp://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Oth.Adl.20.Epitope_tags.AllCell.bed ...

  15. File list: Oth.YSt.50.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.YSt.50.Epitope_tags.AllCell sacCer3 TFs and others Epitope tags Yeast strain SR...3939 http://dbarchive.biosciencedbc.jp/kyushu-u/sacCer3/assembled/Oth.YSt.50.Epitope_tags.AllCell.bed ...

  16. File list: Oth.PSC.10.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.PSC.10.Epitope_tags.AllCell hg19 TFs and others Epitope tags Pluripotent stem c...ell SRX555489 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.PSC.10.Epitope_tags.AllCell.bed ...

  17. File list: Oth.Oth.10.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Oth.10.Epitope_tags.AllCell mm9 TFs and others Epitope tags Others SRX228677,SR...X228676,SRX228679,SRX228678 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Oth.10.Epitope_tags.AllCell.bed ...

  18. File list: Oth.ALL.50.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.50.Epitope_tags.AllCell mm9 TFs and others Epitope tags All cell types SRX1...995,SRX275809,SRX275811 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.ALL.50.Epitope_tags.AllCell.bed ...

  19. File list: Oth.CDV.50.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.CDV.50.Epitope_tags.AllCell hg19 TFs and others Epitope tags Cardiovascular SRX...096360,SRX096362 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.CDV.50.Epitope_tags.AllCell.bed ...

  20. File list: Oth.CDV.10.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.CDV.10.Epitope_tags.AllCell hg19 TFs and others Epitope tags Cardiovascular SRX...096360,SRX096362 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.CDV.10.Epitope_tags.AllCell.bed ...

  1. File list: Oth.Dig.10.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Dig.10.Epitope_tags.AllCell mm9 TFs and others Epitope tags Digestive tract SRX...365692 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Dig.10.Epitope_tags.AllCell.bed ...

  2. File list: Oth.NoD.20.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.NoD.20.Epitope_tags.AllCell sacCer3 TFs and others Epitope tags No description ...http://dbarchive.biosciencedbc.jp/kyushu-u/sacCer3/assembled/Oth.NoD.20.Epitope_tags.AllCell.bed ...

  3. File list: Oth.Dig.20.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Dig.20.Epitope_tags.AllCell mm9 TFs and others Epitope tags Digestive tract SRX...365692 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Dig.20.Epitope_tags.AllCell.bed ...

  4. File list: Oth.CDV.10.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.CDV.10.Epitope_tags.AllCell mm9 TFs and others Epitope tags Cardiovascular SRX1...304813 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.CDV.10.Epitope_tags.AllCell.bed ...

  5. File list: Oth.EmF.05.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.EmF.05.Epitope_tags.AllCell mm9 TFs and others Epitope tags Embryonic fibroblas...RX542102,SRX204644,SRX204643,SRX255462,SRX255460 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.EmF.05.Epitope_tags.AllCell.bed ...

  6. File list: Oth.Kid.10.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Kid.10.Epitope_tags.AllCell hg19 TFs and others Epitope tags Kidney SRX065541,S...RX644719,SRX170375,SRX644723 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Kid.10.Epitope_tags.AllCell.bed ...

  7. File list: Oth.NoD.05.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.NoD.05.Epitope_tags.AllCell hg19 TFs and others Epitope tags No description htt...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.NoD.05.Epitope_tags.AllCell.bed ...

  8. File list: Oth.EmF.50.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.EmF.50.Epitope_tags.AllCell mm9 TFs and others Epitope tags Embryonic fibroblas...RX255460,SRX204644,SRX542102,SRX204643,SRX204642 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.EmF.50.Epitope_tags.AllCell.bed ...

  9. File list: Oth.Unc.10.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Unc.10.Epitope_tags.AllCell sacCer3 TFs and others Epitope tags Unclassified ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/sacCer3/assembled/Oth.Unc.10.Epitope_tags.AllCell.bed ...

  10. File list: Oth.Liv.05.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Liv.05.Epitope_tags.AllCell hg19 TFs and others Epitope tags Liver SRX1165095,S...RX1165103,SRX1165096,SRX1165104,SRX1165100,SRX1165101,SRX1165102,SRX1165090,SRX1165091 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Liv.05.Epitope_tags.AllCell.bed ...

  11. File list: Oth.PSC.20.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.PSC.20.Epitope_tags.AllCell mm9 TFs and others Epitope tags Pluripotent stem ce...822,SRX266828,SRX352996,ERX320411,SRX204802 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.PSC.20.Epitope_tags.AllCell.bed ...

  12. File list: Oth.Brs.50.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Brs.50.Epitope_tags.AllCell hg19 TFs and others Epitope tags Breast SRX667411,S...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Brs.50.Epitope_tags.AllCell.bed ...

  13. File list: Oth.Prs.20.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Prs.20.Epitope_tags.AllCell hg19 TFs and others Epitope tags Prostate SRX084527...,SRX084528,SRX084524 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Prs.20.Epitope_tags.AllCell.bed ...

  14. File list: Oth.PSC.05.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  15. File list: Oth.Kid.50.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Kid.50.Epitope_tags.AllCell hg19 TFs and others Epitope tags Kidney SRX065541,S...RX170376,SRX065542,SRX065543 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Kid.50.Epitope_tags.AllCell.bed ...

  16. File list: Oth.Adl.05.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. File list: Oth.CeL.20.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.CeL.20.Epitope_tags.AllCell dm3 TFs and others Epitope tags Cell line SRX099638...099636 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Oth.CeL.20.Epitope_tags.AllCell.bed ...

  18. File list: Oth.Gon.10.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  19. File list: Oth.NoD.20.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: Oth.CDV.20.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.CDV.20.Epitope_tags.AllCell mm9 TFs and others Epitope tags Cardiovascular SRX1...304813 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.CDV.20.Epitope_tags.AllCell.bed ...

  1. File list: Oth.Myo.10.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Myo.10.Epitope_tags.AllCell mm9 TFs and others Epitope tags Muscle SRX039346,SR...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Myo.10.Epitope_tags.AllCell.bed ...

  2. File list: Oth.Epd.20.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  3. File list: Oth.Liv.20.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Liv.20.Epitope_tags.AllCell hg19 TFs and others Epitope tags Liver SRX1165103,S...RX1165095,SRX1165100,SRX1165101,SRX1165090,SRX1165104,SRX1165102,SRX1165096,SRX1165091 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Liv.20.Epitope_tags.AllCell.bed ...

  4. File list: Oth.CDV.50.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: Oth.Neu.20.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  6. File list: Oth.ALL.05.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.05.Epitope_tags.AllCell mm9 TFs and others Epitope tags All cell types SRX1...460,ERX320411,SRX695808 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.ALL.05.Epitope_tags.AllCell.bed ...

  7. File list: Oth.ALL.05.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.05.Epitope_tags.AllCell hg19 TFs and others Epitope tags All cell types SRX...644715,SRX555489,SRX644719,SRX527876,SRX644723 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.ALL.05.Epitope_tags.AllCell.bed ...

  8. File list: Oth.Unc.20.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: Oth.Myo.05.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Myo.05.Epitope_tags.AllCell mm9 TFs and others Epitope tags Muscle SRX039346,SR...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Myo.05.Epitope_tags.AllCell.bed ...

  10. In silico-accelerated identification of conserved and immunogenic variola/vaccinia T-cell epitopes

    DEFF Research Database (Denmark)

    Moise, Leonard; McMurry, Julie A; Buus, Søren

    2009-01-01

    Epitopes shared by the vaccinia and variola viruses underlie the protective effect of vaccinia immunization against variola infection. We set out to identify a subset of cross-reactive epitopes using bioinformatics and immunological methods. Putative T-cell epitopes were computationally predicted...

  11. Identification and characterization of survivin-derived H-2Kb-restricted CTL epitopes

    DEFF Research Database (Denmark)

    Hofmann, Uta B; Voigt, Heike; Andersen, Mads H

    2009-01-01

    for potential binding K(b)-restricted octamer peptide epitopes. Two epitopes, which bind strongly to K(b), were selected to test their immunogenicity in vivo. Spleen cells from mice vaccinated by intradermal injection of mature DC pulsed with these peptides displayed reactivity to the respective epitopes...

  12. Alterations in the nuclear matrix protein mass correlate with heat-induced inhibition of DNA single-strand-break repair

    International Nuclear Information System (INIS)

    Warters, R.L.; Brizgys, L.M.; Lyons, B.W.

    1987-01-01

    The total protein mass co-isolating with the nuclear matrix or nucleoid from Chinese hamster ovary (CHO) cells was observed to increase in heated cells as a function of increasing exposure temperature between 43 0 C and 45 0 C or of exposure time at any temperature. The sedimentation distance of the CHO cell nucleoid in sucrose gradients increased with increasing exposure time at 45 0 C. Both these nuclear alterations correlated in a log-linear manner with heat-induced inhibition of DNA strand break repair. A two-fold threshold increase in nuclear matrix protein mass preceded any substantial inhibition of repair of DNA single-strand breaks. When preheated cells were incubated at 37 0 C the nuclear matrix protein mass and nucleoid sedimentation recovered with a half-time of about 5 h, while DNA single-strand-break repair recovered with a half-time of about 2 h. When preheated cells were placed at 41 0 C a further increase was observed in the nuclear matrix protein mass and the half-time of DNA strand break repair, while nucleoid sedimentation recovered toward control values. These results implicate alterations in the protein mass of the nuclear matrix in heat-induced inhibition of repair of DNA single-strand breaks. (author)

  13. Robust heat-inducible gene expression by two endogenous hsp70-derived promoters in transgenic Aedes aegypti

    Science.gov (United States)

    Carpenetti, Tiffany L. G.; Aryan, Azadeh; Myles, Kevin M.; Adelman, Zach N.

    2011-01-01

    Aedes aegypti is an important vector of the viruses that cause dengue fever, dengue hemorrhagic fever, and yellow fever. Reverse genetic approaches to the study of gene function in this mosquito have been limited by the lack of a robust inducible promoter to allow precise temporal control over a protein-encoding or hairpin RNA transgene. Likewise, investigations into the molecular and biochemical basis of vector competence would benefit from the ability to activate an anti-pathogen molecule at specific times during infection. We have characterized the ability of genomic sequences derived from two Ae. aegypti hsp70 genes to drive heat-inducible expression of a reporter in both transient and germline transformation contexts. AaHsp70-luciferase transcripts accumulated specifically after heat shock, and displayed a pattern of rapid induction and decay similar to endogenous AaHsp70 genes. Luciferase expression in transgenic Ae. aegypti increased by ∼25-50 fold in whole adults by four hours after heat-shock, with significant activity (∼20 fold) remaining at 24 hr. Heat-induced expression was even more dramatic in midgut tissues, with one strain showing a ∼2500-fold increase in luciferase activity. The AaHsp70 promoters described could be valuable for gene function studies as well as for the precise timing of the expression of anti-pathogen molecules. PMID:22142225

  14. Effect of a Traditional Herbal Prescription, Kyung-Ok-Ko, on Male Mouse Spermatogenic Ability after Heat-Induced Damage

    Directory of Open Access Journals (Sweden)

    Deok-Sang Hwang

    2015-01-01

    Full Text Available Kyung-Ok-Ko (KOK, a well-known traditional Korean medicinal formula, has long been used to invigorate the essential qi. This use of KOK may be associated with reproductive ability as a more modern concept. The protective effect of KOK was evaluated against deterioration of testicular function induced by heat exposure in male mice. Male fertility was disrupted by scrotal heat stress at 43°C for 5 weeks. KOK (0.25, 0.50, and 2.00 g/kg/day was administered orally at 3 h after the stress. To evaluate the protective effect of KOK, body weight, testicular weight, sperm count, sperm motility, and histopathological changes in the testes were evaluated. KOK-treated mice significantly recovered their general health, as evidenced by body weight. KOK-treated mice also showed significantly higher testes weights, sperm counts, and sperm motility than did the heat stress group. KOK-treated mice significantly recovered the morphological appearance of the seminiferous tubules and seminiferous epithelium. Furthermore, KOK-treated mice significantly increased antioxidant enzyme activities and reduced the protein expressions of apoptosis in the testes. KOK significantly protects against heat-induced damage to testicular function in male mice by inhibiting oxidative stress and apoptosis, indicating that KOK may be an effective agent for treatment of heat-induced male infertility.

  15. Comparative characteristic of the methods of protein antigens epitope mapping

    Directory of Open Access Journals (Sweden)

    O. Yu. Galkin

    2014-08-01

    Full Text Available Comparative analysis of experimental methods of epitope mapping of protein antigens has been carried out. The vast majority of known techniques are involved in immunochemical study of the interaction of protein molecules or peptides with antibodies of corresponding specifici­ty. The most effective and widely applicable metho­dological techniques are those that use synthetic and genetically engineered peptides. Over the past 30 years, these groups of methods have travelled a notable evolutionary path up to the maximum automation and the detection of antigenic determinants of various types (linear and conformational epitopes, and mimotopes. Most of epitope searching algorithms were integrated into a computer program, which greatly facilitates the analysis of experimental data and makes it possible to create spatial models. It is possible to use comparative epitope mapping for solving the applied problems; this less time-consuming method is based on the analysis of competition between different antibodies interactions with the same antigen. The physical method of antigenic structure study is X-ray analysis of antigen-antibody complexes, which may be applied only to crystallizing­ proteins, and nuclear magnetic resonance.

  16. High-throughput epitope profiling of snake venom toxins

    DEFF Research Database (Denmark)

    Engmark, Mikael; Andersen, Mikael Rørdam; Laustsen, Andreas Hougaard

    Insight into the molecular details of polyclonal antivenom antibody specificity is a prerequisite for accurate prediction of cross-reactivity and can provide a basis for design of novel antivenoms. In this work, a highthroughput approach was applied to characterize linear elements in epitopes in ...... toxins from four African mamba and three neurotoxic cobra snakes obtained from public databases....

  17. Bioinformatics Analysis of Envelope Glycoprotein E epitopes of ...

    African Journals Online (AJOL)

    The E glycoprotein of dengue virus is responsible for the viral binding to the receptor. The crystal structure of envelope glycoprotein has already been determined. However, where the well-defined Bcell and T-cell epitopes are located is still a question. Because of the large variations among the four dengue genotypes, it is ...

  18. Indirect recognition of HLA epitopes in solid organ transplantation

    NARCIS (Netherlands)

    Geneugelijk, C.C.A.

    2017-01-01

    Alloreactivity due to HLA mismatches between donor and recipient remains the major limiting factor in successful graft outcome after solid organ transplantation. However, the immunogenicity of individual HLA mismatches is highly variable. Therefore, epitope-based HLA matching may be a sophisticated

  19. Catalase epitopes vaccine design for Helicobacter pylori : A ...

    African Journals Online (AJOL)

    Catalase, an important enzyme in the virulence of H. pylori, could be a suitable candidate for vaccine design because it is highly conserved, which is important for the survival of H. pylori; it is expressed in high level and it is exposed on the surface of the bacteria. In this study, we designed epitope-based vaccine for catalase ...

  20. Mast Cells Produce a Unique Chondroitin Sulfate Epitope.

    Science.gov (United States)

    Farrugia, Brooke L; Whitelock, John M; O'Grady, Robert; Caterson, Bruce; Lord, Megan S

    2016-02-01

    The granules of mast cells contain a myriad of mediators that are stored and protected by the sulfated glycosaminoglycan (GAG) chains that decorate proteoglycans. Whereas heparin is the GAG predominantly associated with mast cells, mast cell proteoglycans are also decorated with heparan sulfate and chondroitin sulfate (CS). This study investigated a unique CS structure produced by mast cells that was detected with the antibody clone 2B6 in the absence of chondroitinase ABC digestion. Mast cells in rodent tissue sections were characterized using toluidine blue, Leder stain and the presence of mast cell tryptase. The novel CS epitope was identified in rodent tissue sections and localized to cells that were morphologically similar to cells chemically identified as mast cells. The rodent mast cell-like line RBL-2H3 was also shown to express the novel CS epitope. This epitope co-localized with multiple CS proteoglycans in both rodent tissue and RBL-2H3 cultured cells. These findings suggest that the novel CS epitope that decorates mast cell proteoglycans may play a role in the way these chains are structured in mast cells. © 2016 The Histochemical Society.

  1. Conformational Occlusion of Blockade Antibody Epitopes, a Novel Mechanism of GII.4 Human Norovirus Immune Evasion.

    Science.gov (United States)

    Lindesmith, Lisa C; Mallory, Michael L; Debbink, Kari; Donaldson, Eric F; Brewer-Jensen, Paul D; Swann, Excel W; Sheahan, Timothy P; Graham, Rachel L; Beltramello, Martina; Corti, Davide; Lanzavecchia, Antonio; Baric, Ralph S

    2018-01-01

    Extensive antigenic diversity within the GII.4 genotype of human norovirus is a major driver of pandemic emergence and a significant obstacle to development of cross-protective immunity after natural infection and vaccination. However, human and mouse monoclonal antibody studies indicate that, although rare, antibodies to conserved GII.4 blockade epitopes are generated. The mechanisms by which these epitopes evade immune surveillance are uncertain. Here, we developed a new approach for identifying conserved GII.4 norovirus epitopes. Utilizing a unique set of virus-like particles (VLPs) representing the in vivo -evolved sequence diversity within an immunocompromised person, we identify key residues within epitope F, a conserved GII.4 blockade antibody epitope. The residues critical for antibody binding are proximal to evolving blockade epitope E. Like epitope F, antibody blockade of epitope E was temperature sensitive, indicating that particle conformation regulates antibody access not only to the conserved GII.4 blockade epitope F but also to the evolving epitope E. These data highlight novel GII.4 mechanisms to protect blockade antibody epitopes, map essential residues of a GII.4 conserved epitope, and expand our understanding of how viral particle dynamics may drive antigenicity and antibody-mediated protection by effectively shielding blockade epitopes. Our data support the notion that GII.4 particle breathing may well represent a major mechanism of humoral immune evasion supporting cyclic pandemic virus persistence and spread in human populations. IMPORTANCE In this study, we use norovirus virus-like particles to identify key residues of a conserved GII.4 blockade antibody epitope. Further, we identify an additional GII.4 blockade antibody epitope to be occluded, with antibody access governed by temperature and particle dynamics. These findings provide additional support for particle conformation-based presentation of binding residues mediated by a particle

  2. Plasticity and Epitope Exposure of the HIV-1 Envelope Trimer.

    Science.gov (United States)

    Powell, Rebecca L R; Totrov, Maxim; Itri, Vincenza; Liu, Xiaomei; Fox, Alisa; Zolla-Pazner, Susan

    2017-09-01

    We recently showed that mutations in the HIV-1 envelope (Env) destabilize the V3 loop, rendering neutralization-resistant viruses sensitive to V3-directed monoclonal antibodies (MAbs). Here, we investigated the propagation of this effect on other Env epitopes, with special emphasis on V2 loop exposure. Wild-type JR-FL and 19 mutant JR-FL pseudoviruses were tested for neutralization sensitivity to 21 MAbs specific for epitopes in V2, the CD4 binding site (CD4bs), and the CD4-induced (CD4i) region. Certain glycan mutants, mutations in the gp120 hydrophobic core, and mutations in residues involved in intraprotomer interactions exposed epitopes in the V2i region (which overlies the α4β7 integrin binding site) and the V3 crown, suggesting general destabilization of the distal region of the trimer apex. In contrast, other glycan mutants, mutations affecting interprotomer interactions, and mutations affecting the CD4bs exposed V3 but not V2i epitopes. These data indicate for the first time that V3 can move independently of V2, with V3 pivoting out from its "tucked" position in the trimer while apparently leaving the V2 apex intact. Notably, none of the mutations exposed V2 epitopes without also exposing V3, suggesting that movement of V2 releases V3. Most mutations increased sensitivity to CD4bs-directed MAbs without exposure of the CD4i epitope, implying these mutations facilitate the trimers' maintenance of an intermediate energy state between open and closed conformations. Taken together, these data indicate that several transient Env epitopes can be rendered more accessible to antibodies (Abs) via specific mutations, and this may facilitate the design of V1V2-targeting immunogens. IMPORTANCE Many epitopes of the HIV envelope (Env) spike are relatively inaccessible to antibodies (Abs) compared to their exposure in the open Env conformation induced by receptor binding. However, the reduced infection rate that resulted from the vaccine used in the RV144 HIV-1 vaccine

  3. Localization of functional receptor epitopes on the structure of ciliary neurotrophic factor indicates a conserved, function-related epitope topography among helical cytokines.

    Science.gov (United States)

    Panayotatos, N; Radziejewska, E; Acheson, A; Somogyi, R; Thadani, A; Hendrickson, W A; McDonald, N Q

    1995-06-09

    By rational mutagenesis, receptor-specific functional analysis, and visualization of complex formation in solution, we identified individual amino acid side chains involved specifically in the interaction of ciliary neurotrophic factor (CNTF) with CNTFR alpha and not with the beta-components, gp130 and LIFR. In the crystal structure, the side chains of these residues, which are located in helix A, the AB loop, helix B, and helix D, are surface accessible and are clustered in space, thus constituting an epitope for CNTFR alpha. By the same analysis, a partial epitope for gp130 was also identified on the surface of helix A that faces away from the alpha-epitope. Superposition of the CNTF and growth hormone structures showed that the location of these epitopes on CNTF is analogous to the location of the first and second receptor epitopes on the surface of growth hormone. Further comparison with proposed binding sites for alpha- and beta-receptors on interleukin-6 and leukemia inhibitory factor indicated that this epitope topology is conserved among helical cytokines. In each case, epitope I is utilized by the specificity-conferring component, whereas epitopes II and III are used by accessory components. Thus, in addition to a common fold, helical cytokines share a conserved order of receptor epitopes that is function related.

  4. Structure retrieval in HREM

    International Nuclear Information System (INIS)

    Gribelyuk, M.A.

    1991-01-01

    A new iteration method for direct structure retrieval starting from the exit plane-wave function Ψ e (r) is proposed and tested on models. The imaginary part of the potential cannot be retrieved. The effects of the limited resolution of Ψ e (r) as well as neglect of high-order Laue-zone effects and the choice of the starting potential on the result are discussed. The procedure is found to be preferable to that based on the subsequent approximation method with respect to a higher convergence rate. It is shown that an error as low as 10% may be obtained for the real part of the retrieved potential up to vertical strokeσV(r)tvertical stroke<5. (orig.)

  5. Interactive Information Retrieval

    DEFF Research Database (Denmark)

    Borlund, Pia

    2013-01-01

    The paper introduces the research area of interactive information retrieval (IIR) from a historical point of view. Further, the focus here is on evaluation, because much research in IR deals with IR evaluation methodology due to the core research interest in IR performance, system interaction...... and satisfaction with retrieved information. In order to position IIR evaluation, the Cranfield model and the series of tests that led to the Cranfield model are outlined. Three iconic user-oriented studies and projects that all have contributed to how IIR is perceived and understood today are presented......: The MEDLARS test, the Book House fiction retrieval system, and the OKAPI project. On this basis the call for alternative IIR evaluation approaches motivated by the three revolutions (the cognitive, the relevance, and the interactive revolutions) put forward by Robertson & Hancock-Beaulieu (1992) is presented...

  6. Synthetic B-Cell Epitopes Eliciting Cross-Neutralizing Antibodies: Strategies for Future Dengue Vaccine.

    Directory of Open Access Journals (Sweden)

    Babu Ramanathan

    Full Text Available Dengue virus (DENV is a major public health threat worldwide. A key element in protection from dengue fever is the neutralising antibody response. Anti-dengue IgG purified from DENV-2 infected human sera showed reactivity against several peptides when evaluated by ELISA and epitope extraction techniques. A multi-step computational approach predicted six antigenic regions within the E protein of DENV-2 that concur with the 6 epitopes identified by the combined ELISA and epitope extraction approach. The selected peptides representing B-cell epitopes were attached to a known dengue T-helper epitope and evaluated for their vaccine potency. Immunization of mice revealed two novel synthetic vaccine constructs that elicited good humoral immune responses and produced cross-reactive neutralising antibodies against DENV-1, 2 and 3. The findings indicate new directions for epitope mapping and contribute towards the future development of multi-epitope based synthetic peptide vaccine.

  7. Introduction to information retrieval

    CERN Document Server

    Manning, Christopher D; Schütze, Hinrich

    2008-01-01

    Class-tested and coherent, this textbook teaches classical and web information retrieval, including web search and the related areas of text classification and text clustering from basic concepts. It gives an up-to-date treatment of all aspects of the design and implementation of systems for gathering, indexing, and searching documents; methods for evaluating systems; and an introduction to the use of machine learning methods on text collections. All the important ideas are explained using examples and figures, making it perfect for introductory courses in information retrieval for advanced un

  8. Information Retrieval Evaluation

    CERN Document Server

    Harman, Donna

    2011-01-01

    Evaluation has always played a major role in information retrieval, with the early pioneers such as Cyril Cleverdon and Gerard Salton laying the foundations for most of the evaluation methodologies in use today. The retrieval community has been extremely fortunate to have such a well-grounded evaluation paradigm during a period when most of the human language technologies were just developing. This lecture has the goal of explaining where these evaluation methodologies came from and how they have continued to adapt to the vastly changed environment in the search engine world today. The lecture

  9. Development of retrievability plans

    International Nuclear Information System (INIS)

    Richardson, P.J.

    1999-03-01

    It has become clear, from monitoring of many national programmes for siting of final repositories for radioactive waste disposal, that the potential or otherwise for retrievability of emplaced wastes is the one issue in particular which is repeatedly raised during public consultation and interaction. Although even those repositories which may be constructed over the next decades will operate for many decades more and be sealed only after a long-term monitoring phase, there is little operational pressure to finalise retrievability concepts. However, as siting processes require detailed conceptual designs to be developed, as do the associated safety assessment exercises, it is becoming increasingly recognised that the potential for retrieval must be examined now. This report is the culmination of a short project carried out for the Swedish National Co-ordinator for Nuclear Waste Disposal to examine the situation as regards the development and possible implementation of retrievability as an integral part of a disposal concept for nuclear waste. Because of the short work period involved, it can at best be only an overview, designed to provide a broad picture of current plans. The Swedish Nuclear Power Inspectorate has begun to examine the issue, and a report is due later in 1999. A major collaborative investigation, which began in March 1998, is also currently underway under the auspices of the EU, but only involves implementing agencies from the various Member States. This report is intended to serve as background to these other studies when they appear. Utilising currently available information, as well as personal contacts, those countries currently examining retrievability or reversibility of disposal in some form have been identified. Information regarding these proposals has been collated, and contact made with relevant agencies and national regulatory bodies where possible. The report includes some review of the technical aspects of retrievability, with especial

  10. Epitope diversification driven by non-tumor epitope-specific Th1 and Th17 mediates potent antitumor reactivity.

    Science.gov (United States)

    Ichikawa, Kosuke; Kagamu, Hiroshi; Koyama, Kenichi; Miyabayashi, Takao; Koshio, Jun; Miura, Satoru; Watanabe, Satoshi; Yoshizawa, Hirohisa; Narita, Ichiei

    2012-09-21

    MHC class I-restricted peptide-based vaccination therapies have been conducted to treat cancer patients, because CD8⁺ CTL can efficiently induce apoptosis of tumor cells in an MHC class I-restricted epitope-specific manner. Interestingly, clinical responders are known to demonstrate reactivity to epitopes other than those used for vaccination; however, the mechanism underlying how antitumor T cells with diverse specificity are induced is unclear. In this study, we demonstrated that dendritic cells (DCs) that engulfed apoptotic tumor cells in the presence of non-tumor MHC class II-restricted epitope peptides, OVA(323-339), efficiently presented tumor-associated antigens upon effector-dominant CD4⁺ T cell balance against regulatory T cells (Treg) for the OVA(323-339) epitope. Th1 and Th17 induced tumor-associated antigens presentation of DC, while Th2 ameliorated tumor-antigen presentation for CD8⁺ T cells. Blocking experiments with anti-IL-23p19 antibody and anti-IL-23 receptor indicated that an autocrine mechanism of IL-23 likely mediated the diverted tumor-associated antigens presentation of DC. Tumor-associated antigens presentation of DC induced by OVA(323-339) epitope-specific CD4⁺ T cells resulted in facilitated antitumor immunity in both priming and effector phase in vivo. Notably, this immunotherapy did not require pretreatment to reduce Treg induced by tumor. This strategy may have clinical implications for designing effective antitumor immunotherapies. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Levels of HIV1 gp120 3D B-cell epitopes mutability and variability: searching for possible vaccine epitopes.

    Science.gov (United States)

    Khrustalev, Vladislav Victorovich

    2010-01-01

    We used a DiscoTope 1.2 (http://www.cbs.dtu.dk/services/DiscoTope/), Epitopia (http://epitopia.tau.ac.il/) and EPCES (http://www.t38.physik.tu-muenchen.de/programs.htm) algorithms to map discontinuous B-cell epitopes in HIV1 gp120. The most mutable nucleotides in HIV genes are guanine (because of G to A hypermutagenesis) and cytosine (because of C to U and C to A mutations). The higher is the level of guanine and cytosine usage in third (neutral) codon positions and the lower is their level in first and second codon positions of the coding region, the more stable should be an epitope encoded by this region. We compared guanine and cytosine usage in regions coding for five predicted 3D B-cell epitopes of gp120. To make this comparison we used GenBank resource: 385 sequences of env gene obtained from ten HIV1-infected individuals were studied (http://www.barkovsky.hotmail.ru/Data/Seqgp120.htm). The most protected from nonsynonymous nucleotide mutations of guanine and cytosine 3D B-cell epitope is situated in the first conserved region of gp120 (it is mapped from 66th to 86th amino acid residue). We applied a test of variability to confirm this finding. Indeed, the less mutable predicted B-cell epitope is the less variable one. MEGA4 (standard PAM matrix) was used for the alignments and "VVK Consensus" algorithm (http://www.barkovsky.hotmail.ru) was used for the calculations.

  12. Tunable electron heating induced giant magnetoresistance in the high mobility GaAs/AlGaAs 2D electron system.

    Science.gov (United States)

    Wang, Zhuo; Samaraweera, R L; Reichl, C; Wegscheider, W; Mani, R G

    2016-12-07

    Electron-heating induced by a tunable, supplementary dc-current (I dc ) helps to vary the observed magnetoresistance in the high mobility GaAs/AlGaAs 2D electron system. The magnetoresistance at B = 0.3 T is shown to progressively change from positive to negative with increasing I dc , yielding negative giant-magnetoresistance at the lowest temperature and highest I dc . A two-term Drude model successfully fits the data at all I dc and T. The results indicate that carrier heating modifies a conductivity correction σ 1 , which undergoes sign reversal from positive to negative with increasing I dc , and this is responsible for the observed crossover from positive- to negative- magnetoresistance, respectively, at the highest B.

  13. Development of linear projecting in studies of non-linear flow. Acoustic heating induced by non-periodic sound

    Energy Technology Data Exchange (ETDEWEB)

    Perelomova, Anna [Gdansk University of Technology, Faculty of Applied Physics and Mathematics, ul. Narutowicza 11/12, 80-952 Gdansk (Poland)]. E-mail: anpe@mif.pg.gda.pl

    2006-08-28

    The equation of energy balance is subdivided into two dynamics equations, one describing evolution of the dominative sound, and the second one responsible for acoustic heating. The first one is the famous KZK equation, and the second one is a novel equation governing acoustic heating. The novel dynamic equation considers both periodic and non-periodic sound. Quasi-plane geometry of flow is supposed. Subdividing is provided on the base of specific links of every mode. Media with arbitrary thermic T(p,{rho}) and caloric e(p,{rho}) equations of state are considered. Individual roles of thermal conductivity and viscosity in the heating induced by aperiodic sound in the ideal gases and media different from ideal gases are discussed.

  14. Development of linear projecting in studies of non-linear flow. Acoustic heating induced by non-periodic sound

    Science.gov (United States)

    Perelomova, Anna

    2006-08-01

    The equation of energy balance is subdivided into two dynamics equations, one describing evolution of the dominative sound, and the second one responsible for acoustic heating. The first one is the famous KZK equation, and the second one is a novel equation governing acoustic heating. The novel dynamic equation considers both periodic and non-periodic sound. Quasi-plane geometry of flow is supposed. Subdividing is provided on the base of specific links of every mode. Media with arbitrary thermic T(p,ρ) and caloric e(p,ρ) equations of state are considered. Individual roles of thermal conductivity and viscosity in the heating induced by aperiodic sound in the ideal gases and media different from ideal gases are discussed.

  15. Development of linear projecting in studies of non-linear flow. Acoustic heating induced by non-periodic sound

    International Nuclear Information System (INIS)

    Perelomova, Anna

    2006-01-01

    The equation of energy balance is subdivided into two dynamics equations, one describing evolution of the dominative sound, and the second one responsible for acoustic heating. The first one is the famous KZK equation, and the second one is a novel equation governing acoustic heating. The novel dynamic equation considers both periodic and non-periodic sound. Quasi-plane geometry of flow is supposed. Subdividing is provided on the base of specific links of every mode. Media with arbitrary thermic T(p,ρ) and caloric e(p,ρ) equations of state are considered. Individual roles of thermal conductivity and viscosity in the heating induced by aperiodic sound in the ideal gases and media different from ideal gases are discussed

  16. Foreign Body Retrieval

    Medline Plus

    Full Text Available Toggle navigation Test/Treatment Patient Type Screening/Wellness Disease/Condition Safety En Español More Info Images/Videos About Us News Physician Resources Professions Site Index A-Z Foreign Body Retrieval Foreign ...

  17. Information Retrieval Models

    NARCIS (Netherlands)

    Hiemstra, Djoerd; Göker, Ayse; Davies, John

    2009-01-01

    Many applications that handle information on the internet would be completely inadequate without the support of information retrieval technology. How would we find information on the world wide web if there were no web search engines? How would we manage our email without spam filtering? Much of the

  18. Energy Storage and Retrieval

    Indian Academy of Sciences (India)

    Annual Meetings · Mid Year Meetings · Discussion Meetings · Public Lectures · Lecture Workshops · Refresher Courses · Symposia · Live Streaming. Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 6. Energy Storage and Retrieval The Secondary Battery Route. A K Shukla P Vishnu Kamath.

  19. Foreign Body Retrieval

    Medline Plus

    Full Text Available ... Foreign Body Retrieval Sponsored by Please note RadiologyInfo.org is not a medical facility. Please contact your ... links: For the convenience of our users, RadiologyInfo .org provides links to relevant websites. RadiologyInfo.org , ACR ...

  20. Utah Text Retrieval Project

    Energy Technology Data Exchange (ETDEWEB)

    Hollaar, L A

    1983-10-01

    The Utah Text Retrieval project seeks well-engineered solutions to the implementation of large, inexpensive, rapid text information retrieval systems. The project has three major components. Perhaps the best known is the work on the specialized processors, particularly search engines, necessary to achieve the desired performance and cost. The other two concern the user interface to the system and the system's internal structure. The work on user interface development is not only concentrating on the syntax and semantics of the query language, but also on the overall environment the system presents to the user. Environmental enhancements include convenient ways to browse through retrieved documents, access to other information retrieval systems through gateways supporting a common command interface, and interfaces to word processing systems. The system's internal structure is based on a high-level data communications protocol linking the user interface, index processor, search processor, and other system modules. This allows them to be easily distributed in a multi- or specialized-processor configuration. It also allows new modules, such as a knowledge-based query reformulator, to be added. 15 references.

  1. The Knowledge Retrieval Matrix

    DEFF Research Database (Denmark)

    Gammelgaard, Jens; Ritter, Thomas

    2004-01-01

    AbstractPrevious discussions of knowledge transfer within multinational corporations tended tofocus on the process as an isolated phenomenon and on the factors that impede the process.Less attention has been given to how the individual knowledge worker retrieves or identifies,and then decodes kno...

  2. Music Information Retrieval.

    Science.gov (United States)

    Downie, J. Stephen

    2003-01-01

    Identifies MIR (Music Information Retrieval) computer system problems, historic influences, current state-of-the-art, and future MIR solutions through an examination of the multidisciplinary approach to MIR. Highlights include pitch; temporal factors; harmonics; tone; editorial, textual, and bibliographic facets; multicultural factors; locating…

  3. Information Retrieval in Physics.

    Science.gov (United States)

    Herschman, Arthur

    Discussed in this paper are the information problems in physics and the current program of the American Institute of Physics (AIP) being conducted in an attempt to develop an information retrieval system. The seriousness of the need is described by means of graphs indicating the exponential rise in the number of physics publications in the last…

  4. Distortion of genetically modified organism quantification in processed foods: influence of particle size compositions and heat-induced DNA degradation.

    Science.gov (United States)

    Moreano, Francisco; Busch, Ulrich; Engel, Karl-Heinz

    2005-12-28

    Milling fractions from conventional and transgenic corn were prepared at laboratory scale and used to study the influence of sample composition and heat-induced DNA degradation on the relative quantification of genetically modified organisms (GMO) in food products. Particle size distributions of the obtained fractions (coarse grits, regular grits, meal, and flour) were characterized using a laser diffraction system. The application of two DNA isolation protocols revealed a strong correlation between the degree of comminution of the milling fractions and the DNA yield in the extracts. Mixtures of milling fractions from conventional and transgenic material (1%) were prepared and analyzed via real-time polymerase chain reaction. Accurate quantification of the adjusted GMO content was only possible in mixtures containing conventional and transgenic material in the form of analogous milling fractions, whereas mixtures of fractions exhibiting different particle size distributions delivered significantly over- and underestimated GMO contents depending on their compositions. The process of heat-induced nucleic acid degradation was followed by applying two established quantitative assays showing differences between the lengths of the recombinant and reference target sequences (A, deltal(A) = -25 bp; B, deltal(B) = +16 bp; values related to the amplicon length of the reference gene). Data obtained by the application of method A resulted in underestimated recoveries of GMO contents in the samples of heat-treated products, reflecting the favored degradation of the longer target sequence used for the detection of the transgene. In contrast, data yielded by the application of method B resulted in increasingly overestimated recoveries of GMO contents. The results show how commonly used food technological processes may lead to distortions in the results of quantitative GMO analyses.

  5. An improved Peltier effect-based instrument for critical temperature threshold measurement in cold- and heat-induced urticaria.

    Science.gov (United States)

    Magerl, M; Abajian, M; Krause, K; Altrichter, S; Siebenhaar, F; Church, M K

    2015-10-01

    Cold- and heat-induced urticaria are chronic physical urticaria conditions in which wheals, angioedema or both are evoked by skin exposure to cold and heat respectively. The diagnostic work up of both conditions should include skin provocation tests and accurate determination of critical temperature thresholds (CTT) for producing symptoms in order to be able to predict the potential risk that each individual patient faces and how this may be ameliorated by therapy. To develop and validate TempTest(®) 4, a simple and relatively inexpensive instrument for the accurate determination of CTT which may be used in clinical practice. TempTest(®) 4 has a single 2 mm wide 350 mm U-shaped Peltier element generating a temperature gradient from 4 °C to 44 °C along its length. Using a clear plastic guide placed over the skin after provocation, CTT values may be determined with an accuracy of ±1 °C. Here, TempTest(®) 4 was compared with its much more expensive predecessor, TempTest(®) 3, in inducing wheals in 30 cold urticaria patients. Both TempTest(®) 4 and TempTest(®) 3 induced wheals in all 30 patients between 8 ° and 28 °C. There was a highly significant (P < 0.0001) correlation between the instruments in the CTT values in individual patients. The TempTest(®) 4 is a simple, easy to use, licensed, commercially available and affordable instrument for the determination of CTTs in both cold- and heat-induced urticaria. © 2014 European Academy of Dermatology and Venereology.

  6. Involvement of DNA-PK and ATM in radiation- and heat-induced DNA damage recognition and apoptotic cell death

    International Nuclear Information System (INIS)

    Tomita, Masanori

    2010-01-01

    Exposure to ionizing radiation and hyperthermia results in important biological consequences, e.g. cell death, chromosomal aberrations, mutations, and DNA strand breaks. There is good evidence that the nucleus, specifically cellular DNA, is the principal target for radiation-induced cell lethality. DNA double-strand breaks (DSBs) are considered to be the most serious type of DNA damage induced by ionizing radiation. On the other hand, verifiable mechanisms which can lead to heat-induced cell death are damage to the plasma membrane and/or inactivation of heat-labile proteins caused by protein denaturation and subsequent aggregation. Recently, several reports have suggested that DSBs can be induced after hyperthermia because heat-induced phosphorylated histone H2AX (γ-H2AX) foci formation can be observed in several mammalian cell lines. In mammalian cells, DSBs are repaired primarily through two distinct and complementary mechanisms: non-homologous end joining (NHEJ), and homologous recombination (HR) or homology-directed repair (HDR). DNA-dependent protein kinase (DNA-PK) and ataxia-telangiectasia mutated (ATM) are key players in the initiation of DSB repair and phosphorylate and/or activate many substrates, including themselves. These phosphorylated substrates have important roles in the functioning of cell cycle checkpoints and in cell death, as well as in DSB repair. Apoptotic cell death is a crucial cell suicide mechanism during development and in the defense of homeostasis. If DSBs are unrepaired or misrepaired, apoptosis is a very important system which can protect an organism against carcinogenesis. This paper reviews recently obtained results and current topics concerning the role of DNA-PK and ATM in heat- or radiation-induced apoptotic cell death. (author)

  7. Heat-Induced Changes in Heat Shock Protein Genes Expression in Crossbred and Baladi Pregnant Cows and Their Offspring

    International Nuclear Information System (INIS)

    Khalil, W.K.B.; Nessim, M.Z.; El- Masry, K.A.

    2010-01-01

    The experiment was carried out during August (hot climate) on twelve pregnant cows of six crossbred (50% native Baladi and 50% Brown Swiss) and six native Baladi pregnant cows in the same age and the second parity during their mid-pregnancy as detected by rectal palpation. The experiment was repeated during December (mild climate) on similar twelve pregnant cows. Blood sample was obtained from each cow at the end of August (first group) and at the end of December (second group) to obtain heat shock protein genes expression (HSP72, HSP70.01, HSP70, HSP47, k Dalton and Actin) in pregnant cows under mild and hot climate to find out, which breed is more tolerant to heat stress and to estimate offspring birth weight and their growth performances during suckling period. Comparison was made between hot climate cows group and mild climate cows group to estimate heat- induced changes in both breeds in expression level of the Hsp genes and to compare with their neonate birth weight and growth performances during suckling period. The results revealed that expression level of the Hsp genes (Hsp72, Hsp70.1, Hsp70 and Hsp 47) was higher (p<0.01) in hot season compared to that of mild season. Expression level of the Hsp genes (Hsp70.1, Hsp70 and Hsp 47) was higher (p<0.05) in crossbred cows than in Baldi cows under summer hot season. This indicates that crossbred cows are less heat tolerant than Baladi cows under heat stress climate. Heat induced decrease (p<0.01) in offspring birth weight in Baladi and crossbred by 18.1% and 25%, respectively, in weaning weight by 14.61% and 23.14%, respectively and in body weight gain by 14.61% and 21.18%, respectively

  8. Retrievability, ethics and democracy

    International Nuclear Information System (INIS)

    Jensen, M.; Westerlind, M.

    2000-01-01

    Ethics is always a social concern, an integrated part of laws and regulations. Treatment of ethics as a separate part in the decision making process is therefore always debatable. It cannot be introduced as an extraneous component to compensate for, or to improve, a morally flawed practice, and the margin for unethical practices is strongly circumscribed by regulation in the nuclear field, internationally. However, a discussion on different stakeholders and their different ethical concerns should always be welcome. One example is the implementer's views on ethics. Even if they are in complete parity with existing legal and regulatory goals, the goals may still represent the implementer's own motives and choices. Also, stakeholders may view the laws or regulations as unfair. In making the critique, the stakeholder simply formulates a separate political standpoint. Finally, an alternative discussion is to place existing regulations into an ethical perspective - adding a new dimension to the issues. Retrievability for high level waste repositories is often in focus in ethical discussions. Unfortunately, it is used in many ways and has become an unclear term. It may cover anything from planned recuperation to the property of waste being retrievable in years or tens of years, or in the distant time range of hundreds or thousands of years. The term retrievability is often proposed to cover mainly positive qualities such as the option of later changes to the repository or a new disposal concept. However, as ICRP and others have pointed out, it also implies the possibility of: i) operational exposures, ii) continuing risks of accidental releases, iii) financial provisions to cover operating costs and iv) continuing reliance on institutional control, thus imposing some burdens to future generations. In a certain sense, anything can be retrieved from any repository. There is therefore a need for a clear and operable definition of retrievability requirements, including the

  9. Computer-Aided Design of an Epitope-Based Vaccine against Epstein-Barr Virus

    Directory of Open Access Journals (Sweden)

    Julio Alonso-Padilla

    2017-01-01

    Full Text Available Epstein-Barr virus is a very common human virus that infects 90% of human adults. EBV replicates in epithelial and B cells and causes infectious mononucleosis. EBV infection is also linked to various cancers, including Burkitt’s lymphoma and nasopharyngeal carcinomas, and autoimmune diseases such as multiple sclerosis. Currently, there are no effective drugs or vaccines to treat or prevent EBV infection. Herein, we applied a computer-aided strategy to design a prophylactic epitope vaccine ensemble from experimentally defined T and B cell epitopes. Such strategy relies on identifying conserved epitopes in conjunction with predictions of HLA presentation for T cell epitope selection and calculations of accessibility and flexibility for B cell epitope selection. The T cell component includes 14 CD8 T cell epitopes from early antigens and 4 CD4 T cell epitopes, targeted during the course of a natural infection and providing a population protection coverage of over 95% and 81.8%, respectively. The B cell component consists of 3 experimentally defined B cell epitopes from gp350 plus 4 predicted B cell epitopes from other EBV envelope glycoproteins, all mapping in flexible and solvent accessible regions. We discuss the rationale for the formulation and possible deployment of this epitope vaccine ensemble.

  10. Mobile medical image retrieval

    Science.gov (United States)

    Duc, Samuel; Depeursinge, Adrien; Eggel, Ivan; Müller, Henning

    2011-03-01

    Images are an integral part of medical practice for diagnosis, treatment planning and teaching. Image retrieval has gained in importance mainly as a research domain over the past 20 years. Both textual and visual retrieval of images are essential. In the process of mobile devices becoming reliable and having a functionality equaling that of formerly desktop clients, mobile computing has gained ground and many applications have been explored. This creates a new field of mobile information search & access and in this context images can play an important role as they often allow understanding complex scenarios much quicker and easier than free text. Mobile information retrieval in general has skyrocketed over the past year with many new applications and tools being developed and all sorts of interfaces being adapted to mobile clients. This article describes constraints of an information retrieval system including visual and textual information retrieval from the medical literature of BioMedCentral and of the RSNA journals Radiology and Radiographics. Solutions for mobile data access with an example on an iPhone in a web-based environment are presented as iPhones are frequently used and the operating system is bound to become the most frequent smartphone operating system in 2011. A web-based scenario was chosen to allow for a use by other smart phone platforms such as Android as well. Constraints of small screens and navigation with touch screens are taken into account in the development of the application. A hybrid choice had to be taken to allow for taking pictures with the cell phone camera and upload them for visual similarity search as most producers of smart phones block this functionality to web applications. Mobile information access and in particular access to images can be surprisingly efficient and effective on smaller screens. Images can be read on screen much faster and relevance of documents can be identified quickly through the use of images contained in

  11. 'Multi-epitope-targeted' immune-specific therapy for a multiple sclerosis-like disease via engineered multi-epitope protein is superior to peptides.

    Directory of Open Access Journals (Sweden)

    Nathali Kaushansky

    Full Text Available Antigen-induced peripheral tolerance is potentially one of the most efficient and specific therapeutic approaches for autoimmune diseases. Although highly effective in animal models, antigen-based strategies have not yet been translated into practicable human therapy, and several clinical trials using a single antigen or peptidic-epitope in multiple sclerosis (MS yielded disappointing results. In these clinical trials, however, the apparent complexity and dynamics of the pathogenic autoimmunity associated with MS, which result from the multiplicity of potential target antigens and "epitope spread", have not been sufficiently considered. Thus, targeting pathogenic T-cells reactive against a single antigen/epitope is unlikely to be sufficient; to be effective, immunospecific therapy to MS should logically neutralize concomitantly T-cells reactive against as many major target antigens/epitopes as possible. We investigated such "multi-epitope-targeting" approach in murine experimental autoimmune encephalomyelitis (EAE associated with a single ("classical" or multiple ("complex" anti-myelin autoreactivities, using cocktail of different encephalitogenic peptides vis-a-vis artificial multi-epitope-protein (designated Y-MSPc encompassing rationally selected MS-relevant epitopes of five major myelin antigens, as "multi-epitope-targeting" agents. Y-MSPc was superior to peptide(s in concomitantly downregulating pathogenic T-cells reactive against multiple myelin antigens/epitopes, via inducing more effective, longer lasting peripheral regulatory mechanisms (cytokine shift, anergy, and Foxp3+ CTLA4+ regulatory T-cells. Y-MSPc was also consistently more effective than the disease-inducing single peptide or peptide cocktail, not only in suppressing the development of "classical" or "complex EAE" or ameliorating ongoing disease, but most importantly, in reversing chronic EAE. Overall, our data emphasize that a "multi-epitope-targeting" strategy is required for

  12. Interactive Information Retrieval:

    DEFF Research Database (Denmark)

    Borlund, Pia

    IIR from the perspective of search dedication and task load in order to also include everyday life information seeking? With this presentation, the IIR community is invited to an exchange of ideas and is encouraged to engage in collaborations with the solving of these (and other) issues to our joint......This presentation addresses methodological issues of interactive information retrieval (IIR) evaluation in terms of what it entails to study users' use and interaction with IR systems, as well as their satisfaction with retrieved information. In particular, the presentation focuses on test design...... of the users to ensure a complete and realistic picture to enhance our understanding of IIR. The presentation also reflects on whether a re-thinking of the concept on an information need is necessary. One may ask whether it still makes sense to talk about types of information needs. Or should we rather study...

  13. Introduction to information retrieval

    CERN Document Server

    Manning, Christopher D; Schütze, Hinrich

    2008-01-01

    Class-tested and coherent, this textbook teaches classical and web information retrieval, including web search and the related areas of text classification and text clustering from basic concepts. It gives an up-to-date treatment of all aspects of the design and implementation of systems for gathering, indexing, and searching documents; methods for evaluating systems; and an introduction to the use of machine learning methods on text collections. All the important ideas are explained using examples and figures, making it perfect for introductory courses in information retrieval for advanced undergraduates and graduate students in computer science. Based on feedback from extensive classroom experience, the book has been carefully structured in order to make teaching more natural and effective. Slides and additional exercises (with solutions for lecturers) are also available through the book's supporting website to help course instructors prepare their lectures.

  14. Isolation of monoclonal antibodies with predetermined conformational epitope specificity.

    Directory of Open Access Journals (Sweden)

    Anton M Sholukh

    Full Text Available Existing technologies allow isolating antigen-specific monoclonal antibodies (mAbs from B cells. We devised a direct approach to isolate mAbs with predetermined conformational epitope specificity, using epitope mimetics (mimotopes that reflect the three-dimensional structure of given antigen subdomains. We performed differential biopanning using bacteriophages encoding random peptide libraries and polyclonal antibodies (Abs that had been affinity-purified with either native or denatured antigen. This strategy yielded conformational mimotopes. We then generated mimotope-fluorescent protein fusions, which were used as baits to isolate single memory B cells from rhesus monkeys (RMs. To amplify RM immunoglobulin variable regions, we developed RM-specific PCR primers and generated chimeric simian-human mAbs with predicted epitope specificity. We established proof-of-concept of our strategy by isolating mAbs targeting the conformational V3 loop crown of HIV Env; the new mAbs cross-neutralized viruses of different clades. The novel technology allows isolating mAbs from RMs or other hosts given experimental immunogens or infectious agents.

  15. Optimal selection of epitopes for TXP-immunoaffinity mass spectrometry

    Directory of Open Access Journals (Sweden)

    Joos Thomas

    2010-06-01

    Full Text Available Abstract Background Mass spectrometry (MS based protein profiling has become one of the key technologies in biomedical research and biomarker discovery. One bottleneck in MS-based protein analysis is sample preparation and an efficient fractionation step to reduce the complexity of the biological samples, which are too complex to be analyzed directly with MS. Sample preparation strategies that reduce the complexity of tryptic digests by using immunoaffinity based methods have shown to lead to a substantial increase in throughput and sensitivity in the proteomic mass spectrometry approach. The limitation of using such immunoaffinity-based approaches is the availability of the appropriate peptide specific capture antibodies. Recent developments in these approaches, where subsets of peptides with short identical terminal sequences can be enriched using antibodies directed against short terminal epitopes, promise a significant gain in efficiency. Results We show that the minimal set of terminal epitopes for the coverage of a target protein list can be found by the formulation as a set cover problem, preceded by a filtering pipeline for the exclusion of peptides and target epitopes with undesirable properties. Conclusions For small datasets (a few hundred proteins it is possible to solve the problem to optimality with moderate computational effort using commercial or free solvers. Larger datasets, like full proteomes require the use of heuristics.

  16. Optimal selection of epitopes for TXP-immunoaffinity mass spectrometry.

    Science.gov (United States)

    Planatscher, Hannes; Supper, Jochen; Poetz, Oliver; Stoll, Dieter; Joos, Thomas; Templin, Markus F; Zell, Andreas

    2010-06-25

    Mass spectrometry (MS) based protein profiling has become one of the key technologies in biomedical research and biomarker discovery. One bottleneck in MS-based protein analysis is sample preparation and an efficient fractionation step to reduce the complexity of the biological samples, which are too complex to be analyzed directly with MS. Sample preparation strategies that reduce the complexity of tryptic digests by using immunoaffinity based methods have shown to lead to a substantial increase in throughput and sensitivity in the proteomic mass spectrometry approach. The limitation of using such immunoaffinity-based approaches is the availability of the appropriate peptide specific capture antibodies. Recent developments in these approaches, where subsets of peptides with short identical terminal sequences can be enriched using antibodies directed against short terminal epitopes, promise a significant gain in efficiency. We show that the minimal set of terminal epitopes for the coverage of a target protein list can be found by the formulation as a set cover problem, preceded by a filtering pipeline for the exclusion of peptides and target epitopes with undesirable properties. For small datasets (a few hundred proteins) it is possible to solve the problem to optimality with moderate computational effort using commercial or free solvers. Larger datasets, like full proteomes require the use of heuristics.

  17. Epitope Mapping of Monoclonal Antibody PMab-52 Against Cat Podoplanin.

    Science.gov (United States)

    Chang, Yao-Wen; Kaneko, Mika K; Yamada, Shinji; Kato, Yukinari

    2018-02-02

    The mucin-type membrane glycoprotein podoplanin (PDPN) is frequently overexpressed in numerous malignant cancers, including squamous cell carcinoma, germinal neoplasia, mesothelioma, lung cancer, oral cancer, and brain tumor. PDPN expression is strongly associated with cancer progression and poor prognosis. Furthermore, PDPN binds to C-type lectin-like receptor 2 (CLEC-2) on platelets, followed by PDPN-mediated platelet aggregation to facilitate tumor metastasis. We have previously reported a novel anti-cat PDPN (cPDPN) monoclonal antibody (mAb), PMab-52, which specifically detects cPDPN using flow cytometry analysis and successfully identifies cPDPN in feline squamous cell carcinomas. However, the specific binding epitope of cPDPN for PMab-52 remains unelucidated. In this study, a series of deletion or point mutants of cPDPN were utilized for investigating the binding epitopes of PMab-52 using flow cytometry and Western blotting. The findings of this study revealed that the critical epitopes of platelet aggregation-stimulating domain 4 (PLAG4) of cPDPN are responsible for the binding of PMab-52 to cPDPN.

  18. Epitope mapping of the domains of human angiotensin converting enzyme.

    Science.gov (United States)

    Kugaevskaya, Elena V; Kolesanova, Ekaterina F; Kozin, Sergey A; Veselovsky, Alexander V; Dedinsky, Ilya R; Elisseeva, Yulia E

    2006-06-01

    Somatic angiotensin converting enzyme (sACE), contains in its single chain two homologous domains (called N- and C-domains), each bearing a functional zinc-dependent active site. The present study aims to define the differences between two sACE domains and to localize experimentally revealed antigenic determinants (B-epitopes) in the recently determined three-dimensional structure of testicular tACE. The predicted linear antigenic determinants of human sACE were determined by peptide scanning ("PEPSCAN") approach. Essential difference was demonstrated between locations of the epitopes in the N- and C-domains. Comparison of arrangement of epitopes in the human domains with the corresponding sequences of some mammalian sACEs enabled to classify the revealed antigenic determinants as variable or conserved areas. The location of antigenic determinants with respect to various structural elements and to functionally important sites of the human sACE C-domain was estimated. The majority of antigenic sites of the C-domain were located at the irregular elements and at the boundaries of secondary structure elements. The data show structural differences between the sACE domains. The experimentally revealed antigenic determinants were in agreement with the recently determined crystal tACE structure. New potential applications are open to successfully produce mono-specific and group-specific antipeptide antibodies.

  19. JINR information retrieval system

    International Nuclear Information System (INIS)

    Arnaudov, D.D.; Govorun, N.N.

    1975-01-01

    The organization of the main files of the JINR Information Retrieval System is described. There are four main files in the System. They are as follows: MD file that consists of abstracts of documents; OMPOD file where the index records of documents are gathered; MZD file that consists of list heads, and OMD file- the file of descriptors. The last three files are considered in some detail. The System is realized in the COBOL language on the CDC computer

  20. Affective Music Information Retrieval

    OpenAIRE

    Wang, Ju-Chiang; Yang, Yi-Hsuan; Wang, Hsin-Min

    2015-01-01

    Much of the appeal of music lies in its power to convey emotions/moods and to evoke them in listeners. In consequence, the past decade witnessed a growing interest in modeling emotions from musical signals in the music information retrieval (MIR) community. In this article, we present a novel generative approach to music emotion modeling, with a specific focus on the valence-arousal (VA) dimension model of emotion. The presented generative model, called \\emph{acoustic emotion Gaussians} (AEG)...

  1. Automated Medical Literature Retrieval

    Directory of Open Access Journals (Sweden)

    David Hawking

    2012-09-01

    Full Text Available Background The constantly growing publication rate of medical research articles puts increasing pressure on medical specialists who need to be aware of the recent developments in their field. The currently used literature retrieval systems allow researchers to find specific papers; however the search task is still repetitive and time-consuming. Aims In this paper we describe a system that retrieves medical publications by automatically generating queries based on data from an electronic patient record. This allows the doctor to focus on medical issues and provide an improved service to the patient, with higher confidence that it is underpinned by current research. Method Our research prototype automatically generates query terms based on the patient record and adds weight factors for each term. Currently the patient’s age is taken into account with a fuzzy logic derived weight, and terms describing blood-related anomalies are derived from recent blood test results. Conditionally selected homonyms are used for query expansion. The query retrieves matching records from a local index of PubMed publications and displays results in descending relevance for the given patient. Recent publications are clearly highlighted for instant recognition by the researcher. Results Nine medical specialists from the Royal Adelaide Hospital evaluated the system and submitted pre-trial and post-trial questionnaires. Throughout the study we received positive feedback as doctors felt the support provided by the prototype was useful, and which they would like to use in their daily routine. Conclusion By supporting the time-consuming task of query formulation and iterative modification as well as by presenting the search results in order of relevance for the specific patient, literature retrieval becomes part of the daily workflow of busy professionals.

  2. The Wikipedia Image Retrieval Task

    NARCIS (Netherlands)

    T. Tsikrika (Theodora); J. Kludas

    2010-01-01

    htmlabstractThe wikipedia image retrieval task at ImageCLEF provides a testbed for the system-oriented evaluation of visual information retrieval from a collection of Wikipedia images. The aim is to investigate the effectiveness of retrieval approaches that exploit textual and visual evidence in the

  3. DORS: DDC Online Retrieval System.

    Science.gov (United States)

    Liu, Songqiao; Svenonius, Elaine

    1991-01-01

    Describes the Dewey Online Retrieval System (DORS), which was developed at the University of California, Los Angeles (UCLA), to experiment with classification-based search strategies in online catalogs. Classification structures in automated information retrieval are discussed; and specifications for a classification retrieval interface are…

  4. Small-angle X-ray scattering studies of metastable intermediates of beta-lactoglobulin isolated after heat-induced aggregation

    DEFF Research Database (Denmark)

    Carrotta, R.; Arleth, L.; Pedersen, J.S.

    2003-01-01

    Small-angle x-ray scattering was used for studying intermediate species, isolated after heat-induced aggregation of the A variant of bovine P-lactoglobulin. The intermediates were separated in two fractions, the heated metastable dimer and heated metastable oligomers larger than the dimer. The pa...

  5. Effect of extraction pH on heat-induced aggregation, gelation and microstructure of protein isolate from quinoa (Chenopodium quinoa Willd)

    NARCIS (Netherlands)

    Ruiz, Geraldine Avila; Xiao, Wukai; Boekel, van Tiny; Minor, Marcel; Stieger, Markus

    2016-01-01

    The aim of this study was to determine the influence of extraction pH on heat-induced aggregation, gelation and microstructure of suspensions of protein isolates extracted from quinoa (Chenopodium quinoa Willd). Quinoa seed protein was extracted by alkaline treatment at various pH values (pH 8

  6. Retrievable Inferior Vena Cava Filters: Factors that Affect Retrieval Success

    Energy Technology Data Exchange (ETDEWEB)

    Geisbuesch, Philipp, E-mail: philippgeisbuesch@gmx.de; Benenati, James F.; Pena, Constantino S.; Couvillon, Joseph; Powell, Alex; Gandhi, Ripal; Samuels, Shaun; Uthoff, Heiko [Baptist Cardiac and Vascular Institute, Division of Vascular and Interventional Radiology (United States)

    2012-10-15

    Purpose: To report and analyze the indications, procedural success, and complications of retrievable inferior vena cava filters (rIVCF) placement and to identify parameters that influence retrieval attempt and failure. Methods: Between January 2005 and December 2010, a total of 200 patients (80 men, median age 67 years, range 11-95 years) received a rIVCF with the clinical possibility that it could be removed. All patients with rIVCF were prospectively entered into a database and followed until retrieval or a decision not to retrieve the filter was made. A retrospective analysis of this database was performed. Results: Sixty-one percent of patients had an accepted indication for filter placement; 39% of patients had a relative indication. There was a tendency toward a higher retrieval rate in patients with relative indications (40% vs. 55%, P = 0.076). Filter placement was technically successful in all patients, with no procedure-related mortality. The retrieval rate was 53%. Patient age of >80 years (odds ratio [OR] 0.056, P > 0.0001) and presence of malignancy (OR 0.303, P = 0.003) was associated with a significantly reduced probability for attempted retrieval. Retrieval failure occurred in 7% (6 of 91) of all retrieval attempts. A time interval of > 90 days between implantation and attempted retrieval was associated with retrieval failure (OR 19.8, P = 0.009). Conclusions: Patient age >80 years and a history of malignancy are predictors of a reduced probability for retrieval attempt. The rate of retrieval failure is low and seems to be associated with a time interval of >90 days between filter placement and retrieval.

  7. Retrievable Inferior Vena Cava Filters: Factors that Affect Retrieval Success

    International Nuclear Information System (INIS)

    Geisbüsch, Philipp; Benenati, James F.; Peña, Constantino S.; Couvillon, Joseph; Powell, Alex; Gandhi, Ripal; Samuels, Shaun; Uthoff, Heiko

    2012-01-01

    Purpose: To report and analyze the indications, procedural success, and complications of retrievable inferior vena cava filters (rIVCF) placement and to identify parameters that influence retrieval attempt and failure. Methods: Between January 2005 and December 2010, a total of 200 patients (80 men, median age 67 years, range 11–95 years) received a rIVCF with the clinical possibility that it could be removed. All patients with rIVCF were prospectively entered into a database and followed until retrieval or a decision not to retrieve the filter was made. A retrospective analysis of this database was performed. Results: Sixty-one percent of patients had an accepted indication for filter placement; 39% of patients had a relative indication. There was a tendency toward a higher retrieval rate in patients with relative indications (40% vs. 55%, P = 0.076). Filter placement was technically successful in all patients, with no procedure-related mortality. The retrieval rate was 53%. Patient age of >80 years (odds ratio [OR] 0.056, P > 0.0001) and presence of malignancy (OR 0.303, P = 0.003) was associated with a significantly reduced probability for attempted retrieval. Retrieval failure occurred in 7% (6 of 91) of all retrieval attempts. A time interval of > 90 days between implantation and attempted retrieval was associated with retrieval failure (OR 19.8, P = 0.009). Conclusions: Patient age >80 years and a history of malignancy are predictors of a reduced probability for retrieval attempt. The rate of retrieval failure is low and seems to be associated with a time interval of >90 days between filter placement and retrieval.

  8. Designing and overproducing a tandem epitope of gp350/220 that shows a potential to become an EBV vaccine

    Directory of Open Access Journals (Sweden)

    Widodo

    2018-03-01

    Full Text Available Background: Epstein-Barr virus (EBV can cause cancer in people from around the world. There is no EBV vaccine available for use on a global scale. However, emerging evidence suggests that the epitope on the gp350/220 capsid protein may be developed into an EBV vaccine. Nevertheless, the production of small, single epitope is challenging of stability issues and possible alteration of peptide structure. In this study, a tandem epitope was developed consisting of three single epitopes, aimed to improve stability, antigenicity and preserve epitope structure. Materials and methods: A tandem epitope was designed using bioinformatics based on the epitope structure of the gp350/220 protein. The tandem epitope structure was analyzed using a protein folding method with Abalone software, which was further refined via YASARA force field and molecular repairing using a FoldX method. Immunogenicity was examined with Epitopia software, whereas allergen properties were tested using AlgPred. The pattern of the tandem epitope binding with anti-gp350/220 antibodies was performed using Z-dock and snugDock. The tandem epitope was then overproduced in E. coli strain BL21 as a host cell. Result: Our model demonstrated a successfully designed and overproduced tandem epitope. The tandem epitope demonstrated a similar structure compared with the epitope of whole protein gp350/220. Our epitope also demonstrated non-allergen and antigenicity properties, and possessed antibody binding patterns consistent with whole protein gp350/220. Conclusion and recommendation: These data suggest a novel tandem epitope composed of three similar epitopes demonstrates antigenicity, structure, and binding properties consistent with whole protein gp350/220. We also demonstrate successful production of the tandem epitope using E. coli strain BL21 as a host. Future in vivo experimental animal research is necessary to test the ability of this tandem epitope to stimulate antibody production

  9. EpiJen: a server for multistep T cell epitope prediction

    Directory of Open Access Journals (Sweden)

    Guan Pingping

    2006-03-01

    Full Text Available Abstract Background The main processing pathway for MHC class I ligands involves degradation of proteins by the proteasome, followed by transport of products by the transporter associated with antigen processing (TAP to the endoplasmic reticulum (ER, where peptides are bound by MHC class I molecules, and then presented on the cell surface by MHCs. The whole process is modeled here using an integrated approach, which we call EpiJen. EpiJen is based on quantitative matrices, derived by the additive method, and applied successively to select epitopes. EpiJen is available free online. Results To identify epitopes, a source protein is passed through four steps: proteasome cleavage, TAP transport, MHC binding and epitope selection. At each stage, different proportions of non-epitopes are eliminated. The final set of peptides represents no more than 5% of the whole protein sequence and will contain 85% of the true epitopes, as indicated by external validation. Compared to other integrated methods (NetCTL, WAPP and SMM, EpiJen performs best, predicting 61 of the 99 HIV epitopes used in this study. Conclusion EpiJen is a reliable multi-step algorithm for T cell epitope prediction, which belongs to the next generation of in silico T cell epitope identification methods. These methods aim to reduce subsequent experimental work by improving the success rate of epitope prediction.

  10. Characterization of a linear epitope on Chlamydia trachomatis serovar L2 DnaK-like protein

    DEFF Research Database (Denmark)

    Ozkokmen, D; Birkelund, Svend; Christiansen, Gunna

    1994-01-01

    A cytoplasmic 75-kDa immunogen from Chlamydia trachomatis serovar L2 has previously been characterized as being similar to the Escherichia coli heat shock protein DnaK. We have localized a linear epitope for one monoclonal antibody specific for C. trachomatis DnaK. By use of a recombinant DNA...... technique, the epitope was limited to 14 amino acids. With synthetic peptides, the epitope was further limited to eight amino acids. Six of these amino acids are conserved in bovine HSP70, which has a known three-dimensional structure. The amino acid sequence homologous to the epitope is located in a linear...

  11. [Immunoreactivity of chimeric proteins carrying poliovirus epitopes on the VP6 of rotavirus as a vector].

    Science.gov (United States)

    Pan, X-X; Zhao, B-X; Teng, Y-M; Xia, W-Y; Wang, J; Li, X-F; Liao, G-Y; Yang, С; Chen, Y-D

    2016-01-01

    Rotavirus and poliovirus continue to present significant risks and burden of disease to children in developing countries. Developing a combined vaccine may effectively prevent both illnesses and may be advantageous in terms of maximizing compliance and vaccine coverage at the same visit. Recently, we sought to generate a vaccine vector by incorporating multiple epitopes into the rotavirus group antigenic protein, VP6. In the present study, a foreign epitope presenting a system using VP6 as a vector was created with six sites on the outer surface of the vector that could be used for insertion of foreign epitopes, and three VP6-based PV1 epitope chimeric proteins were constructed. The chimeric proteins were confirmed by immunoblot, immunofluorescence assay, and injected into guinea pigs to analyze the epitope-specific humoral response. Results showed that these chimeric proteins reacted with anti-VP6F and -PV1 antibodies, and elicited antibodies against both proteins in guinea pigs. Antibodies against the chimeric proteins carrying PV1 epitopes neutralized rotavirus Wa and PV1 infection in vitro. Our study contributes to a better understanding of the use of VP6-based vectors as multiple-epitope delivery vehicles and the epitopes displayed in this form could be considered for development of epitope-based vaccines against rotavirus and poliovirus.

  12. Machine learning-based methods for prediction of linear B-cell epitopes.

    Science.gov (United States)

    Wang, Hsin-Wei; Pai, Tun-Wen

    2014-01-01

    B-cell epitope prediction facilitates immunologists in designing peptide-based vaccine, diagnostic test, disease prevention, treatment, and antibody production. In comparison with T-cell epitope prediction, the performance of variable length B-cell epitope prediction is still yet to be satisfied. Fortunately, due to increasingly available verified epitope databases, bioinformaticians could adopt machine learning-based algorithms on all curated data to design an improved prediction tool for biomedical researchers. Here, we have reviewed related epitope prediction papers, especially those for linear B-cell epitope prediction. It should be noticed that a combination of selected propensity scales and statistics of epitope residues with machine learning-based tools formulated a general way for constructing linear B-cell epitope prediction systems. It is also observed from most of the comparison results that the kernel method of support vector machine (SVM) classifier outperformed other machine learning-based approaches. Hence, in this chapter, except reviewing recently published papers, we have introduced the fundamentals of B-cell epitope and SVM techniques. In addition, an example of linear B-cell prediction system based on physicochemical features and amino acid combinations is illustrated in details.

  13. Prediction of linear B-cell epitopes of hepatitis C virus for vaccine development

    Science.gov (United States)

    2015-01-01

    Background High genetic heterogeneity in the hepatitis C virus (HCV) is the major challenge of the development of an effective vaccine. Existing studies for developing HCV vaccines have mainly focused on T-cell immune response. However, identification of linear B-cell epitopes that can stimulate B-cell response is one of the major tasks of peptide-based vaccine development. Owing to the variability in B-cell epitope length, the prediction of B-cell epitopes is much more complex than that of T-cell epitopes. Furthermore, the motifs of linear B-cell epitopes in different pathogens are quite different (e. g. HCV and hepatitis B virus). To cope with this challenge, this work aims to propose an HCV-customized sequence-based prediction method to identify B-cell epitopes of HCV. Results This work establishes an experimentally verified dataset comprising the B-cell response of HCV dataset consisting of 774 linear B-cell epitopes and 774 non B-cell epitopes from the Immune Epitope Database. An interpretable rule mining system of B-cell epitopes (IRMS-BE) is proposed to select informative physicochemical properties (PCPs) and then extracts several if-then rule-based knowledge for identifying B-cell epitopes. A web server Bcell-HCV was implemented using an SVM with the 34 informative PCPs, which achieved a training accuracy of 79.7% and test accuracy of 70.7% better than the SVM-based methods for identifying B-cell epitopes of HCV and the two general-purpose methods. This work performs advanced analysis of the 34 informative properties, and the results indicate that the most effective property is the alpha-helix structure of epitopes, which influences the connection between host cells and the E2 proteins of HCV. Furthermore, 12 interpretable rules are acquired from top-five PCPs and achieve a sensitivity of 75.6% and specificity of 71.3%. Finally, a conserved promising vaccine candidate, PDREMVLYQE, is identified for inclusion in a vaccine against HCV. Conclusions This work

  14. Epitope-dependent functional effects of celiac disease autoantibodies on transglutaminase 2

    DEFF Research Database (Denmark)

    Hnida, Kathrin; Stamnaes, Jorunn; du Pré, M Fleur

    2016-01-01

    Transglutaminase 2 (TG2) is a Ca(2+)-dependent cross-linking enzyme involved in the pathogenesis of CD. We have previously characterized a panel of anti-TG2 mAbs generated from gut plasma cells of celiac patients and identified four epitopes (epitopes 1-4) located in the N-terminal part of TG2...... of epitope 1-targeting B cells to keep TG2 active and protected from oxidation might explain why generation of epitope 1-targeting plasma cells seems to be favored in celiac patients....

  15. Guenter Tulip Filter Retrieval Experience: Predictors of Successful Retrieval

    International Nuclear Information System (INIS)

    Turba, Ulku Cenk; Arslan, Bulent; Meuse, Michael; Sabri, Saher; Macik, Barbara Gail; Hagspiel, Klaus D.; Matsumoto, Alan H.; Angle, John F.

    2010-01-01

    We report our experience with Guenter Tulip filter placement indications, retrievals, and procedural problems, with emphasis on alternative retrieval techniques. We have identified 92 consecutive patients in whom a Guenter Tulip filter was placed and filter removal attempted. We recorded patient demographic information, filter placement and retrieval indications, procedures, standard and nonstandard filter retrieval techniques, complications, and clinical outcomes. The mean time to retrieval for those who experienced filter strut penetration was statistically significant [F(1,90) = 8.55, p = 0.004]. Filter strut(s) IVC penetration and successful retrieval were found to be statistically significant (p = 0.043). The filter hook-IVC relationship correlated with successful retrieval. A modified guidewire loop technique was applied in 8 of 10 cases where the hook appeared to penetrate the IVC wall and could not be engaged with a loop snare catheter, providing additional technical success in 6 of 8 (75%). Therefore, the total filter retrieval success increased from 88 to 95%. In conclusion, the Guenter Tulip filter has high successful retrieval rates with low rates of complication. Additional maneuvers such as a guidewire loop method can be used to improve retrieval success rates when the filter hook is endothelialized.

  16. Monetary rewards influence retrieval orientations.

    Science.gov (United States)

    Halsband, Teresa M; Ferdinand, Nicola K; Bridger, Emma K; Mecklinger, Axel

    2012-09-01

    Reward anticipation during learning is known to support memory formation, but its role in retrieval processes is so far unclear. Retrieval orientations, as a reflection of controlled retrieval processing, are one aspect of retrieval that might be modulated by reward. These processes can be measured using the event-related potentials (ERPs) elicited by retrieval cues from tasks with different retrieval requirements, such as via changes in the class of targeted memory information. To determine whether retrieval orientations of this kind are modulated by reward during learning, we investigated the effects of high and low reward expectancy on the ERP correlates of retrieval orientation in two separate experiments. The reward manipulation at study in Experiment 1 was associated with later memory performance, whereas in Experiment 2, reward was directly linked to accuracy in the study task. In both studies, the participants encoded mixed lists of pictures and words preceded by high- or low-reward cues. After 24 h, they performed a recognition memory exclusion task, with words as the test items. In addition to a previously reported material-specific effect of retrieval orientation, a frontally distributed, reward-associated retrieval orientation effect was found in both experiments. These findings suggest that reward motivation during learning leads to the adoption of a reward-associated retrieval orientation to support the retrieval of highly motivational information. Thus, ERP retrieval orientation effects not only reflect retrieval processes related to the sought-for materials, but also relate to the reward conditions with which items were combined during encoding.

  17. Multiple linear B-cell epitopes of classical swine fever virus glycoprotein E2 expressed in E.coli as multiple epitope vaccine induces a protective immune response

    Directory of Open Access Journals (Sweden)

    Wei Jian-Chao

    2011-07-01

    Full Text Available Abstract Classical swine fever is a highly contagious disease of swine caused by classical swine fever virus, an OIE list A pathogen. Epitope-based vaccines is one of the current focuses in the development of new vaccines against classical swine fever virus (CSFV. Two B-cell linear epitopes rE2-ba from the E2 glycoprotein of CSFV, rE2-a (CFRREKPFPHRMDCVTTTVENED, aa844-865 and rE2-b (CKEDYRYAISSTNEIGLLGAGGLT, aa693-716, were constructed and heterologously expressed in Escherichia coli as multiple epitope vaccine. Fifteen 6-week-old specified-pathogen-free (SPF piglets were intramuscularly immunized with epitopes twice at 2-week intervals. All epitope-vaccinated pigs could mount an anamnestic response after booster vaccination with neutralizing antibody titers ranging from 1:16 to 1:256. At this time, the pigs were subjected to challenge infection with a dose of 1 × 106 TCID50 virulent CSFV strain. After challenge infection, all of the rE2-ba-immunized pigs were alive and without symptoms or signs of CSF. In contrast, the control pigs continuously exhibited signs of CSF and had to be euthanized because of severe clinical symptoms at 5 days post challenge infection. The data from in vivo experiments shown that the multiple epitope rE2-ba shown a greater protection (similar to that of HCLV vaccine than that of mono-epitope peptide(rE2-a or rE2-b. Therefore, The results demonstrated that this multiple epitope peptide expressed in a prokaryotic system can be used as a potential DIVA (differentiating infected from vaccinated animals vaccine. The E.coli-expressed E2 multiple B-cell linear epitopes retains correct immunogenicity and is able to induce a protective immune response against CSFV infection.

  18. Music retrieval in ICOR

    Science.gov (United States)

    Finsterle, Lutz; Fischer, Stephan; Rimac, Ivica; Steinmetz, Ralf

    1999-08-01

    In this paper we describe music retrieval in ICOR, a project of Darmstadt TU. It is the goal of ICOR to find new interfaces to support applications of music video and music CDs. Although the project consists of audio and video analysis we concentrate on a description of the audio algorithms in this paper. We describe our MPEG-7 like data structure to store meta information for music pieces and explain which algorithms we use to analyze the content of music pieces automatically. We currently use an applause detection to distinguish live music from studio recordings, a genre classifier to distinguish pieces with beats form classical music, and a singer recognition.

  19. Monitored retrievable storage status

    International Nuclear Information System (INIS)

    Carlson, J.H.

    1985-01-01

    The Department of Energy (DOE) is preparing a proposal for Congressional consideration of the inclusion of a monitored retrievable storage (MRS) facility as part of the Federal Nuclear Waste Management System. The DOE plans to submit the proposal package to the Congress by January 15, 1986. The proposed preferred location of the MRS facility is the former Clinch River Breeder site in the state of Tennessee. If the Congress approves implementation of the MRS proposal, it is estimated that the facility could be licensed and operational in ten years

  20. Monitored retrievable storage design

    International Nuclear Information System (INIS)

    Woods, W.D.

    1985-01-01

    The Nuclear Waste Policy Act of 1982 (NWPA) established a national policy for the safe storage and disposal of spent nuclear fuel and high-level radioactive waste. The NWPA requires that DOE... ''submit a proposal to Congress on the need for and feasibility of one or more Monitored Retrievable Storage (MRS) Facilities''... In subsequent evaluations of the commercial nuclear waste management system, DOE has identified important advantages in providing an MRS Facility as an integral part of the total system. The integral MRS Facility serves as an independent, centralized spent nuclear fuel and high-level waste handling and packaging facility with a safe temporary storage capacity

  1. Multimedia Information Retrieval

    CERN Document Server

    Rueger, Stefan

    2009-01-01

    At its very core multimedia information retrieval means the process of searching for and finding multimedia documents; the corresponding research field is concerned with building the best possible multimedia search engines. The intriguing bit here is that the query itself can be a multimedia excerpt: For example, when you walk around in an unknown place and stumble across an interesting landmark, would it not be great if you could just take a picture with your mobile phone and send it to a service that finds a similar picture in a database and tells you more about the building -- and about its

  2. Information, conservation and retrieval

    Energy Technology Data Exchange (ETDEWEB)

    Eng, T [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Norberg, E [National Swedish Archives, Stockholm (Sweden); Torbacke, J [Stockholm Univ. (Sweden). Dept. of History; Jensen, M [Swedish Radiation Protection Inst., Stockholm (Sweden)

    1996-12-01

    The seminar took place on the Swedish ship for transportation of radioactive wastes, M/S Sigyn, which at summer time is used for exhibitions. The seminar treated items related to general information needs in society and questions related to radioactive waste, i.e. how knowledge about a waste repository should be passed on to future generations. Three contributions are contained in the report from the seminar and are indexed separately: `Active preservation - otherwise no achieves`; `The conservation and dissemination of information - A democratic issue`; and, `Conservation and retrieval of information - Elements of a strategy to inform future societies about nuclear waste repositories`.

  3. Information, conservation and retrieval

    International Nuclear Information System (INIS)

    Eng, T.; Norberg, E.; Torbacke, J.

    1996-12-01

    The seminar took place on the Swedish ship for transportation of radioactive wastes, M/S Sigyn, which at summer time is used for exhibitions. The seminar treated items related to general information needs in society and questions related to radioactive waste, i.e. how knowledge about a waste repository should be passed on to future generations. Three contributions are contained in the report from the seminar and are indexed separately: 'Active preservation - otherwise no achieves'; 'The conservation and dissemination of information - A democratic issue'; and, 'Conservation and retrieval of information - Elements of a strategy to inform future societies about nuclear waste repositories'

  4. Drosophila UNC-45 prevents heat-induced aggregation of skeletal muscle myosin and facilitates refolding of citrate synthase

    Energy Technology Data Exchange (ETDEWEB)

    Melkani, Girish C.; Lee, Chi F.; Cammarato, Anthony [Department of Biology and the Molecular Biology Institute, San Diego State University, San Diego, CA 92182-4614 (United States); Bernstein, Sanford I., E-mail: sbernst@sciences.sdsu.edu [Department of Biology and the Molecular Biology Institute, San Diego State University, San Diego, CA 92182-4614 (United States)

    2010-05-28

    UNC-45 belongs to the UCS (UNC-45, CRO1, She4p) domain protein family, whose members interact with various classes of myosin. Here we provide structural and biochemical evidence that Escherichia coli-expressed Drosophila UNC-45 (DUNC-45) maintains the integrity of several substrates during heat-induced stress in vitro. DUNC-45 displays chaperone function in suppressing aggregation of the muscle myosin heavy meromyosin fragment, the myosin S-1 motor domain, {alpha}-lactalbumin and citrate synthase. Biochemical evidence is supported by electron microscopy, which reveals the first structural evidence that DUNC-45 prevents inter- or intra-molecular aggregates of skeletal muscle heavy meromyosin caused by elevated temperatures. We also demonstrate for the first time that UNC-45 is able to refold a denatured substrate, urea-unfolded citrate synthase. Overall, this in vitro study provides insight into the fate of muscle myosin under stress conditions and suggests that UNC-45 protects and maintains the contractile machinery during in vivo stress.

  5. [Suppressive Effects of Extract of Cedar Wood on Heat-induced Expression of Cellular Heat Shock Protein].

    Science.gov (United States)

    Miyakoshi, Junji; Matsubara, Eri; Narita, Eijiro; Koyama, Shin; Shimizu, Yoko; Kawai, Shuichi

    2018-01-01

     In recent years, highly antimicrobial properties of cedar heartwood essential oil against the wood-rotting fungi and pathogenic fungi have been reported in several papers. Antimicrobial properties against oral bacteria by hinokitiol contained in Thujopsis have been also extensively studied. The relation of naturally derived components and human immune system has been studied in some previous papers. In the present study, we focused on Japanese cedar, which has the widest artificial afforestation site in the country among various tree species. Extract oil was obtained from mixture of sapwood and heartwood of about 40-year cedar grown in Oguni, Kumamoto, Japan. We examined the influence of extract components from Japanese cedar woods on the expression of heat shock protein 70 (Hsp70) during heating, and on the micronucleus formation induced by the treatment of bleomycin as a DNA damaging agent. Cell lines used in this study were human fetal glial cells (SVGp12) and human glioma cells (MO54). Remarkable suppression of the Hsp70 expression induced by heating at 43°C was detected by the treatment of cedar extract in both SVGp12 and MO54 cells. We also found that cedar extract had an inhibitory tendency to reduce the micronucleus formation induced by bleomycin. From these results, the extract components from Japanese cedar woods would have an inhibitory effect of the stress response as a suppression of the heat-induced Hsp70 expression, and might have a reductive effect on carcinogenicity.

  6. Effects of Pressure, Temperature, Treatment Time, and Storage on Rheological, Textural, and Structural Properties of Heat-Induced Chickpea Gels

    Directory of Open Access Journals (Sweden)

    María Dolores Alvarez

    2015-04-01

    Full Text Available Pressure-induced gelatinization of chickpea flour (CF was studied in combination with subsequent temperature-induced gelatinization. CF slurries (with 1:5 flour-to-water ratio and CF in powder form were treated with high hydrostatic pressure (HHP, temperature (T, and treatment time (t at three levels (200, 400, 600 MPa; 10, 25, 50 °C; 5, 15, 25 min. In order to investigate the effect of storage (S, half of the HHP-treated CF slurries were immediately analyzed for changes in oscillatory rheological properties under isothermal heating at 75 °C for 15 min followed by cooling to 25 °C. The other half of the HHP-treated CF slurries were refrigerated (at 4 °C for one week and subsequently analyzed for changes in oscillatory properties under the same heating conditions as the unrefrigerated samples. HHP-treated CF in powder form was analyzed for changes in textural properties of heat-induced CF gels under isothermal heating at 90 °C for 5 min and subsequent cooling to 25 °C. Structural changes during gelatinization were investigated using microscopy. Pressure had a more significant effect on rheological and textural properties, followed by T and treatment t (in that order. Gel aging in HHP-treated CF slurries during storage was supported by rheological measurements.

  7. New insights into heat induced structural changes of pectin methylesterase on fluorescence spectroscopy and molecular modeling basis

    Science.gov (United States)

    Nistor, Oana Viorela; Stănciuc, Nicoleta; Aprodu, Iuliana; Botez, Elisabeta

    2014-07-01

    Heat-induced structural changes of Aspergillus oryzae pectin methylesterase (PME) were studied by means of fluorescence spectroscopy and molecular modeling, whereas the functional enzyme stability was monitored by inactivation studies. The fluorescence spectroscopy experiments were performed at two pH value (4.5 and 7.0). At both pH values, the phase diagrams were linear, indicating the presence of two molecular species induced by thermal treatment. A red shift of 7 nm was observed at neutral pH by increasing temperature up to 60 °C, followed by a blue shift of 4 nm at 70 °C, suggesting significant conformational rearrangements. The quenching experiments using acrylamide and iodide demonstrate a more flexible conformation of enzyme with increasing temperature, especially at neutral pH. The experimental results were complemented with atomic level observations on PME model behavior after performing molecular dynamics simulations at different temperatures. The inactivation kinetics of PME in buffer solutions was fitted using a first-order kinetics model, resulting in activation energy of 241.4 ± 7.51 kJ mol-1.

  8. Ethics issues in retrievability

    International Nuclear Information System (INIS)

    Jensen, M.; Larsson, C.M.; Norden, M.

    2000-01-01

    We can isolate some issues, which should not be unresolved for a longer period of time. Disputes over well-defined waste management options fall in this category. The concept of retrievability has a possibility to invoke a series of questions in the minds of both specialists and non-specialists. It is intrinsically vague, in that it may refer to different phases in the repository's life, and to both open and closed repositories in the long time frame. Requirements for retrievability opens a series of issues, including open-ended philosophical question, which may give the impressions that things are not properly taken care of, since the experts differ in opinion. If such disputes cannot be resolved by consulting the existing legal framework, efforts should be made to put them to trial in the proper forum, i.e. parliament and national or local government or authorities, depending on the problem. In contrast, the value of institutional controls can easily be seen as an ethical value, whether included in the regulation of not. It has the potential to deter human intrusion and to allow remedial action by carrying information about a repository. (author)

  9. Analysis of potato virus Y coat protein epitopes recognized by three commercial monoclonal antibodies.

    Science.gov (United States)

    Tian, Yan-Ping; Hepojoki, Jussi; Ranki, Harri; Lankinen, Hilkka; Valkonen, Jari P T

    2014-01-01

    Potato virus Y (PVY, genus Potyvirus) causes substantial economic losses in solanaceous plants. Routine screening for PVY is an essential part of seed potato certification, and serological assays are often used. The commercial, commonly used monoclonal antibodies, MAb1128, MAb1129, and MAb1130, recognize the viral coat protein (CP) of PVY and distinguish PVYN strains from PVYO and PVYC strains, or detect all PVY strains, respectively. However, the minimal epitopes recognized by these antibodies have not been identified. SPOT peptide array was used to map the epitopes in CP recognized by MAb1128, MAb1129, and MAb1130. Then alanine replacement as well as N- and C-terminal deletion analysis of the identified peptide epitopes was done to determine critical amino acids for antibody recognition and the respective minimal epitopes. The epitopes of all antibodies were located within the 30 N-terminal-most residues. The minimal epitope of MAb1128 was 25NLNKEK30. Replacement of 25N or 27N with alanine weakened the recognition by MAb1128, and replacement of 26L, 29E, or 30K nearly precluded recognition. The minimal epitope for MAb1129 was 16RPEQGSIQSNP26 and the most critical residues for recognition were 22I and 23Q. The epitope of MAb1130 was defined by residues 5IDAGGS10. Mutation of residue 6D abrogated and mutation of 9G strongly reduced recognition of the peptide by MAb1130. Amino acid sequence alignment demonstrated that these epitopes are relatively conserved among PVY strains. Finally, recombinant CPs were produced to demonstrate that mutations in the variable positions of the epitope regions can affect detection with the MAbs. The epitope data acquired can be compared with data on PVY CP-encoding sequences produced by laboratories worldwide and utilized to monitor how widely the new variants of PVY can be detected with current seed potato certification schemes or during the inspection of imported seed potatoes as conducted with these MAbs.

  10. A high-throughput shotgun mutagenesis approach to mapping B-cell antibody epitopes.

    Science.gov (United States)

    Davidson, Edgar; Doranz, Benjamin J

    2014-09-01

    Characterizing the binding sites of monoclonal antibodies (mAbs) on protein targets, their 'epitopes', can aid in the discovery and development of new therapeutics, diagnostics and vaccines. However, the speed of epitope mapping techniques has not kept pace with the increasingly large numbers of mAbs being isolated. Obtaining detailed epitope maps for functionally relevant antibodies can be challenging, particularly for conformational epitopes on structurally complex proteins. To enable rapid epitope mapping, we developed a high-throughput strategy, shotgun mutagenesis, that enables the identification of both linear and conformational epitopes in a fraction of the time required by conventional approaches. Shotgun mutagenesis epitope mapping is based on large-scale mutagenesis and rapid cellular testing of natively folded proteins. Hundreds of mutant plasmids are individually cloned, arrayed in 384-well microplates, expressed within human cells, and tested for mAb reactivity. Residues are identified as a component of a mAb epitope if their mutation (e.g. to alanine) does not support candidate mAb binding but does support that of other conformational mAbs or allows full protein function. Shotgun mutagenesis is particularly suited for studying structurally complex proteins because targets are expressed in their native form directly within human cells. Shotgun mutagenesis has been used to delineate hundreds of epitopes on a variety of proteins, including G protein-coupled receptor and viral envelope proteins. The epitopes mapped on dengue virus prM/E represent one of the largest collections of epitope information for any viral protein, and results are being used to design better vaccines and drugs. © 2014 John Wiley & Sons Ltd.

  11. IMMUNOCAT—A Data Management System for Epitope Mapping Studies

    Directory of Open Access Journals (Sweden)

    Jo L. Chung

    2010-01-01

    Full Text Available To enable rationale vaccine design, studies of molecular and cellular mechanisms of immune recognition need to be linked with clinical studies in humans. A major challenge in conducting such translational research studies lies in the management and integration of large amounts and various types of data collected from multiple sources. For this purpose, we have established “IMMUNOCAT”, an interactive data management system for the epitope discovery research projects conducted by our group. The system provides functions to store, query, and analyze clinical and experimental data, enabling efficient, systematic, and integrative data management. We demonstrate how IMMUNOCAT is utilized in a large-scale research contract that aims to identify epitopes in common allergens recognized by T cells from human donors, in order to facilitate the rational design of allergy vaccines. At clinical sites, demographic information and disease history of each enrolled donor are captured, followed by results of an allergen skin test and blood draw. At the laboratory site, T cells derived from blood samples are tested for reactivity against a panel of peptides derived from common human allergens. IMMUNOCAT stores results from these T cell assays along with MHC:peptide binding data, results from RAST tests for antibody titers in donor serum, and the respective donor HLA typing results. Through this system, we are able to perform queries and integrated analyses of the various types of data. This provides a case study for the use of bioinformatics and information management techniques to track and analyze data produced in a translational research study aimed at epitope identification.

  12. IMMUNOCAT-a data management system for epitope mapping studies.

    Science.gov (United States)

    Chung, Jo L; Sun, Jian; Sidney, John; Sette, Alessandro; Peters, Bjoern

    2010-01-01

    To enable rationale vaccine design, studies of molecular and cellular mechanisms of immune recognition need to be linked with clinical studies in humans. A major challenge in conducting such translational research studies lies in the management and integration of large amounts and various types of data collected from multiple sources. For this purpose, we have established "IMMUNOCAT", an interactive data management system for the epitope discovery research projects conducted by our group. The system provides functions to store, query, and analyze clinical and experimental data, enabling efficient, systematic, and integrative data management. We demonstrate how IMMUNOCAT is utilized in a large-scale research contract that aims to identify epitopes in common allergens recognized by T cells from human donors, in order to facilitate the rational design of allergy vaccines. At clinical sites, demographic information and disease history of each enrolled donor are captured, followed by results of an allergen skin test and blood draw. At the laboratory site, T cells derived from blood samples are tested for reactivity against a panel of peptides derived from common human allergens. IMMUNOCAT stores results from these T cell assays along with MHC:peptide binding data, results from RAST tests for antibody titers in donor serum, and the respective donor HLA typing results. Through this system, we are able to perform queries and integrated analyses of the various types of data. This provides a case study for the use of bioinformatics and information management techniques to track and analyze data produced in a translational research study aimed at epitope identification.

  13. Some epitopes conservation in non structural 3 protein dengue virus serotype 4

    Directory of Open Access Journals (Sweden)

    Tegar A. P. Siregar

    2016-03-01

    Full Text Available AbstrakLatar belakang: Protein Non Struktural 3 (NS3 virus dengue menginduksi respon antibodi netralisasidan respon sel T CD4+ dan CD8+, serta berperan dalam replikasi virus. Protein NS3 memiliki epitopepitopsel T dan B yang terdapat perbedaan kelestarian pada berbagai strain virus dengue serotipe 4(DENV-4. Penelitian ini bertujuan untuk mengetahui kelestarian epitop sel T dan B pada protein NS3DENV-4 strain-strain dunia dan keempat serotipe virus dengue strain Indonesia.Metode: Penelitian ini dilakukan di Departemen Mikrobiologi Fakultas Kedokteran UI sejak Juni 2013 - April2014. Sekuens asam amino NS3 DENV-4 strain 081 didapatkan setelah produk PCR gen NS3 DENV-4 081disekuensing. Epitop-epitop sel T dan sel B protein NS3 DENV-4 081 dianalisis dan dibandingkan dengansekuens asam amino protein NS3 dari 124 strain DENV-4 di dunia dan keempat serotipe DENV strain Indonesia.Strain-strain dunia merupakan strain yang ada di benua Amerika (Venezuela, Colombia, dll dan Asia (Cina,Singapura, dll. Referensi posisi epitop sel T dan B protein NS3 diperoleh dari laporan penelitian terdahulu.Hasil: Delapan epitop sel T dan 2 epitop sel B dari protein NS3 DENV-4 081 ternyata identik dan lestaripada protein NS3 dari 124 strain DENV-4 dunia. Epitop sel B di posisi asam amino 537-544 pada proteinNS3 DENV-4 081 ternyata identik dan lestari dengan epitop sel B protein NS3 dari keempat serotipeDENV strain Indonesia.Kesimpulan: Kelestarian yang luas dari epitop sel T dan B pada hampir seluruh strain DENV-4 dunia danserotipe-serotipe DENV strain Indonesia. (Health Science Journal of Indonesia 2015;6:126-31Kata kunci: virus dengue, protein NS3, epitop sel T, epitop sel B AbstractBackground: Non Structural 3 (NS3 protein of dengue virus (DENV is known to induce antibody, CD4+and CD8+ T cell responses, and playing role in viral replication. NS3 protein has T and B cell epitopes,which has conservation difference between DENV-4 strains. This study aimed to identify

  14. EM-21 Retrieval Knowledge Center: Waste Retrieval Challenges

    Energy Technology Data Exchange (ETDEWEB)

    Fellinger, Andrew P.; Rinker, Michael W.; Berglin, Eric J.; Minichan, Richard L.; Poirier, Micheal R.; Gauglitz, Phillip A.; Martin, Bruce A.; Hatchell, Brian K.; Saldivar, Eloy; Mullen, O Dennis; Chapman, Noel F.; Wells, Beric E.; Gibbons, Peter W.

    2009-04-10

    EM-21 is the Waste Processing Division of the Office of Engineering and Technology, within the U.S. Department of Energy’s (DOE) Office of Environmental Management (EM). In August of 2008, EM-21 began an initiative to develop a Retrieval Knowledge Center (RKC) to provide the DOE, high level waste retrieval operators, and technology developers with centralized and focused location to share knowledge and expertise that will be used to address retrieval challenges across the DOE complex. The RKC is also designed to facilitate information sharing across the DOE Waste Site Complex through workshops, and a searchable database of waste retrieval technology information. The database may be used to research effective technology approaches for specific retrieval tasks and to take advantage of the lessons learned from previous operations. It is also expected to be effective for remaining current with state-of-the-art of retrieval technologies and ongoing development within the DOE Complex. To encourage collaboration of DOE sites with waste retrieval issues, the RKC team is co-led by the Savannah River National Laboratory (SRNL) and the Pacific Northwest National Laboratory (PNNL). Two RKC workshops were held in the Fall of 2008. The purpose of these workshops was to define top level waste retrieval functional areas, exchange lessons learned, and develop a path forward to support a strategic business plan focused on technology needs for retrieval. The primary participants involved in these workshops included retrieval personnel and laboratory staff that are associated with Hanford and Savannah River Sites since the majority of remaining DOE waste tanks are located at these sites. This report summarizes and documents the results of the initial RKC workshops. Technology challenges identified from these workshops and presented here are expected to be a key component to defining future RKC-directed tasks designed to facilitate tank waste retrieval solutions.

  15. EM-21 Retrieval Knowledge Center: Waste Retrieval Challenges

    International Nuclear Information System (INIS)

    Fellinger, Andrew P.; Rinker, Michael W.; Berglin, Eric J.; Minichan, Richard L.; Poirier, Micheal R.; Gauglitz, Phillip A.; Martin, Bruce A.; Hatchell, Brian K.; Saldivar, Eloy; Mullen, O Dennis; Chapman, Noel F.; Wells, Beric E.; Gibbons, Peter W.

    2009-01-01

    EM-21 is the Waste Processing Division of the Office of Engineering and Technology, within the U.S. Department of Energy's (DOE) Office of Environmental Management (EM). In August of 2008, EM-21 began an initiative to develop a Retrieval Knowledge Center (RKC) to provide the DOE, high level waste retrieval operators, and technology developers with centralized and focused location to share knowledge and expertise that will be used to address retrieval challenges across the DOE complex. The RKC is also designed to facilitate information sharing across the DOE Waste Site Complex through workshops, and a searchable database of waste retrieval technology information. The database may be used to research effective technology approaches for specific retrieval tasks and to take advantage of the lessons learned from previous operations. It is also expected to be effective for remaining current with state-of-the-art of retrieval technologies and ongoing development within the DOE Complex. To encourage collaboration of DOE sites with waste retrieval issues, the RKC team is co-led by the Savannah River National Laboratory (SRNL) and the Pacific Northwest National Laboratory (PNNL). Two RKC workshops were held in the Fall of 2008. The purpose of these workshops was to define top level waste retrieval functional areas, exchange lessons learned, and develop a path forward to support a strategic business plan focused on technology needs for retrieval. The primary participants involved in these workshops included retrieval personnel and laboratory staff that are associated with Hanford and Savannah River Sites since the majority of remaining DOE waste tanks are located at these sites. This report summarizes and documents the results of the initial RKC workshops. Technology challenges identified from these workshops and presented here are expected to be a key component to defining future RKC-directed tasks designed to facilitate tank waste retrieval solutions

  16. Docking of B-cell epitope antigen to specific hepatitis B antibody

    Indian Academy of Sciences (India)

    The interaction of pres1 region of hepatitis B virus B-cell epitope antigen with specific hepatitis B neutralizing monoclonal antibody was examined by docking study. We modelled the 3D complex structure of B-cell epitope antigen residues CTTPAQGNSMFPSCCCTKPTDGNCY by homology modelling and docked it with the ...

  17. Homology building as a means to define antigenic epitopes on dihydrofolate reductase (DHFR) from Plasmodium falciparum

    DEFF Research Database (Denmark)

    Alifrangis, Michael; Christensen, Inge T; Jørgensen, Flemming S

    2004-01-01

    in the gene coding for Pf-DHFR. Furthermore, we wanted to study the potential use of homology models in general and of Pf-DHFR in particular in predicting antigenic malarial surface epitopes. METHODS: A homology model of Pf-DHFR domain was employed to define an epitope for the development of site...

  18. IgE epitopes of intact and digested Ara h 1

    DEFF Research Database (Denmark)

    Bøgh, Katrine Lindholm; Nielsen, H.; Madsen, Charlotte Bernhard

    2012-01-01

    epitopes have been suggested to be of great importance. ObjectiveThe aim of this study was to identify IgE specific epitopes of intact and digested Ara h 1, and to compare epitope patterns between humans and rats. MethodsSera from five peanut allergic patients and five Brown Norway rats were used...... to identify intact and digested Ara h 1-specific IgE epitopes by competitive immunoscreening of a phage-displayed random hepta-mer peptide library using polyclonal IgE from the individual sera. The resulting peptide sequences were mapped on the surface of a three-dimensional structure of the Ara h 1 molecule...... to mimic epitopes using a computer-based algorithm. ResultsPatients as well as rats were shown to have individual IgE epitope patterns. All epitope mimics were conformational and found to cluster into three different areas of the Ara h 1 molecule. Five epitope motifs were identified by patient IgE, which...

  19. MHC class I epitope binding prediction trained on small data sets

    DEFF Research Database (Denmark)

    Lundegaard, Claus; Nielsen, Morten; Lamberth, K.

    2004-01-01

    The identification of potential T-cell epitopes is important for development of new human or vetenary vaccines, both considering single protein/subunit vaccines, and for epitope/peptide vaccines as such. The highly diverse MHC class I alleles bind very different peptides, and accurate binding pre...... in situations where only very limited data are available for training....

  20. Immunotherapy for Alzheimer's disease: DNA- and protein-based epitope vaccines.

    Science.gov (United States)

    Davtyan, Hayk; Petrushina, Irina; Ghochikyan, Anahit

    2014-01-01

    Active immunotherapy for Alzheimer's disease (AD) is aimed to induce antibodies specific to amyloid-beta (Aβ) that are capable to reduce the level of Aβ in the CNS of Alzheimer's disease patients. First clinical trial AN-1792 that was based on vaccination with full-length Aβ42 showed that safe and effective AD vaccine should induce high titers of anti-Aβ antibodies without activation of harmful autoreactive T cells. Replacement of self-T cell epitope with foreign epitope, keeping self-B cell epitope intact, may allow to induce high titers of anti-Aβ antibodies while avoiding the activation of T cells specific to Aβ. Here we describe the protocols for evaluation of AD DNA- or multiple antigenic peptide (MAP)-based epitope vaccines composed of Aβ(1-11) B cell epitope fused to synthetic T cell epitope PADRE (Aβ(1-11)-PADRE). All protocols could be used for testing any epitope vaccine constructed in your lab and composed of other T cell epitopes using the appropriate peptides in tests for evaluation of humoral and cellular immune responses.

  1. Expression of Hemagglutinin–Neuraminidase and fusion epitopes of Newcastle Disease Virus in transgenic tobacco

    Directory of Open Access Journals (Sweden)

    Amir Ghaffar Shahriari

    2016-07-01

    Conclusion: Developments in genetic engineering have led to plant-based systems for recombinant vaccine production. In this research, tobacco plant was used to express F and HN epitopes of NDV. Our results indicate that for the production of recombinant vaccine, it is a novel strategy to use concatenated epitopes without their genetic fusion onto larger scaffold structure such as viral coat protein.

  2. Cicero, Retrieving the Honorable

    Directory of Open Access Journals (Sweden)

    William A. Frank

    2014-06-01

    Full Text Available From Marcus Tullius Cicero’s philosophical writings, the author first draws out a modest network of ideas that informs his understanding of what it means to be a good man (vir bonus. Then, he finds in Cicero the idea of a befitting mutuality among four distinctively human capacities: a faculty for inquiry into and love for truth manifest in words and actions (reason; a disposition for the recognition of and attraction to things of worth beyond self-interest (the honorable; an acute sense of one own spheres of responsibility along with facility for speaking and acting appropriately within them (appropriate action, and fostering and extending the bonds of mutual personal relations grounded in justice and benevolence (society. Against the background of deep commitments in modernity to hedonism and autonomous individualism, the author proposes a retrieval of the virtue of the honorable as an attractive alternative.

  3. Retrievability: An international overview

    International Nuclear Information System (INIS)

    Richardson, P.J.

    2000-01-01

    Using available information from the published literature and material obtained from a network of contacts, a short introductory overview of international developments in the field of retrievability of emplaced nuclear waste was produced for the Swedish National Siting Coordinator for Nuclear Waste Disposal. This examined the issue in terms of a number of basic questions: Definition, Need, Design Implications, Safeguards for Fissile Material, Public Acceptability and Safety Assessment. The report was submitted in February 1999, and acted as a catalyst for the organisation of an international seminar by KASAM, the Swedish National Council for Nuclear Waste (these proceedings). This paper describes the report contents, and points to the invited papers at the seminar which expand on and update the limited descriptions in the original report. (author)

  4. Beyond information retrieval: information discovery and multimedia information retrieval

    OpenAIRE

    Roberto Raieli

    2017-01-01

    The paper compares the current methodologies for search and discovery of information and information resources: terminological search and term-based language, own of information retrieval (IR); semantic search and information discovery, being developed mainly through the language of linked data; semiotic search and content-based language, experienced by multimedia information retrieval (MIR).MIR semiotic methodology is, then, detailed.

  5. Insulated hsp70B' promoter: stringent heat-inducible activity in replication-deficient, but not replication-competent adenoviruses.

    Science.gov (United States)

    Rohmer, Stanimira; Mainka, Astrid; Knippertz, Ilka; Hesse, Andrea; Nettelbeck, Dirk M

    2008-04-01

    Key to the realization of gene therapy is the development of efficient and targeted gene transfer vectors. Therapeutic gene transfer by replication-deficient or more recently by conditionally replication-competent/oncolytic adenoviruses has shown much promise. For specific applications, however, it will be advantageous to provide vectors that allow for external control of gene expression. The efficient cellular heat shock system in combination with available technology for focused and controlled hyperthermia suggests heat-regulated transcription control as a promising tool for this purpose. We investigated the feasibility of a short fragment of the human hsp70B' promoter, with and without upstream insulator elements, for the regulation of transgene expression by replication-deficient or oncolytic adenoviruses. Two novel adenoviral vectors with an insulated hsp70B' promoter were developed and showed stringent heat-inducible gene expression with induction ratios up to 8000-fold. In contrast, regulation of gene expression from the hsp70B' promoter without insulation was suboptimal. In replication-competent/oncolytic adenoviruses regulation of the hsp70B' promoter was lost specifically during late replication in permissive cells and could not be restored by the insulators. We developed novel adenovirus gene transfer vectors that feature improved and stringent regulation of transgene expression from the hsp70B' promoter using promoter insulation. These vectors have potential for gene therapy applications that benefit from external modulation of therapeutic gene expression or for combination therapy with hyperthermia. Furthermore, our study reveals that vector replication can deregulate inserted cellular promoters, an observation which is of relevance for the development of replication-competent/oncolytic gene transfer vectors. (c) 2008 John Wiley & Sons, Ltd.

  6. Definition of natural T cell antigens with mimicry epitopes obtained from dedicated synthetic peptide libraries.

    Science.gov (United States)

    Hiemstra, H S; van Veelen, P A; Schloot, N C; Geluk, A; van Meijgaarden, K E; Willemen, S J; Leunissen, J A; Benckhuijsen, W E; Amons, R; de Vries, R R; Roep, B O; Ottenhoff, T H; Drijfhout, J W

    1998-10-15

    Progress has recently been made in the use of synthetic peptide libraries for the identification of T cell-stimulating ligands. T cell epitopes identified from synthetic libraries are mimics of natural epitopes. Here we show how the mimicry epitopes obtained from synthetic peptide libraries enable unambiguous identification of natural T cell Ags. Synthetic peptide libraries were screened with Mycobacterium tuberculosis-reactive and -autoreactive T cell clones. In two cases, database homology searches with mimicry epitopes isolated from a dedicated synthetic peptide library allowed immediate identification of the natural antigenic protein. In two other cases, an amino acid pattern that reflected the epitope requirements of the T cell was determined by substitution and omission mixture analysis. Subsequently, the natural Ag was identified from databases using this refined pattern. This approach opens new perspectives for rapid and reliable Ag definition, representing a feasible alternative to the biochemical and genetic approaches described thus far.

  7. Chimeric peptide constructs comprising linear B-cell epitopes: application to the serodiagnosis of infectious diseases.

    Science.gov (United States)

    Lu, Yudong; Li, Zhong; Teng, Huan; Xu, Hongke; Qi, Songnan; He, Jian'an; Gu, Dayong; Chen, Qijun; Ma, Hongwei

    2015-08-21

    Linear B-cell epitopes are ideal biomarkers for the serodiagnosis of infectious diseases. However, the long-predicted diagnostic value of epitopes has not been realized. Here, we demonstrated a method, diagnostic epitopes in four steps (DEIFS), that delivers a combination of epitopes for the serodiagnosis of infectious diseases with a high success rate. Using DEIFS for malaria, we identified 6 epitopes from 8 peptides and combined them into 3 chimeric peptide constructs. Along with 4 other peptides, we developed a rapid diagnostic test (RDT), which is able to differentiate Plasmodium falciparum (P. falciparum) from Plasmodium vivax (P. vivax) infections with 95.6% overall sensitivity and 99.1% overall specificity. In addition to applications in diagnosis, DEIFS could also be used in the diagnosis of virus and bacterium infections, discovery of vaccine candidates, evaluation of vaccine potency, and study of disease progression.

  8. Identification and fine mapping of a linear B cell epitope of human vimentin

    DEFF Research Database (Denmark)

    Dam, Catharina Essendrup; Houen, Gunnar; Hansen, Paul R.

    2014-01-01

    Knowledge about antibody-antigen interactions is important for the understanding of the immune system mechanisms and for supporting development of drugs and biomarkers. A tool for identification of these antigenic epitopes of specific antibodies is epitope mapping. In this study, a modified enzyme......-linked immunosorbent assay was applied for epitope mapping of a mouse monoclonal vimentin antibody using overlapping resin-bound peptides covering the entire vimentin protein. The minimal epitope required for binding was identified as the LDSLPLVD sequence using N- and C-terminally truncated peptides. The peptide...... sequence LDSLPLVDTH was identified as the complete epitope, corresponding to amino acids 428-437 in the C-terminal end of the human vimentin protein. Alanine scanning and functionality scanning applying substituted peptides were used to identify amino acids essential for antibody reactivity. In particular...

  9. Designing Probes for Immunodiagnostics: Structural Insights into an Epitope Targeting Burkholderia Infections.

    Science.gov (United States)

    Capelli, Riccardo; Matterazzo, Elena; Amabili, Marco; Peri, Claudio; Gori, Alessandro; Gagni, Paola; Chiari, Marcella; Lertmemongkolchai, Ganjana; Cretich, Marina; Bolognesi, Martino; Colombo, Giorgio; Gourlay, Louise J

    2017-10-13

    Structure-based epitope prediction drives the design of diagnostic peptidic probes to reveal specific antibodies elicited in response to infections. We previously identified a highly immunoreactive epitope from the peptidoglycan-associated lipoprotein (Pal) antigen from Burkholderia pseudomallei, which could also diagnose Burkholderia cepacia infections. Here, considering the high phylogenetic conservation within Burkholderia species, we ask whether cross-reactivity can be reciprocally displayed by the synthetic epitope from B. cenocepacia. We perform comparative analyses of the conformational preferences and diagnostic performances of the corresponding epitopes from the two Burkholderia species when presented in the context of the full-length proteins or as isolated peptides. The effects of conformation on the diagnostic potential and cross-reactivity of Pal peptide epitopes are rationalized on the basis of the 1.8 Å crystal structure of B. cenocepacia Pal and through computational analyses. Our results are discussed in the context of designing new diagnostic molecules for the early detection of infectious diseases.

  10. Structural analysis of linear and conformational epitopes of allergens

    Science.gov (United States)

    Ivanciuc, Ovidiu; Schein, Catherine H.; Garcia, Tzintzuni; Oezguen, Numan; Negi, Surendra S.; Braun, Werner

    2009-01-01

    In many countries regulatory agencies have adopted safety guidelines, based on bioinformatics rules from the WHO/FAO and EFSA recommendations, to prevent potentially allergenic novel foods or agricultural products from reaching consumers. We created the Structural Database of Allergenic Proteins (SDAP, http://fermi.utmb.edu/SDAP/) to combine data that had previously been available only as flat files on Web pages or in the literature. SDAP was designed to be user friendly, to be of maximum use to regulatory agencies, clinicians, as well as to scientists interested in assessing the potential allergenic risk of a protein. We developed methods, unique to SDAP, to compare the physicochemical properties of discrete areas of allergenic proteins to known IgE epitopes. We developed a new similarity measure, the property distance (PD) value that can be used to detect related segments in allergens with clinical observed crossreactivity. We have now expanded this work to obtain experimental validation of the PD index as a quantitative predictor of IgE cross-reactivity, by designing peptide variants with predetermined PD scores relative to known IgE epitopes. In complementary work we show how sequence motifs characteristic of allergenic proteins in protein families can be used as fingerprints for allergenicity. PMID:19121639

  11. Selection of SARS-Coronavirus-specific B cell epitopes by phage peptide library screening and evaluation of the immunological effect of epitope-based peptides on mice

    International Nuclear Information System (INIS)

    Yu Hua; Jiang Lifang; Fang Danyun; Yan Huijun; Zhou Jingjiao; Zhou Junmei; Liang Yu; Gao Yang; Zhao, Wei; Long Beiguo

    2007-01-01

    Antibodies to SARS-Coronavirus (SARS-CoV)-specific B cell epitopes might recognize the pathogen and interrupt its adherence to and penetration of host cells. Hence, these epitopes could be useful for diagnosis and as vaccine constituents. Using the phage-displayed peptide library screening method and purified Fab fragments of immunoglobulin G (IgG Fab) from normal human sera and convalescent sera from SARS-CoV-infected patients as targets, 11 B cell epitopes of SARS-CoV spike glycoprotein (S protein) and membrane protein (M protein) were screened. After a bioinformatics tool was used to analyze these epitopes, four epitope-based S protein dodecapeptides corresponding to the predominant epitopes were chosen for synthesis. Their antigenic specificities and immunogenicities were studied in vitro and in vivo. Flow cytometry and ELISPOT analysis of lymphocytes as well as a serologic analysis of antibody showed that these peptides could trigger a rapid, highly effective, and relatively safe immune response in BALB/c mice. These findings might aid development of SARS diagnostics and vaccines. Moreover, the role of S and M proteins as important surface antigens is confirmed

  12. Identification of candidate genes and molecular markers for heat-induced brown discoloration of seed coats in cowpea [Vigna unguiculata (L.) Walp].

    Science.gov (United States)

    Pottorff, Marti; Roberts, Philip A; Close, Timothy J; Lonardi, Stefano; Wanamaker, Steve; Ehlers, Jeffrey D

    2014-05-01

    Heat-induced browning (Hbs) of seed coats is caused by high temperatures which discolors the seed coats of many legumes, affecting the visual appearance and quality of seeds. The genetic determinants underlying Hbs in cowpea are unknown. We identified three QTL associated with the heat-induced browning of seed coats trait, Hbs-1, Hbs-2 and Hbs-3, using cowpea RIL populations IT93K-503-1 (Hbs positive) x CB46 (hbs negative) and IT84S-2246 (Hbs positive) x TVu14676 (hbs negative). Hbs-1 was identified in both populations, accounting for 28.3% -77.3% of the phenotypic variation. SNP markers 1_0032 and 1_1128 co-segregated with the trait. Within the syntenic regions of Hbs-1 in soybean, Medicago and common bean, several ethylene forming enzymes, ethylene responsive element binding factors and an ACC oxidase 2 were observed. Hbs-1 was identified in a BAC clone in contig 217 of the cowpea physical map, where ethylene forming enzymes were present. Hbs-2 was identified in the IT93K-503-1 x CB46 population and accounted for of 9.5 to 12.3% of the phenotypic variance. Hbs-3 was identified in the IT84S-2246 x TVu14676 population and accounted for 6.2 to 6.8% of the phenotypic variance. SNP marker 1_0640 co-segregated with the heat-induced browning phenotype. Hbs-3 was positioned on BAC clones in contig512 of the cowpea physical map, where several ACC synthase 1 genes were present. The identification of loci determining heat-induced browning of seed coats and co-segregating molecular markers will enable transfer of hbs alleles into cowpea varieties, contributing to higher quality seeds.

  13. ArrayPitope: Automated Analysis of Amino Acid Substitutions for Peptide Microarray-Based Antibody Epitope Mapping

    DEFF Research Database (Denmark)

    Hansen, Christian Skjødt; Østerbye, Thomas; Marcatili, Paolo

    2017-01-01

    -reactivity. B cell epitopes are typically classified as either linear epitopes, i.e. short consecutive segments from the protein sequence or conformational epitopes adapted through native protein folding. Recent advances in high-density peptide microarrays enable high-throughput, high-resolution identification...

  14. A novel multi-variant epitope ensemble vaccine against avian leukosis virus subgroup J.

    Science.gov (United States)

    Wang, Xiaoyu; Zhou, Defang; Wang, Guihua; Huang, Libo; Zheng, Qiankun; Li, Chengui; Cheng, Ziqiang

    2017-12-04

    The hypervariable antigenicity and immunosuppressive features of avian leukosis virus subgroup J (ALV-J) has led to great challenges to develop effective vaccines. Epitope vaccine will be a perspective trend. Previously, we identified a variant antigenic neutralizing epitope in hypervariable region 1 (hr1) of ALV-J, N-LRDFIA/E/TKWKS/GDDL/HLIRPYVNQS-C. BLAST analysis showed that the mutation of A, E, T and H in this epitope cover 79% of all ALV-J strains. Base on this data, we designed a multi-variant epitope ensemble vaccine comprising the four mutation variants linked with glycine and serine. The recombinant multi-variant epitope gene was expressed in Escherichia coli BL21. The expressed protein of the variant multi-variant epitope gene can react with positive sera and monoclonal antibodies of ALV-J, while cannot react with ALV-J negative sera. The multi-variant epitope vaccine that conjugated Freund's adjuvant complete/incomplete showed high immunogenicity that reached the titer of 1:64,000 at 42 days post immunization and maintained the immune period for at least 126 days in SPF chickens. Further, we demonstrated that the antibody induced by the variant multi-variant ensemble epitope vaccine recognized and neutralized different ALV-J strains (NX0101, TA1, WS1, BZ1224 and BZ4). Protection experiment that was evaluated by clinical symptom, viral shedding, weight gain, gross and histopathology showed 100% chickens that inoculated the multi-epitope vaccine were well protected against ALV-J challenge. The result shows a promising multi-variant epitope ensemble vaccine against hypervariable viruses in animals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Contextual Bandits for Information Retrieval

    NARCIS (Netherlands)

    Hofmann, K.; Whiteson, S.; de Rijke, M.

    2011-01-01

    In this paper we give an overview of and outlook on research at the intersection of information retrieval (IR) and contextual bandit problems. A critical problem in information retrieval is online learning to rank, where a search engine strives to improve the quality of the ranked result lists it

  16. Retrieval Practice Benefits Deductive Inference

    Science.gov (United States)

    Eglington, Luke G.; Kang, Sean H. K.

    2018-01-01

    Retrieval practice has been shown to benefit learning. However, the benefit has sometimes been attenuated with more complex materials that require integrating multiple units of information. Critically, Tran et al. "Psychonomic Bulletin & Review, 22," 135-140 (2015) found that retrieval practice improves sentence memory but not the…

  17. Topology of Document Retrieval Systems.

    Science.gov (United States)

    Everett, Daniel M.; Cater, Steven C.

    1992-01-01

    Explains the use of a topological structure to examine the closeness between documents in retrieval systems and analyzes the topological structure of a vector-space model, a fuzzy-set model, an extended Boolean model, a probabilistic model, and a TIRS (Topological Information Retrieval System) model. Proofs for the results are appended. (17…

  18. Intelligent Information Retrieval: An Introduction.

    Science.gov (United States)

    Gauch, Susan

    1992-01-01

    Discusses the application of artificial intelligence to online information retrieval systems and describes several systems: (1) CANSEARCH, from MEDLINE; (2) Intelligent Interface for Information Retrieval (I3R); (3) Gausch's Query Reformulation; (4) Environmental Pollution Expert (EP-X); (5) PLEXUS (gardening); and (6) SCISOR (corporate…

  19. How to average logarithmic retrievals?

    Directory of Open Access Journals (Sweden)

    B. Funke

    2012-04-01

    Full Text Available Calculation of mean trace gas contributions from profiles obtained by retrievals of the logarithm of the abundance rather than retrievals of the abundance itself are prone to biases. By means of a system simulator, biases of linear versus logarithmic averaging were evaluated for both maximum likelihood and maximum a priori retrievals, for various signal to noise ratios and atmospheric variabilities. These biases can easily reach ten percent or more. As a rule of thumb we found for maximum likelihood retrievals that linear averaging better represents the true mean value in cases of large local natural variability and high signal to noise ratios, while for small local natural variability logarithmic averaging often is superior. In the case of maximum a posteriori retrievals, the mean is dominated by the a priori information used in the retrievals and the method of averaging is of minor concern. For larger natural variabilities, the appropriateness of the one or the other method of averaging depends on the particular case because the various biasing mechanisms partly compensate in an unpredictable manner. This complication arises mainly because of the fact that in logarithmic retrievals the weight of the prior information depends on abundance of the gas itself. No simple rule was found on which kind of averaging is superior, and instead of suggesting simple recipes we cannot do much more than to create awareness of the traps related with averaging of mixing ratios obtained from logarithmic retrievals.

  20. Vocabulary Control for Information Retrieval.

    Science.gov (United States)

    Lancaster, F. W.

    This book deals with properties of vocabularies for indexing and searching document collections; the construction, organization, display, and maintenance of these vocabularies; and the vocabulary as a factor affecting the performance of retrieval systems. Most of the text is concerned with vocabularies for post-coordinate retrieval systems, with…

  1. Affinity study on bovine serum albumin's peptides to amphiphilic gold nanoparticles: A test of epitopes and non-epitopes

    Science.gov (United States)

    Yuan, Ming; Li, Wanrong; Yang, Mingming; Huang, Xiufeng; Bai, Zhijun; Liu, Yushuang; Cai, Weijun; Wang, Yuqin; Zhang, Feng

    2017-09-01

    It is an inevitable event that nanoparticles (NPs) will encounter proteins/peptides in nano-medicine, so it has been significant to know their interaction mechanism before in vivo applications. Previously, a 105-amino-acid sequence had been reported as the binding site between bovine serum albumin (BSA) and amphiphilic polymer coated gold nanoparticles (AP-AuNPs) along with a mortise-tenon joint hypothesis. This article tested the affinity difference between two epitope peptide sequences such as: LGEYGFQNALIVR (S1), DAFLGSFLYEYSR (S2) and one non-epitope peptide sequence as: FDEHVKLVNELTEF (S3). With the photoluminescent amino acid residues, the fluorescence quenching method based on the nanometal surface energy transfer (NSET) principle was able to study the thermodynamics of the current binding system. The binding constants (Ka) were determined and followed the order as: Ka-S1 > Ka-S2 >> Ka-S3. Moreover, Hill constants indicated that cooperativity only presented in the interactions of AP-AuNP with either S1 or S2, but not for S3. Moreover, gel electrophoresis, surface plasmon resonance, atomic force microscopy and three dimensional fluorescence microscopy were all also used to comprehensively analyse the binding interaction mechanism. These results further provided useful information to better understand the mortise-tenon joint, which might find applications to nanofabrication and biomedicine.

  2. Bayesian aerosol retrieval algorithm for MODIS AOD retrieval over land

    Science.gov (United States)

    Lipponen, Antti; Mielonen, Tero; Pitkänen, Mikko R. A.; Levy, Robert C.; Sawyer, Virginia R.; Romakkaniemi, Sami; Kolehmainen, Ville; Arola, Antti

    2018-03-01

    We have developed a Bayesian aerosol retrieval (BAR) algorithm for the retrieval of aerosol optical depth (AOD) over land from the Moderate Resolution Imaging Spectroradiometer (MODIS). In the BAR algorithm, we simultaneously retrieve all dark land pixels in a granule, utilize spatial correlation models for the unknown aerosol parameters, use a statistical prior model for the surface reflectance, and take into account the uncertainties due to fixed aerosol models. The retrieved parameters are total AOD at 0.55 µm, fine-mode fraction (FMF), and surface reflectances at four different wavelengths (0.47, 0.55, 0.64, and 2.1 µm). The accuracy of the new algorithm is evaluated by comparing the AOD retrievals to Aerosol Robotic Network (AERONET) AOD. The results show that the BAR significantly improves the accuracy of AOD retrievals over the operational Dark Target (DT) algorithm. A reduction of about 29 % in the AOD root mean square error and decrease of about 80 % in the median bias of AOD were found globally when the BAR was used instead of the DT algorithm. Furthermore, the fraction of AOD retrievals inside the ±(0.05+15 %) expected error envelope increased from 55 to 76 %. In addition to retrieving the values of AOD, FMF, and surface reflectance, the BAR also gives pixel-level posterior uncertainty estimates for the retrieved parameters. The BAR algorithm always results in physical, non-negative AOD values, and the average computation time for a single granule was less than a minute on a modern personal computer.

  3. Systematic screening for novel, serologically reactive Hepatitis E Virus epitopes

    Directory of Open Access Journals (Sweden)

    Osterman Andreas

    2012-01-01

    Full Text Available Abstract Background The National Institutes of Health classified Hepatitis E as an emerging disease since Hepatitis E Virus (HEV is the major cause of acute hepatitis in developing countries. Interestingly, an increasing number of sporadic cases of HEV infections are described in industrialized countries as zoonosis from domestic livestock. Despite the increasing relevance of this pathogen in clinical virology, commercial antibody assays are mainly based on fragments of HEV open reading frame (ORF 2 and ORF3. The largest ORF1 (poly-protein, however, is not part of current testing formats. Methods From a synthesized full length HEV genotype 1 cDNA-bank we constructed a complete HEV gene library consisting of 15 respective HEV ORF domains. After bacterial expression and purification of nine recombinant HEV proteins under denaturating conditions serum profiling experiments using 55 sera from patients with known infection status were performed in microarray format. SPSS software assessed the antigenic potential of these nine ORF domains in comparison to seven commercial HEV antigens (genotype 1 and 3 by performing receiver operator characteristics, logistic regression and correlation analysis. Results HEV antigens produced with our method for serum profiling experiments exhibit the same quality and characteristics as commercial antigens. Serum profiling experiments detected Y, V and X domains as ORF1-antigens with potentially comparable diagnostic significance as the well established epitopes of ORF2 and ORF3. However no obvious additional increase in sensitivity or specificity was achieved in diagnostic testing as revealed by bioinformatic analysis. Additionally we found that the C-terminal domain of the potential transmembrane protein ORF3 is responsible for IgG and IgM seroreactivity. Data suggest that there might be a genotype specific seroreactivity of homologous ORF2-antigens. Conclusions The diagnostic value of identified ORF1 epitopes might

  4. Venous duplex and pathologic differences in thrombus characteristics between de novo deep vein thrombi and endovenous heat-induced thrombi.

    Science.gov (United States)

    Santin, Brian J; Lohr, Joanne M; Panke, Thomas W; Neville, Patrick M; Felinski, Melissa M; Kuhn, Brian A; Recht, Matthew H; Muck, Patrick E

    2015-04-01

    Superficial venous reflux disease has been treated with endovenous ablation techniques for more than 15 years. Thrombi discovered in the postoperative period are referred to as endovenous heat-induced thrombi (EHIT). In spite of the few studies of the ultrasound differentiation between EHIT and deep vein thrombi (DVT), there remains a paucity of literature regarding the evaluation of ultrasound examination and pathologic differentiation. Six Yorkshire cross swine underwent femoral vein thrombosis by suture ligation or endovenous radiofrequency ablation. At 1 week after the procedure, each femoral vein was imaged by color Duplex ultrasound and sent for histologic interpretation for differentiation between EHIT and DVT. Five blinded vascular surgery faculty, two vascular surgery fellows, and three vascular surgery residents reviewed the ultrasound images. Thrombi associated with radiofrequency ablation demonstrated a greater degree of hypercellular response, fibroblastic reaction, and edema (3.42 vs 2.92; 3.75 vs 2.42; 2.83 vs 1.33). Specimens harvested from the iatrogenic-induced DVT swine demonstrated a more prolific response to trichrome staining (3.42 vs 2.67). Evidence of revascularization was found in all of the EHIT specimens but in 33% of DVT specimens. On the basis of histologic findings, the pathologist predicted correct modality 92% of the time. Subgroup analysis comparing paired specimens from each swine failed to demonstrate any marked pathologic differences. Recorded ultrasound images from EHIT and DVT samples were reviewed by fellows, residents, and vascular surgery staff to determine whether clot was stationary or free-floating (n = 111; 93%), evidence of retracted or adherent vein (n = 105; 88%), and absence of color flow (n = 102; 85%). The degree of occlusion (partial vs total) and degree of distention of a visualized vein were least likely to be agreed on by reviewers (n = 95; 79% each, respectively). In subgroup (DVT vs EHIT) analyses, the

  5. PepMapper: a collaborative web tool for mapping epitopes from affinity-selected peptides.

    Directory of Open Access Journals (Sweden)

    Wenhan Chen

    Full Text Available Epitope mapping from affinity-selected peptides has become popular in epitope prediction, and correspondingly many Web-based tools have been developed in recent years. However, the performance of these tools varies in different circumstances. To address this problem, we employed an ensemble approach to incorporate two popular Web tools, MimoPro and Pep-3D-Search, together for taking advantages offered by both methods so as to give users more options for their specific purposes of epitope-peptide mapping. The combined operation of Union finds as many associated peptides as possible from both methods, which increases sensitivity in finding potential epitopic regions on a given antigen surface. The combined operation of Intersection achieves to some extent the mutual verification by the two methods and hence increases the likelihood of locating the genuine epitopic region on a given antigen in relation to the interacting peptides. The Consistency between Intersection and Union is an indirect sufficient condition to assess the likelihood of successful peptide-epitope mapping. On average from 27 tests, the combined operations of PepMapper outperformed either MimoPro or Pep-3D-Search alone. Therefore, PepMapper is another multipurpose mapping tool for epitope prediction from affinity-selected peptides. The Web server can be freely accessed at: http://informatics.nenu.edu.cn/PepMapper/

  6. Identification and characterization of two linear epitope motifs in hepatitis E virus ORF2 protein.

    Directory of Open Access Journals (Sweden)

    Heng Wang

    Full Text Available Hepatitis E virus (HEV is responsible for hepatitis E, which represents a global public health problem. HEV genotypes 3 and 4 are reported to be zoonotic, and animals are monitored for HEV infection in the interests of public hygiene and food safety. The development of novel diagnostic methods and vaccines for HEV in humans is thus important topics of research. Opening reading frame (ORF 2 of HEV includes both linear and conformational epitopes and is regarded as the primary candidate for vaccines and diagnostic tests. We investigated the precise location of the HEV epitopes in the ORF2 protein. We prepared four monoclonal antibodies (mAbs against genotype 4 ORF2 protein and identified two linear epitopes, G438IVIPHD444 and Y457DNQH461, corresponding to two of these mAbs using phage display biopanning technology. Both these epitopes were speculated to be universal to genotypes 1, 2, 3, 4, and avian HEVs. We also used two 12-mer fragments of ORF2 protein including these two epitopes to develop a peptide-based enzyme-linked immunosorbent assay (ELISA to detect HEV in serum. This assay demonstrated good specificity but low sensitivity compared with the commercial method, indicating that these two epitopes could serve as potential candidate targets for diagnosis. Overall, these results further our understanding of the epitope distribution of HEV ORF2, and provide important information for the development of peptide-based immunodiagnostic tests to detect HEV in serum.

  7. Differential Recognition of Mycobacterium tuberculosis-Specific Epitopes as a Function of Tuberculosis Disease History.

    Science.gov (United States)

    Scriba, Thomas J; Carpenter, Chelsea; Pro, Sebastian Carrasco; Sidney, John; Musvosvi, Munyaradzi; Rozot, Virginie; Seumois, Grégory; Rosales, Sandy L; Vijayanand, Pandurangan; Goletti, Delia; Makgotlho, Edward; Hanekom, Willem; Hatherill, Mark; Peters, Bjoern; Sette, Alessandro; Arlehamn, Cecilia S Lindestam

    2017-09-15

    Individuals with a history of tuberculosis (TB) disease are at elevated risk of disease recurrence. The underlying cause is not known, but one explanation is that previous disease results in less-effective immunity against Mycobacterium tuberculosis (Mtb). We hypothesized that the repertoire of Mtb-derived epitopes recognized by T cells from individuals with latent Mtb infection differs as a function of previous diagnosis of active TB disease. T-cell responses to peptide pools in samples collected from an adult screening and an adolescent validation cohort were measured by IFN-γ enzyme-linked immunospot assay or intracellular cytokine staining. We identified a set of "type 2" T-cell epitopes that were recognized at 10-fold-lower levels in Mtb-infected individuals with a history of TB disease less than 6 years ago than in those without previous TB. By contrast, "type 1" epitopes were recognized equally well in individuals with or without previous TB. The differential epitope recognition was not due to differences in HLA class II binding, memory phenotypes, or gene expression in the responding T cells. Instead, "TB disease history-sensitive" type 2 epitopes were significantly (P < 0.0001) more homologous to sequences from bacteria found in the human microbiome than type 1 epitopes. Preferential loss of T-cell reactivity to Mtb epitopes that are homologous to bacteria in the microbiome in persons with previous TB disease may reflect long-term effects of antibiotic TB treatment on the microbiome.

  8. Automated identification of complementarity determining regions (CDRs) reveals peculiar characteristics of CDRs and B cell epitopes.

    Science.gov (United States)

    Ofran, Yanay; Schlessinger, Avner; Rost, Burkhard

    2008-11-01

    Exact identification of complementarity determining regions (CDRs) is crucial for understanding and manipulating antigenic interactions. One way to do this is by marking residues on the antibody that interact with B cell epitopes on the antigen. This, of course, requires identification of B cell epitopes, which could be done by marking residues on the antigen that bind to CDRs, thus requiring identification of CDRs. To circumvent this vicious circle, existing tools for identifying CDRs are based on sequence analysis or general biophysical principles. Often, these tools, which are based on partial data, fail to agree on the boundaries of the CDRs. Herein we present an automated procedure for identifying CDRs and B cell epitopes using consensus structural regions that interact with the antigens in all known antibody-protein complexes. Consequently, we provide the first comprehensive analysis of all CDR-epitope complexes of known three-dimensional structure. The CDRs we identify only partially overlap with the regions suggested by existing methods. We found that the general physicochemical properties of both CDRs and B cell epitopes are rather peculiar. In particular, only four amino acids account for most of the sequence of CDRs, and several types of amino acids almost never appear in them. The secondary structure content and the conservation of B cell epitopes are found to be different than previously thought. These characteristics of CDRs and epitopes may be instrumental in choosing which residues to mutate in experimental search for epitopes. They may also assist in computational design of antibodies and in predicting B cell epitopes.

  9. Epitope Identification and Application for Diagnosis of Duck Tembusu Virus Infections in Ducks

    Directory of Open Access Journals (Sweden)

    Chenxi Li

    2016-11-01

    Full Text Available Duck Tembusu virus (DTMUV causes substantial egg drop disease. DTMUV was first identified in China and rapidly spread to Malaysia and Thailand. The antigenicity of the DTMUV E protein has not yet been characterized. Here, we investigated antigenic sites on the E protein using the non-neutralizing monoclonal antibodies (mAbs 1F3 and 1A5. Two minimal epitopes were mapped to 221LD/NLPW225 and 87YAEYI91 by using phage display and mutagenesis. DTMUV-positive duck sera reacted with the epitopes, thus indicating the importance of the minimal amino acids of the epitopes for antibody-epitope binding. The performance of the dot blotting assay with the corresponding positive sera indicated that YAEYI was DTMUV type-specific, whereas 221LD/NLPW225 was a cross-reactive epitope for West Nile virus (WNV, dengue virus (DENV, and Japanese encephalitis virus (JEV and corresponded to conserved and variable amino acid sequences among these strains. The structure model of the E protein revealed that YAEYI and LD/NLPW were located on domain (D II, which confirmed that DII might contain a type-specific non-neutralizing epitope. The YAEYI epitope-based antigen demonstrated its diagnostic potential by reacting with high specificity to serum samples obtained from DTMUV-infected ducks. Based on these observations, a YAEYI-based serological test could be used for DTMUV surveillance and could differentiate DTMUV infections from JEV or WNV infections. These findings provide new insights into the organization of epitopes on flavivirus E proteins that might be valuable for the development of epitope-based serological diagnostic tests for DTMUV.

  10. Interactive Exploration for Image Retrieval

    Directory of Open Access Journals (Sweden)

    Jérôme Fournier

    2005-08-01

    Full Text Available We present a new version of our content-based image retrieval system RETIN. It is based on adaptive quantization of the color space, together with new features aiming at representing the spatial relationship between colors. Color analysis is also extended to texture. Using these powerful indexes, an original interactive retrieval strategy is introduced. The process is based on two steps for handling the retrieval of very large image categories. First, a controlled exploration method of the database is presented. Second, a relevance feedback method based on statistical learning is proposed. All the steps are evaluated by experiments on a generalist database.

  11. Rhetorical relations for information retrieval

    DEFF Research Database (Denmark)

    Lioma, Christina; Larsen, Birger; Lu, Wei

    2012-01-01

    -called discourse structure has been applied successfully to several natural language processing tasks. This work studies the use of rhetorical relations for Information Retrieval (IR): Is there a correlation between certain rhetorical relations and retrieval performance? Can knowledge about a document’s rhetorical...... relations be useful to IR? We present a language model modification that considers rhetorical relations when estimating the relevance of a document to a query. Empirical evaluation of different versions of our model on TREC settings shows that certain rhetorical relations can benefit retrieval effectiveness...

  12. Large-scale validation of methods for cytotoxic T-lymphocyte epitope prediction

    DEFF Research Database (Denmark)

    Larsen, Mette Voldby; Lundegaard, Claus; Lamberth, K.

    2007-01-01

    BACKGROUND: Reliable predictions of Cytotoxic T lymphocyte (CTL) epitopes are essential for rational vaccine design. Most importantly, they can minimize the experimental effort needed to identify epitopes. NetCTL is a web-based tool designed for predicting human CTL epitopes in any given protein....... of the other methods achieved a sensitivity of 0.64. The NetCTL-1.2 method is available at http://www.cbs.dtu.dk/services/NetCTL.All used datasets are available at http://www.cbs.dtu.dk/suppl/immunology/CTL-1.2.php....

  13. T-cell recognition is shaped by epitope sequence conservation in the host proteome and microbiome

    DEFF Research Database (Denmark)

    Bresciani, Anne Gøther; Paul, Sinu; Schommer, Nina

    2016-01-01

    or allergen with the conservation of its sequence in the human proteome or the healthy human microbiome. Indeed, performing such comparisons on large sets of validated T-cell epitopes, we found that epitopes that are similar with self-antigens above a certain threshold showed lower immunogenicity, presumably...... as a result of negative selection of T cells capable of recognizing such peptides. Moreover, we also found a reduced level of immune recognition for epitopes conserved in the commensal microbiome, presumably as a result of peripheral tolerance. These findings indicate that the existence (and potentially...

  14. A novel monoclonal antibody to a defined peptide epitope in MUC16

    DEFF Research Database (Denmark)

    Marcos-Silva, Lara; Ricardo, Sara; Chen, Kowa

    2015-01-01

    with the tandem-repeat region, their epitopes appear to be conformational dependent and not definable by a short peptide. Aberrant glycoforms of MUC16 may constitute promising targets for diagnostic and immunotherapeutic intervention, and it is important to develop well-defined immunogens for induction of potent...... immunodominant linear peptide epitopes within the tandem repeat. We developed one monoclonal antibody, 5E11, reactive with a minimum epitope with the sequence FNTTER. This sequence contains potential N- and O-glycosylation sites and, interestingly, glycosylation blocked binding of 5E11. In immunochemistry...

  15. CD4+ T cells targeting dominant and cryptic epitopes from Bacillus anthracis Lethal Factor

    Directory of Open Access Journals (Sweden)

    Stephanie eAscough

    2016-01-01

    Full Text Available Anthrax is an endemic infection in many countries, particularly in the developing world. The causative agent, Bacillus anthracis, mediates disease through the secretion of binary exotoxins. Until recently, research into adaptive immunity targeting this bacterial pathogen has largely focused on the humoral response to these toxins. There is, however, growing recognition that cellular immune responses involving IFNγ producing CD4+ T cells also contribute significantly to a protective memory response. An established concept in adaptive immunity to infection is that during infection of host cells, new microbial epitopes may be revealed, leading to immune recognition of so called ‘cryptic’ or ‘subdominant’ epitopes. We analysed the response to both cryptic and immunodominant T cell epitopes derived from the toxin component lethal factor and presented by a range of HLA-DR alleles. Using IFNγ-ELISPOT assays we characterised epitopes that elicited a response following immunisation with synthetic peptide and the whole protein and tested their capacities to bind purified HLA-DR molecules in vitro. We found that DR1 transgenics demonstrated T cell responses to a greater number of domain III cryptic epitopes than other HLA-DR transgenics, and that this pattern was repeated with the immunodominant epitopes, a greater proportion of these epitopes induced a T cell response when presented within the context of the whole protein. Immunodominant epitopes LF457-476 and LF467-487 were found to induce a T cell response to the peptide, as well as to the whole native LF protein in DR1 and DR15, but not in DR4 trangenics. The analysis of Domain I revealed the presence of several unique cryptic epitopes all of which showed a strong to moderate relative binding affinity to HLA-DR4 molecules. However, none of the cryptic epitopes from either domain III or I displayed notably high binding affinities across all HLA-DR alleles assayed. These responses were

  16. Reliable B cell epitope predictions: impacts of method development and improved benchmarking

    DEFF Research Database (Denmark)

    Kringelum, Jens Vindahl; Lundegaard, Claus; Lund, Ole

    2012-01-01

    biomedical applications such as; rational vaccine design, development of disease diagnostics and immunotherapeutics. However, experimental mapping of epitopes is resource intensive making in silico methods an appealing complementary approach. To date, the reported performance of methods for in silico mapping...... evaluation data set improved from 0.712 to 0.727. Our results thus demonstrate that given proper benchmark definitions, B-cell epitope prediction methods achieve highly significant predictive performances suggesting these tools to be a powerful asset in rational epitope discovery. The updated version...

  17. Ab-initio conformational epitope structure prediction using genetic algorithm and SVM for vaccine design.

    Science.gov (United States)

    Moghram, Basem Ameen; Nabil, Emad; Badr, Amr

    2018-01-01

    T-cell epitope structure identification is a significant challenging immunoinformatic problem within epitope-based vaccine design. Epitopes or antigenic peptides are a set of amino acids that bind with the Major Histocompatibility Complex (MHC) molecules. The aim of this process is presented by Antigen Presenting Cells to be inspected by T-cells. MHC-molecule-binding epitopes are responsible for triggering the immune response to antigens. The epitope's three-dimensional (3D) molecular structure (i.e., tertiary structure) reflects its proper function. Therefore, the identification of MHC class-II epitopes structure is a significant step towards epitope-based vaccine design and understanding of the immune system. In this paper, we propose a new technique using a Genetic Algorithm for Predicting the Epitope Structure (GAPES), to predict the structure of MHC class-II epitopes based on their sequence. The proposed Elitist-based genetic algorithm for predicting the epitope's tertiary structure is based on Ab-Initio Empirical Conformational Energy Program for Peptides (ECEPP) Force Field Model. The developed secondary structure prediction technique relies on Ramachandran Plot. We used two alignment algorithms: the ROSS alignment and TM-Score alignment. We applied four different alignment approaches to calculate the similarity scores of the dataset under test. We utilized the support vector machine (SVM) classifier as an evaluation of the prediction performance. The prediction accuracy and the Area Under Receiver Operating Characteristic (ROC) Curve (AUC) were calculated as measures of performance. The calculations are performed on twelve similarity-reduced datasets of the Immune Epitope Data Base (IEDB) and a large dataset of peptide-binding affinities to HLA-DRB1*0101. The results showed that GAPES was reliable and very accurate. We achieved an average prediction accuracy of 93.50% and an average AUC of 0.974 in the IEDB dataset. Also, we achieved an accuracy of 95

  18. Application of phage peptide display technology for the study of food allergen epitopes.

    Science.gov (United States)

    Chen, Xueni; Dreskin, Stephen C

    2017-06-01

    Phage peptide display technology has been used to identify IgE-binding mimotopes (mimics of natural epitopes) that mimic conformational epitopes. This approach is effective in the characterization of those epitopes that are important for eliciting IgE-mediated allergic responses by food allergens and those that are responsible for cross-reactivity among allergenic food proteins. Application of this technology will increase our understanding of the mechanisms whereby food allergens elicit allergic reactions, will facilitate the discovery of diagnostic reagents and may lead to mimotope-based immunotherapy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Identification of a variant antigenic neutralizing epitope in hypervariable region 1 of avian leukosis virus subgroup J.

    Science.gov (United States)

    Hou, Minbo; Zhou, Defang; Li, Gen; Guo, Huijun; Liu, Jianzhu; Wang, Guihua; Zheng, Qiankun; Cheng, Ziqiang

    2016-03-08

    Avian leukosis virus subgroup J (ALV-J) is a hypervariable oncogenic retrovirus that causes great economic loss in poultry. Antigenic variations in the variable regions make the development of an effective vaccine a challenging task. In the present study, we identified a variant antigenic neutralizing epitope using reverse vaccinology methods. First, we predicted the B-cell epitopes in gp85 gene of ALV-J strains by DNAman and bioinformatics. Fourteen candidate epitopes were selected and linked in tandem with glycines or serines as a multi-epitope gene. The expressed protein of multi-epitope gene can induce high-titer antibody that can recognize nature ALV-J and neutralize the infectivity of ALV-J strains. Next, we identified a high effective epitope using eight overlapping fragments of gp85 gene reacting with mAb 2D5 and anti-multi-epitope sera. The identified epitope contained one of the predicted epitopes and localized in hyervariable region 1 (hr1), indicating a variant epitope. To better understand if the variants of the epitope have a good antigenicity, we synthesized four variants to react with mAb 2D5 and anti-ALV-J sera. The result showed that all variants could react with the two kinds of antibodies though they showed different antigenicity, while could not react with ALV-J negative sera. Thus, the variant antigenic neutralizing epitope was determined as 137-LRDFIA/E/TKWKS/GDDL/HLIRPYVNQS-158. The result shows a potential use of this variant epitopes as a novel multi-epitope vaccine against ALV-J in poultry. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Discovery of novel targets for multi-epitope vaccines: Screening of HIV-1 genomes using association rule mining

    Directory of Open Access Journals (Sweden)

    Piontkivska Helen

    2009-07-01

    Full Text Available Abstract Background Studies have shown that in the genome of human immunodeficiency virus (HIV-1 regions responsible for interactions with the host's immune system, namely, cytotoxic T-lymphocyte (CTL epitopes tend to cluster together in relatively conserved regions. On the other hand, "epitope-less" regions or regions with relatively low density of epitopes tend to be more variable. However, very little is known about relationships among epitopes from different genes, in other words, whether particular epitopes from different genes would occur together in the same viral genome. To identify CTL epitopes in different genes that co-occur in HIV genomes, association rule mining was used. Results Using a set of 189 best-defined HIV-1 CTL/CD8+ epitopes from 9 different protein-coding genes, as described by Frahm, Linde & Brander (2007, we examined the complete genomic sequences of 62 reference HIV sequences (including 13 subtypes and sub-subtypes with approximately 4 representative sequences for each subtype or sub-subtype, and 18 circulating recombinant forms. The results showed that despite inclusion of recombinant sequences that would be expected to break-up associations of epitopes in different genes when two different genomes are recombined, there exist particular combinations of epitopes (epitope associations that occur repeatedly across the world-wide population of HIV-1. For example, Pol epitope LFLDGIDKA is found to be significantly associated with epitopes GHQAAMQML and FLKEKGGL from Gag and Nef, respectively, and this association rule is observed even among circulating recombinant forms. Conclusion We have identified CTL epitope combinations co-occurring in HIV-1 genomes including different subtypes and recombinant forms. Such co-occurrence has important implications for design of complex vaccines (multi-epitope vaccines and/or drugs that would target multiple HIV-1 regions at once and, thus, may be expected to overcome challenges

  1. Topic structure for information retrieval

    NARCIS (Netherlands)

    He, J.; Sanderson, M.; Zhai, C.; Zobel, J.; Allan, J.; Aslam, J.A.

    2009-01-01

    In my research, I propose a coherence measure, with the goal of discovering and using topic structures within and between documents, of which I explore its extensions and applications in information retrieval.

  2. Ontology-based Information Retrieval

    DEFF Research Database (Denmark)

    Styltsvig, Henrik Bulskov

    In this thesis, we will present methods for introducing ontologies in information retrieval. The main hypothesis is that the inclusion of conceptual knowledge such as ontologies in the information retrieval process can contribute to the solution of major problems currently found in information...... retrieval. This utilization of ontologies has a number of challenges. Our focus is on the use of similarity measures derived from the knowledge about relations between concepts in ontologies, the recognition of semantic information in texts and the mapping of this knowledge into the ontologies in use......, as well as how to fuse together the ideas of ontological similarity and ontological indexing into a realistic information retrieval scenario. To achieve the recognition of semantic knowledge in a text, shallow natural language processing is used during indexing that reveals knowledge to the level of noun...

  3. Retrieving Balloon Data in Flight

    Data.gov (United States)

    National Aeronautics and Space Administration — NASA's Ultra Long Duration Balloon (ULDB) program will soon make flights lasting up to 100 days. Some flights may generate high data rates and retrieving this data...

  4. Retrieval processes in social identification

    OpenAIRE

    Griffiths, Alexander Ivor

    2015-01-01

    The utility of selective retrieval processes in our everyday lives is evident across the varied contexts we are subjected to as human beings. Memory is characterised by an unlimited storage capacity, but limited retrieval capacity. Subsequently, we are selective in what we remember in a given context in order to use memory in an adaptive manner. Previous theory places memory at the centre of deriving and maintaining a sense of self and personal identity. In contrast however, the extent to whi...

  5. The GRAPE aerosol retrieval algorithm

    Directory of Open Access Journals (Sweden)

    G. E. Thomas

    2009-11-01

    Full Text Available The aerosol component of the Oxford-Rutherford Aerosol and Cloud (ORAC combined cloud and aerosol retrieval scheme is described and the theoretical performance of the algorithm is analysed. ORAC is an optimal estimation retrieval scheme for deriving cloud and aerosol properties from measurements made by imaging satellite radiometers and, when applied to cloud free radiances, provides estimates of aerosol optical depth at a wavelength of 550 nm, aerosol effective radius and surface reflectance at 550 nm. The aerosol retrieval component of ORAC has several incarnations – this paper addresses the version which operates in conjunction with the cloud retrieval component of ORAC (described by Watts et al., 1998, as applied in producing the Global Retrieval of ATSR Cloud Parameters and Evaluation (GRAPE data-set.

    The algorithm is described in detail and its performance examined. This includes a discussion of errors resulting from the formulation of the forward model, sensitivity of the retrieval to the measurements and a priori constraints, and errors resulting from assumptions made about the atmospheric/surface state.

  6. Analysis of Conformational B-Cell Epitopes in the Antibody-Antigen Complex Using the Depth Function and the Convex Hull.

    Directory of Open Access Journals (Sweden)

    Wei Zheng

    Full Text Available The prediction of conformational b-cell epitopes plays an important role in immunoinformatics. Several computational methods are proposed on the basis of discrimination determined by the solvent-accessible surface between epitopes and non-epitopes, but the performance of existing methods is far from satisfying. In this paper, depth functions and the k-th surface convex hull are used to analyze epitopes and exposed non-epitopes. On each layer of the protein, we compute relative solvent accessibility and four different types of depth functions, i.e., Chakravarty depth, DPX, half-sphere exposure and half space depth, to analyze the location of epitopes on different layers of the proteins. We found that conformational b-cell epitopes are rich in charged residues Asp, Glu, Lys, Arg, His; aliphatic residues Gly, Pro; non-charged residues Asn, Gln; and aromatic residue Tyr. Conformational b-cell epitopes are rich in coils. Conservation of epitopes is not significantly lower than that of exposed non-epitopes. The average depths (obtained by four methods for epitopes are significantly lower than that of non-epitopes on the surface using the Wilcoxon rank sum test. Epitopes are more likely to be located in the outer layer of the convex hull of a protein. On the benchmark dataset, the cumulate 10th convex hull covers 84.6% of exposed residues on the protein surface area, and nearly 95% of epitope sites. These findings may be helpful in building a predictor for epitopes.

  7. Epitope finding in Zika virus molecule:The first world report

    Institute of Scientific and Technical Information of China (English)

    Somsri Wiwanitkit; Viroj Wiwanitkit

    2017-01-01

    Zika virus infection is a new problematic virus infection that becomes the present public health problem. Now this mosquito borne infectious disease can be seen worldwide and can cause dengue-like infection. In addition, it can also induce trans-placental infection and result in congenital neurological defect. To prevent this infec-tion, there is still no specific vaccine. To find a new vaccine, finding epitope is the first step. Here, the authors report the study to find epitope within Zika virus molecule. According to this study, the appropriate epitopes can be seen. This is the first world report on epitope finding for Zika virus. The data can be useful for further vaccine development.

  8. Identification of murine T-cell epitopes in Ebola virus nucleoprotein

    International Nuclear Information System (INIS)

    Simmons, Graham; Lee, Anee; Rennekamp, Andrew J.; Fan Xin; Bates, Paul; Shen Hao

    2004-01-01

    CD8 T cells play an important role in controlling Ebola infection and in mediating vaccine-induced protective immunity, yet little is known about antigenic targets in Ebola that are recognized by CD8 T cells. Overlapping peptides were used to identify major histocompatibility complex class I-restricted epitopes in mice immunized with vectors encoding Ebola nucleoprotein (NP). CD8 T-cell responses were mapped to a H-2 d -restricted epitope (NP279-288) and two H-2 b -restricted epitopes (NP44-52 and NP288-296). The identification of these epitopes will facilitate studies of immune correlates of protection and the evaluation of vaccine strategies in murine models of Ebola infection

  9. High-resolution mapping of linear antibody epitopes using ultrahigh-density peptide microarrays

    DEFF Research Database (Denmark)

    Buus, Søren; Rockberg, Johan; Forsström, Björn

    2012-01-01

    Antibodies empower numerous important scientific, clinical, diagnostic, and industrial applications. Ideally, the epitope(s) targeted by an antibody should be identified and characterized, thereby establishing antibody reactivity, highlighting possible cross-reactivities, and perhaps even warning...... against unwanted (e.g. autoimmune) reactivities. Antibodies target proteins as either conformational or linear epitopes. The latter are typically probed with peptides, but the cost of peptide screening programs tends to prohibit comprehensive specificity analysis. To perform high-throughput, high......-resolution mapping of linear antibody epitopes, we have used ultrahigh-density peptide microarrays generating several hundred thousand different peptides per array. Using exhaustive length and substitution analysis, we have successfully examined the specificity of a panel of polyclonal antibodies raised against...

  10. A synthetic glycan microarray enables epitope mapping of plant cell wall glycan-directed antibodies

    DEFF Research Database (Denmark)

    Ruprecht, Colin; Bartetzko, Max P; Senf, Deborah

    2017-01-01

    In the last three decades, more than 200 monoclonal antibodies have been raised against most classes of plant cell wall polysaccharides by different laboratories world-wide. These antibodies are widely used to identify differences in plant cell wall components in mutants, organ and tissue types......, and developmental stages. Despite their importance and broad use, the precise binding epitope for only a few of these antibodies has been determined. Here, we use a plant glycan microarray equipped with 88 synthetic oligosaccharides to comprehensively map the epitopes of plant cell wall glycan-directed antibodies....... Our results reveal the binding epitopes for 78 arabinogalactan-, rhamnogalacturonan-, xylan-, and xyloglucan-directed antibodies. We demonstrate that, with knowledge of the exact epitopes recognized by individual antibodies, specific glycosyl hydrolases can be implemented into immunological cell wall...

  11. Structural and Dynamic Insight into Hirudin Epitopes-HLA- DRB1 ...

    African Journals Online (AJOL)

    It is produced in the salivary glands of the leech Hirudo .... for epitope selection has a specific algorithm and was developed in ..... from Plasmodium falciparum pre-erythrocytic-stage antigens ... Comar M. Identification of a vaccine against.

  12. The Advantages of Multi-Epitope Tumor Antigens as an Approach to Treating Breast Cancer

    National Research Council Canada - National Science Library

    Kiertscher, Sylvia

    1999-01-01

    .... We hypothesized that the processing and presentation of multiple tumor antigen epitopes by DC is a more efficient and effective way of stimulating T cell responses than current HLA-restricted peptide-based methods...

  13. Intergenic sequence between Arabidopsis caseinolytic protease B-cytoplasmic/heat shock protein100 and choline kinase genes functions as a heat-inducible bidirectional promoter.

    Science.gov (United States)

    Mishra, Ratnesh Chandra; Grover, Anil

    2014-11-01

    In Arabidopsis (Arabidopsis thaliana), the At1g74310 locus encodes for caseinolytic protease B-cytoplasmic (ClpB-C)/heat shock protein100 protein (AtClpB-C), which is critical for the acquisition of thermotolerance, and At1g74320 encodes for choline kinase (AtCK2) that catalyzes the first reaction in the Kennedy pathway for phosphatidylcholine biosynthesis. Previous work has established that the knockout mutants of these genes display heat-sensitive phenotypes. While analyzing the AtClpB-C promoter and upstream genomic regions in this study, we noted that AtClpB-C and AtCK2 genes are head-to-head oriented on chromosome 1 of the Arabidopsis genome. Expression analysis showed that transcripts of these genes are rapidly induced in response to heat stress treatment. In stably transformed Arabidopsis plants harboring this intergenic sequence between head-to-head oriented green fluorescent protein and β-glucuronidase reporter genes, both transcripts and proteins of the two reporters were up-regulated upon heat stress. Four heat shock elements were noted in the intergenic region by in silico analysis. In the homozygous transfer DNA insertion mutant Salk_014505, 4,393-bp transfer DNA is inserted at position -517 upstream of ATG of the AtClpB-C gene. As a result, AtCk2 loses proximity to three of the four heat shock elements in the mutant line. Heat-inducible expression of the AtCK2 transcript was completely lost, whereas the expression of AtClpB-C was not affected in the mutant plants. Our results suggest that the 1,329-bp intergenic fragment functions as a heat-inducible bidirectional promoter and the region governing the heat inducibility is possibly shared between the two genes. We propose a model in which AtClpB-C shares its regulatory region with heat-induced choline kinase, which has a possible role in heat signaling. © 2014 American Society of Plant Biologists. All Rights Reserved.

  14. Substantial gaps in knowledge of Bordetella pertussis antibody and T cell epitopes relevant for natural immunity and vaccine efficacy

    Science.gov (United States)

    Vaughan, Kerrie; Seymour, Emily; Peters, Bjoern; Sette, Alessandro

    2016-01-01

    The recent increase in whooping cough in vaccinated populations has been attributed to waning immunity associated with the acellular vaccine. The Immune Epitope Database (IEDB) is a repository of immune epitope data from the published literature and includes T cell and antibody epitopes for human pathogens. The IEDB conducted a review of the epitope literature, which revealed 300 Bordetella pertussis-related epitopes from 39 references. Epitope data are currently available for six virulence factors of B. pertussis: pertussis toxin, pertactin, fimbrial 2, fimbrial 3, adenylate cyclase and filamentous hemagglutinin. The majority of epitopes were defined for antibody reactivity; fewer T cell determinants were reported. Analysis of available protective correlates data revealed a number of candidate epitopes; however few are defined in humans and few have been shown to be protective. Moreover, there are a limited number of studies defining epitopes from natural infection versus whole cell or acellular/subunit vaccines. The relationship between epitope location and structural features, as well as antigenic drift (SNP analysis) was also investigated. We conclude that the cumulative data is yet insufficient to address many fundamental questions related to vaccine failure and this underscores the need for further investigation of B. pertussis immunity at the molecular level. PMID:24530743

  15. Microarray glycan profiling reveals algal fucoidan epitopes in diverse marine metazoans

    DEFF Research Database (Denmark)

    Asunción Salmeán, Armando; Hervé, Cécile; Jørgensen, Bodil

    2017-01-01

    Despite the biological importance and pharmacological potential of glycans from marine organisms, there are many unanswered questions regarding their distribution, function, and evolution. Here we describe microarray-based glycan profiling of a diverse selection of marine animals using antibodies...... raised against fucoidan isolated from a brown alga. We demonstrate the presence of two fucoidan epitopes in six animals belonging to three phyla including Porifera, Molusca, and Chordata. We studied the spatial distribution of these epitopes in Cliona celata ("boring sponge") and identified...

  16. Expression of goose parvovirus whole VP3 protein and its epitopes in Escherichia coli cells.

    Science.gov (United States)

    Tarasiuk, K; Woźniakowski, G; Holec-Gąsior, L

    2015-01-01

    The aim of this study was the expression of goose parvovirus capsid protein (VP3) and its epitopes in Escherichia coli cells. Expression of the whole VP3 protein provided an insufficient amount of protein. In contrast, the expression of two VP3 epitopes (VP3ep4, VP3ep6) in E. coli, resulted in very high expression levels. This may suggest that smaller parts of the GPV antigenic determinants are more efficiently expressed than the complete VP3 gene.

  17. Construction and characterization of 3A-epitope-tagged foot-and-mouth disease virus.

    Science.gov (United States)

    Ma, Xueqing; Li, Pinghua; Sun, Pu; Bai, Xingwen; Bao, Huifang; Lu, Zengjun; Fu, Yuanfang; Cao, Yimei; Li, Dong; Chen, Yingli; Qiao, Zilin; Liu, Zaixin

    2015-04-01

    Nonstructural protein 3A of foot-and-mouth disease virus (FMDV) is a partially conserved protein of 153 amino acids (aa) in most FMDVs examined to date. Specific deletion in the FMDV 3A protein has been associated with the inability of FMDV to grow in primary bovine cells and cause disease in cattle. However, the aa residues playing key roles in these processes are poorly understood. In this study, we constructed epitope-tagged FMDVs containing an 8 aa FLAG epitope, a 9 aa haemagglutinin (HA) epitope, and a 10 aa c-Myc epitope to substitute residues 94-101, 93-101, and 93-102 of 3A protein, respectively, using a recently developed O/SEA/Mya-98 FMDV infectious cDNA clone. Immunofluorescence assay (IFA), Western blot and sequence analysis showed that the epitope-tagged viruses stably maintained and expressed the foreign epitopes even after 10 serial passages in BHK-21 cells. The epitope-tagged viruses displayed growth properties and plaque phenotypes similar to those of the parental virus in BHK-21 cells. However, the epitope-tagged viruses exhibited lower growth rates and smaller plaque size phenotypes than those of the parental virus in primary fetal bovine kidney (FBK) cells, but similar growth properties and plaque phenotypes to those of the recombinant viruses harboring 93-102 deletion in 3A. These results demonstrate that the decreased ability of FMDV to replicate in primary bovine cells was not associated with the length of 3A, and the genetic determinant thought to play key role in decreased ability to replicate in primary bovine cells could be reduced from 93-102 residues to 8 aa residues at positions 94-101 in 3A protein. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Conformational occlusion of blockade antibody epitopes, a novel mechanism of GII.4 human norovirus immune evasion

    OpenAIRE

    Lindesmith, Lisa C.; Mallory, Michael L.; Debbink, Kari; Donaldson, Eric F.; Brewer-Jensen, Paul D.; Swann, Excel W.; Sheahan, Timothy P.; Graham, Rachel L.; Beltramello, Martina; Corti, Davide; Lanzavecchia, Antonio; Baric, Ralph S.

    2018-01-01

    ABSTRACT Extensive antigenic diversity within the GII.4 genotype of human norovirus is a major driver of pandemic emergence and a significant obstacle to development of cross-protective immunity after natural infection and vaccination. However, human and mouse monoclonal antibody studies indicate that, although rare, antibodies to conserved GII.4 blockade epitopes are generated. The mechanisms by which these epitopes evade immune surveillance are uncertain. Here, we developed a new approach f...

  19. Screening and identification of novel B cell epitopes of Toxoplasma gondii SAG1

    OpenAIRE

    Wang, Yanhua; Wang, Guangxiang; Zhang, Delin; Yin, Hong; Wang, Meng

    2013-01-01

    Background The identification of protein epitopes is useful for diagnostic purposes and for the development of peptide vaccines. In this study, the epitopes of Toxoplasma gondii SAG1 were identified using synthetic peptide techniques with the aid of bioinformatics. Findings Eleven peptides derived from T. gondii SAG1 were assessed by ELISA using pig sera from different time points after infection. Four (PS4, PS6, PS10 and PS11), out of the eleven peptides tested were recognized by all sera. T...

  20. Depigmented allergoids reveal new epitopes with capacity to induce IgG blocking antibodies.

    Science.gov (United States)

    López-Matas, M Angeles; Gallego, Mayte; Iraola, Víctor; Robinson, Douglas; Carnés, Jerónimo

    2013-01-01

    The synthesis of allergen-specific blocking IgGs that interact with IgE after allergen immunotherapy (SIT) has been related to clinical efficacy. The objectives were to investigate the epitope specificity of IgG-antibodies induced by depigmented-polymerized (Dpg-Pol) allergoids and unmodified allergen extracts, and examine IgE-blocking activity of induced IgG-antibodies. Rabbits were immunized with native and Dpg-Pol extracts of birch pollen, and serum samples were obtained. Recognition of linear IgG-epitopes of Bet v 1 and Bet v 2 and the capacity of these IgG-antibodies to block binding of human-IgE was determined. Serum from rabbits immunized with native extracts recognised 11 linear epitopes from Bet v 1, while that from Dpg-Pol-immunized animals recognised 8. For Bet v 2, 8 epitopes were recognized by IgG from native immunized animals, and 9 from Dpg-Pol immunized one. Dpg-Pol and native immunized serum did not always recognise the same epitopes, but specific-IgG from both could block human-IgE binding sites for native extract. Depigmented-polymerized birch extract stimulates the synthesis of specific IgG-antibodies which recognize common but also novel epitopes compared with native extracts. IgG-antibodies induced by Dpg-Pol effectively inhibit human-IgE binding to allergens which may be part of the mechanism of action of SIT.

  1. EPMLR: sequence-based linear B-cell epitope prediction method using multiple linear regression.

    Science.gov (United States)

    Lian, Yao; Ge, Meng; Pan, Xian-Ming

    2014-12-19

    B-cell epitopes have been studied extensively due to their immunological applications, such as peptide-based vaccine development, antibody production, and disease diagnosis and therapy. Despite several decades of research, the accurate prediction of linear B-cell epitopes has remained a challenging task. In this work, based on the antigen's primary sequence information, a novel linear B-cell epitope prediction model was developed using the multiple linear regression (MLR). A 10-fold cross-validation test on a large non-redundant dataset was performed to evaluate the performance of our model. To alleviate the problem caused by the noise of negative dataset, 300 experiments utilizing 300 sub-datasets were performed. We achieved overall sensitivity of 81.8%, precision of 64.1% and area under the receiver operating characteristic curve (AUC) of 0.728. We have presented a reliable method for the identification of linear B cell epitope using antigen's primary sequence information. Moreover, a web server EPMLR has been developed for linear B-cell epitope prediction: http://www.bioinfo.tsinghua.edu.cn/epitope/EPMLR/ .

  2. Multiple epitopes in a dodecapeptide of myelin basic protein determined bymonoclonal antibodies

    International Nuclear Information System (INIS)

    Price, J.O.; Whitaker, J.N.; Vasu, R.I.; Metzger, D.W.

    1986-01-01

    Three custom synthesized myelin basic protein (MBP) peptides, bovine peptide 79-88, human peptide 80-89, and human peptide 82-91, were used to produce four murine monoclonal antibodies (MAb) that were selected on the basis of reaction in a solid phase radioimmunoassay (SRIA) with human MBP. The MAb were compared with respect to antigen specificity against intact MBP and 10 overlapping MBP peptides. One MAb recognized an epitope near the amino-terminus of bovine MBP peptide 79-88. A second MAb was directed towards an epitope that is more reactive in human MBP peptide 45-89 than in intact MBP, but is not recognized in any of the small MBP peptides examined. The third MAb detected an epitope near the middle of human MBP peptide 80-89, whereas the fourth MAb reacted with the carboxyl-terminal portion of human MBP peptide 82-91. Epitopes recognized in SRIA were sometimes not detected by the same MAb in a fluid phase double antibody radioimmunoassay. These results demonstrate the multiplicity of potential epitopes in a dodecapeptide of MBP and do not support the concept of a single, dominant epitope in the region of MBP peptide 80-89

  3. Nanoallergens: A multivalent platform for studying and evaluating potency of allergen epitopes in cellular degranulation

    Science.gov (United States)

    Deak, Peter E; Vrabel, Maura R; Pizzuti, Vincenzo J; Kiziltepe, Tanyel

    2016-01-01

    Degranulation caused by type I hypersensitivity (allergies) is a complex biophysical process, and available experimental models for studying relevant immunoglobulin E binding epitopes on allergen proteins lack the ability to adequately evaluate, rank, and associate these epitopes individually and with each other. In this study, we propose a new allergy model system for studying potential allergen epitopes using nanoallergens, liposomes modified to effectively display IgE binding epitopes/haptens. By utilizing the covalently conjugated lipid tails on two hapten molecules (dinitrophenol and dansyl), hapten molecules were successfully incorporated into liposomes with high precision to form nanoallergens. Nanoallergens, with precisely controlled high-particle valency, can trigger degranulation with much greater sensitivity than commonly used bovine serum albumin conjugates. In rat basophil leukemia cell experiments, nanoallergens with only 2% hapten loading were able to trigger degranulation in vitro at concentrations as low as 10 pM. Additionally, unlike bovine serum albumin-hapten conjugates, nanoallergens allow exact control over particle size and valency. By varying the nanoallergen parameters such as size, valency, monovalent affinity of hapten, and specific IgE ratios, we exposed the importance of these variables on degranulation intensity while demonstrating nanoallergens’ potential for evaluating both high- and low-affinity epitopes. The data presented in this article establish nanoallergen platform as a reliable and versatile allergy model to study and evaluate allergen epitopes in mast cell degranulation. PMID:27188517

  4. Elaborative Retrieval: Do Semantic Mediators Improve Memory?

    Science.gov (United States)

    Lehman, Melissa; Karpicke, Jeffrey D.

    2016-01-01

    The elaborative retrieval account of retrieval-based learning proposes that retrieval enhances retention because the retrieval process produces the generation of semantic mediators that link cues to target information. We tested 2 assumptions that form the basis of this account: that semantic mediators are more likely to be generated during…

  5. The role of retrieval mode and retrieval orientation in retrieval practice: insights from comparing recognition memory testing formats and restudying.

    Science.gov (United States)

    Gao, Chuanji; Rosburg, Timm; Hou, Mingzhu; Li, Bingbing; Xiao, Xin; Guo, Chunyan

    2016-12-01

    The effectiveness of retrieval practice for aiding long-term memory, referred to as the testing effect, has been widely demonstrated. However, the specific neurocognitive mechanisms underlying this phenomenon remain unclear. In the present study, we sought to explore the role of pre-retrieval processes at initial testing on later recognition performance by using event-related potentials (ERPs). Subjects studied two lists of words (Chinese characters) and then performed a recognition task or a source memory task, or restudied the word lists. At the end of the experiment, subjects received a final recognition test based on the remember-know paradigm. Behaviorally, initial testing (active retrieval) enhanced memory retention relative to restudying (passive retrieval). The retrieval mode at initial testing was indexed by more positive-going ERPs for unstudied items in the active-retrieval tasks than in passive retrieval from 300 to 900 ms. Follow-up analyses showed that the magnitude of the early ERP retrieval mode effect (300-500 ms) was predictive of the behavioral testing effect later on. In addition, the ERPs for correctly rejected new items during initial testing differed between the two active-retrieval tasks from 500 to 900 ms, and this ERP retrieval orientation effect predicted differential behavioral testing gains between the two active-retrieval conditions. Our findings confirm that initial testing promotes later retrieval relative to restudying, and they further suggest that adopting pre-retrieval processing in the forms of retrieval mode and retrieval orientation might contribute to these memory enhancements.

  6. Overlapping CD8+ and CD4+ T-cell epitopes identification for the progression of epitope-based peptide vaccine from nucleocapsid and glycoprotein of emerging Rift Valley fever virus using immunoinformatics approach.

    Science.gov (United States)

    Adhikari, Utpal Kumar; Rahman, M Mizanur

    2017-12-01

    Rift Valley fever virus (RVFV) is an emergent arthropod-borne zoonotic infectious viral pathogen which causes fatal diseases in the humans and ruminants. Currently, no effective and licensed vaccine is available for the prevention of RVFV infection in endemic as well as in non-endemic regions. So, an immunoinformatics-driven genome-wide screening approach was performed for the identification of overlapping CD8+ and CD4+ T-cell epitopes and also linear B-cell epitopes from the conserved sequences of the nucleocapsid (N) and glycoprotein (G) of RVFV. We identified overlapping 99.39% conserved 1 CD8+ T-cell epitope (MMHPSFAGM) from N protein and 100% conserved 7 epitopes (AVFALAPVV, LAVFALAPV, FALAPVVFA, VFALAPVVF, IAMTVLPAL, FFDWFSGLM, and FLLIYLGRT) from G protein and also identified IL-4 and IFN-γ induced (99.39% conserved) 1 N protein CD4+ T-cell epitope (HMMHPSFAGMVDPSL) and 100% conserved 5 G protein CD4+ T-cell epitopes (LPALAVFALAPVVFA, PALAVFALAPVVFAE, GIAMTVLPALAVFAL, GSWNFFDWFSGLMSW, and FFLLIYLGRTGLSKM). The overlapping CD8+ and CD4+ T-cell epitopes were bound with most conserved HLA-C*12:03 and HLA-DRB1*01:01, respectively with the high binding affinity (kcal/mol). The combined population coverage analysis revealed that the allele frequencies of these epitopes are high in endemic and non-endemic regions. Besides, we found 100% conserved and non-allergenic 2 decamer B-cell epitopes, GVCEVGVQAL and RVFNCIDWVH of G protein had the sequence similarity with the nonamer CD8+ T-cell epitopes, VCEVGVQAL and RVFNCIDWV, respectively. Consequently, these epitopes may be used for the development of epitope-based peptide vaccine against emerging RVFV. However, in vivo and in vitro experiments are required for their efficient use as a vaccine. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Konjac flour improved textural and water retention properties of transglutaminase-mediated, heat-induced porcine myofibrillar protein gel: Effect of salt level and transglutaminase incubation.

    Science.gov (United States)

    Chin, Koo B; Go, Mi Y; Xiong, Youling L

    2009-03-01

    Functional properties of heat-induced gels prepared from microbial transglutaminase (TG)-treated porcine myofibrillar protein (MP) containing sodium caseinate with or without konjac flour (KF) under various salt concentrations (0.1, 0.3 and 0.6MNaCl) were evaluated. The mixed MP gels with KF exhibited improved cooking yields at all salt concentrations. TG treatment greatly enhanced gel strength and elasticity (storage modulus, G') at 0.6M NaCl, but not at lower salt concentrations. The combination of KF and TG improved the gel strength at 0.1 and 0.3M NaCl and G' at all salt concentrations, when compared with non-TG controls. Incubation of MP suspensions (sols) with TG promoted the disappearance of myosin heavy chain and the production of polymers. The TG-treated MP mixed gels had a compact structure, compared to those without TG, and the KF incorporation modified the gel matrix and increased its water-holding capacity. Results from differential scanning calorimetry suggested possible interactions of MP with KF, which may explain the changes in the microstructure of the heat-induced gels.

  8. Electrokinetically driven continuous-flow enrichment of colloidal particles by Joule heating induced temperature gradient focusing in a convergent-divergent microfluidic structure.

    Science.gov (United States)

    Zhao, Cunlu; Ge, Zhengwei; Song, Yongxin; Yang, Chun

    2017-09-07

    Enrichment of colloidal particles in continuous flow has not only numerous applications but also poses a great challenge in controlling physical forces that are required for achieving particle enrichment. Here, we for the first time experimentally demonstrate the electrokinetically-driven continuous-flow enrichment of colloidal particles with Joule heating induced temperature gradient focusing (TGF) in a microfluidic convergent-divergent structure. We consider four mechanisms of particle transport, i.e., advection due to electroosmosis, electrophoresis, dielectrophoresis and, and further clarify their roles in the particle enrichment. It is experimentally determined and numerically verified that the particle thermophoresis plays dominant roles in enrichment of all particle sizes considered in this study and the combined effect of electroosmosis-induced advection and electrophoresis is mainly to transport particles to the zone of enrichment. Specifically, the enrichment of particles is achieved with combined DC and AC voltages rather than a sole DC or AC voltage. A numerical model is formulated with consideration of the abovementioned four mechanisms, and the model can rationalize the experimental observations. Particularly, our analysis of numerical and experimental results indicates that thermophoresis which is usually an overlooked mechanism of material transport is crucial for the successful electrokinetic enrichment of particles with Joule heating induced TGF.

  9. Radiation and thermal characteristics of L5178Y-sensitive cells and usefulness of eosin staining method to detect heat-induced cell death

    Energy Technology Data Exchange (ETDEWEB)

    Nishioka, Yasuji (Hiroshima Univ. (Japan). School of Medicine)

    1990-08-01

    Radiosensitivity, thermosensitivity, drug sensitivity and their combined effects were investigated in mouse L5178Y-wild cells (LY-W) and L5178Y-sensitive cells (LY-S). The following results were obtained: LY-S were more radiosensitive than LY-W but were similar in their thermosensitivity. Thermotolerance induction was similar but the decay was faster in LY-W which had a shorter doubling time. The radiosensitizing effect of heating was similar in both cell lines. The thermal enhancement ratio was higher for a longer duration of heating at 42degC than for a shorter duration at 44degC, both of which exhibited a similar level of survival when applied alone. The eosin staining method was useful to detect heat-induced interphase death and thermal sensitizing effects of drugs. In LY-W, interphase death was the main mode of hyperthermic cell killing and was independent of the hyperthermic temperature, whereas in LY-S, the percentage of interphase death increased with the hyperthermic temperature. Procaine and bleomycin sensitized both cells to heat. Survival estimated by the eosin staining method shifted towards that obtained by colony forming method in heated LY-S after procaine. Sensitization to heat by procaine suggests that interphase death after hyperthermia is probably due to membrane damage. Comparison of the present work with previous ones, further suggests that with an increase in thermosensitivity, there is an increase in heat-induced interphase death. (author) 67 refs.

  10. Radiation and thermal characteristics of L5178Y-sensitive cells and usefulness of eosin staining method to detect heat-induced cell death

    International Nuclear Information System (INIS)

    Nishioka, Yasuji

    1990-01-01

    Radiosensitivity, thermosensitivity, drug sensitivity and their combined effects were investigated in mouse L5178Y-wild cells (LY-W) and L5178Y-sensitive cells (LY-S). The following results were obtained: LY-S were more radiosensitive than LY-W but were similar in their thermosensitivity. Thermotolerance induction was similar but the decay was faster in LY-W which had a shorter doubling time. The radiosensitizing effect of heating was similar in both cell lines. The thermal enhancement ratio was higher for a longer duration of heating at 42degC than for a shorter duration at 44degC, both of which exhibited a similar level of survival when applied alone. The eosin staining method was useful to detect heat-induced interphase death and thermal sensitizing effects of drugs. In LY-W, interphase death was the main mode of hyperthermic cell killing and was independent of the hyperthermic temperature, whereas in LY-S, the percentage of interphase death increased with the hyperthermic temperature. Procaine and bleomycin sensitized both cells to heat. Survival estimated by the eosin staining method shifted towards that obtained by colony forming method in heated LY-S after procaine. Sensitization to heat by procaine suggests that interphase death after hyperthermia is probably due to membrane damage. Comparison of the present work with previous ones, further suggests that with an increase in thermosensitivity, there is an increase in heat-induced interphase death. (author) 67 refs

  11. Information retrieval in particle physics

    International Nuclear Information System (INIS)

    Oyanagi, Yoshio

    1983-01-01

    Various information retrieval systems for elementary particle physics are introduced. Scientific information has been distributed in the form of books, periodicals or preprints. Some periodicals include the abstracts of information only. Recently, computer systems, by which the information retrieval can be easily done, have been developed. The construction of networks connecting various computer systems is in progress. It is possible to call the data base of Rutherford Laboratory from a telephone terminal of Laurence Berkeley Laboratory. The access to the Network by British Science Research Council can be made from DESY or CERN. The examples of on-line information retrieval in Japan are presented. Some of the periodicals of secondary information and data books are also introduced. (Kato, T.)

  12. Context based multimedia information retrieval

    DEFF Research Database (Denmark)

    Mølgaard, Lasse Lohilahti

    The large amounts of digital media becoming available require that new approaches are developed for retrieving, navigating and recommending the data to users in a way that refl ects how we semantically perceive the content. The thesis investigates ways to retrieve and present content for users...... topics from a large collection of the transcribed speech to improve retrieval of spoken documents. The context modelling is done using a variant of probabilistic latent semantic analysis (PLSA), to extract properties of the textual sources that refl ect how humans perceive context. We perform PLSA...... of Wikipedia , as well as text-based semantic similarity. The final aspect investigated is how to include some of the structured data available in Wikipedia to include temporal information. We show that a multiway extension of PLSA makes it possible to extract temporally meaningful topics, better than using...

  13. B-1 cell immunoglobulin directed against oxidation-specific epitopes

    Directory of Open Access Journals (Sweden)

    Dimitrios eTsiantoulas

    2013-01-01

    Full Text Available Natural antibodies (NAbs are pre-existing antibodies with germline origin that arise in the absence of previous exposure to foreign antigens. NAbs are produced by B-1 lymphocytes and are primarily of the IgM isotype. There is accumulating evidence that - in addition to their role in antimicrobial host defense - NAbs exhibit important housekeeping functions by facilitating the non-immunogenic clearance of apoptotic cells as well as the removal of (neo-self antigens. These properties are largely mediated by the ability of NAbs to recognize highly conserved and endogenously generated structures, which are exemplified by so-called oxidation-specific epitopes (OSEs that are products of lipid peroxidation. The generation of OSEs as well as their interaction with the immune system have been studied extensively in the context of atherosclerosis, a chronic inflammatory disease of the vascular wall that is characterized by the accumulation of cellular debris and oxidized low-density lipoproteins (OxLDL. Both apoptotic cells as well as OxLDL carry OSEs that are targeted by NAbs. Therefore, OSEs represent stress-induced neo-self structures that mediate recognition of metabolic waste (e.g. cellular debris by NAbs, allowing its safe disposal, which has fundamental implications in health and disease.

  14. The immune epitope database (IEDB) 3.0

    Science.gov (United States)

    Vita, Randi; Overton, James A.; Greenbaum, Jason A.; Ponomarenko, Julia; Clark, Jason D.; Cantrell, Jason R.; Wheeler, Daniel K.; Gabbard, Joseph L.; Hix, Deborah; Sette, Alessandro; Peters, Bjoern

    2015-01-01

    The IEDB, www.iedb.org, contains information on immune epitopes—the molecular targets of adaptive immune responses—curated from the published literature and submitted by National Institutes of Health funded epitope discovery efforts. From 2004 to 2012 the IEDB curation of journal articles published since 1960 has caught up to the present day, with >95% of relevant published literature manually curated amounting to more than 15 000 journal articles and more than 704 000 experiments to date. The revised curation target since 2012 has been to make recent research findings quickly available in the IEDB and thereby ensure that it continues to be an up-to-date resource. Having gathered a comprehensive dataset in the IEDB, a complete redesign of the query and reporting interface has been performed in the IEDB 3.0 release to improve how end users can access this information in an intuitive and biologically accurate manner. We here present this most recent release of the IEDB and describe the user testing procedures as well as the use of external ontologies that have enabled it. PMID:25300482

  15. Information retrieval in digital environments

    CERN Document Server

    Dinet, Jérôme

    2014-01-01

    Information retrieval is a central and essential activity. It is indeed difficult to find a human activity that does not need to retrieve information in an environment which is often increasingly digital: moving and navigating, learning, having fun, communicating, informing, making a decision, etc. Most human activities are intimately linked to our ability to search quickly and effectively for relevant information, the stakes are sometimes extremely important: passing an exam, voting, finding a job, remaining autonomous, being socially connected, developing a critical spirit, or simply surviv

  16. From Viral genome to specific peptide epitopes - Methods for identifying porcine T cell epitopes based on in silico predictions, in vitro identification and ex vivo verification

    DEFF Research Database (Denmark)

    Pedersen, Lasse Eggers; Rasmussen, Michael; Harndahl, Mikkel

    The affinity for and stability of peptides bound by major histocompatibility complex (MHC) class I molecules are instrumental factors in presentation of viral epitopes to cytotoxic T lymphocytes (CTLs). In swine, such peptide presentations by swine leukocyte antigens (SLA) are crucial for swine i...

  17. The first human epitope map of the alphaviral E1 and E2 proteins reveals a new E2 epitope with significant virus neutralizing activity.

    Directory of Open Access Journals (Sweden)

    Ann R Hunt

    2010-07-01

    Full Text Available Venezuelan equine encephalitis virus (VEEV is responsible for VEE epidemics that occur in South and Central America and the U.S. The VEEV envelope contains two glycoproteins E1 (mediates cell membrane fusion and E2 (binds receptor and elicits virus neutralizing antibodies. Previously we constructed E1 and E2 epitope maps using murine monoclonal antibodies (mMAbs. Six E2 epitopes (E2(c,d,e,f,g,h bound VEEV-neutralizing antibody and mapped to amino acids (aa 182-207. Nothing is known about the human antibody repertoire to VEEV or epitopes that engage human virus-neutralizing antibodies. There is no specific treatment for VEE; however virus-neutralizing mMAbs are potent protective and therapeutic agents for mice challenged with VEEV by either peripheral or aerosol routes. Therefore, fully human MAbs (hMAbs with virus-neutralizing activity should be useful for prevention or clinical treatment of human VEE.We used phage-display to isolate VEEV-specific hFabs from human bone marrow donors. These hFabs were characterized by sequencing, specificity testing, VEEV subtype cross-reactivity using indirect ELISA, and in vitro virus neutralization capacity. One E2-specific neutralizing hFAb, F5n, was converted into IgG, and its binding site was identified using competitive ELISA with mMAbs and by preparing and sequencing antibody neutralization-escape variants.Using 11 VEEV-reactive hFabs we constructed the first human epitope map for the alphaviral surface proteins E1 and E2. We identified an important neutralization-associated epitope unique to the human immune response, E2 aa115-119. Using a 9 A resolution cryo-electron microscopy map of the Sindbis virus E2 protein, we showed the probable surface location of this human VEEV epitope.The VEEV-neutralizing capacity of the hMAb F5 nIgG is similar to that exhibited by the humanized mMAb Hy4 IgG. The Hy4 IgG has been shown to limit VEEV infection in mice both prophylactically and therapeutically. Administration

  18. Epitope-Specific Tolerance Modes Differentially Specify Susceptibility to Proteolipid Protein-Induced Experimental Autoimmune Encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Lei Wang

    2017-11-01

    Full Text Available Immunization with myelin components can elicit experimental autoimmune encephalomyelitis (EAE. EAE susceptibility varies between mouse strains, depending on the antigen employed. BL/6 mice are largely resistant to EAE induction with proteolipid protein (PLP, probably a reflection of antigen-specific tolerance. However, the extent and mechanism(s of tolerance to PLP remain unclear. Here, we identified three PLP epitopes in PLP-deficient BL/6 mice. PLP-sufficient mice did not respond against two of these, whereas tolerance was “leaky” for an epitope with weak predicted MHCII binding, and only this epitope was encephalitogenic. In TCR transgenic mice, the “EAE-susceptibility-associated” epitope was “ignored” by specific CD4 T cells, whereas the “resistance-associated” epitope induced clonal deletion and Treg induction in the thymus. Central tolerance was autoimmune regulator dependent and required expression and presentation of PLP by thymic epithelial cells (TECs. TEC-specific ablation of PLP revealed that peripheral tolerance, mediated by dendritic cells through recessive tolerance mechanisms (deletion and anergy, could largely compensate for a lack of central tolerance. However, adoptive EAE was exacerbated in mice lacking PLP in TECs, pointing toward a non-redundant role of the thymus in dominant tolerance to PLP. Our findings reveal multiple layers of tolerance to a central nervous system autoantigen that vary among epitopes and thereby specify disease susceptibility. Understanding how different modalities of tolerance apply to distinct T cell epitopes of a target in autoimmunity has implications for antigen-specific strategies to therapeutically interfere with unwanted immune reactions against self.

  19. Monoclonal antibodies to molluskan hemocyanin from Concholepas concholepas demonstrate common and specific epitopes among subunits.

    Science.gov (United States)

    Oliva, Harold; Moltedo, Bruno; De Ioannes, Pablo; Faunes, Fernando; De Ioannes, Alfredo E; Becker, María Inés

    2002-10-01

    We studied the reactivity of mouse monoclonal antibodies (MAbs) against the hemocyanin from the Chilean marine gastropod Concholepas concholepas (CCH). This protein has been successfully used as a carrier to produce antibodies to haptens and peptides. All MAbs (13) belonging to IgG subclass exhibit dissociation constants (K(d)) from 1 x 10(-7) M to 1 x 10(-9) M. MAbs were characterized by enzyme-linked immunosorbant assay (ELISA) using CCH treated with different procedures, including dissociation into CCH-A and CCH-B subunits, Western blot, enzymatic digestion, chemical deglycosylation, and thermal denaturation. MAbs were classified into three categories, according to subunit specificity by ELISA. The epitope distribution shows that CCH subunits display common epitopes (group I, 5 MAbs, 1H5, 2A8, 3A5, 3B3, and 3E3), as well as specific epitopes for CCH-A subunits (group II, 3 MAbs, 1B8, 4D8, and 8E5) and for CCH-B subunits (group III, 5 MAbs, 1A4, 1E4, 2H10, 3B7, and 7B4). The results can be summarized as follows: (1). six antibodies react with thermal denatured CCH, suggesting that they recognize linear epitopes, whereas seven recognize conformational epitopes; (2). oxidation of carbohydrate moieties does not affect the binding of the MAbs; (3). enzymatic digestion of CCH decreases the reactivity of all antibodies irrespective of the protease used (elastase or trypsin); (4). bringing together the above data, in addition to epitopic complementarity analysis, we identified 12 different epitopes on the CCH molecule recognized by these MAbs. The anti-CCH MAbs presented here can be useful tools to understand the subunit organization of the CCH and its complex structure, which can explain its immunogenic and immunostimulating properties in mammals.

  20. A Novel Multi-Epitope Vaccine For Cross Protection Against Hepatitis C Virus (HCV: An Immunoinformatics Approach

    Directory of Open Access Journals (Sweden)

    Mokhtar Nosrati

    2017-02-01

    Full Text Available Background: Hepatitis C virus (HCV causes acute and chronic human hepatitis infections. Due to the high genetic diversity and high rates of mutations in the genetic material so far there is no approved vaccine against HCV. Materials and Methods: The aim of this study was to determination B and T cell conserved epitopes of E1 and E2 proteins from HCV and construction of a chimeric peptide as a novel epitope based vaccine for cross-protection against the virus. For this, one B and T-cell epitope from both E1 and E2 which was predicted by EPMLR and Propred-1 server and had the highest score and antigenicity in VaxiJen 2.0 and PAP servers were selected for construction of chimeric protein as a multi-epitope vaccine. Results: The results of this study showed that the chimeric peptide had high antigenicity score and stability.Results also showed that most epitopes of E1 were located in two spectra consist of (45-65,88-107 and 148-182 while the results about B-cell epitopes of E2 showed that this protein had much less epitope than E1. The most epitope predicted for E2 were located in (12-24 and 35-54 spectra Conclusion:  In conclusion, epitope based vaccine which was designed by immunoinformatics methods could be considered as a novel and effective vaccine for cross-protection against HCV infection.

  1. Can mutational GC-pressure create new linear B-cell epitopes in herpes simplex virus type 1 glycoprotein B?

    Science.gov (United States)

    Khrustalev, Vladislav Victorovich

    2009-01-01

    We showed that GC-content of nucleotide sequences coding for linear B-cell epitopes of herpes simplex virus type 1 (HSV1) glycoprotein B (gB) is higher than GC-content of sequences coding for epitope-free regions of this glycoprotein (G + C = 73 and 64%, respectively). Linear B-cell epitopes have been predicted in HSV1 gB by BepiPred algorithm ( www.cbs.dtu.dk/services/BepiPred ). Proline is an acrophilic amino acid residue (it is usually situated on the surface of protein globules, and so included in linear B-cell epitopes). Indeed, the level of proline is much higher in predicted epitopes of gB than in epitope-free regions (17.8% versus 1.8%). This amino acid is coded by GC-rich codons (CCX) that can be produced due to nucleotide substitutions caused by mutational GC-pressure. GC-pressure will also lead to disappearance of acrophobic phenylalanine, isoleucine, methionine and tyrosine coded by GC-poor codons. Results of our "in-silico directed mutagenesis" showed that single nonsynonymous substitutions in AT to GC direction in two long epitope-free regions of gB will cause formation of new linear epitopes or elongation of previously existing epitopes flanking these regions in 25% of 539 possible cases. The calculations of GC-content and amino acid content have been performed by CodonChanges algorithm ( www.barkovsky.hotmail.ru ).

  2. Bibliometric-enhanced information retrieval

    NARCIS (Netherlands)

    Mayr, Philipp; Scharnhorst, Andrea; Larsen, Birger; Schaer, Philipp; Mutschke, Peter

    2014-01-01

    Bibliometric techniques are not yet widely used to enhance retrieval processes in digital libraries, although they offer value-added effects for users. In this workshop we will explore how statistical modelling of scholarship, such as Bradfordizing or network analysis of coauthorship network, can

  3. Photopolarimetric Retrievals of Snow Properties

    Science.gov (United States)

    Ottaviani, M.; van Diedenhoven, B.; Cairns, B.

    2015-01-01

    Polarimetric observations of snow surfaces, obtained in the 410-2264 nm range with the Research Scanning Polarimeter onboard the NASA ER-2 high-altitude aircraft, are analyzed and presented. These novel measurements are of interest to the remote sensing community because the overwhelming brightness of snow plagues aerosol and cloud retrievals based on airborne and spaceborne total reflection measurements. The spectral signatures of the polarized reflectance of snow are therefore worthwhile investigating in order to provide guidance for the adaptation of algorithms currently employed for the retrieval of aerosol properties over soil and vegetated surfaces. At the same time, the increased information content of polarimetric measurements allows for a meaningful characterization of the snow medium. In our case, the grains are modeled as hexagonal prisms of variable aspect ratios and microscale roughness, yielding retrievals of the grains' scattering asymmetry parameter, shape and size. The results agree with our previous findings based on a more limited data set, with the majority of retrievals leading to moderately rough crystals of extreme aspect ratios, for each scene corresponding to a single value of the asymmetry parameter.

  4. Formaldehyde OMI operational retrieval upgrades

    Science.gov (United States)

    Gonzalez Abad, G.; Chance, K.; Liu, X.

    2013-05-01

    Total column of formaldehyde (HCHO), a proxy for biogenic emissions, can be observed from satellites using the ultraviolet region of the spectrum. The operational HCHO retrievals from the Ozone Monitoring Instrument (OMI) on board the AURA satellite, part of NASA's A-train constellation of Earth Observing satellites, are described. The operational retrieval, based on a basic optical absorption spectroscopy (BOAS) algorithm, has been affected by the degradation of the instrument especially from 2008 onwards. The most significant problems are the unrealistic increasing high background concentrations of HCHO retrieved from OMI and the row anomaly. An upgrade for the original operational algorithm is therefore needed to ensure its trend quality and to account for these difficulties. The strategies implemented to deal with the instrumental degradation are presented here. Air mass factors (AMFs) in the current fitting window show significant wavelength dependence. Fitting uncertainties can potentially be improved by including shorter wavelengths as long as the AMFs wavelength dependence is taken into account. As part of these improvements a look-up table of wavelength-dependent AMFs have been calculated. Using this new table it is possible to retrieve the HCHO total column directly, weighting the HCHO cross sections with the wavelength-dependent AMFs. Additionally, the pixels affected by the row anomaly are now flagged in the level 2 data generated with the upgraded algorithm.

  5. The Ecosystem of Information Retrieval

    Science.gov (United States)

    Rodriguez-Munoz, Jose-Vicente; Martinez-Mendez, Francisco-Javier; Pastor-Sanchez, Juan-Antonio

    2012-01-01

    Introduction: This paper presents an initial proposal for a formal framework that, by studying the metric variables involved in information retrieval, can establish the sequence of events involved and how to perform it. Method: A systematic approach from the equations of Shannon and Weaver to establish the decidability of information retrieval…

  6. Information Retrieval for Ecological Syntheses

    Science.gov (United States)

    Bayliss, Helen R.; Beyer, Fiona R.

    2015-01-01

    Research syntheses are increasingly being conducted within the fields of ecology and environmental management. Information retrieval is crucial in any synthesis in identifying data for inclusion whilst potentially reducing biases in the dataset gathered, yet the nature of ecological information provides several challenges when compared with…

  7. Information Retrieval in Virtual Universities

    Science.gov (United States)

    Puustjärvi, Juha; Pöyry, Päivi

    2006-01-01

    Information retrieval in the context of virtual universities deals with the representation, organization, and access to learning objects. The representation and organization of learning objects should provide the learner with an easy access to the learning objects. In this article, we give an overview of the ONES system, and analyze the relevance…

  8. Wind Retrieval using Marine Radars

    Science.gov (United States)

    2011-09-30

    utilized to remove the 180° directional ambiguity in SAR wave retrieval ( Engen and Johnson, 1995). We have observed a strong dependency of the...1629–1642, Sep 2007. Engen , G., and H. Johnson, “SAR ocean wave inversion using image cross spectra”, IEEE Trans. Geosci. Remote Sensing, vol. 33

  9. Phase 2, Solid waste retrieval strategy

    International Nuclear Information System (INIS)

    Johnson, D.M.

    1994-01-01

    Solid TRU retrieval, Phase 1 is scheduled to commence operation in 1998 at 218W-4C-T01 and complete recovery of the waste containers in 2001. Phase 2 Retrieval will recover the remaining buried TRU waste to be retrieved and provide the preliminary characterization by non-destructive means to allow interim storage until processing for disposal. This document reports on researching the characterization documents to determine the types of wastes to be retrieved and where located, waste configurations, conditions, and required methods for retrieval. Also included are discussions of wastes encompassed by Phase 2 for which there are valid reasons to not retrieve

  10. Phase 2, Solid waste retrieval strategy

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, D.M.

    1994-09-29

    Solid TRU retrieval, Phase 1 is scheduled to commence operation in 1998 at 218W-4C-T01 and complete recovery of the waste containers in 2001. Phase 2 Retrieval will recover the remaining buried TRU waste to be retrieved and provide the preliminary characterization by non-destructive means to allow interim storage until processing for disposal. This document reports on researching the characterization documents to determine the types of wastes to be retrieved and where located, waste configurations, conditions, and required methods for retrieval. Also included are discussions of wastes encompassed by Phase 2 for which there are valid reasons to not retrieve.

  11. Developmental Localization and Methylesterification of Pectin Epitopes during Somatic Embryogenesis of Banana (Musa spp. AAA)

    Science.gov (United States)

    Xu, Chunxiang; Zhao, Lu; Pan, Xiao; Šamaj, Jozef

    2011-01-01

    Background The plant cell walls play an important role in somatic embryogenesis and plant development. Pectins are major chemical components of primary cell walls while homogalacturonan (HG) is the most abundant pectin polysaccharide. Developmental regulation of HG methyl-esterification degree is important for cell adhesion, division and expansion, and in general for proper organ and plant development. Methodology/Principal Findings Developmental localization of pectic homogalacturonan (HG) epitopes and the (1→4)-β-D-galactan epitope of rhamnogalacturonan I (RG-I) and degree of pectin methyl-esterification (DM) were studied during somatic embryogenesis of banana (Musa spp. AAA). Histological analysis documented all major developmental stages including embryogenic cells (ECs), pre-globular, globular, pear-shaped and cotyledonary somatic embryos. Histochemical staining of extracellularly secreted pectins with ruthenium red showed the most intense staining at the surface of pre-globular, globular and pear-shaped somatic embryos. Biochemical analysis revealed developmental regulation of galacturonic acid content and DM in diverse embryogenic stages. Immunodots and immunolabeling on tissue sections revealed developmental regulation of highly methyl-esterified HG epitopes recognized by JIM7 and LM20 antibodies during somatic embryogenesis. Cell walls of pre-globular/globular and late-stage embryos contained both low methyl-esterified HG epitopes as well as partially and highly methyl-esterified ones. Extracellular matrix which covered surface of early developing embryos contained pectin epitopes recognized by 2F4, LM18, JIM5, JIM7 and LM5 antibodies. De-esterification of cell wall pectins by NaOH caused a decrease or an elimination of immunolabeling in the case of highly methyl-esterified HG epitopes. However, immunolabeling of some low methyl-esterified epitopes appeared stronger after this base treatment. Conclusions/Significance These data suggest that both low

  12. Clinical Control of HIV-1 by Cytotoxic T Cells Specific for Multiple Conserved Epitopes.

    Science.gov (United States)

    Murakoshi, Hayato; Akahoshi, Tomohiro; Koyanagi, Madoka; Chikata, Takayuki; Naruto, Takuya; Maruyama, Rie; Tamura, Yoshiko; Ishizuka, Naoki; Gatanaga, Hiroyuki; Oka, Shinichi; Takiguchi, Masafumi

    2015-05-01

    Identification and characterization of CD8(+) T cells effectively controlling HIV-1 variants are necessary for the development of AIDS vaccines and for studies of AIDS pathogenesis, although such CD8(+) T cells have been only partially identified. In this study, we sought to identify CD8(+) T cells controlling HIV-1 variants in 401 Japanese individuals chronically infected with HIV-1 subtype B, in which protective alleles HLA-B*57 and HLA-B*27 are very rare, by using comprehensive and exhaustive methods. We identified 13 epitope-specific CD8(+) T cells controlling HIV-1 in Japanese individuals, though 9 of these epitopes were not previously reported. The breadths of the T cell responses to the 13 epitopes were inversely associated with plasma viral load (P = 2.2 × 10(-11)) and positively associated with CD4 count (P = 1.2 × 10(-11)), indicating strong synergistic effects of these T cells on HIV-1 control in vivo. Nine of these epitopes were conserved among HIV-1 subtype B-infected individuals, whereas three out of four nonconserved epitopes were cross-recognized by the specific T cells. These findings indicate that these 12 epitopes are strong candidates for antigens for an AIDS vaccine. The present study highlighted a strategy to identify CD8(+) T cells controlling HIV-1 and demonstrated effective control of HIV-1 by those specific for 12 conserved or cross-reactive epitopes. HLA-B*27-restricted and HLA-B*57-restricted cytotoxic T lymphocytes (CTLs) play a key role in controlling HIV-1 in Caucasians and Africans, whereas it is unclear which CTLs control HIV-1 in Asian countries, where HLA-B*57 and HLA-B*27 are very rare. A recent study showed that HLA-B*67:01 and HLA-B*52:01-C*12:02 haplotypes were protective alleles in Japanese individuals, but it is unknown whether CTLs restricted by these alleles control HIV-1. In this study, we identified 13 CTLs controlling HIV-1 in Japan by using comprehensive and exhaustive methods. They included 5 HLA-B*52:01-restricted

  13. Analysis of the epitope structure of Plum pox virus coat protein.

    Science.gov (United States)

    Candresse, Thierry; Saenz, Pilar; García, Juan Antonio; Boscia, Donato; Navratil, Milan; Gorris, Maria Teresa; Cambra, Mariano

    2011-05-01

    Typing of the particular Plum pox virus (PPV) strain responsible in an outbreak has important practical implications and is frequently performed using strain-specific monoclonal antibodies (MAbs). Analysis in Western blots of the reactivity of 24 MAbs to a 112-amino-acid N-terminal fragment of the PPV coat protein (CP) expressed in Escherichia coli showed that 21 of the 24 MAbs recognized linear or denaturation-insensitive epitopes. A series of eight C-truncated CP fragments allowed the mapping of the epitopes recognized by the MAbs. In all, 14 of them reacted to the N-terminal hypervariable region, defining a minimum of six epitopes, while 7 reacted to the beginning of the core region, defining a minimum of three epitopes. Sequence comparisons allowed the more precise positioning of regions recognized by several MAbs, including those recognized by the 5B-IVIA universal MAb (amino acids 94 to 100) and by the 4DG5 and 4DG11 D serogroup-specific MAbs (amino acids 43 to 64). A similar approach coupled with infectious cDNA clone mutagenesis showed that a V74T mutation in the N-terminus of the CP abolished the binding of the M serogroup-specific AL MAb. Taken together, these results provide a detailed positioning of the epitopes recognized by the most widely used PPV detection and typing MAbs.

  14. In Silico Prediction of T and B Cell Epitopes of Der f 25 in Dermatophagoides farinae

    Directory of Open Access Journals (Sweden)

    Xiaohong Li

    2014-01-01

    Full Text Available The house dust mites are major sources of indoor allergens for humans, which induce asthma, rhinitis, dermatitis, and other allergic diseases. Der f 25 is a triosephosphate isomerase, representing the major allergen identified in Dermatophagoides farinae. The objective of this study was to predict the B and T cell epitopes of Der f 25. In the present study, we analyzed the physiochemical properties, function motifs and domains, and structural-based detailed features of Der f 25 and predicted the B cell linear epitopes of Der f 25 by DNAStar protean system, BPAP, and BepiPred 1.0 server and the T cell epitopes by NetMHCIIpan-3.0 and NetMHCII-2.2. As a result, the sequence and structure analysis identified that Der f 25 belongs to the triosephosphate isomerase family and exhibited a triosephosphate isomerase pattern (PS001371. Eight B cell epitopes (11–18, 30–35, 71–77, 99–107, 132–138, 173–187, 193–197, and 211–224 and five T cell epitopes including 26–34, 38–54, 66–74, 142–151, and 239–247 were predicted in this study. These results can be used to benefit allergen immunotherapies and reduce the frequency of mite allergic reactions.

  15. Characterization of CD4 T Cell Epitopes of Infliximab and Rituximab Identified from Healthy Donors

    Directory of Open Access Journals (Sweden)

    Moustafa Hamze

    2017-05-01

    Full Text Available The chimeric antibodies anti-CD20 rituximab (Rtx and anti-TNFα infliximab (Ifx induce antidrug antibodies (ADAs in many patients with inflammatory diseases. Because of the key role of CD4 T lymphocytes in the initiation of antibody responses, we localized the CD4 T cell epitopes of Rtx and Ifx. With the perspective to anticipate immunogenicity of therapeutic antibodies, identification of the CD4 T cell epitopes was performed using cells collected in healthy donors. Nine T cell epitopes were identified in the variable chains of both antibodies by deriving CD4 T cell lines raised against either Rtx or Ifx. The T cell epitopes often exhibited a good affinity for human leukocyte antigen (HLA-DR molecules and were part of the peptides identified by MHC-associated peptide proteomics assay from HLA-DR molecules of dendritic cells (DCs loaded with the antibodies. Two-third of the T cell epitopes identified from the healthy donors stimulated peripheral blood mononuclear cells from patients having developed ADAs against Rtx or Ifx and promoted the secretion of a diversity of cytokines. These data emphasize the predictive value of evaluating the T cell repertoire of healthy donors and the composition of peptides bound to HLA-DR of DCs to anticipate and prevent immunogenicity of therapeutic antibodies.

  16. Epitope Mapping of Metuximab on CD147 Using Phage Display and Molecular Docking

    Directory of Open Access Journals (Sweden)

    Bifang He

    2013-01-01

    Full Text Available Metuximab is the generic name of Licartin, a new drug for radioimmunotherapy of hepatocellular carcinoma. Although it is known to be a mouse monoclonal antibody against CD147, the complete epitope mediating the binding of metuximab to CD147 remains unknown. We panned the Ph.D.-12 phage display peptide library against metuximab and got six mimotopes. The following bioinformatics analysis based on mimotopes suggested that metuximab recognizes a conformational epitope composed of more than 20 residues. The residues of its epitope may include T28, V30, K36, L38, K57, F74, D77, S78, D79, D80, Q81, G83, S86, N98, Q100, L101, H102, G103, P104, V131, P132, and K191. The homology modeling of metuximab and the docking of CD147 to metuximab were also performed. Based on the top one docking model, the epitope was predicted to contain 28 residues: AGTVFTTV (23–30, I37, D45, E84, V88, EPMGTANIQLH (92–102, VPP (131–133, Q164, and K191. Almost half of the residues predicted on the basis of mimotope analysis also appear in the docking result, indicating that both results are reliable. As the predicted epitopes of metuximab largely overlap with interfaces of CD147-CD147 interactions, a structural mechanism of metuximab is proposed as blocking the formation of CD147 dimer.

  17. RB4CD12 epitope expression and heparan sulfate disaccharide composition in brain vasculature.

    Science.gov (United States)

    Hosono-Fukao, Tomomi; Ohtake-Niimi, Shiori; Nishitsuji, Kazuchika; Hossain, Md Motarab; van Kuppevelt, Toin H; Michikawa, Makoto; Uchimura, Kenji

    2011-11-01

    RB4CD12 is a phage display antibody that recognizes a heparan sulfate (HS) glycosaminoglycan epitope. The epitope structure is proposed to contain a trisulfated disaccharide, [-IdoA(2-OSO(3))-GlcNSO(3) (6-OSO(3))-], which supports HS binding to various macromolecules such as growth factors and cytokines in central nervous tissues. Chemically modified heparins that lack the trisulfated disaccharides failed to inhibit the RB4CD12 recognition of HS chains. To determine the localization of the RB4CD12 anti-HS epitope in the brain, we performed an immunohistochemical analysis for cryocut sections of mouse brain. The RB4CD12 staining signals were colocalized with laminin and were detected abundantly in the vascular basement membrane. Bacterial heparinases eliminated the RB4CD12 staining signals. The RB4CD12 epitope localization was confirmed by immunoelectron microscopy. Western blotting analysis revealed that the size of a major RB4CD12-positive molecule is ∼460 kDa in a vessel-enriched fraction of the mouse brain. Disaccharide analysis with reversed-phase ion-pair HPLC showed that [-IdoA(2-OSO(3))-GlcNSO(3) (6-OSO(3))-] trisulfated disaccharide residues are present in HS purified from the vessel-enriched brain fraction. These results indicated that the RB4CD12 anti-HS epitope exists in large quantities in the brain vascular basement membrane. Copyright © 2011 Wiley-Liss, Inc.

  18. Identification of a serotype-independent linear epitope of foot-and-mouth disease virus.

    Science.gov (United States)

    Yang, Baolin; Wang, Mingxia; Liu, Wenming; Xu, Zhiqiang; Wang, Haiwei; Yang, Decheng; Ma, Wenge; Zhou, Guohui; Yu, Li

    2017-12-01

    Foot-and-mouth disease (FMD), caused by foot-and-mouth disease virus (FMDV), is a highly contagious infectious disease that affects domestic and wild cloven-hoofed animals worldwide. VP2 is a structural protein of FMDV. In this study, an FMDV serotype-independent monoclonal antibody (MAb), 10B10, against the viral capsid protein VP2 was generated, and a series of GST fusion proteins expressing a truncated peptide of VP2 was subjected to Western blot analysis using MAb 10B10. Their results indicated that the peptide 8 TLLEDRILT 16 of VP2 is the minimal requirement of the epitope recognized by MAb 10B10. Importantly, this linear epitope was highly conserved among all seven serotypes of FMDV in a sequence alignment analysis. Subsequent alanine-scanning mutagenesis analysis revealed that the residues Thr 8 and Asp 12 of the epitope were crucial for MAb-10B10 binding. Furthermore, Western blot analysis also revealed that the MAb 10B10-directed epitope could be recognized by positive sera from FMDV-infected cattle. The discovery that MAb 10B10 recognizes a serotype-independent linear epitope of FMDV suggests potential applications for this MAb in the development of serotype-independent tests for FMDV.

  19. Screening and identification of novel B cell epitopes of Toxoplasma gondii SAG1.

    Science.gov (United States)

    Wang, Yanhua; Wang, Guangxiang; Zhang, Delin; Yin, Hong; Wang, Meng

    2013-04-30

    The identification of protein epitopes is useful for diagnostic purposes and for the development of peptide vaccines. In this study, the epitopes of Toxoplasma gondii SAG1 were identified using synthetic peptide techniques with the aid of bioinformatics. Eleven peptides derived from T. gondii SAG1 were assessed by ELISA using pig sera from different time points after infection. Four (PS4, PS6, PS10 and PS11), out of the eleven peptides tested were recognized by all sera. Then, shorter peptides that were derived from PS4, PS6, PS10 and PS11 were predicted using bioinformatics and tested by experimentation. Four out of nine shorter peptides were identified successfully (amino acids 106-120, 166-180, 289-300 and 313-332). We have precisely located the epitopes of T. gondii SAG1 using pig sera collected at different time points after infection. The identified epitopes may be useful for the further study of epitope-based vaccines and diagnostic reagents.

  20. Development of a multi-epitope peptide vaccine inducing robust T cell responses against brucellosis using immunoinformatics based approaches.

    Science.gov (United States)

    Saadi, Mahdiye; Karkhah, Ahmad; Nouri, Hamid Reza

    2017-07-01

    Current investigations have demonstrated that a multi-epitope peptide vaccine targeting multiple antigens could be considered as an ideal approach for prevention and treatment of brucellosis. According to the latest findings, the most effective immunogenic antigens of brucella to induce immune responses are included Omp31, BP26, BLS, DnaK and L7-L12. Therefore, in the present study, an in silico approach was used to design a novel multi-epitope vaccine to elicit a desirable immune response against brucellosis. First, five novel T-cell epitopes were selected from Omp31, BP26, BLS, DnaK and L7-L12 proteins using different servers. In addition, helper epitopes selected from Tetanus toxin fragment C (TTFrC) were applied to induce CD4+ helper T lymphocytes (HTLs) responses. Selected epitopes were fused together by GPGPG linkers to facilitate the immune processing and epitope presentation. Moreover, cholera toxin B (CTB) was linked to N terminal of vaccine construct as an adjuvant by using EAAAK linker. A multi-epitope vaccine was designed based on predicted epitopes which was 377 amino acid residues in length. Then, the physico-chemical properties, secondary and tertiary structures, stability, intrinsic protein disorder, solubility and allergenicity of this multi-epitope vaccine were assessed using immunoinformatics tools and servers. Based on obtained results, a soluble, and non-allergic protein with 40.59kDa molecular weight was constructed. Expasy ProtParam classified this chimeric protein as a stable protein and also 89.8% residues of constructed vaccine were located in favored regions of the Ramachandran plot. Furthermore, this multi-epitope peptide vaccine was able to strongly induce T cell and B-cell mediated immune responses. In conclusion, immunoinformatics analysis indicated that this multi-epitope peptide vaccine can be effectively expressed and potentially be used for prophylactic or therapeutic usages against brucellosis. Copyright © 2017 Elsevier B.V. All

  1. To retrieve or not to retrieve: These are the issues

    International Nuclear Information System (INIS)

    Hyde, R.A.; Dahlmeir, M.M.; Nickelson, D.F.; Swanson, S.P.

    1997-10-01

    There are many factors that must be evaluated when determining whether a buried mixed waste site should be retrieved and subsequently stored, treated, and/or disposed of or if some other action is more appropriate. The criteria developed for the evaluation of remedial actions at mixed waste sites under Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) regulation EPA, provide an excellent methodology for deciding upon a preferred action even if the site is not under CERCLA regulation. Each topic for evaluation in the criteria is not mutually exclusive, and many tradeoffs must be reviewed. The criteria have been broken down into a number of categories: overall protection of human health and the environment; compliance with Applicable or Relevant and Appropriate Requirements (ARARs); long-term effectiveness and permanence; reduction of toxicity, mobility, and volume; short-term effectiveness; implementability; cost; state acceptance; and community acceptance. Once the data is gathered, a Hazards Analysis must be performed to understand the risks of the site to workers, the public, and the environment. The Hazard Analysis is critical in helping personnel understand the associated issues so that an effective evaluation can take place. The intent of this paper is not to focus on a particular site, but to provide information that is useful for many problem holders to better understand the issues associated with buried mixed waste retrieval. Ultimately, these issues affect the final decision of whether or not retrieval is a feasible alternative

  2. Anaplasma marginale major surface protein 2 CD4+-T-cell epitopes are evenly distributed in conserved and hypervariable regions (HVR), whereas linear B-cell epitopes are predominantly located in the HVR.

    Science.gov (United States)

    Abbott, Jeffrey R; Palmer, Guy H; Howard, Chris J; Hope, Jayne C; Brown, Wendy C

    2004-12-01

    Organisms in the genus Anaplasma express an immunodominant major surface protein 2 (MSP2), composed of a central hypervariable region (HVR) flanked by highly conserved regions. Throughout Anaplasma marginale infection, recombination results in the sequential appearance of novel MSP2 variants and subsequent control of rickettsemia by the immune response, leading to persistent infection. To determine whether immune evasion and selection for variant organisms is associated with a predominant response against HVR epitopes, T-cell and linear B-cell epitopes were localized by measuring peripheral blood gamma interferon-secreting cells, proliferation, and antibody binding to 27 overlapping peptides spanning MSP2 in 16 cattle. Similar numbers of MSP2-specific CD4(+) T-cell epitopes eliciting responses of similar magnitude were found in conserved and hypervariable regions. T-cell epitope clusters recognized by the majority of animals were identified in the HVR (amino acids [aa] 171 to 229) and conserved regions (aa 101 to 170 and 272 to 361). In contrast, linear B-cell epitopes were concentrated in the HVR, residing within hydrophilic sequences. The pattern of recognition of epitope clusters by T cells and of HVR epitopes by B cells is consistent with the influence of protein structure on epitope recognition.

  3. Metabolite responses to exogenous application of nitrogen, cytokinin, and ethylene inhibitors in relation to heat-induced senescence in creeping bentgrass.

    Directory of Open Access Journals (Sweden)

    David Jespersen

    Full Text Available The exogenous application of ethylene inhibitors, cytokinins, or nitrogen has previously been shown to suppress heat-induced senescence and improve heat tolerance in cool-season grasses. The objectives of this study were to examine metabolic profiles altered by exogenous treatment of creeping bentgrass with an ethylene inhibitor, cytokinin or nitrogen under heat stress and to determine metabolic pathways regulated by those compounds in association with their effectiveness for improving heat tolerance. Creeping bentgrass (Agostis stolonifera plants (cv. Penncross were foliar sprayed with 18 mM carbonyldiamide (N source, 25 μM aminoethoxyvinylglycine (AVG, ethylene inhibitor, 25 μM zeatin riboside (ZR, cytokinin, or a water control, and then exposed to 20/15°C (day/night or 35/30°C (heat stress in growth chambers. All three exogenous treatments suppressed leaf senescence, as manifested by increased turf quality and chlorophyll content, and reduced electrolyte leakage under heat stress. Polar metabolite profiling identified increases in the content of certain organic acids (i.e. citric and malic acid, sugar alcohols, disaccharides (sucrose, and decreased accumulations of monosaccharides (i.e. glucose and fructose with exogenous treatment of N, AVG, or ZR at the previously mentioned concentrations when compared to the untreated control under heat stress. Nitrogen stimulated amino acid accumulation whereas AVG and ZR reduced amino acid accumulation compared to the untreated control under heat stress. These results revealed that the alleviation of heat-induced leaf senescence by N, AVG, and ZR could be due to changes in the accumulation of metabolites involved in osmoregulation, antioxidant metabolism, carbon and nitrogen metabolism, as well as stress signaling molecules.

  4. The use of HPLC-MS in T-cell epitope identification.

    Science.gov (United States)

    Lemmel, Claudia; Stevanović, Stefan

    2003-03-01

    The hunt for T-cell epitopes is going on because hopes are set on such peptide sequences for diagnosis and vaccine development in the fight against infectious and tumor diseases. In addition to a variety of other techniques used in T-cell epitope identification, mass spectrometers coupled to microcapillary liquid chromatography have now become an important and sensitive tool in separation, detection, and sequence analysis of highly complex natural major histocompatibility complex (MHC) ligand mixtures. In this article, we review the basics of mass spectrometric techniques and their on-line coupling to microcapillary liquid chromatography (microcap-LC). Furthermore, we introduce current strategies for the identification of new T-cell epitopes using microcapillary liquid chromatography-mass spectrometry (microcap-LC-MS).

  5. Characterization of two conformational epitopes of the Chlamydia trachomatis serovar L2 DnaK immunogen

    DEFF Research Database (Denmark)

    Birkelund, Svend; Mygind, P; Holm, A

    1996-01-01

    this protein. By use of recombinant DNA techniques, we located the epitopes for two MAbs in the C-terminal variable part. Although the antibodies reacted in an immunoblot assay, it was not possible to map the epitopes completely by use of 16-mer synthetic peptides displaced by one amino acid corresponding......Chlamydia trachomatis DnaK is an important immunogen in chlamydial infections. DnaK is composed of a conserved N-terminal ATP-binding domain and a variable C-terminal peptide-binding domain. To locate the immunogenic part of C. trachomatis Dnak, we generated monoclonal antibodies (MAbs) against...... with the two antibodies. The epitopes were found not to overlap. To obtain DnaK fragments recognized by the antibodies with the same affinity as native C. trachomatis DnaK, it was necessary to express, respectively, regions of 127 and 77 amino acids. The MAbs described in this study thus recognized...

  6. Elucidation of the TMab-6 Monoclonal Antibody Epitope Against Telomerase Reverse Transcriptase.

    Science.gov (United States)

    Kaneko, Mika K; Yamada, Shinji; Itai, Shunsuke; Chang, Yao-Wen; Nakamura, Takuro; Yanaka, Miyuki; Harada, Hiroyuki; Suzuki, Hiroyoshi; Kato, Yukinari

    2018-05-03

    Telomerase reverse transcriptase (TERT) and mutations of the TERT promoter are significant in the pathogenesis of 1p/19q-codeleted oligodendrogliomas and isocitrate dehydrogenase gene wild-type glioblastomas, as well as melanomas and squamous cell carcinomas. We previously developed an antihuman TERT monoclonal antibody (mAb), TMab-6, which is applicable in immunohistochemistry for human tissues. However, the binding epitope of TMab-6 against TERT is yet to be elucidated. In this study, enzyme-linked immunosorbent assay and immunohistochemistry were utilized for investigating the epitope of TMab-6. The findings revealed that the critical epitope of TMab-6 is the TERT sequence PSTSRPPRPWD; Thr310 and Ser311 of TERT are especially significant amino acids for TMab-6 recognition.

  7. In silico cloning and B/T cell epitope prediction of triosephosphate isomerase from Echinococcus granulosus.

    Science.gov (United States)

    Wang, Fen; Ye, Bin

    2016-10-01

    Cystic echinococcosis is a worldwide zoonosis caused by Echinococcus granulosus. Because the methods of diagnosis and treatment for cystic echinococcosis were limited, it is still necessary to screen target proteins for the development of new anti-hydatidosis vaccine. In this study, the triosephosphate isomerase gene of E. granulosus was in silico cloned. The B cell and T cell epitopes were predicted by bioinformatics methods. The cDNA sequence of EgTIM was composition of 1094 base pairs, with an open reading frame of 753 base pairs. The deduced amino acid sequences were composed of 250 amino acids. Five cross-reactive epitopes, locating on 21aa-35aa, 43aa-57aa, 94aa-107aa, 115-129aa, and 164aa-183aa, could be expected to serve as candidate epitopes in the development of vaccine against E. granulosus. These results could provide bases for gene cloning, recombinant expression, and the designation of anti-hydatidosis vaccine.

  8. Mature Epitope Density - A strategy for target selection based on immunoinformatics and exported prokaryotic proteins

    DEFF Research Database (Denmark)

    Santos, Anderson R; Pereira, Vanessa Bastos; Barbosa, Eudes

    2013-01-01

    . However, currently available tools do not account for the concentration of epitope products in the mature protein product and its relation to the reliability of target selection. RESULTS: We developed a computational strategy based on measuring the epitope's concentration in the mature protein, called...... Mature Epitope Density (MED). Our method, though simple, is capable of identifying promising vaccine targets. Our online software implementation provides a computationally light and reliable analysis of bacterial exoproteins and their potential for vaccines or diagnosis projects against pathogenic...... proteins were confirmed as related. There was no experimental evidence of antigenic or pathogenic contributions for three of the highest MED-scored Mtb proteins. Hence, these three proteins could represent novel putative vaccine and drug targets for Mtb. A web version of MED is publicly available online...

  9. Characterization of an immunodominant cancer-specific O-glycopeptide epitope in murine podoplanin (OTS8)

    DEFF Research Database (Denmark)

    Steentoft, Catharina; Schjoldager, Katrine T; Cló, Emiliano

    2010-01-01

    antibody 237, developed to a spontaneous murine fibrosarcoma, was shown to be directed to murine podoplanin (OTS8) with truncated Tn O-glycans. Our understanding of such cancer-specific auto-antibodies to truncated glycoforms of glycoproteins is limited. Here we have investigated immunogenicity...... of a chemoenzymatically produced Tn-glycopeptide derived from the putative murine podoplanin O-glycopeptide epitope. We found that the Tn O-glycopeptide was highly immunogenic in mice and produced a Tn-glycoform specific response with no reactivity against unglycosylated peptides or the O-glycopeptide with extended O......-glycan (STn and T glycoforms). The immunodominant epitope was strictly dependent on the peptide sequence, required Tn at a specific single Thr residue (Thr(77)), and antibodies to the epitope were not found in naive mice. We further tested a Tn O-glycopeptide library derived from human podoplanin...

  10. Impact of retrievability of repository design

    International Nuclear Information System (INIS)

    Heijdra, J.J.; Gaag, J. v.d.; Prij, J.

    1995-01-01

    In this paper the impact of the retrievability on the design of the repository will be handled. Retrievability of radioactive waste from a repository in geological formations has received increasing attention during recent years. It is obvious that this retrievability will have consequences in terms of mining engineering, safety and cost. The purpose of the present study is to evaluate cost consequences by comparing two extreme options for retrievable storage. (author). 6 refs., 3 figs

  11. Automated information retrieval using CLIPS

    Science.gov (United States)

    Raines, Rodney Doyle, III; Beug, James Lewis

    1991-01-01

    Expert systems have considerable potential to assist computer users in managing the large volume of information available to them. One possible use of an expert system is to model the information retrieval interests of a human user and then make recommendations to the user as to articles of interest. At Cal Poly, a prototype expert system written in the C Language Integrated Production System (CLIPS) serves as an Automated Information Retrieval System (AIRS). AIRS monitors a user's reading preferences, develops a profile of the user, and then evaluates items returned from the information base. When prompted by the user, AIRS returns a list of items of interest to the user. In order to minimize the impact on system resources, AIRS is designed to run in the background during periods of light system use.

  12. Database, expert systems, information retrieval

    International Nuclear Information System (INIS)

    Fedele, P.; Grandoni, G.; Mammarella, M.C.

    1989-12-01

    The great debate concerning the Italian high-school reform has induced a ferment of activity among the most interested and sensible of people. This was clearly demonstrated by the course 'Innovazione metodologico-didattica e tecnologie informatiche' organized for the staff of the 'lstituto Professionale L. Einaudi' of Lamezia Terme. The course was an interesting opportunity for discussions and interaction between the world of School and computer technology used in the Research field. This three day course included theoretical and practical lessons, showing computer facilities that could be useful for teaching. During the practical lessons some computer tools were presented from the very simple Electronic Sheets to the more complicated information Retrieval on CD-ROM interactive realizations. The main topics will be discussed later. They are: Modelling, Data Base, Integrated Information Systems, Expert Systems, Information Retrieval. (author)

  13. Construction, emplacement, and retrievability (preclosure)

    International Nuclear Information System (INIS)

    McClain, W.

    1985-01-01

    Each of the three preclosure subgroups of the Construction, Emplacement, and Retrievability Working Group adopted a six-step approach to identify and assess current needs in geotechnical modeling and characterization. This approach may be summarized as follows: identify phenomena related to emplacement of high-level nuclear wastes, identify types of models which are required to calculate the phenomena, establish the input data needs for the models, assess the current availability of the models, assess the current status of documentation, verification, and validation of the models, and determine the adequacy of instrumentation and measurement techniques to (a) validate the models, where necessary, and (b) obtain input data for design. Systematic application of these six steps leads to the establishment of the research requirements for geotechnical modeling and characterization. A summary of modeling techniques which apply to the three subsequent sections on construction, emplacement, and retrievability is presented. Research needs, which apply to all preclosure activities, are summarized

  14. Hooked on Music Information Retrieval

    Directory of Open Access Journals (Sweden)

    W. Bas de Haas

    2011-04-01

    Full Text Available This article provides a reply to 'Lure(d into listening: The potential of cognition-based music information retrieval,' in which Henkjan Honing discusses the potential impact of his proposed Listen, Lure & Locate project on Music Information Retrieval (MIR. Honing presents some critical remarks on data-oriented approaches in MIR, which we endorse. To place these remarks in context, we first give a brief overview of the state of the art of MIR research. Then we present a series of arguments that show why purely data-oriented approaches are unlikely to take MIR research and applications to a more advanced level. Next, we propose our view on MIR research, in which the modelling of musical knowledge has a central role. Finally, we elaborate on the ideas in Honing's paper from a MIR perspective in this paper and propose some additions to the Listen, Lure & Locate project.

  15. Topic Models in Information Retrieval

    Science.gov (United States)

    2007-08-01

    Information Processing Systems, Cambridge, MA, MIT Press, 2004. Brown, P.F., Della Pietra, V.J., deSouza, P.V., Lai, J.C. and Mercer, R.L., Class-based...2003. http://www.wkap.nl/prod/b/1-4020-1216-0. Croft, W.B., Lucia , T.J., Cringean, J., and Willett, P., Retrieving Documents By Plausible Inference

  16. Retrievability in an ethical perspective

    International Nuclear Information System (INIS)

    Thunberg, A.-M.

    2000-01-01

    At the outset, a short summary is given of how the ethical discussion developed historically, all from the so-called double KASAM principle of 1987 - safety in operation, combined with reparability, with controls not necessary, but not impossible - until the phase of focusing on retrievability as a result of a deepened ethical discussion. The ethical development is seen schematically according to two phases. The concept of retrievability functions as a symbol for the shift from the first to the second phase. Intergenerational equity is interpreted as an obligation to maximize the safety of future generations, whilst imposing a minimum of risks, burdens and costs. The basic disposal concept is an intrinsically definitive and non-retrievable one. The second phase carries over from the first its principle of the total responsibility of our generation, but interprets the principle of intergenerational equity as also including equal opportunities. This leads to the following conclusion: What is at stake is a precarious act of balance, with a preserved equal weight for the two principles in each decision and every measure. Finally, some questions for future treatment are put, and the author draws the following conclusions. We can hardly advance further than to manufacture an interactive waste management system, allowing us to involve present and future generations in an open, flexible, and non-preconstrained decision making process. In such a process, retrievability presents itself as an inescapable dimension. But at the same time we cannot guarantee future generations freedom to act without providing for them a repository which is designed to be finally closed. (author)

  17. Temporal Formation and Immunolocalization of an Endospore Surface Epitope During Pasteuria penetrans Sporogenesis.

    Science.gov (United States)

    Brito, J A; Preston, J F; Dickson, D W; Giblin-Davis, R M; Williams, D S; Aldrich, H C; Rice, J D

    2003-09-01

    The synthesis and localization of an endospore surface epitope associated with the development of Pasteuria penetrans was determined using a monoclonal antibody (MAb) as a probe. Nematodes, uninfected or infected with P. penetrans, were harvested at 12, 16, 24, and 38 days after inoculation (DAI) and then examined to determine the developmental stage of the bacterium. Vegetative growth of P. penetrans was observed only in infected nematodes harvested at 12 and 16 DAI, whereas cells at different stages of sporulation and mature endospores were observed at 24 and 38 DAI. ELISA and immunoblot analysis revealed that the adhesin-associated epitope was first detected at 24 DAI, and increased in the later stages of sporogenesis. These results indicate that the synthesis of adhesin-related proteins occurred at a certain developmental stage relative to the sporulation process, and was associated with endospore maturation. Immunofluorescence microscopy indicated that the distribution of the epitope is nearly uniform on the periphery of each spore, as defined by parasporal fibers. Immunocytochemistry at the ultrastructural level indicated a distribution of the epitope over the parasporal fibers. The epitope also was detected over other structures such as sporangium and exosporium during the sporogenesis process, but it was not observed over the cortex, inner-spore coat, outer-spore coat, or protoplasm. The appearance of the adhesin epitope first at stage III of sporogenesis and its presence on the parasporal fibers are consistent with an adhesin-related role in the attachment of the mature endospore to the cuticle of the nematode host.

  18. Depigmented Allergoids Reveal New Epitopes with Capacity to Induce IgG Blocking Antibodies

    Directory of Open Access Journals (Sweden)

    M. Angeles López-Matas

    2013-01-01

    Full Text Available Background. The synthesis of allergen-specific blocking IgGs that interact with IgE after allergen immunotherapy (SIT has been related to clinical efficacy. The objectives were to investigate the epitope specificity of IgG-antibodies induced by depigmented-polymerized (Dpg-Pol allergoids and unmodified allergen extracts, and examine IgE-blocking activity of induced IgG-antibodies. Methods. Rabbits were immunized with native and Dpg-Pol extracts of birch pollen, and serum samples were obtained. Recognition of linear IgG-epitopes of Bet v 1 and Bet v 2 and the capacity of these IgG-antibodies to block binding of human-IgE was determined. Results. Serum from rabbits immunized with native extracts recognised 11 linear epitopes from Bet v 1, while that from Dpg-Pol-immunized animals recognised 8. For Bet v 2, 8 epitopes were recognized by IgG from native immunized animals, and 9 from Dpg-Pol immunized one. Dpg-Pol and native immunized serum did not always recognise the same epitopes, but specific-IgG from both could block human-IgE binding sites for native extract. Conclusions. Depigmented-polymerized birch extract stimulates the synthesis of specific IgG-antibodies which recognize common but also novel epitopes compared with native extracts. IgG-antibodies induced by Dpg-Pol effectively inhibit human-IgE binding to allergens which may be part of the mechanism of action of SIT.

  19. In Silico Perspectives on the Prediction of the PLP's Epitopes involved in Multiple Sclerosis.

    Science.gov (United States)

    Zamanzadeh, Zahra; Ataei, Mitra; Nabavi, Seyed Massood; Ahangari, Ghasem; Sadeghi, Mehdi; Sanati, Mohammad Hosein

    2017-03-01

    Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system (CNS). The main cause of the MS is yet to be revealed, but the most probable theory is based on the molecular mimicry that concludes some infections in the activation of T cells against brain auto-antigens that initiate the disease cascade. The Purpose of this research is the prediction of the auto-antigen potency of the myelin proteolipid protein (PLP) in multiple sclerosis. As there wasn't any tertiary structure of PLP available in the Protein Data Bank (PDB) and in order to characterize the structural properties of the protein, we modeled this protein using prediction servers. Meta prediction method, as a new perspective in silico , was performed to fi nd PLPs epitopes. For this purpose, several T cell epitope prediction web servers were used to predict PLPs epitopes against Human Leukocyte Antigens (HLA). The overlap regions, as were predicted by most web servers were selected as immunogenic epitopes and were subjected to the BLASTP against microorganisms. Three common regions, AA 58-74 , AA 161-177 , and AA 238-254 were detected as immunodominant regions through meta-prediction. Investigating peptides with more than 50% similarity to that of candidate epitope AA 58-74 in bacteria showed a similar peptide in bacteria (mainly consistent with that of clostridium and mycobacterium) and spike protein of Alphacoronavirus 1, Canine coronavirus, and Feline coronavirus. These results suggest that cross reaction of the immune system to PLP may have originated from a bacteria or viral infection, and therefore molecular mimicry might have an important role in the progression of MS. Through reliable and accurate prediction of the consensus epitopes, it is not necessary to synthesize all PLP fragments and examine their immunogenicity experimentally ( in vitro ). In this study, the best encephalitogenic antigens were predicted based on bioinformatics tools that may provide reliable

  20. Epitope Dampening Monotypic Measles Virus Hemagglutinin Glycoprotein Results in Resistance to Cocktail of Monoclonal Antibodies

    Science.gov (United States)

    Lech, Patrycja J.; Tobin, Gregory J.; Bushnell, Ruth; Gutschenritter, Emily; Pham, Linh D.; Nace, Rebecca; Verhoeyen, Els; Cosset, François-Loïc; Muller, Claude P.; Russell, Stephen J.; Nara, Peter L.

    2013-01-01

    The measles virus (MV) is serologically monotypic. Life-long immunity is conferred by a single attack of measles or following vaccination with the MV vaccine. This is contrary to viruses such as influenza, which readily develop resistance to the immune system and recur. A better understanding of factors that restrain MV to one serotype may allow us to predict if MV will remain monotypic in the future and influence the design of novel MV vaccines and therapeutics. MV hemagglutinin (H) glycoprotein, binds to cellular receptors and subsequently triggers the fusion (F) glycoprotein to fuse the virus into the cell. H is also the major target for neutralizing antibodies. To explore if MV remains monotypic due to a lack of plasticity of the H glycoprotein, we used the technology of Immune Dampening to generate viruses with rationally designed N-linked glycosylation sites and mutations in different epitopes and screened for viruses that escaped monoclonal antibodies (mAbs). We then combined rationally designed mutations with naturally selected mutations to generate a virus resistant to a cocktail of neutralizing mAbs targeting four different epitopes simultaneously. Two epitopes were protected by engineered N-linked glycosylations and two epitopes acquired escape mutations via two consecutive rounds of artificial selection in the presence of mAbs. Three of these epitopes were targeted by mAbs known to interfere with receptor binding. Results demonstrate that, within the epitopes analyzed, H can tolerate mutations in different residues and additional N-linked glycosylations to escape mAbs. Understanding the degree of change that H can tolerate is important as we follow its evolution in a host whose immunity is vaccine induced by genotype A strains instead of multiple genetically distinct wild-type MVs. PMID:23300970

  1. The POM monoclonals: a comprehensive set of antibodies to non-overlapping prion protein epitopes.

    Directory of Open Access Journals (Sweden)

    Magdalini Polymenidou

    Full Text Available PrP(Sc, a misfolded and aggregated form of the cellular prion protein PrP(C, is the only defined constituent of the transmissible agent causing prion diseases. Expression of PrP(C in the host organism is necessary for prion replication and for prion neurotoxicity. Understanding prion diseases necessitates detailed structural insights into PrP(C and PrP(Sc. Towards this goal, we have developed a comprehensive collection of monoclonal antibodies denoted POM1 to POM19 and directed against many different epitopes of mouse PrP(C. Three epitopes are located within the N-terminal octarepeat region, one is situated within the central unstructured region, and four epitopes are discontinuous within the globular C-proximal domain of PrP(C. Some of these antibodies recognize epitopes that are resilient to protease digestion in PrP(Sc. Other antibodies immunoprecipitate PrP(C, but not PrP(Sc. A third group was found to immunoprecipitate both PrP isoforms. Some of the latter antibodies could be blocked with epitope-mimicking peptides, and incubation with an excess of these peptides allowed for immunochromatography of PrP(C and PrP(Sc. Amino-proximal antibodies were found to react with repetitive PrP(C epitopes, thereby vastly increasing their avidity. We have also created functional single-chain miniantibodies from selected POMs, which retained the binding characteristics despite their low molecular mass. The POM collection, thus, represents a unique set of reagents allowing for studies with a variety of techniques, including western blotting, ELISA, immunoprecipitation, conformation-dependent immunoassays, and plasmon surface plasmon resonance-based assays.

  2. Epitope-based peptide vaccine design and target site depiction against Ebola viruses: an immunoinformatics study.

    Science.gov (United States)

    Khan, M A; Hossain, M U; Rakib-Uz-Zaman, S M; Morshed, M N

    2015-07-01

    Ebola viruses (EBOVs) have been identified as an emerging threat in recent year as it causes severe haemorrhagic fever in human. Epitope-based vaccine design for EBOVs remains a top priority because a mere progress has been made in this regard. Another reason is the lack of antiviral drug and licensed vaccine although there is a severe outbreak in Central Africa. In this study, we aimed to design an epitope-based vaccine that can trigger a significant immune response as well as to prognosticate inhibitor that can bind with potential drug target sites using various immunoinformatics and docking simulation tools. The capacity to induce both humoral and cell-mediated immunity by T cell and B cell was checked for the selected protein. The peptide region spanning 9 amino acids from 42 to 50 and the sequence TLASIGTAF were found as the most potential B and T cell epitopes, respectively. This peptide could interact with 12 HLAs and showed high population coverage up to 80.99%. Using molecular docking, the epitope was further appraised for binding against HLA molecules to verify the binding cleft interaction. In addition with this, the allergenicity of the epitopes was also evaluated. In the post-therapeutic strategy, docking study of predicted 3D structure identified suitable therapeutic inhibitor against targeted protein. However, this computational epitope-based peptide vaccine designing and target site prediction against EBOVs open up a new horizon which may be the prospective way in Ebola viruses research; the results require validation by in vitro and in vivo experiments. © 2015 John Wiley & Sons Ltd.

  3. Allergen and Epitope Targets of Mouse-Specific T Cell Responses in Allergy and Asthma

    Directory of Open Access Journals (Sweden)

    Véronique Schulten

    2018-02-01

    Full Text Available Mouse allergy has become increasingly common, mainly affecting laboratory workers and inner-city households. To date, only one major allergen, namely Mus m 1, has been described. We sought to identify T cell targets in mouse allergic patients. PBMC from allergic donors were expanded with either murine urine or epithelial extract and subsequently screened for cytokine production (IL-5 and IFNγ in response to overlapping peptides spanning the entire Mus m 1 sequence, peptides from various Mus m 1 isoforms [major urinary proteins (MUPs], peptides from mouse orthologs of known allergens from other mammalian species and peptides from proteins identified by immunoproteomic analysis of IgE/IgG immunoblots of mouse urine and epithelial extracts. This approach let to the identification of 106 non-redundant T cell epitopes derived from 35 antigens. Three major T cell-activating regions were defined in Mus m 1 alone. Moreover, our data show that immunodominant epitopes were largely shared between Mus m 1 and other MUPs even from different species, suggesting that sequence conservation in different allergens is a determinant for immunodominance. We further identified several novel mouse T cell antigens based on their homology to known mammalian allergens. Analysis of cohort-specific T cell responses revealed that rhinitis and asthmatic patients recognized different epitope repertoires. Epitopes defined herein can be formulated into an epitope “megapool” used to diagnose mouse allergy and study mouse-specific T cell responses directly ex vivo. This analysis of T cell epitopes provides a good basis for future studies to increase our understanding of the immunopathology associated with MO-allergy and asthma.

  4. Positive-unlabeled learning for the prediction of conformational B-cell epitopes

    Science.gov (United States)

    2015-01-01

    Background The incomplete ground truth of training data of B-cell epitopes is a demanding issue in computational epitope prediction. The challenge is that only a small fraction of the surface residues of an antigen are confirmed as antigenic residues (positive training data); the remaining residues are unlabeled. As some of these uncertain residues can possibly be grouped to form novel but currently unknown epitopes, it is misguided to unanimously classify all the unlabeled residues as negative training data following the traditional supervised learning scheme. Results We propose a positive-unlabeled learning algorithm to address this problem. The key idea is to distinguish between epitope-likely residues and reliable negative residues in unlabeled data. The method has two steps: (1) identify reliable negative residues using a weighted SVM with a high recall; and (2) construct a classification model on the positive residues and the reliable negative residues. Complex-based 10-fold cross-validation was conducted to show that this method outperforms those commonly used predictors DiscoTope 2.0, ElliPro and SEPPA 2.0 in every aspect. We conducted four case studies, in which the approach was tested on antigens of West Nile virus, dihydrofolate reductase, beta-lactamase, and two Ebola antigens whose epitopes are currently unknown. All the results were assessed on a newly-established data set of antigen structures not bound by antibodies, instead of on antibody-bound antigen structures. These bound structures may contain unfair binding information such as bound-state B-factors and protrusion index which could exaggerate the epitope prediction performance. Source codes are available on request. PMID:26681157

  5. GPS-MBA: computational analysis of MHC class II epitopes in type 1 diabetes.

    Science.gov (United States)

    Cai, Ruikun; Liu, Zexian; Ren, Jian; Ma, Chuang; Gao, Tianshun; Zhou, Yanhong; Yang, Qing; Xue, Yu

    2012-01-01

    As a severe chronic metabolic disease and autoimmune disorder, type 1 diabetes (T1D) affects millions of people world-wide. Recent advances in antigen-based immunotherapy have provided a great opportunity for further treating T1D with a high degree of selectivity. It is reported that MHC class II I-A(g7) in the non-obese diabetic (NOD) mouse and human HLA-DQ8 are strongly linked to susceptibility to T1D. Thus, the identification of new I-A(g7) and HLA-DQ8 epitopes would be of great help to further experimental and biomedical manipulation efforts. In this study, a novel GPS-MBA (MHC Binding Analyzer) software package was developed for the prediction of I-A(g7) and HLA-DQ8 epitopes. Using experimentally identified epitopes as the training data sets, a previously developed GPS (Group-based Prediction System) algorithm was adopted and improved. By extensive evaluation and comparison, the GPS-MBA performance was found to be much better than other tools of this type. With this powerful tool, we predicted a number of potentially new I-A(g7) and HLA-DQ8 epitopes. Furthermore, we designed a T1D epitope database (TEDB) for all of the experimentally identified and predicted T1D-associated epitopes. Taken together, this computational prediction result and analysis provides a starting point for further experimental considerations, and GPS-MBA is demonstrated to be a useful tool for generating starting information for experimentalists. The GPS-MBA is freely accessible for academic researchers at: http://mba.biocuckoo.org.

  6. 76 FR 51374 - Direct Discovery of HLA Associated Influenza Epitopes Isolated From Human Cells for Vaccine and...

    Science.gov (United States)

    2011-08-18

    ... direct-discovery technology for use in FDA laboratories. C. Eligibility Information The technology...] Direct Discovery of HLA Associated Influenza Epitopes Isolated From Human Cells for Vaccine and... technology to molecularly characterize peptide epitopes that are processed and presented on soluble HLA...

  7. High-throughput sequencing enhanced phage display enables the identification of patient-specific epitope motifs in serum

    DEFF Research Database (Denmark)

    Christiansen, Anders; Kringelum, Jens Vindahl; Hansen, Christian Skjødt

    2015-01-01

    of the bioinformatic approach was demonstrated by identifying epitopes of a prominent peanut allergen, Ara h 1, in sera from patients with severe peanut allergy. The identified epitopes were confirmed by high-density peptide micro-arrays. The present study demonstrates that high-throughput sequencing can empower phage...

  8. Comparative analysis of evolutionarily conserved motifs of epidermal growth factor receptor 2 (HER2) predicts novel potential therapeutic epitopes

    DEFF Research Database (Denmark)

    Deng, Xiaohong; Zheng, Xuxu; Yang, Huanming

    2014-01-01

    druggable epitopes/targets. We employed the PROSITE Scan to detect structurally conserved motifs and PRINTS to search for linearly conserved motifs of ECD HER2. We found that the epitopes recognized by trastuzumab and pertuzumab are located in the predicted conserved motifs of ECD HER2, supporting our...

  9. Full protection of swine against foot-and-mouth disease by a bivalent B-cell epitope dendrimer peptide

    NARCIS (Netherlands)

    Blanco, Esther; Guerra, Beatriz; Torre, de la Beatriz; Defaus, Sira; Dekker, A.; Andreu, D.; Sobrino, Francisco

    2016-01-01

    Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals. We have reported (Cubillos et al., 2008) that a synthetic dendrimeric peptide consisting of four copies of a B-cell epitope [VP1(136–154)] linked through thioether bonds to a T-cell epitope [3A(21–35)

  10. Analysis of pectic epitopes recognised by hybridoma and phage display monoclonal antibodies using defined oligosaccharides, polysaccharides, and enzymatic degradation

    DEFF Research Database (Denmark)

    Willats, William George Tycho; Limberg, G.; Buchholt, H.C.

    2000-01-01

    occurs where specific but undefined methyl-esterification patterns are present on HG domains, although fully de-esterified HG samples contain sub-optimal JIM5 epitopes. The persistence of mAb binding to epitopes in pectic antigens, with 41% blockwise esterification (P41) and 43% random esterification (F...

  11. Credibility improves topical blog post retrieval

    NARCIS (Netherlands)

    Weerkamp, W.; de Rijke, M.

    2008-01-01

    Topical blog post retrieval is the task of ranking blog posts with respect to their relevance for a given topic. To improve topical blog post retrieval we incorporate textual credibility indicators in the retrieval process. We consider two groups of indicators: post level (determined using

  12. Interactive information seeking, behaviour and retrieval

    CERN Document Server

    Ruthven, Ian

    2011-01-01

    Information retrieval (IR) is a complex human activity supported by sophisticated systems. This book covers the whole spectrum of information retrieval, including: history and background information; behaviour and seeking task-based information; searching and retrieval approaches to investigating information; and, evaluation interfaces for IR.

  13. Functional alarming and information retrieval

    International Nuclear Information System (INIS)

    Goodstein, L.P.

    1985-08-01

    This paper deals with two facets of the design and efficient utilisation by operating personnel of computer-based interfaces for monitoring and the supervisory control of complex industrial systems - e.g., power stations, chemical plants, etc. These are alarming and information retrieval both of which are extremely sensitive to computerisation. For example, the advent of computers for display requires that some means of assuring easy and rapid access to large amounts of relevant stored information be found. In this paper, alarming and information retrieval are linked together through a multilevel functional description of the target plant. This representation serves as a framework for structuring the access to information as well as defining associated ''alarms'' at the various descriptive levels. Particular attention is paid to the level where mass and energy flows and balances are relevant. It is shown that the number of alarms here is reduced considerably while information about content and interrelationships is enhanced - which at the same time eases the retrieval problem. (author)

  14. Interactive Information Retrieval: An Introduction

    Directory of Open Access Journals (Sweden)

    Borlund, Pia

    2013-09-01

    Full Text Available The paper introduces the research area of interactive information retrieval (IIR from a historical point of view. Further, the focus here is on evaluation, because much research in IR deals with IR evaluation methodology due to the core research interest in IR performance, system interaction and satisfaction with retrieved information. In order to position IIR evaluation, the Cranfield model and the series of tests that led to the Cranfield model are outlined. Three iconic user-oriented studies and projects that all have contributed to how IIR is perceived and understood today are presented: The MEDLARS test, the Book House fiction retrieval system, and the OKAPI project. On this basis the call for alternative IIR evaluation approaches motivated by the three revolutions (the cognitive, the relevance, and the interactive revolutions put forward by Robertson & Hancock-Beaulieu (1992 is presented. As a response to this call the 'IIR evaluation model' by Borlund (e.g., 2003a is introduced. The objective of the IIR evaluation model is to facilitate IIR evaluation as close as possible to actual information searching and IR processes, though still in a relatively controlled evaluation environment, in which the test instrument of a simulated work task situation plays a central part.

  15. Retrieval of Mir Solar Array

    Science.gov (United States)

    Rutledge, Sharon K.; deGroh, Kim K.

    1999-01-01

    A Russian solar array panel removed in November 1997 from the non-articulating photovoltaic array on the Mir core module was returned to Earth on STS-89 in January 1998. The panel had been exposed to low Earth orbit (LEO) for 10 years prior to retrieval. The retrieval provided a unique opportunity to study the effects of the LEO environment on a functional solar array. To take advantage of this opportunity, a team composed of members from RSC-Energia (Russia), the Boeing Company, and the following NASA Centers--Johnson Space Center, Kennedy Space Center, Langley Research Center, Marshall Space Flight Center, and Lewis Research Center--was put together to analyze the array. After post-retrieval inspections at the Spacehab Facility at Kennedy in Florida, the array was shipped to Lewis in Cleveland for electrical performance tests, closeup photodocumentation, and removal of selected solar cells and blanket material. With approval from RSC-Energia, five cell pairs and their accompanying blanket and mesh material, and samples of painted handrail materials were selected for removal on the basis of their ability to provide degradation information. Sites were selected that provided different sizes and shapes of micrometeoroid impacts and different levels of surface contamination. These materials were then distributed among the team for round robin testing.

  16. Retrieval.

    OpenAIRE

    Clay, Allyson

    1990-01-01

    Allyson Clay’s "Traces of a City in the Spaces Between Some People" is a series of twenty diptychs contrasting fabricated faux finishing with expressionist painting and text. The fabricated paint applications evoke city surfaces like concrete and granite; they also evoke modernist painting.  Unlike modernist painting, however, the faux surfaces are decorative and mechanically painted. The choice to have the surfaces fabricated serves to disrupt the egoism of modern abstraction and the im...

  17. [Chemical modification of allergen leading to changes in its epitopic activity].

    Science.gov (United States)

    Babakhin, A A; Gushchin, I S; Andreev, S M; Petrukhina, A I; Viler, A V; Stokinger, B; Nolte, G; Dubuske, L M; Khaitov, R M; Petrpv, R V

    1999-01-01

    Modification of a model allergen ovalbumin (OA) with succinylation led to a decrease of its allergenicity measured by passive cutaneous anaphylaxis reaction, RAST inhibition assay and basophil histamine release. Modified OA stimulated OA-specific T-cell hybrid 3DO-548 to produce IL-2 at the same level as in case of non-modified OA. Modified OA did not induce anti-OA IgE, but did induce anti-OA IgG antibodies. This approach to chemical modification of allergen-selective blockade of B-cell epitopes while not affecting T-cell epitopes suggests new opportunities in creation of safe and effective allergovaccines.

  18. Interaction of an immunodominant epitope with Ia molecules in T-cell activation

    DEFF Research Database (Denmark)

    Adorini, L; Sette, A; Buus, S

    1988-01-01

    The amino acid sequence corresponding to residues 107-116 of hen egg-white lysozyme (HEL) has been identified as containing an immunodominant T-cell epitope recognized in association with the I-Ed molecule. The immunodominance of this epitope in HEL-primed H-2d mice was demonstrated by analysis o......-120)-peptide was found to be immunogenic in H-2d mice. Thus, a single semiconservative substitution drastically reduces binding capacity and abolishes immunogenicity, suggesting that a strict correlation exists between binding of a peptide to Ia molecules and its immunogenicity....

  19. Bioinformatics prediction of swine MHC class I epitopes from Porcine Reproductive and Respiratory Syndrome Virus

    DEFF Research Database (Denmark)

    Welner, Simon; Nielsen, Morten; Lund, Ole

    an effective CTL response against PRRSV, we have taken a bioinformatics approach to identify common PRRSV epitopes predicted to react broadly with predominant swine MHC (SLA) alleles. First, the genomic integrity and sequencing method was examined for 334 available complete PRRSV type 2 genomes leaving 104...... by the PopCover algorithm, providing a final list of 54 epitopes prioritized according to maximum coverage of PRRSV strains and SLA alleles. This bioinformatics approach provides a rational strategy for selecting peptides for a CTL-activating vaccine with broad coverage of both virus and swine diversity...

  20. Cutting edge: identification of novel T cell epitopes in Lol p5a by computational prediction.

    Science.gov (United States)

    de Lalla, C; Sturniolo, T; Abbruzzese, L; Hammer, J; Sidoli, A; Sinigaglia, F; Panina-Bordignon, P

    1999-08-15

    Although atopic allergy affects Lol p5a allergen from rye grass. In vitro binding studies confirmed the promiscuous binding characteristics of these peptides. Moreover, most of the predicted ligands were novel T cell epitopes that were able to stimulate T cells from atopic patients. We generated a panel of Lol p5a-specific T cell clones, the majority of which recognized the peptides in a cross-reactive fashion. The computational prediction of DR ligands might thus allow the design of T cell epitopes with potential useful application in novel immunotherapy strategies.

  1. Hepatitis C virus epitope exposure and neutralization by antibodies is affected by time and temperature

    DEFF Research Database (Denmark)

    Sabo, Michelle C; Luca, Vincent C; Ray, Stuart C

    2012-01-01

    A recent study with flaviviruses suggested that structural dynamics of the virion impact antibody neutralization via exposure of ostensibly cryptic epitopes. To determine whether this holds true for the distantly related hepatitis C virus (HCV), whose neutralizing epitopes may be obscured...... by a glycan shield, apolipoprotein interactions, and the hypervariable region on the E2 envelope protein, we assessed how time and temperature of pre-incubation altered monoclonal antibody (MAb) neutralization of HCV. Notably, several MAbs showed increased inhibitory activity when pre-binding was performed...

  2. The Neutralizing Linear Epitope of Human Herpesvirus 6A Glycoprotein B Does Not Affect Virus Infectivity.

    Science.gov (United States)

    Wakata, Aika; Kanemoto, Satoshi; Tang, Huamin; Kawabata, Akiko; Nishimura, Mitsuhiro; Jasirwan, Chyntia; Mahmoud, Nora Fahmy; Mori, Yasuko

    2018-03-01

    Human herpesvirus 6A (HHV-6A) glycoprotein B (gB) is a glycoprotein consisting of 830 amino acids and is essential for the growth of the virus. Previously, we reported that a neutralizing monoclonal antibody (MAb) called 87-y-13 specifically reacts with HHV-6A gB, and we identified its epitope residue at asparagine (Asn) 347 on gB. In this study, we examined whether the epitope recognized by the neutralizing MAb is essential for HHV-6A infection. We constructed HHV-6A bacterial artificial chromosome (BAC) genomes harboring substitutions at Asn347, namely, HHV-6A BACgB(N347K) and HHV-6A BACgB(N347A). These mutant viruses could be reconstituted and propagated in the same manner as the wild type and their revertants, and MAb 87-y-13 could not inhibit infection by either mutant. In a cell-cell fusion assay, Asn at position 347 on gB was found to be nonessential for cell-cell fusion. In addition, in building an HHV-6A gB homology model, we found that the epitope of the neutralizing MAb is located on domain II of gB and is accessible to solvents. These results indicate that Asn at position 347, the linear epitope of the neutralizing MAb, does not affect HHV-6A infectivity. IMPORTANCE Glycoprotein B (gB) is one of the most conserved glycoproteins among all herpesviruses and is a key factor for virus entry. Therefore, antibodies targeted to gB may neutralize virus entry. Human herpesvirus 6A (HHV-6A) encodes gB, which is translated to a protein of about 830 amino acids (aa). Using a monoclonal antibody (MAb) for HHV-6A gB, which has a neutralizing linear epitope, we analyzed the role of its epitope residue, N347, in HHV-6A infectivity. Interestingly, this gB linear epitope residue, N347, was not essential for HHV-6A growth. By constructing a homology model of HHV-6A gB, we found that N347 was located in the region corresponding to domain II. Therefore, with regard to its neutralizing activity against HHV-6A infection, the epitope on gB might be exposed to solvents

  3. MuPeXI: prediction of neo-epitopes from tumor sequencing data

    DEFF Research Database (Denmark)

    Bjerregaard, Anne-Mette; Nielsen, Morten; Hadrup, Sine Reker

    2017-01-01

    Personalization of immunotherapies such as cancer vaccines and adoptive T cell therapy depends on identification of patient-specific neo-epitopes that can be specifically targeted. MuPeXI, the mutant peptide extractor and informer, is a program to identify tumor-specific peptides and assess...... their potential to be neo-epitopes. The program input is a file with somatic mutation calls, a list of HLA types, and optionally a gene expression profile. The output is a table with all tumor-specific peptides derived from nucleotide substitutions, insertions, and deletions, along with comprehensive annotation...

  4. Relating the new language models of information retrieval to the traditional retrieval models

    NARCIS (Netherlands)

    Hiemstra, Djoerd; de Vries, A.P.

    During the last two years, exciting new approaches to information retrieval were introduced by a number of different research groups that use statistical language models for retrieval. This paper relates the retrieval algorithms suggested by these approaches to widely accepted retrieval algorithms

  5. Retrieval Attempts Enhance Learning, but Retrieval Success (versus Failure) Does Not Matter

    Science.gov (United States)

    Kornell, Nate; Klein, Patricia Jacobs; Rawson, Katherine A.

    2015-01-01

    Retrieving information from memory enhances learning. We propose a 2-stage framework to explain the benefits of retrieval. Stage 1 takes place as one attempts to retrieve an answer, which activates knowledge related to the retrieval cue. Stage 2 begins when the answer becomes available, at which point appropriate connections are strengthened and…

  6. From viral genome to specific peptide epitopes: methods for identifying porcine T cell epitopes based on in silico predictions, in vitro identification and ex vivo verification

    DEFF Research Database (Denmark)

    Pedersen, Lasse Eggers; Rasmussen, Michael; Harndah, Mikkel

    2013-01-01

    to predict likely candidates for peptide-SLA binding. These results were combined with binding predictions generated by the algorithm, NetMHCpan (http://www.cbs.dtu.dk/services/NetMHCpan/) in order to select peptide candidates for in vitro analysis. The correlation between high affinity and high stability.......000 peptides. T cell epitopes were identified using peptide-SLA complexes assembled into fluorescent tetramers to stain swine influenza specific CTLs derived from immunized animals and MHC-defined pigs vaccinated against foot-and-mouth disease virus. These results demonstrate the broad applicability of methods...... originally developed for analysis of human leukocyte antigen (HLA) presentation of peptides. The methods presented provide a timely and cost-effective approach to CTL epitope discovery that can be applied to diseases of swine and of other mammalian species of interest....

  7. Conservation and diversity of influenza A H1N1 HLA-restricted T cell epitope candidates for epitope-based vaccines.

    Directory of Open Access Journals (Sweden)

    Paul Thiamjoo Tan

    2010-01-01

    Full Text Available The immune-related evolution of influenza viruses is exceedingly complex and current vaccines against influenza must be reformulated for each influenza season because of the high degree of antigenic drift among circulating influenza strains. Delay in vaccine production is a serious problem in responding to a pandemic situation, such as that of the current H1N1 strain. Immune escape is generally attributed to reduced antibody recognition of the viral hemagglutinin and neuraminidase proteins whose rate of mutation is much greater than that of the internal non-structural proteins. As a possible alternative, vaccines directed at T cell epitope domains of internal influenza proteins, that are less susceptible to antigenic variation, have been investigated.HLA transgenic mouse strains expressing HLA class I A*0201, A*2402, and B*0702, and class II DRB1*1501, DRB1*0301 and DRB1*0401 were immunized with 196 influenza H1N1 peptides that contained residues of highly conserved proteome sequences of the human H1N1, H3N2, H1N2, H5N1, and avian influenza A strains. Fifty-four (54 peptides that elicited 63 HLA-restricted peptide-specific T cell epitope responses were identified by IFN-gamma ELISpot assay. The 54 peptides were compared to the 2007-2009 human H1N1 sequences for selection of sequences in the design of a new candidate H1N1 vaccine, specifically targeted to highly-conserved HLA-restricted T cell epitopes.Seventeen (17 T cell epitopes in PB1, PB2, and M1 were selected as vaccine targets based on sequence conservation over the past 30 years, high functional avidity, non-identity to human peptides, clustered localization, and promiscuity to multiple HLA alleles. These candidate vaccine antigen sequences may be applicable to any avian or human influenza A virus.

  8. Multimedia information retrieval theory and techniques

    CERN Document Server

    Raieli, Roberto

    2013-01-01

    Novel processing and searching tools for the management of new multimedia documents have developed. Multimedia Information Retrieval (MMIR) is an organic system made up of Text Retrieval (TR); Visual Retrieval (VR); Video Retrieval (VDR); and Audio Retrieval (AR) systems. So that each type of digital document may be analysed and searched by the elements of language appropriate to its nature, search criteria must be extended. Such an approach is known as the Content Based Information Retrieval (CBIR), and is the core of MMIR. This novel content-based concept of information handling needs to be integrated with more traditional semantics. Multimedia Information Retrieval focuses on the tools of processing and searching applicable to the content-based management of new multimedia documents. Translated from Italian by Giles Smith, the book is divided in to two parts. Part one discusses MMIR and related theories, and puts forward new methodologies; part two reviews various experimental and operating MMIR systems, a...

  9. A Unified Mathematical Definition of Classical Information Retrieval.

    Science.gov (United States)

    Dominich, Sandor

    2000-01-01

    Presents a unified mathematical definition for the classical models of information retrieval and identifies a mathematical structure behind relevance feedback. Highlights include vector information retrieval; probabilistic information retrieval; and similarity information retrieval. (Contains 118 references.) (Author/LRW)

  10. Structure-Based Design of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses to a Conserved Epitope

    Energy Technology Data Exchange (ETDEWEB)

    Pierce, Brian G.; Boucher, Elisabeth N.; Piepenbrink, Kurt H.; Ejemel, Monir; Rapp, Chelsea A.; Thomas, William D.; Sundberg, Eric J.; Weng, Zhiping; Wang, Yang; Diamond, Michael S.

    2017-08-09

    Despite recent advances in therapeutic options, hepatitis C virus (HCV) remains a severe global disease burden, and a vaccine can substantially reduce its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response; thus, an effective vaccine must target conserved, functionally important epitopes. Using the structure of a broadly neutralizing antibody in complex with a conserved linear epitope from the HCV E2 envelope glycoprotein (residues 412 to 423; epitope I), we performed structure-based design of immunogens to induce antibody responses to this epitope. This resulted in epitope-based immunogens based on a cyclic defensin protein, as well as a bivalent immunogen with two copies of the epitope on the E2 surface. We solved the X-ray structure of a cyclic immunogen in complex with the HCV1 antibody and confirmed preservation of the epitope conformation and the HCV1 interface. Mice vaccinated with our designed immunogens produced robust antibody responses to epitope I, and their serum could neutralize HCV. Notably, the cyclic designs induced greater epitope-specific responses and neutralization than the native peptide epitope. Beyond successfully designing several novel HCV immunogens, this study demonstrates the principle that neutralizing anti-HCV antibodies can be induced by epitope-based, engineered vaccines and provides the basis for further efforts in structure-based design of HCV vaccines.

    IMPORTANCEHepatitis C virus is a leading cause of liver disease and liver cancer, with approximately 3% of the world's population infected. To combat this virus, an effective vaccine would have distinct advantages over current therapeutic options, yet experimental vaccines have not been successful to date, due in part to the virus's high sequence variability leading to immune escape. In this study, we rationally designed several vaccine immunogens based on the structure of a conserved epitope that

  11. Information retrieval and individual differences

    Directory of Open Access Journals (Sweden)

    Polona Vilar

    2008-01-01

    Full Text Available The paper presents individual differences, which are found in studies of information retrieval with emphasis on models of personality traits, cognitive and learning styles. It pays special attention to those models which are most often included in studies of information behaviour,information seeking,perceptions of IR systems, etc., but also brings forward some models which have not yet been included in such studies. Additionally, the relationship between different individual characteristics and individual’s chosen profession or academic area is discussed. In this context,the paper presents how investigation of individual differences can be useful in the design of IR systems.

  12. Six sigma for revenue retrieval.

    Science.gov (United States)

    Plonien, Cynthia

    2013-01-01

    Deficiencies in revenue retrieval due to failures in obtaining charges have contributed to a negative bottom line for numerous hospitals. Improving documentation practices through a Six Sigma process improvement initiative can minimize opportunities for errors through reviews and instill structure for compliance and consistency. Commitment to the Six Sigma principles with continuous monitoring of outcomes and constant communication of results to departments, management, and payers is a strong approach to reducing the financial impact of denials on an organization's revenues and expenses. Using Six Sigma tools can help improve the organization's financial performance not only for today, but also for health care's uncertain future.

  13. Identification of novel HLA-A(*)0201-restricted CTL epitopes from Pokemon.

    Science.gov (United States)

    Yuan, Bangqing; Zhao, Lin; Xian, Ronghua; Zhao, Gang

    2012-01-01

    Pokemon is a member of the POK family of transcriptional repressors and aberrant overexpressed in various human cancers. Therefore, the related peptide epitopes derived from Pokemon is essential for the development of specific immunotherapy of malignant tumors. In this study, we predicted and identified HLA-A(*)0201-restricted cytotoxic T lymphocyte (CTL) epitopes derived from Pokemon with computer-based epitope prediction, peptide-binding assay and testing of the induced CTLs toward different kinds of carcinoma cells. The results demonstrated that effectors induced by peptides of Pokemon containing residues 32-40, 61-69, 87-95, and 319-327 could specifically secrete IFN-γ and lyse tumor cell lines of Pokemon-positive and HLA-A2-matched. The results suggest that Pokemon32, Pokemon61, Pokemon87, and Pokemon319 peptides are novel HLA-A(*)0201-restricted restricted CTL epitopes, and could be utilized in the cancer immunotherapy against a broad spectrum of tumors. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. A dominant EV71-specific CD4+ T cell epitope is highly conserved among human enteroviruses.

    Directory of Open Access Journals (Sweden)

    Ruicheng Wei

    Full Text Available CD4+ T cell-mediated immunity plays a central role in determining the immunopathogenesis of viral infections. However, the role of CD4+ T cells in EV71 infection, which causes hand, foot and mouth disease (HFMD, has yet to be elucidated. We applied a sophisticated method to identify promiscuous CD4+ T cell epitopes contained within the sequence of the EV71 polyprotein. Fifteen epitopes were identified, and three of them are dominant ones. The most dominant epitope is highly conserved among enterovirus species, including HFMD-related coxsackieviruses, HFMD-unrelated echoviruses and polioviruses. Furthermore, the CD4+ T cells specific to the epitope indeed cross-reacted with the homolog of poliovirus 3 Sabin. Our findings imply that CD4+ T cell responses to poliovirus following vaccination, or to other enteroviruses to which individuals may be exposed in early childhood, may have a modulating effect on subsequent CD4+ T cell response to EV71 infection or vaccine.

  15. Feasibility of Cowpea chlorotic mottle virus-like particles as scaffold for epitope presentations

    NARCIS (Netherlands)

    Hassani-Mehraban, A.; Creutzburg, S.; Heereveld, van L.; Kormelink, R.J.M.

    2015-01-01

    Within the last decade Virus-Like Particles (VLPs) have increasingly received attention from scientists for their use as a carrier of (peptide) molecules or as scaffold to present epitopes for use in subunit vaccines. To test the feasibility of Cowpea chlorotic mottle virus (CCMV) particles as a

  16. Factor H and Properdin Recognize Different Epitopes on Renal Tubular Epithelial Heparan Sulfate

    NARCIS (Netherlands)

    Zaferani, Azadeh; Vives, Romain R.; van der Pol, Pieter; Navis, Gerjan J.; Daha, Mohamed R.; van Kooten, Cees; Lortat-Jacob, Hugues; Seelen, Marc A.; van den Born, Jacob

    2012-01-01

    During proteinuria, renal tubular epithelial cells become exposed to ultrafiltrate-derived serum proteins, including complement factors. Recently, we showed that properdin binds to tubular heparan sulfates (HS). We now document that factor H also binds to tubular HS, although to a different epitope

  17. Characterization of binding specificities of bovine leucocyte class I molecules: impacts for rational epitope discovery

    DEFF Research Database (Denmark)

    Hansen, Andreas M.; Rasmussen, Michael; Svitek, Nicholas

    2014-01-01

    confirmed experimentally. This study demonstrates how biochemical high-throughput assays combined with immunoinformatics can be used to characterize the peptide-binding motifs of BoLA-I molecules, boosting performance of MHC peptide-binding prediction methods, and empowering rational epitope discovery...

  18. Conflicting selective forces affect T cell receptor contacts in an immunodominant human immunodeficiency virus epitope

    DEFF Research Database (Denmark)

    Iversen, Astrid K N; Stewart-Jones, Guillaume; Learn, Gerald H

    2006-01-01

    two principal, diametrically opposed evolutionary pathways that exclusively affect T cell-receptor contact residues. One pathway was characterized by acquisition of CTL escape mutations and the other by selection for wild-type amino acids. The pattern of CTL responses to epitope variants shaped which...

  19. Identification of an adeno-associated virus binding epitope for AVB sepharose affinity resin

    Directory of Open Access Journals (Sweden)

    Qiang Wang

    Full Text Available Recent successes of adeno-associated virus (AAV–based gene therapy have created a demand for large-scale AAV vector manufacturing and purification techniques for use in clinical trials and beyond. During the development of purification protocols for rh.10, hu.37, AAV8, rh.64R1, AAV3B, and AAV9 vectors, based on a widely used affinity resin, AVB sepharose (GE, we found that, under the same conditions, different serotypes have different affinities to the resin, with AAV3B binding the best and AAV9 the poorest. Further analysis revealed a surface-exposed residue (amino acid number 665 in AAV8 VP1 numbering differs between the high-affinity AAV serotypes (serine in AAV3B, rh.10, and hu.37 and the low-affinity ones (asparagine in AAV8, rh.64R1, and AAV9. The residue locates within a surface-exposed, variable epitope flanked by highly conserved residues. The substitution of the epitope in AAV8, rh.64R1, and AAV9 with the corresponding epitope of AAV3B (SPAKFA resulted in greatly increased affinity to AVB sepharose with no reduction in the vectors’ in vitro potency. The presence of the newly identified AVB-binding epitope will be useful for affinity resin selection for the purification of novel AAV serotypes. It also suggests the possibility of vector engineering to yield a universal affinity chromatography purification method for multiple AAV serotypes.

  20. Towards a consensus on datasets and evaluation metrics for developing B-cell epitope prediction tools

    DEFF Research Database (Denmark)

    Greenbaum, Jason A.; Andersen, Pernille; Blythe, Martin

    2007-01-01

    and immunology communities. Improving the accuracy of B-cell epitope prediction methods depends on a community consensus on the data and metrics utilized to develop and evaluate such tools. A workshop, sponsored by the National Institute of Allergy and Infectious Disease (NIAID), was recently held in Washington...

  1. Label free targeted detection and quantification of celiac disease immunogenic epitopes by mass spectrometry

    NARCIS (Netherlands)

    Broeck, van den H.C.; Cordewener, J.H.G.; Nessen, M.A.; America, A.H.P.; Meer, van der I.M.

    2015-01-01

    Celiac disease (CD) is a food-related disease caused by certain gluten peptides containing T-cell stimulating epitopes from wheat, rye, and barley. CD-patients have to maintain a gluten-free diet and are therefore dependent on reliable testing and labeling of gluten-free products. So far, the

  2. DPD epitope-specific glutamic acid decarboxylase GAD)65 autoantibodies in children with Type 1 diabetes

    Science.gov (United States)

    To study whether DPD epitope-specific glutamate decarboxylase autoantibodies are found more frequently in children with milder forms of Type 1 diabetes. We prospectively evaluated 75 children with new-onset autoimmune Type 1 diabetes, in whom we collected demographic, anthropometric and clinical dat...

  3. Characterisation of a protective linear B cell epitope against feline parvoviruses

    NARCIS (Netherlands)

    Langeveld, J.P.; Martinez Torrecuadrada, J.; Boshuizen, R.S.; Meloen, R.H.; Ignacio Casal, J.

    2001-01-01

    Monoclonal antibody 3C9 was the starting material in the definition of the epitope that led to the synthesis of the first efficient peptide vaccine against a viral disease (canine parvovirus) in the natural host (dog). In this report, we have analysed the specificity of the antibody at the single

  4. Conservation of HIV-1 T cell epitopes across time and clades

    DEFF Research Database (Denmark)

    Levitz, Lauren; Koita, Ousmane A; Sangare, Kotou

    2012-01-01

    HIV genomic sequence variability has complicated efforts to generate an effective globally relevant vaccine. Regions of the viral genome conserved in sequence and across time may represent the "Achilles' heel" of HIV. In this study, highly conserved T-cell epitopes were selected using immunoinfor...

  5. Prediction and identification of mouse cytotoxic T lymphocyte epitopes in Ebola virus glycoproteins

    Directory of Open Access Journals (Sweden)

    Wu Shipo

    2012-06-01

    Full Text Available Abstract Background Ebola viruses (EBOVs cause severe hemorrhagic fever with a high mortality rate. At present, there are no licensed vaccines or efficient therapies to combat EBOV infection. Previous studies have shown that both humoral and cellular immune responses are crucial for controlling Ebola infection. CD8+ T cells play an important role in mediating vaccine-induced protective immunity. The objective of this study was to identify H-2d-specific T cell epitopes in EBOV glycoproteins (GPs. Results Computer-assisted algorithms were used to predict H-2d-specific T cell epitopes in two species of EBOV (Sudan and Zaire GP. The predicted peptides were synthesized and identified in BALB/c mice immunized with replication-deficient adenovirus vectors expressing the EBOV GP. Enzyme-linked immunospot assays and intracellular cytokine staining showed that the peptides RPHTPQFLF (Sudan EBOV, GPCAGDFAF and LYDRLASTV (Zaire EBOV could stimulate splenoctyes in immunized mice to produce large amounts of interferon-gamma. Conclusion Three peptides within the GPs of two EBOV strains were identified as T cell epitopes. The identification of these epitopes should facilitate the evaluation of vaccines based on the Ebola virus glycoprotein in a BALB/c mouse model.

  6. State of the art and challenges in sequence based T-cell epitope prediction

    DEFF Research Database (Denmark)

    Lundegaard, Claus; Hoof, Ilka; Lund, Ole

    2010-01-01

    Sequence based T-cell epitope predictions have improved immensely in the last decade. From predictions of peptide binding to major histocompatibility complex molecules with moderate accuracy, limited allele coverage, and no good estimates of the other events in the antigen-processing pathway, the...

  7. The design and implementation of the immune epitope database and analysis resource

    DEFF Research Database (Denmark)

    Peters, B.; Sidney, J.; Bourne, P.

    2005-01-01

    Epitopes are defined as parts of antigens interacting with receptors of the immune system. Knowledge about their intrinsic structure and how they affect the immune response is required to continue development of techniques that detect, monitor, and fight diseases. Their scientific importance is r...

  8. Thyroid Autoantibodies Display both “Original Antigenic Sin” and Epitope Spreading

    OpenAIRE

    McLachlan, Sandra M.; Rapoport, Basil

    2017-01-01

    Evidence for original antigenic sin in spontaneous thyroid autoimmunity is revealed by autoantibody interactions with immunodominant regions on thyroid autoantigens, thyroglobulin (Tg), thyroid peroxidase (TPO), and the thyrotropin receptor (TSHR) A-subunit. In contrast, antibodies induced by immunization of rabbits or mice recognize diverse epitopes. Recognition of immunodominant regions persists despite fluctuations in autoantibody levels following treatment or over time. The enhancement of...

  9. Distribution of some pectic and arabinogalactan protein epitopes during Solanum lycopersicum (L.) adventitious root development.

    Science.gov (United States)

    Sala, Katarzyna; Malarz, Katarzyna; Barlow, Peter W; Kurczyńska, Ewa U

    2017-01-25

    The adventitious roots (AR) of plants share the same function as primary and lateral roots (LR), although their development is mainly an adaptive reaction to stress conditions. Regeneration of grafted plants is often accompanied by AR formation thus making the grafting technique a good model for studying AR initiation and development and their means of emergence. Pectins and arabinogalactan proteins (AGP) are helpful markers of particular cellular events, such as programmed cell death (PCD), elongation, proliferation or other differentiation events that accompany AR development. However, little is known about the distribution of pectins and AGPs during AR ontogeny, either in the primordium or stem tissues from which AR arise or their correspondence with these events during LR formation. AR were developed from different stem tissues such as parenchyma, xylem rays and the cambium, depending on the stem age and treatment (grafting versus cutting) of the parental tissue. Immunochemical analysis of the presence of pectic (LM8, LM19, LM20) and AGP (JIM8, JIM13, JIM16) epitopes in AR and AR-associated tissues showed differential, tissue-specific distributions of these epitopes. Two pectic epitopes (LM19, LM20) were developmentally regulated and the occurrence of the LM8 xylogalacturonan epitope in the root cap of the AR differed from other species described so far. AGP epitopes were abundantly present in the cytoplasmic compartments (mainly the tonoplast) and were correlated with the degree of cell vacuolisation. JIM8 and JIM13 epitopes were detected in the more advanced stages of primordium development, whereas the JIM16 epitope was present from the earliest division events of the initial AR cells. The comparison between AR and LR showed quantitative (AGP,) and qualitative (pectins) differences. The chemical compositions of adventitious and lateral root cells show differences that correlate with the different origins of these cells. In AR, developmental changes in the

  10. CTL escape mediated by proteasomal destruction of an HIV-1 cryptic epitope.

    Directory of Open Access Journals (Sweden)

    Sylvain Cardinaud

    2011-05-01

    Full Text Available Cytotoxic CD8+ T cells (CTLs play a critical role in controlling viral infections. HIV-infected individuals develop CTL responses against epitopes derived from viral proteins, but also against cryptic epitopes encoded by viral alternative reading frames (ARF. We studied here the mechanisms of HIV-1 escape from CTLs targeting one such cryptic epitope, Q9VF, encoded by an HIVgag ARF and presented by HLA-B*07. Using PBMCs of HIV-infected patients, we first cloned and sequenced proviral DNA encoding for Q9VF. We identified several polymorphisms with a minority of proviruses encoding at position 5 an aspartic acid (Q9VF/5D and a majority encoding an asparagine (Q9VF/5N. We compared the prevalence of each variant in PBMCs of HLA-B*07+ and HLA-B*07- patients. Proviruses encoding Q9VF/5D were significantly less represented in HLA-B*07+ than in HLA-B*07- patients, suggesting that Q9FV/5D encoding viruses might be under selective pressure in HLA-B*07+ individuals. We thus analyzed ex vivo CTL responses directed against Q9VF/5D and Q9VF/5N. Around 16% of HLA-B*07+ patients exhibited CTL responses targeting Q9VF epitopes. The frequency and the magnitude of CTL responses induced with Q9VF/5D or Q9VF/5N peptides were almost equal indicating a possible cross-reactivity of the same CTLs on the two peptides. We then dissected the cellular mechanisms involved in the presentation of Q9VF variants. As expected, cells infected with HIV strains encoding for Q9VF/5D were recognized by Q9VF/5D-specific CTLs. In contrast, Q9VF/5N-encoding strains were neither recognized by Q9VF/5N- nor by Q9VF/5D-specific CTLs. Using in vitro proteasomal digestions and MS/MS analysis, we demonstrate that the 5N variation introduces a strong proteasomal cleavage site within the epitope, leading to a dramatic reduction of Q9VF epitope production. Our results strongly suggest that HIV-1 escapes CTL surveillance by introducing mutations leading to HIV ARF-epitope destruction by proteasomes.

  11. The immune epitope database: a historical retrospective of the first decade.

    Science.gov (United States)

    Salimi, Nima; Fleri, Ward; Peters, Bjoern; Sette, Alessandro

    2012-10-01

    As the amount of biomedical information available in the literature continues to increase, databases that aggregate this information continue to grow in importance and scope. The population of databases can occur either through fully automated text mining approaches or through manual curation by human subject experts. We here report our experiences in populating the National Institute of Allergy and Infectious Diseases sponsored Immune Epitope Database and Analysis Resource (IEDB, http://iedb.org), which was created in 2003, and as of 2012 captures the epitope information from approximately 99% of all papers published to date that describe immune epitopes (with the exception of cancer and HIV data). This was achieved using a hybrid model based on automated document categorization and extensive human expert involvement. This task required automated scanning of over 22 million PubMed abstracts followed by classification and curation of over 13 000 references, including over 7000 infectious disease-related manuscripts, over 1000 allergy-related manuscripts, roughly 4000 related to autoimmunity, and 1000 transplant/alloantigen-related manuscripts. The IEDB curation involves an unprecedented level of detail, capturing for each paper the actual experiments performed for each different epitope structure. Key to enabling this process was the extensive use of ontologies to ensure rigorous and consistent data representation as well as interoperability with other bioinformatics resources, including the Protein Data Bank, Chemical Entities of Biological Interest, and the NIAID Bioinformatics Resource Centers. A growing fraction of the IEDB data derives from direct submissions by research groups engaged in epitope discovery, and is being facilitated by the implementation of novel data submission tools. The present explosion of information contained in biological databases demands effective query and display capabilities to optimize the user experience. Accordingly, the

  12. IgE versus IgG4 epitopes of the peanut allergen Ara h 1 in patients with severe allergy

    DEFF Research Database (Denmark)

    Bøgh, Katrine Lindholm; Nielsen, H.; Eiwegger, T.

    2014-01-01

    epitopes. Objective: The aim of this study was to compare Ara h 1-specific IgE and IgG4 epitope recognition patterns in patients with severe peanut allergy, applying a method allowing for identification of both linear and conformational epitopes. Methods: Polyclonal sera from three individual patients......, suffering from severe allergic reaction to peanuts, including anaphylaxis, were used to analyse the IgE and IgG4 epitope recognition patterns of the major peanut allergen Ara h 1. Epitope identification was conducted by competitive immuno-screening of a phage-displayed random heptamer peptide library...

  13. Innovative grout/retrieval demonstration final report

    International Nuclear Information System (INIS)

    Loomis, G.G.; Thompson, D.N.

    1995-01-01

    This report presents the results of an evaluation of an innovative retrieval technique for buried transuranic waste. Application of this retrieval technique was originally designed for full pit retrieval; however, it applies equally to a hot spot retrieval technology. The technique involves grouting the buried soil waste matrix with a jet grouting procedure, applying an expansive demolition grout to the matrix, and retrieving the debris. The grouted matrix provides an agglomeration of fine soil particles and contaminants resulting in an inherent contamination control during the dusty retrieval process. A full-scale field demonstration of this retrieval technique was performed on a simulated waste pit at the Idaho National Engineering Laboratory. Details are reported on all phases of this proof-of-concept demonstration including pit construction, jet grouting activities, application of the demolition grout, and actual retrieval of the grouted pit. A quantitative evaluation of aerosolized soils and rare earth tracer spread is given for all phases of the demonstration, and these results are compared to a baseline retrieval activity using conventional retrieval means. 8 refs., 47 figs., 10 tabs

  14. Biomedical information retrieval across languages.

    Science.gov (United States)

    Daumke, Philipp; Markü, Kornél; Poprat, Michael; Schulz, Stefan; Klar, Rüdiger

    2007-06-01

    This work presents a new dictionary-based approach to biomedical cross-language information retrieval (CLIR) that addresses many of the general and domain-specific challenges in current CLIR research. Our method is based on a multilingual lexicon that was generated partly manually and partly automatically, and currently covers six European languages. It contains morphologically meaningful word fragments, termed subwords. Using subwords instead of entire words significantly reduces the number of lexical entries necessary to sufficiently cover a specific language and domain. Mediation between queries and documents is based on these subwords as well as on lists of word-n-grams that are generated from large monolingual corpora and constitute possible translation units. The translations are then sent to a standard Internet search engine. This process makes our approach an effective tool for searching the biomedical content of the World Wide Web in different languages. We evaluate this approach using the OHSUMED corpus, a large medical document collection, within a cross-language retrieval setting.

  15. Conservaton and retrieval of information

    International Nuclear Information System (INIS)

    Jensen, M.

    1993-01-01

    This is a summary of the findings of a Nordic working group formed in 1990 and given the task of establishing a basis for a common Nordic view of the need for information conservation for nuclear waste repositories by investigating the following: (1) the type of information that should be conserved; (2) the form in which the information should be kept; (3) the quality of the information as regards both type and form; and (4) the problems of future retrieval of information, including retrieval after very long periods of time. High-level waste from nuclear power generation will remain radioactive for very long times even though the major part of the radioactivity will have decayed within 1000 yr. Certain information about the waste must be kept for long time periods because future generations may-intentionally or inadvertently-come into contact with the radioactive waste. Current day waste management would benefit from an early identification of documents to be part of an archive for radioactive waste repositories. The same reasoning is valid for repositories for other toxic wastes

  16. Tat protein vaccination of cynomolgus macaques influences SHIV-89.6P cy243 epitope variability.

    Science.gov (United States)

    Ridolfi, Barbara; Genovese, Domenico; Argentini, Claudio; Maggiorella, Maria Teresa; Sernicola, Leonardo; Buttò, Stefano; Titti, Fausto; Borsetti, Alessandra; Ensoli, Barbara

    2008-02-01

    In a previous study we showed that vaccination with the native Tat protein controlled virus replication in five out of seven monkeys against challenge with the simian human immunodeficiency virus (SHIV)-89.6P cy243 and that this protection correlated with T helper (Th)-1 response and cytotoxic T lymphocyte (CTL) activity. To address the evolution of the SHIV-89.6P cy243 both in control and vaccinated infected monkeys, the sequence of the human immunodeficiency virus (HIV)-1 Tat protein and the C2-V3 Env region of the proviral-DNA-derived clones were analyzed in both control and vaccinated but unprotected animals. We also performed analysis of the T cell epitope using a predictive epitope model taking into consideration the phylogeny of the variants. Our results suggest that even though the viral evolution observed in both groups of monkeys was directed toward variations in the major histocompatibility complex (MHC)-I epitopes, in the control animals it was associated with mutational escape of such epitopes. On the contrary, it is possible that viral evolution in the vaccinated monkeys was linked to mutations that arose to keep high the viral fitness. In the vaccinated animals the reduction of epitope variability, obtained prompting the immune system by vaccination and inducing a specific immunological response against virus, was able to reduce the emergence of escape mutants. Thus the intervention of host's selective forces in driving CTL escape mutants and in modulating viral fitness appeared to be different in the two groups of monkeys. We concluded that in the vaccinated unprotected animals, vaccination with the Tat protein induced a broad antiviral response, as demonstrated by the reduced ability to develop escape mutants, which is known to help in the control of viral replication.

  17. Thyroid Autoantibodies Display both “Original Antigenic Sin” and Epitope Spreading

    Directory of Open Access Journals (Sweden)

    Sandra M. McLachlan

    2017-12-01

    Full Text Available Evidence for original antigenic sin in spontaneous thyroid autoimmunity is revealed by autoantibody interactions with immunodominant regions on thyroid autoantigens, thyroglobulin (Tg, thyroid peroxidase (TPO, and the thyrotropin receptor (TSHR A-subunit. In contrast, antibodies induced by immunization of rabbits or mice recognize diverse epitopes. Recognition of immunodominant regions persists despite fluctuations in autoantibody levels following treatment or over time. The enhancement of spontaneously arising pathogenic TSHR antibodies in transgenic human thyrotropin receptor/NOD.H2h4 mice by injecting a non-pathogenic form of TSHR A-subunit protein also provides evidence for original antigenic sin. From other studies, antigen presentation by B cells, not dendritic cells, is likely responsible for original antigenic sin. Recognition of restricted epitopes on the large glycosylated thyroid autoantigens (60-kDa A-subunit, 100-kDa TPO, and 600-kDa Tg facilitates exploring the amino acid locations in the immunodominant regions. Epitope spreading has also been revealed by autoantibodies in thyroid autoimmunity. In humans, and in mice that spontaneously develop autoimmunity to all three thyroid autoantigens, autoantibodies develop first to Tg and later to TPO and the TSHR A-subunit. The pattern of intermolecular epitope spreading is related in part to the thyroidal content of Tg, TPO and TSHR A-subunit and to the molecular sizes of these proteins. Importantly, the epitope spreading pattern provides a rationale for future antigen-specific manipulation to block the development of all thyroid autoantibodies by inducing tolerance to Tg, first in the autoantigen cascade. Because of its abundance, Tg may be the autoantigen of choice to explore antigen-specific treatment, preventing the development of pathogenic TSHR antibodies.

  18. Mapping of Minimal Motifs of B-Cell Epitopes on Human Zona Pellucida Glycoprotein-3

    Directory of Open Access Journals (Sweden)

    Wan-Xiang Xu

    2012-01-01

    Full Text Available The human zona pellucida glycoprotein-3 (hZP3 by virtue of its critical role during fertilization has been proposed as a promising candidate antigen to develop a contraceptive vaccine. In this direction, it is imperative to map minimal motifs of the B cell epitopes (BCEs so as to avoid ZP-specific oophoritogenic T cell epitopes (TCEs in the ZP3-based immunogens. In this study, based on known results of mapping marmoset and bonnet monkey ZP3 (mstZP3 and bmZP3, two predictable epitopes23–30  and  301–320 on hZP3 were first confirmed and five minimal motifs within four epitopes on hZP3 were defined using serum to recombinant hZP3a22–176 or hZP3b177–348 as well as a biosynthetic peptide strategy. These defined minimal motifs were QPLWLL23–28 for hZP323–30, MQVTDD103–108 for hZP393–110, EENW178–181 for hZP3172–190, as well as SNSWF306–310 and EGP313–315 for hZP3301–320, respectively. Furthermore, the antigenicity of two peptides for hZP3172–187 and hZP3301–315 and specificity of the antibody response to these peptides were also evaluated, which produced high-titer antibodies in immunized animals that were capable of reacting to ZP on human oocytes, r-hZP3b177–348 protein, as well as r-hZP3172–190, r-hZP3303–310, and r-hZP3313–320 epitope peptides fused with truncated GST188 protein.

  19. Epitope mapping of monoclonal antibodies directed to aminopeptidase A and their relevance for albuminuria in mice.

    Science.gov (United States)

    Gerlofs-Nijland, Miriam E; Assmann, Karel J M; van Son, Jacco P H F; Dijkman, Henry B P M; te Loeke, Nathalie A J M; van der Zee, Ruurd; Wetzels, Jack F M; Groenen, Patricia J T A

    2003-01-01

    We have shown previously that injection of specific combinations of anti-aminopeptidase A monoclonal antibodies induces an acute massive albuminuria in mice. This albuminuria is neither dependent on systemic mediators of inflammation nor angiotensin II. In this study, we examined the contribution of two individual antibodies, the enzyme-inhibiting antibody ASD-37 and the non-enzyme-inhibiting antibody ASD-41, in the induction of albuminuria as well as the interactions between these two monoclonals. In addition, we have mapped the epitopes of both antibodies using in vitro coupled transcription/translation of specifically designed cDNA fragments followed by immunoprecipitation, and using peptide enzyme-linked immunosorbent assay in case of a continuous epitope. A single intravenous injection of 4 mg of either ASD-37 or ASD-41 did not induce albuminuria. This dose of ASD-37 did not completely inhibit enzyme activity. The combination of 4 mg ASD-37/41 (1:1 weight ratio) induced albuminuria and almost completely inhibited enzyme activity. Similar results were obtained with a combination of ASD-37/41 in a 1:39 or 39:1 weight ratio. Administration of 2 mg ASD-41 24 h before injection of 2 mg ASD-37 significantly enhanced albuminuria. The epitope of ASD-37 is located at the C-terminal end of aminopeptidase A, whereas the ASD-41 epitope is mapped near the enzyme active site. Our data suggest that ASD-41 modulates the binding of ASD-37 to its epitope and/or vice versa. As a consequence, ASD-37 and ASD-41 act synergistically, not only in inhibiting enzyme activity but also in inducing albuminuria. Copyright 2003 S. Karger AG, Basel

  20. Cytomegalovirus (CMV) Epitope-Specific CD4+ T Cells Are Inflated in HIV+ CMV+ Subjects.

    Science.gov (United States)

    Abana, Chike O; Pilkinton, Mark A; Gaudieri, Silvana; Chopra, Abha; McDonnell, Wyatt J; Wanjalla, Celestine; Barnett, Louise; Gangula, Rama; Hager, Cindy; Jung, Dae K; Engelhardt, Brian G; Jagasia, Madan H; Klenerman, Paul; Phillips, Elizabeth J; Koelle, David M; Kalams, Spyros A; Mallal, Simon A

    2017-11-01

    Select CMV epitopes drive life-long CD8 + T cell memory inflation, but the extent of CD4 memory inflation is poorly studied. CD4 + T cells specific for human CMV (HCMV) are elevated in HIV + HCMV + subjects. To determine whether HCMV epitope-specific CD4 + T cell memory inflation occurs during HIV infection, we used HLA-DR7 (DRB1*07:01) tetramers loaded with the glycoprotein B DYSNTHSTRYV (DYS) epitope to characterize circulating CD4 + T cells in coinfected HLA-DR7 + long-term nonprogressor HIV subjects with undetectable HCMV plasma viremia. DYS-specific CD4 + T cells were inflated among these HIV + subjects compared with those from an HIV - HCMV + HLA-DR7 + cohort or with HLA-DR7-restricted CD4 + T cells from the HIV-coinfected cohort that were specific for epitopes of HCMV phosphoprotein-65, tetanus toxoid precursor, EBV nuclear Ag 2, or HIV gag protein. Inflated DYS-specific CD4 + T cells consisted of effector memory or effector memory-RA + subsets with restricted TCRβ usage and nearly monoclonal CDR3 containing novel conserved amino acids. Expression of this near-monoclonal TCR in a Jurkat cell-transfection system validated fine DYS specificity. Inflated cells were polyfunctional, not senescent, and displayed high ex vivo levels of granzyme B, CX 3 CR1, CD38, or HLA-DR but less often coexpressed CD38 + and HLA-DR + The inflation mechanism did not involve apoptosis suppression, increased proliferation, or HIV gag cross-reactivity. Instead, the findings suggest that intermittent or chronic expression of epitopes, such as DYS, drive inflation of activated CD4 + T cells that home to endothelial cells and have the potential to mediate cytotoxicity and vascular disease. Copyright © 2017 by The American Association of Immunologists, Inc.

  1. CD4+ T-cell epitope prediction using antigen processing constraints.

    Science.gov (United States)

    Mettu, Ramgopal R; Charles, Tysheena; Landry, Samuel J

    2016-05-01

    T-cell CD4+ epitopes are important targets of immunity against infectious diseases and cancer. State-of-the-art methods for MHC class II epitope prediction rely on supervised learning methods in which an implicit or explicit model of sequence specificity is constructed using a training set of peptides with experimentally tested MHC class II binding affinity. In this paper we present a novel method for CD4+ T-cell eptitope prediction based on modeling antigen-processing constraints. Previous work indicates that dominant CD4+ T-cell epitopes tend to occur adjacent to sites of initial proteolytic cleavage. Given an antigen with known three-dimensional structure, our algorithm first aggregates four types of conformational stability data in order to construct a profile of stability that allows us to identify regions of the protein that are most accessible to proteolysis. Using this profile, we then construct a profile of epitope likelihood based on the pattern of transitions from unstable to stable regions. We validate our method using 35 datasets of experimentally measured CD4+ T cell responses of mice bearing I-Ab or HLA-DR4 alleles as well as of human subjects. Overall, our results show that antigen processing constraints provide a significant source of predictive power. For epitope prediction in single-allele systems, our approach can be combined with sequence-based methods, or used in instances where little or no training data is available. In multiple-allele systems, sequence-based methods can only be used if the allele distribution of a population is known. In contrast, our approach does not make use of MHC binding prediction, and is thus agnostic to MHC class II genotypes. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Estudo do efeito de distintos períodos de fixação em formalina e métodos de recuperação antigênica na técnica de imuno-histoquímica Study of the effect of different fixation times in formalin and methods of antigen retrieval in immunohistochemistry

    Directory of Open Access Journals (Sweden)

    Maria Teresa de Seixas Alves

    2005-02-01

    Full Text Available Avaliou-se a influência do tempo de fixação em formalina neutra tamponada a 10% e dos diferentes métodos de resgate de sítio antigênico induzido pelo calor [heat induced epitope retrieval (HIER] para a imunoexpressão dos anticorpos anti-antígeno nuclear de proliferação celular (PCNA e anti-AE1AE3 (citoqueratinas, empregados por apresentarem imunocoloração nuclear e citoplasmática ou submembranosa. Foram estudadas cinco tonsilas provenientes de amigdalectomias realizadas no Hospital São Paulo da Escola Paulista de Medicina da Universidade de São Paulo (UNIFESP/EPM, as quais foram seccionadas em 0,5cm² cada, fixadas em formalina, por períodos de tempo de seis, 12, 18, 24 e 48 horas e embebidas em parafina. Foram feitos cortes com 4mim em lâminas silanizadas. Para o estudo imuno-histoquímico utilizamos os anticorpos anti-PCNA e AE1AE3, empregando os três métodos de resgate de sítio antigênico: banho-maria, microondas e panela de pressão. A positividade na imunoexpressão do PCNA foi avaliada através da relação núcleos corados/total de núcleos x 100. A intensidade da coloração resultante foi avaliada através da utilização dos programas Corel Photo Paint 9 e UT Morph 2.0. Com relação à recuperação antigênica, concluímos que, para o anticorpo anti-PCNA no material fixado nos períodos de nosso estudo, os melhores resultados foram obtidos com o uso do microondas. O aumento do tempo de fixação interferiu na queda da imunopositividade do PCNA, em especial após o período de 24 horas. Em relação ao parâmetro intensidade de coloração para AE1AE3 nenhum dos métodos foi superior. A metodologia estudada para a análise semiquantitativa na intensidade da reação coincidiu com os resultados obtidos na avaliação criteriosa de cada uma das lâminas.The effects of fixation time in buffered formaline at 10% on different methods of antigenic site retrieval induced by heat (HIER for the detection of the expression

  3. Identification of broadly reactive epitopes targeting major glycoproteins of Herpes simplex virus (HSV) 1 and 2 - An immunoinformatics analysis.

    Science.gov (United States)

    Chauhan, Varun; Goyal, Kapil; Singh, Mini P

    2018-07-01

    Infections due to both HSV-1 and HSV-2 constitute an enormous health burden worldwide. Development of vaccine against herpes infections is a WHO supported public health priority. The viral glycoproteins have always been the major hotspots for vaccine designing. The present study was aimed to identify the conserved T and B cell epitopes in the major glycoproteins of both HSV-1 and HSV-2 via rigorous computational approaches. Identification of promiscuous T cell epitopes is of utmost importance in vaccine designing as such epitopes are capable of binding to several allelic forms of HLA and could generate effective immune response in the host. The criteria designed for identification of T and B cell epitopes was that it should be conserved in both HSV-1 and 2, promiscuous, have high affinity towards HLA alleles, should be located on the surface of glycoproteins and not be present in the glycosylation sites. This study led to the identification of 17 HLA Class II and 26 HLA Class I T cell epitopes, 9 linear and some conformational B cell epitopes. The identified T cell epitopes were further subjected to molecular docking analysis to analyze their binding patterns. Altogether we have identified 4 most promising regions in glycoproteins (2-gB, 1-gD, 1-gH) of HSV-1 and 2 which are promiscuous to HLA Class II alleles and have overlapping HLA Class I and B cell epitopes, which could be very useful in generating both arms of immune response in the host i.e. adaptive as well as humoral immunity. Further the authors propose the cross-validation of the identified epitopes in experimental settings for confirming their immunogenicity to support the present findings. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Identification of two novel rabbit hemorrhagic disease virus (RHDV) B cell epitopes and evaluation of its immunoprotection against RHDV.

    Science.gov (United States)

    DeSheng, Kong; HuaiRan, Liu; JiaSen, Liu; Zuo, Yu; Qian, Jiang; DongChun, Guo; XiaoLiang, Hu; FengJie, Wang; QianQian, Huang; LianDong, Qu

    2015-07-01

    The VP60 protein of rabbit hemorrhagic disease virus (RHDV) is a structural protein with important roles in viral replication and assembly. In this study, we immunized BALB/c mice with the RHDV-TP strain. Six monoclonal antibodies (mAbs) were selected and characterized by enzyme-linked immunosorbent assay, Western blotting, and indirectly immunofluorescence analysis (IFA). All six mAbs (AD4, AG10, BC9, BE8, BH3, and DE2) had positive reactions with recombinant VP60 as analyzed by IFA, but only two (AG10 and DE2) reacted with denatured RHDV by Western blotting. Fifty-four partially overlapping fragments of the VP60 gene were expressed with His or Glutathione S-transferase (GST) tags to identify the epitopes recognized by AG10 and DE2. These two epitopes were located at the C-terminal of VP60 and were longer (64 and 53 amino acids, respectively) than normal B cell epitopes. However, both AG10 and DE2 also interacted with RHDV2 VP60 expressed in insect cells. Amino acid alignments of the AG10 and DE2 epitope regions between RHDV and RHDV2 VP60 indicated several mutations, suggesting that the epitopes recognized by the mAbs AG10 and DE2 were discontinuous. Epitope immunogenicity was evaluated by inoculating specific pathogen-free rabbits with saline, purified DE2 epitope, or RHDV inactive vaccine. Rabbits immunized with the DE2 epitope developed high levels of RHDV-specific antibodies but no cellular immune response and died after challenge with RHDV-HYD isolate. Despite their lack of neutralizing activity, these mAb reagents and epitopes may have useful clinical applications and will be valuable tools in further studies of the structure and function of the RHDV VP60 protein.

  5. Retrieving fear memories, as time goes by…

    Science.gov (United States)

    Do Monte, Fabricio H.; Quirk, Gregory J.; Li, Bo; Penzo, Mario A.

    2016-01-01

    Fear conditioning researches have led to a comprehensive picture of the neuronal circuit underlying the formation of fear memories. In contrast, knowledge about the retrieval of fear memories is much more limited. This disparity may stem from the fact that fear memories are not rigid, but reorganize over time. To bring clarity and raise awareness on the time-dependent dynamics of retrieval circuits, we review current evidence on the neuronal circuitry participating in fear memory retrieval at both early and late time points after conditioning. We focus on the temporal recruitment of the paraventricular nucleus of the thalamus, and its BDNFergic efferents to the central nucleus of the amygdala, for the retrieval and maintenance of fear memories. Finally, we speculate as to why retrieval circuits change across time, and the functional benefits of recruiting structures such as the paraventricular nucleus into the retrieval circuit. PMID:27217148

  6. Information retrieval implementing and evaluating search engines

    CERN Document Server

    Büttcher, Stefan; Cormack, Gordon V

    2016-01-01

    Information retrieval is the foundation for modern search engines. This textbook offers an introduction to the core topics underlying modern search technologies, including algorithms, data structures, indexing, retrieval, and evaluation. The emphasis is on implementation and experimentation; each chapter includes exercises and suggestions for student projects. Wumpus -- a multiuser open-source information retrieval system developed by one of the authors and available online -- provides model implementations and a basis for student work. The modular structure of the book allows instructors to use it in a variety of graduate-level courses, including courses taught from a database systems perspective, traditional information retrieval courses with a focus on IR theory, and courses covering the basics of Web retrieval. In addition to its classroom use, Information Retrieval will be a valuable reference for professionals in computer science, computer engineering, and software engineering.

  7. Glutamic acid decarboxylase-derived epitopes with specific domains expand CD4(+CD25(+ regulatory T cells.

    Directory of Open Access Journals (Sweden)

    Guojiang Chen

    Full Text Available BACKGROUND: CD4(+CD25(+ regulatory T cell (Treg-based immunotherapy is considered a promising regimen for controlling the progression of autoimmune diabetes. In this study, we tested the hypothesis that the therapeutic effects of Tregs in response to the antigenic epitope stimulation depend on the structural properties of the epitopes used. METHODOLOGY/PRINCIPAL FINDINGS: Splenic lymphocytes from nonobese diabetic (NOD mice were stimulated with different glutamic acid decarboxylase (GAD-derived epitopes for 7-10 days and the frequency and function of Tregs was analyzed. We found that, although all expanded Tregs showed suppressive functions in vitro, only p524 (GAD524-538-expanded CD4(+CD25(+ T cells inhibited diabetes development in the co-transfer models, while p509 (GAD509-528- or p530 (GAD530-543-expanded CD4(+CD25(+ T cells had no such effects. Using computer-guided molecular modeling and docking methods, the differences in structural characteristics of these epitopes and the interaction mode (including binding energy and identified domains in the epitopes between the above-mentioned epitopes and MHC class II I-A(g7 were analyzed. The theoretical results showed that the epitope p524, which induced protective Tregs, possessed negative surface-electrostatic potential and bound two chains of MHC class II I-A(g7, while the epitopes p509 and p530 which had no such ability exhibited positive surface-electrostatic potential and bound one chain of I-A(g7. Furthermore, p524 bound to I-A(g7 more stably than p509 and p530. Of importance, we hypothesized and subsequently confirmed experimentally that the epitope (GAD570-585, p570, which displayed similar characteristics to p524, was a protective epitope by showing that p570-expanded CD4(+CD25(+ T cells suppressed the onset of diabetes in NOD mice. CONCLUSIONS/SIGNIFICANCE: These data suggest that molecular modeling-based structural analysis of epitopes may be an instrumental tool for prediction of

  8. ArrayPitope: Automated Analysis of Amino Acid Substitutions for Peptide Microarray-Based Antibody Epitope Mapping

    DEFF Research Database (Denmark)

    Hansen, Christian Skjødt; Østerbye, Thomas; Marcatili, Paolo

    2017-01-01

    and characterization of linear B cell epitopes. Using exhaustive amino acid substitution analysis of peptides originating from target antigens, these microarrays can be used to address the specificity of polyclonal antibodies raised against such antigens containing hundreds of epitopes. However, the interpretation....... The application takes as input quantitative peptide data of fully or partially substituted overlapping peptides from a given antigen sequence and identifies epitope residues (residues that are significantly affected by substitutions) and visualize the selectivity towards each residue by sequence logo plots...

  9. Generation and Characterization of Monoclonal Antibodies against a Cyclic Variant of Hepatitis C Virus E2 Epitope 412-422

    Science.gov (United States)

    Sandomenico, Annamaria; Leonardi, Antonio; Berisio, Rita; Sanguigno, Luca; Focà, Giuseppina; Focà, Annalia; Ruggiero, Alessia; Doti, Nunzianna; Muscariello, Livio; Barone, Daniela; Farina, Claudio; Owsianka, Ania; Vitagliano, Luigi

    2016-01-01

    ABSTRACT The hepatitis C virus (HCV) E2 envelope glycoprotein is crucial for virus entry into hepatocytes. A conserved region of E2 encompassing amino acids 412 to 423 (epitope I) and containing Trp420, a residue critical for virus entry, is recognized by several broadly neutralizing antibodies. Peptides embodying this epitope I sequence adopt a β-hairpin conformation when bound to neutralizing monoclonal antibodies (MAbs) AP33 and HCV1. We therefore generated new mouse MAbs that were able to bind to a cyclic peptide containing E2 residues 412 to 422 (C-epitope I) but not to the linear counterpart. These MAbs bound to purified E2 with affinities of about 50 nM, but they were unable to neutralize virus infection. Structural analysis of the complex between C-epitope I and one of our MAbs (C2) showed that the Trp420 side chain is largely buried in the combining site and that the Asn417 side chain, which is glycosylated in E2 and solvent exposed in other complexes, is slightly buried upon C2 binding. Also, the orientation of the cyclic peptide in the antibody-combining site is rotated by 180° compared to the orientations of the other complexes. All these structural features, however, do not explain the lack of neutralization activity. This is instead ascribed to the high degree of selectivity of the new MAbs for the cyclic epitope and to their inability to interact with the epitope in more flexible and extended conformations, which recent data suggest play a role in the mechanisms of neutralization escape. IMPORTANCE Hepatitis C virus (HCV) remains a major health care burden, affecting almost 3% of the global population. The conserved epitope comprising residues 412 to 423 of the viral E2 glycoprotein is a valid vaccine candidate because antibodies recognizing this region exhibit potent neutralizing activity. This epitope adopts a β-hairpin conformation when bound to neutralizing MAbs. We explored the potential of cyclic peptides mimicking this structure to elicit

  10. Interdisciplinary Evaluation of Broadly-Reactive HLA Class II Restricted Epitopes Eliciting HIV-Specific CD4+T Cell Responses

    DEFF Research Database (Denmark)

    Buggert, M.; Norström, M.; Lundegaard, Claus

    2011-01-01

    , the functional and immunodominant discrepancies of CD4+ T cell responses targeting promiscuous MHC II restricted HIV epitopes remains poorly defined. Thus, utilization of interdisciplinary approaches might aid revealing broadly- reactive peptides eliciting CD4 + T cell responses. Methods: We utilized the novel...... bioinformatic prediction program NetMHCIIpan to select 64 optimized MHC II restricted epitopes located in the HIV Gag, Pol, Env, Nef and Tat regions. The epitopes were selected to cover the global diversity of the virus (multiple subtypes) and the human immune system(diverse MHC II types). Optimized...

  11. Inhibition and Promotion of Heat-Induced Gelation of Whey Proteins in the Presence of Calcium by Addition of Sodium Caseinate.

    Science.gov (United States)

    Nguyen, Bach T; Balakrishnan, Gireeshkumar; Jacquette, Boris; Nicolai, Taco; Chassenieux, Christophe; Schmitt, Christophe; Bovetto, Lionel

    2016-11-14

    Heat-induced aggregation and gelation of aqueous solutions of whey protein isolate (WPI) in the presence of sodium caseinate (SC) and CaCl 2 was studied at pH 6.6. The effect of adding SC (0-100 g/L) on the structure of the aggregates and the gels was investigated by light scattering and confocal laser scanning microscopy at different CaCl 2 concentration ([CaCl 2 ] = 0-30 mM). The gelation process was studied by oscillatory shear rheology. At the whey protein concentrations studied here (34 and 60 g/L), no gels were formed in the absence of CaCl 2 and SC. However, WPI solutions gelled above a critical CaCl 2 concentration that increased with increasing SC concentration. In the absence of CaCl 2 , WPI gels were formed only above a critical SC concentration. The critical SC concentration needed to induce WPI gelation decreased weakly when CaCl 2 was added. In an intermediate range of CaCl 2 concentrations, gels were formed both at low and high SC concentrations, but not at intermediate SC concentrations. Finally, at high CaCl 2 concentrations gels were formed at all SC concentrations. The gelation rate and the gel structure of the gels formed at low and high casein concentrations were very different. The effect of SC on the thermal gelation of WPI was interpreted by competition for Ca 2+ , a chaperon effect, and microphase separation.

  12. Comparison of radiosensitivity and thermosensitivity among three types of cultured mammalian cells and detection of heat-induced cell killing by eosin-staining method

    Energy Technology Data Exchange (ETDEWEB)

    Kashiwado, Kouzou

    1988-12-01

    Radiosensitivity, Thermosensitivity and their combined sensitivity on cell death were studied using mouse L5178Y, mouse FM3A and human Burkitt lymphoma. Eosin-staining method was tested for counting the heat-induced dead cells. The results obtained in the present study were as follows: (1) In irradiation with /sup 60/Co gamma-rays D/sub 0/ values of 1.3 Gy, 1.4 Gy and 1.7 Gy were obtained for Burkitt lymphoma, L5178Y and FM3A respectively. (2) By heating at 43degC, T/sub 0/ values of 4.1 min, 12.5 min and 32 min were obtained for L5178Y, FM3A and Burkitt lymphoma respectively. (3) Thermotolerance decay depended on cell doubling time, that is, the shorter the doubling time, the faster the decay. Furthermore, the cell line with the higher thermosensitivity showed a faster decay of thermotolerance for the three cell lines used in the present study. (4) The radiosensitizing effects were nearly the same in all three cell lines. (5) Using eosin-staining method, the cell survival curves after hyperthermia were ascertained and compared with those obtained by colony forming method. In L5178Y the survival curves obtained by the two methods were nearly the same. In FM3A only some correlation was found betweewn the cell survival curves obtained by the two methods but in Burkitt lymphoma no correlation was found. (author) 52 refs.

  13. Comparison of radiosensitivity and thermosensitivity among three types of cultured mammalian cells and detection of heat-induced cell killing by eosin-staining method

    International Nuclear Information System (INIS)

    Kashiwado, Kouzou

    1988-01-01

    Radiosensitivity, Thermosensitivity and their combined sensitivity on cell death were studied using mouse L5178Y, mouse FM3A and human Burkitt lymphoma. Eosin-staining method was tested for counting the heat-induced dead cells. The results obtained in the present study were as follows: 1) In irradiation with 60 Co gamma-rays D 0 values of 1.3 Gy, 1.4 Gy and 1.7 Gy were obtained for Burkitt lymphoma, L5178Y and FM3A respectively. 2) By heating at 43degC, T 0 values of 4.1 min, 12.5 min and 32 min were obtained for L5178Y, FM3A and Burkitt lymphoma respectively. 3) Thermotolerance decay depended on cell doubling time, that is, the shorter the doubling time, the faster the decay. Furthermore, the cell line with the higher thermosensitivity showed a faster decay of thermotolerance for the three cell lines used in the present study. 4) The radiosensitizing effects were nearly the same in all three cell lines. 5) Using eosin-staining method, the cell survival curves after hyperthermia were ascertained and compared with those obtained by colony forming method. In L5178Y the survival curves obtained by the two methods were nearly the same. In FM3A only some correlation was found betweewn the cell survival curves obtained by the two methods but in Burkitt lymphoma no correlation was found. (author) 52 refs

  14. Differences in heat-induced cell killing as determined in three mammalian cell lines do not correspond with the extent of heat radiosensitization

    International Nuclear Information System (INIS)

    Kampinga, H.H.; Jorritsma, J.B.M.; Burgman, P.; Konings, A.W.T.

    1986-01-01

    Three different cell lines, Ehrlich ascites tumour (EAT) cells, HeLa S 3 cells and LM mouse fibroblasts, were used to investigate whether or not the extent of heat killing (44 0 C) and heat radio-sensitization (44 0 C before 0-6 Gy X-irradiation) are related. Although HeLa cells were the most heat-resistant cell line and showed the least heat radiosensitization, we found that the most heat-sensitive EAT cells (D 0 , EAT = 8.0 min; D 0 , LM = 10.0 min; D 0 , HeLa = 12.5 min) showed less radiosensitization than the more heat-resistant LM fibroblasts (TERsub(HeLa)< TERsub(EAT)< TERsub(LM)). Therefore, it is concluded that the routes leading to heat-induced cell death are not identical to those determining heat radiosensitization. Furthermore the inactivation of DNA polymerase α and β activities by heat seemed not to correlate with heat survival alone but showed a positive relationship to heat radiosensitization. The possibility of these enzymes being a determinant in heat radiosensitization is discussed. (author)

  15. Effect of extraction pH on heat-induced aggregation, gelation and microstructure of protein isolate from quinoa (Chenopodium quinoa Willd).

    Science.gov (United States)

    Ruiz, Geraldine Avila; Xiao, Wukai; van Boekel, Martinus; Minor, Marcel; Stieger, Markus

    2016-10-15

    The aim of this study was to determine the influence of extraction pH on heat-induced aggregation, gelation and microstructure of suspensions of protein isolates extracted from quinoa (Chenopodium quinoa Willd). Quinoa seed protein was extracted by alkaline treatment at various pH values (pH 8 (E8), 9 (E9), 10 (E10) and 11 (E11)), followed by acid precipitation. The obtained protein isolates were freeze dried. The protein isolates E8 and E9 resulted in a lower protein yield as well as less protein denaturation. These isolates also had a higher protein purity, more protein bands at higher molecular weights, and a higher protein solubility in the pH range of 3-4.5, compared to the isolates E10 and E11. Heating the 10%w/w protein isolate suspensions E8 and E9 led to increased aggregation, and semi-solid gels with a dense microstructure were formed. The isolate suspensions E10 and E11, on the other hand, aggregated less, did not form self-supporting gels and had loose particle arrangements. We conclude that extraction pH plays an important role in determining the functionality of quinoa protein isolates. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. An improved model of heat-induced hyperalgesia--repetitive phasic heat pain causing primary hyperalgesia to heat and secondary hyperalgesia to pinprick and light touch.

    Science.gov (United States)

    Jürgens, Tim P; Sawatzki, Alexander; Henrich, Florian; Magerl, Walter; May, Arne

    2014-01-01

    This study tested a modified experimental model of heat-induced hyperalgesia, which improves the efficacy to induce primary and secondary hyperalgesia and the efficacy-to-safety ratio reducing the risk of tissue damage seen in other heat pain models. Quantitative sensory testing was done in eighteen healthy volunteers before and after repetitive heat pain stimuli (60 stimuli of 48°C for 6 s) to assess the impact of repetitive heat on somatosensory function in conditioned skin (primary hyperalgesia area) and in adjacent skin (secondary hyperalgesia area) as compared to an unconditioned mirror image control site. Additionally, areas of flare and secondary hyperalgesia were mapped, and time course of hyperalgesia determined. After repetitive heat pain conditioning we found significant primary hyperalgesia to heat, and primary and secondary hyperalgesia to pinprick and to light touch (dynamic mechanical allodynia). Acetaminophen (800 mg) reduced pain to heat or pinpricks only marginally by 11% and 8%, respectively (n.s.), and had no effect on heat hyperalgesia. In contrast, the areas of flare (-31%) and in particular of secondary hyperalgesia (-59%) as well as the magnitude of hyperalgesia (-59%) were significantly reduced (all pheat pain induces significant peripheral sensitization (primary hyperalgesia to heat) and central sensitization (punctate hyperalgesia and dynamic mechanical allodynia). These findings are relevant to further studies using this model of experimental heat pain as it combines pronounced peripheral and central sensitization, which makes a convenient model for combined pharmacological testing of analgesia and anti-hyperalgesia mechanisms related to thermal and mechanical input.

  17. IMAGE DESCRIPTIONS FOR SKETCH BASED IMAGE RETRIEVAL

    OpenAIRE

    SAAVEDRA RONDO, JOSE MANUEL; SAAVEDRA RONDO, JOSE MANUEL

    2008-01-01

    Due to the massive use of Internet together with the proliferation of media devices, content based image retrieval has become an active discipline in computer science. A common content based image retrieval approach requires that the user gives a regular image (e.g, a photo) as a query. However, having a regular image as query may be a serious problem. Indeed, people commonly use an image retrieval system because they do not count on the desired image. An easy alternative way t...

  18. Document image retrieval through word shape coding.

    Science.gov (United States)

    Lu, Shijian; Li, Linlin; Tan, Chew Lim

    2008-11-01

    This paper presents a document retrieval technique that is capable of searching document images without OCR (optical character recognition). The proposed technique retrieves document images by a new word shape coding scheme, which captures the document content through annotating each word image by a word shape code. In particular, we annotate word images by using a set of topological shape features including character ascenders/descenders, character holes, and character water reservoirs. With the annotated word shape codes, document images can be retrieved by either query keywords or a query document image. Experimental results show that the proposed document image retrieval technique is fast, efficient, and tolerant to various types of document degradation.

  19. Wellhead bowl protector and retrieving tool

    International Nuclear Information System (INIS)

    Young, J.A.

    1991-01-01

    This patent describes improvement in a wellhead protection system including a wear bushing and a retrieving tool. The improvement comprises a wear bushing supported within the wellhead, wherein the wear bushing includes an enlarged upper end having an external support shoulder for engagement with an internal support shoulder formed in the wellhead; wherein the wear bushing further includes an internal circumferential slot intersected by at least one vertically extending slot, the vertical slot extending from the circumferential slot to the upper end of the wear bushing; a retrieving tool having at least one outwardly biased, retractable lug member mounted thereon; and wherein the retrieving tool includes an enlarged portion adapted to be received within the enlarged upper end of the wear bushing. This patent also describes a method of retrieving a wear bushing from a wellhead comprising the steps of: lowering a retrieving tool into the wellhead for locking engagement with the wear bushing; aligning the retrieving tool with the wear bushing for automatically forcing lug members carried by the retrieving tool outwardly into locking engagement with the wear bushing; monitoring drill string weight for determining engagement of the retrieving tool with the wear bushing, wherein a substantial decrease in drill string weight is an indication that the retrieving tool is engaged with the wear bushing; and removing the wear bushing from the wellhead

  20. Scalable Distributed Architectures for Information Retrieval

    National Research Council Canada - National Science Library

    Lu, Zhihong

    1999-01-01

    .... Our distributed architectures exploit parallelism in information retrieval on a cluster of parallel IR servers using symmetric multiprocessors, and use partial collection replication and selection...

  1. Experimental database retrieval system 'DARTS'

    International Nuclear Information System (INIS)

    Aoyagi, Tetsuo; Tani, Keiji; Haginoya, Hirobumi; Naito, Shinjiro.

    1989-02-01

    In JT-60, a large tokamak device of Japan Atomic Energy Research Institute (JAERI), a plasma is fired for 5 ∼ 10 seconds at intervals of about 10 minutes. The each firing is called a shot. Plasma diagnostic data are edited as JT-60 experimental database at every shot cycle and are stored in a large-scale computer (FACOM-M780). Experimentalists look up the data for specific shots which they want to analyze and consider. As the total number of shots increases, they find a difficulty in the looking-up work. In order that they can easily access to their objective shot data or shot group data by using a computer terminal, 'DARTS' (DAtabase ReTrieval System) has been developed. This report may provide enough information on DARTS handling for users. (author)

  2. Personalized Mobile Information Retrieval System

    Directory of Open Access Journals (Sweden)

    Okkyung Choi

    2012-04-01

    Full Text Available Building a global Network Relations with the internet has made huge changes in personal information system and even comments left on a webpage of SNS(Social Network Services are appreciated as important elements that would provide valuable information for someone. Social Network is a relation between individuals or groups, represented in a graph model, which converts the concept of psychological and social relations into a logical structure by using node and link. But, most of the current personalized systems on the basis of Social Network are built and constructed mainly in the PC environment, and the systems are neither designed nor implemented in mobile environment. Hence, the objective of this study is to propose methods of providing Personalized Mobile Information Retrieval System using NFC (Near Field Communication Smartphone, which will be then used for Smartphone users. Besides, this study aims to verify its efficiency through a comparative analysis of existing studies.

  3. Conservation and retrieval of information

    International Nuclear Information System (INIS)

    Jensen, M.

    1993-01-01

    High-level waste from nuclear power generation will remain radioactive for thousands of years even though 99% of the radioactivity will have decayed within the first millennium. For a hypothetical group involved in future actions to retrieve or repair a repository, information about its location, design, and content would be necessary. The need of such groups can be used to design the information that should be kept in a waste archive. Two main strategies exist for long-germ information transfer, one which links information thorough successive transfers of archived material and other forms of knowledge in society, and one - such as marking the site with a monument - relying upon a direct link from the present to the distant future. Digital methods are not recommended for long-term storage, but digital processing may be a valuable tool to structure information summaries, and in the creation of better long-lasting records. Advances in archive management should also be pursued to widen the choice of information carriers of high durability. In the Nordic countries, during the first few thousand years, and perhaps up to the next period of glaciation, monuments at a repository site may be used to warn the public of the presence of dangerous waste. But messages from such markers may pose interpretation problems as we have today for messages left by earlier societies such as rune inscriptions. Since the national borders may change in the time scale relevant for nuclear waste, the creation of an international archive for all radioactive wastes would represent an improvement as regards conservation and retrieval of information. (EG)

  4. Identifikasi epitop dari Streptococcus mutans terhadap sekretori Imunoglobulin A saliva (The identification of Streptococcus mutans epitopes to secretory Immunoglobulin A saliva

    Directory of Open Access Journals (Sweden)

    Anita Yuliati

    2005-09-01

    Full Text Available S. mutans is one of the etiology agent of dental caries, these bacteria have a surface protein of about 185 kDa named Ag I/II. The secretory of sIgA saliva to Ag I/II of S.mutans has shown to be able to prevent colonization in human oral cavity. Peptides derived from the 824 to 853 residues of the P region of antigen I/II S. mutans related to the pathogenesis of dental caries. The aim of this study was to identify the overlapping sequence of amino acids (epitope derived from the 624 to 853 residues of P of antigen I/II S. mutans to sIgA saliva on caries and caries-free subject in a observational cross sectional study. The P region of antigen I/II S.mutans was cut into 22 peptides of 9 mer sequences with an overlapping of 8 mer and an offset of 1 mer, synthesized on polyethylene pins and tested for the reactivity with an ELISA indirect method to sIgA saliva on caries and caries-free subject. The results of this study showed that amino acid sequences with TPPVKP (832–837 and TAPTKPTY (838–845 were reactive to sIgA saliva on caries and caries-free subject. The conclusion of this study was that the overlapping common sequence of amino acid (epitopes corresponding to TPPVKP (832–837 and TAPTKPTY (838–845 was identified as caries marker epitopes in human.

  5. Conserved B-cell epitopes among human bocavirus species indicate potential diagnostic targets.

    Directory of Open Access Journals (Sweden)

    Zhuo Zhou

    Full Text Available BACKGROUND: Human bocavirus species 1-4 (HBoV1-4 have been associated with respiratory and enteric infections in children. However, the immunological mechanisms in response to HBoV infections are not fully understood. Though previous studies have shown cross-reactivities between HBoV species, the epitopes responsible for this phenomenon remain unknown. In this study, we used genomic and immunologic approaches to identify the reactive epitopes conserved across multiple HBoV species and explored their potential as the basis of a novel diagnostic test for HBoVs. METHODOLOGY/PRINCIPAL FINDINGS: We generated HBoV1-3 VP2 gene fragment phage display libraries (GFPDLs and used these libraries to analyze mouse antisera against VP2 protein of HBoV1, 2, and 3, and human sera positive for HBoVs. Using this approach, we mapped four epitope clusters of HBoVs and identified two immunodominant peptides--P1 (¹MSDTDIQDQQPDTVDAPQNT²⁰, and P2 (¹⁶²EHAYPNASHPWDEDVMPDL¹⁸⁰--that are conserved among HBoV1-4. To confirm epitope immunogenicity, we immunized mice with the immunodominant P1 and P2 peptides identified in our screen and found that they elicited high titer antibodies in mice. These two antibodies could only recognize the VP2 of HBoV 1-4 in Western blot assays, rather than those of the two other parvoviruses human parvovirus B19 and human parvovirus 4 (PARV4. Based on our findings, we evaluated epitope-based peptide-IgM ELISAs as potential diagnostic tools for HBoVs IgM antibodies. We found that the P1+P2-IgM ELISA showed a higher sensitivity and specificity in HBoVs IgM detection than the assays using a single peptide. CONCLUSIONS/SIGNIFICANCE: The identification of the conserved B-cell epitopes among human bocavirus species contributes to our understanding of immunological cross-reactivities of HBoVs, and provides important insights for the development of HBoV diagnostic tools.

  6. Functional-anatomic study of episodic retrieval using fMRI. I. Retrieval effort versus retrieval success.

    Science.gov (United States)

    Buckner, R L; Koutstaal, W; Schacter, D L; Wagner, A D; Rosen, B R

    1998-04-01

    A number of recent functional imaging studies have identified brain areas activated during tasks involving episodic memory retrieval. The identification of such areas provides a foundation for targeted hypotheses regarding the more specific contributions that these areas make to episodic retrieval. As a beginning effort toward such an endeavor, whole-brain functional magnetic resonance imaging (fMRI) was used to examine 14 subjects during episodic word recognition in a block-designed fMRI experiment. Study conditions were manipulated by presenting either shallow or deep encoding tasks. This manipulation yielded two recognition conditions that differed with regard to retrieval effort and retrieval success: shallow encoding yielded low levels of recognition success with high levels of retrieval effort, and deep encoding yielded high levels of recognition success with low levels of effort. Many brain areas were activated in common by these two recognition conditions compared to a low-level fixation condition, including left and right prefrontal regions often detected during PET episodic retrieval paradigms (e.g., R. L. Buckner et al., 1996, J. Neurosci. 16, 6219-6235) thereby generalizing these findings to fMRI. Characterization of the activated regions in relation to the separate recognition conditions showed (1) bilateral anterior insular regions and a left dorsal prefrontal region were more active after shallow encoding, when retrieval demanded greatest effort, and (2) right anterior prefrontal cortex, which has been implicated in episodic retrieval, was most active during successful retrieval after deep encoding. We discuss these findings in relation to component processes involved in episodic retrieval and in the context of a companion study using event-related fMRI.

  7. Statistical Language Models and Information Retrieval: Natural Language Processing Really Meets Retrieval

    NARCIS (Netherlands)

    Hiemstra, Djoerd; de Jong, Franciska M.G.

    2001-01-01

    Traditionally, natural language processing techniques for information retrieval have always been studied outside the framework of formal models of information retrieval. In this article, we introduce a new formal model of information retrieval based on the application of statistical language models.

  8. Identification of a novel linear B-cell epitope using a monoclonal antibody against the carboxy terminus of the canine distemper virus nucleoprotein and sequence analysis of the identified epitope in different CDV isolates.

    Science.gov (United States)

    Yi, Li; Cao, Zhigang; Tong, Mingwei; Cheng, Yuening; Yang, Yong; Li, Shuang; Wang, Jianke; Lin, Peng; Sun, Yaru; Zhang, Miao; Cheng, Shipeng

    2017-09-29

    The Nucleoprotein (NP) is the most abundant and highly immunogenic protein in canine distemper virus (CDV), playing an important role in CDV viral replication and assembly. In this study, a specific monoclonal antibody, named C8, was produced against the NP protein C terminal (amino acids 401-523). A linear N protein epitope was identified by subjecting a series of partially overlapping synthesized peptides to enzyme-linked immunosorbent assay (ELISA) analysis.The results indicated that 444 GDKYPIHFNDER 455 was the minimal linear epitope that could be recognized by mAb C8. Sequence alignments demonstrated that this linear epitope is less conserved among three CDV genotypes. We next analyzed the level of conservation of the defined epitope in19 Chinese CDV clinical isolates, and it has one site variation in amino acid among these CDV isolations. 2 isolates have the amino acid mutations F451L, while one has P448Ssubstitution.Phylogenetic analysis showed the two isolates with F451Lsubstitution had a closer relationship in a virulent strain ZJ-7, so the epitope may be a significant tag associated with virus virulence. This collection of mAb along with defined linear epitope may provide useful reagents for investigations of NP protein function and the development of CDV specific diagnostics.

  9. Greater epitope recognition of shrimp allergens by children than by adults suggests that shrimp sensitization decreases with age.

    Science.gov (United States)

    Ayuso, Rosalía; Sánchez-Garcia, Silvia; Lin, Jing; Fu, Zhiyan; Ibáñez, María Dolores; Carrillo, Teresa; Blanco, Carlos; Goldis, Marina; Bardina, Ludmila; Sastre, Joaquín; Sampson, Hugh A

    2010-06-01

    Shellfish allergy is a long-lasting disorder typically affecting adults. Despite its high prevalence, there is limited information about allergenic shrimp proteins and the epitopes implicated in such allergic reactions. We sought to identify the IgE-binding epitopes of the 4 shrimp allergens and to characterize epitope recognition profiles of children and adults with shrimp allergy. Fifty-three subjects, 34 children and 19 adults, were selected with immediate allergic reactions to shrimp, increased shrimp-specific serum IgE levels, and positive immunoblot binding to shrimp. Study subjects and 7 nonatopic control subjects were tested by means of peptide microarray for IgE binding with synthetic overlapping peptides spanning the sequences of Litopenaeus vannamei shrimp tropomyosin, arginine kinase (AK), myosin light chain (MLC), and sarcoplasmic calcium-binding protein (SCP). The Wilcoxon test was used to determine significant differences in z scores between patients and control subjects. The median shrimp IgE level was 4-fold higher in children than in adults (47 vs 12.5 kU(A)/L). The frequency of allergen recognition was higher in children (tropomyosin, 81% [94% for children and 61% for adults]; MLC, 57% [70% for children and 31% for adults]; AK, 51% [67% for children and 21% for adults]; and SCP, 45% [59% for children and 21% for adults]), whereas control subjects showed negligible binding. Seven IgE-binding regions were identified in tropomyosin by means of peptide microarray, confirming previously identified shrimp epitopes. In addition, 3 new epitopes were identified in tropomyosin (epitopes 1, 3, and 5b-c), 5 epitopes were identified in MLC, 3 epitopes were identified in SCP, and 7 epitopes were identified in AK. Interestingly, frequency of individual epitope recognition, as well as intensity of IgE binding, was significantly greater in children than in adults for all 4 proteins. Children with shrimp allergy have greater shrimp-specific IgE antibody levels and

  10. Broadly reactive human CD8 T cells that recognize an epitope conserved between VZV, HSV and EBV.

    Directory of Open Access Journals (Sweden)

    Christopher Chiu

    2014-03-01

    Full Text Available Human herpesviruses are important causes of potentially severe chronic infections for which T cells are believed to be necessary for control. In order to examine the role of virus-specific CD8 T cells against Varicella Zoster Virus (VZV, we generated a comprehensive panel of potential epitopes predicted in silico and screened for T cell responses in healthy VZV seropositive donors. We identified a dominant HLA-A*0201-restricted epitope in the VZV ribonucleotide reductase subunit 2 and used a tetramer to analyze the phenotype and function of epitope-specific CD8 T cells. Interestingly, CD8 T cells responding to this VZV epitope also recognized homologous epitopes, not only in the other α-herpesviruses, HSV-1 and HSV-2, but also the γ-herpesvirus, EBV. Responses against these epitopes did not depend on previous infection with the originating virus, thus indicating the cross-reactive nature of this T cell population. Between individuals, the cells demonstrated marked phenotypic heterogeneity. This was associated with differences in functional capacity related to increased inhibitory receptor expression (including PD-1 along with decreased expression of co-stimulatory molecules that potentially reflected their stimulation history. Vaccination with the live attenuated Zostavax vaccine did not efficiently stimulate a proliferative response in this epitope-specific population. Thus, we identified a human CD8 T cell epitope that is conserved in four clinically important herpesviruses but that was poorly boosted by the current adult VZV vaccine. We discuss the concept of a "pan-herpesvirus" vaccine that this discovery raises and the hurdles that may need to be overcome in order to achieve this.

  11. Recombinant immunotoxin for cancer treatment with low immunogenicity by identification and silencing of human T-cell epitopes

    OpenAIRE

    Mazor, Ronit; Eberle, Jaime A.; Hu, Xiaobo; Vassall, Aaron N.; Onda, Masanori; Beers, Richard; Lee, Elizabeth C.; Kreitman, Robert J.; Lee, Byungkook; Baker, David; King, Chris; Hassan, Raffit; Benhar, Itai; Pastan, Ira

    2014-01-01

    Recombinant immunotoxins have produced complete remissions in leukemia patients where many doses can be given but are less active in patients with solid tumors because their immune system makes antidrug antibodies, which inactivate the immunotoxin. To suppress the immune response, we have identified and largely silenced the T-cell epitopes responsible for the immune response. A redesigned immunotoxin with T-cell epitope mutations is highly cytotoxic to cell lines and to cells isolated from ca...

  12. Indirect detection of an epitope-specific response to HIV-1 gp120 immunization in human subjects.

    Directory of Open Access Journals (Sweden)

    Evgeny Shmelkov

    Full Text Available A specific response of human serum neutralizing antibodies (nAb to a conformational epitope as a result of vaccination of human subjects with the surface envelope glycoprotein (gp120 of HIV-1 has not previously been documented. Here, we used computational analysis to assess the epitope-specific responses of human subjects, which were immunized with recombinant gp120 immunogens in the VAX003 and VAX004 clinical trials. Our computational methodology--a variation of sieve analysis--compares the occurrence of specific nAb targeted conformational 3D epitopes on viruses from infected individuals who received vaccination to the occurrence of matched epitopes in the viruses infecting placebo subjects. We specifically studied seven crystallographically defined nAb targeted conformational epitopes in the V3 loop, an immunogenic region of gp120. Of the six epitopes present in the immunogens and targeted by known monoclonal neutralizing antibodies, only the one targeted by the anti-V3 nAb 2219 exhibited a significant reduction in occurrence in vaccinated subjects compared to the placebo group. This difference occurred only in the VAX003 Thailand cohort. No difference was seen between vaccinated and placebo groups for the occurrence of an epitope that was not present in the immunogen. Thus, it can be theorized that a specific 2219-like human neutralizing antibody immune response to AIDSVAX immunization occurred in the VAX003 cohort, and that this response protected subjects from a narrow subset of HIV-1 viruses circulating in Thailand in the 1990s and bearing the conformational epitope targeted by the neutralizing antibody 2219.

  13. Interactive storage and retrieval of pathologist's observations

    International Nuclear Information System (INIS)

    Trauger, G.M.; Dagle, G.E.; Watson, C.R.; McIntyre, J.M.

    1980-01-01

    A system was developed for interactive storage and retrieval of pathologic observations. Data are entered on a CRT terminal using modified SNOP (Systematized Nomenclature of Pathology) codes. They are then stored and processed in a PDP 11/70 computer, and are retrieved on demand, utilizing DATATRIEVE and a variety of reports convenient for statistical analysis

  14. Information Retrieval and the Philosophy of Language.

    Science.gov (United States)

    Blair, David C.

    2003-01-01

    Provides an overview of some of the main ideas in the philosophy of language that have relevance to the issues of information retrieval, focusing on the description of the intellectual content. Highlights include retrieval problems; recall and precision; words and meanings; context; externalism and the philosophy of language; and scaffolding and…

  15. Retrieval from Memory: Vulnerable or Inviolable?

    Science.gov (United States)

    Jones, Dylan M.; Marsh, John E.; Hughes, Robert W.

    2012-01-01

    We show that retrieval from semantic memory is vulnerable even to the mere presence of speech. Irrelevant speech impairs semantic fluency--namely, lexical retrieval cued by a semantic category name--but only if it is meaningful (forward speech compared to reversed speech or words compared to nonwords). Moreover, speech related semantically to the…

  16. Peer to Peer Information Retrieval: An Overview

    NARCIS (Netherlands)

    Tigelaar, A.S.; Hiemstra, D.; Trieschnigg, D.

    2012-01-01

    Peer-to-peer technology is widely used for file sharing. In the past decade a number of prototype peer-to-peer information retrieval systems have been developed. Unfortunately, none of these have seen widespread real- world adoption and thus, in contrast with file sharing, information retrieval is

  17. Peer to Peer Information Retrieval: An Overview

    NARCIS (Netherlands)

    Tigelaar, A.S.; Hiemstra, Djoerd; Trieschnigg, Rudolf Berend

    Peer-to-peer technology is widely used for file sharing. In the past decade a number of prototype peer-to-peer information retrieval systems have been developed. Unfortunately, none of these have seen widespread real- world adoption and thus, in contrast with file sharing, information retrieval is

  18. MARC Coding of DDC for Subject Retrieval.

    Science.gov (United States)

    Wajenberg, Arnold S.

    1983-01-01

    Recommends an expansion of MARC codes for decimal class numbers to enhance automated subject retrieval. Five values for a second indicator and two new subfields are suggested for encoding hierarchical relationships among decimal class numbers. Additional subfields are suggested to enhance retrieval through analysis of synthesized numbers in…

  19. Exploiting citation contexts for physics retrieval

    DEFF Research Database (Denmark)

    Dabrowska, Anna; Larsen, Birger

    2015-01-01

    The text surrounding citations within scientific papers may contain terms that usefully describe cited documents and can benefit retrieval. We present a preliminary study that investigates appending ci- tation contexts from citing documents to cited documents in the iSearch test collection. We ex...... in a large collection of physics papers, paving the way for future research that exploits citation contexts for retrieval....

  20. BIR 2014 - Bibliometric-enhanced Information Retrieval

    DEFF Research Database (Denmark)

    This first “Bibliometric-enhanced Information Retrieval” (BIR 2014) workshop1 aims to engage with the IR community about possible links to bibliometrics and scholarly communication. Bibliometric techniques are not yet widely used to enhance retrieval processes in digital libraries, although...... analysis of co-authorship network, can improve retrieval services for specific communities, as well as for large, cross-domain collections. This workshop aims to raise awareness of the missing link between information retrieval (IR) and bibliometrics / scientometrics and to create a common ground...... for the incorporation of bibliometric-enhanced services into retrieval at the digital library interface. Our interests include information retrieval, information seeking, science modelling, network analysis, and digital libraries. The goal is to apply insights from bibliometrics, scientometrics, and informetrics...

  1. Compact binary hashing for music retrieval

    Science.gov (United States)

    Seo, Jin S.

    2014-03-01

    With the huge volume of music clips available for protection, browsing, and indexing, there is an increased attention to retrieve the information contents of the music archives. Music-similarity computation is an essential building block for browsing, retrieval, and indexing of digital music archives. In practice, as the number of songs available for searching and indexing is increased, so the storage cost in retrieval systems is becoming a serious problem. This paper deals with the storage problem by extending the supervector concept with the binary hashing. We utilize the similarity-preserving binary embedding in generating a hash code from the supervector of each music clip. Especially we compare the performance of the various binary hashing methods for music retrieval tasks on the widely-used genre dataset and the in-house singer dataset. Through the evaluation, we find an effective way of generating hash codes for music similarity estimation which improves the retrieval performance.

  2. Generating Concise Rules for Human Motion Retrieval

    Science.gov (United States)

    Mukai, Tomohiko; Wakisaka, Ken-Ichi; Kuriyama, Shigeru

    This paper proposes a method for retrieving human motion data with concise retrieval rules based on the spatio-temporal features of motion appearance. Our method first converts motion clip into a form of clausal language that represents geometrical relations between body parts and their temporal relationship. A retrieval rule is then learned from the set of manually classified examples using inductive logic programming (ILP). ILP automatically discovers the essential rule in the same clausal form with a user-defined hypothesis-testing procedure. All motions are indexed using this clausal language, and the desired clips are retrieved by subsequence matching using the rule. Such rule-based retrieval offers reasonable performance and the rule can be intuitively edited in the same language form. Consequently, our method enables efficient and flexible search from a large dataset with simple query language.

  3. Prediction of T-cell Epitopes for Therapeutic and Prophylactic Vaccines

    DEFF Research Database (Denmark)

    Larsen, Mette Voldby

    2007-01-01

    : The bacteria Mycobacterium tuberculosis, Influenza A virus, HIV, Yellow fever virus, and West Nile virus. For each of the above-mentioned viruses, a number of predicted CTL epitopes was subsequently selected in such a way that they together constitute a broad coverage of the available viral strains. Part IV......The spread of existing infectious diseases and the emergence of new ones call for efficient methods for vaccine development. Some of the important players in conferring immunity against pathogens are the Cytotoxic T Lymphocytes (CTL), which eliminate infected cells. Due to their deleterious effects...... vaccine design as well as for diagnostic purposes and is the centre of focus of this thesis: Part I of the thesis is an introduction to the field. In part II, I describe how we generated a method, NetCTL, for predicting CTL epitopes by integrating existing methods for predicting proteasomal cleavage, TAP...

  4. Microarray Glycan Profiling Reveals Algal Fucoidan Epitopes in Diverse Marine Metazoans

    Directory of Open Access Journals (Sweden)

    Armando A. Salmeán

    2017-09-01

    Full Text Available Despite the biological importance and pharmacological potential of glycans from marine organisms, there are many unanswered questions regarding their distribution, function, and evolution. Here we describe microarray-based glycan profiling of a diverse selection of marine animals using antibodies raised against fucoidan isolated from a brown alga. We demonstrate the presence of two fucoidan epitopes in six animals belonging to three phyla including Porifera, Molusca, and Chordata. We studied the spatial distribution of these epitopes in Cliona celata (“boring sponge” and identified their restricted localization on the surface of internal chambers. Our results show the potential of high-throughput screening and probes commonly used in plant and algal cell wall biology to study the diversity and distribution of glycan structures in metazoans.

  5. Mapping of Epitopes Occurring in Bovine α(s1)-Casein Variants by Peptide Microarray Immunoassay.

    Science.gov (United States)

    Lisson, Maria; Erhardt, Georg

    2016-01-01

    Immunoglobulin E epitope mapping of milk proteins reveals important information about their immunologic properties. Genetic variants of αS1-casein, one of the major allergens in bovine milk, are until now not considered when discussing the allergenic potential. Here we describe the complete procedure to assess the allergenicity of αS1-casein variants B and C, which are frequent in most breeds, starting from milk with identification and purification of casein variants by isoelectric focusing (IEF) and anion-exchange chromatography, followed by in vitro gastrointestinal digestion of the casein variants, identification of the resulting peptides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), in silico analysis of the variant-specific peptides as allergenic epitopes, and determination of their IgE-binding properties by microarray immunoassay with cow's milk allergic human sera.

  6. Epitope-dependent mechanisms of CD27 neutralization revealed by X-ray crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Obmolova, Galina; Teplyakov, Alexey; Malia, Thomas J.; Wunderler, Nicole; Kwok, Deborah; Barone, Linda; Sweet, Raymond; Ort, Tatiana; Scully, Michael; Gilliland, Gary L. (Janssen)

    2017-03-01

    CD27 is a T and B cell co-stimulatory protein of the TNF receptor superfamily dependent on the availability of the TNF-like ligand CD70. Two anti-CD27 neutralizing monoclonal antibodies were obtained from mouse hybridoma and subsequently humanized and optimized for binding the target. The two antibodies are similar in terms of their CD27-binding affinity and ability to block NF-κB signaling, however their clearance rates in monkeys are very different. The pharmacokinetics profiles could be epitope dependent. To identify the epitopes, we determined the crystal structure of the ternary complex between CD27 and the Fab fragments of these non-competing antibodies. The structure reveals the binding modes of the antibodies suggesting that their mechanisms of action are distinctly different and provides a possible explanation of the in vivo data.

  7. Specific T-cell epitopes for immunoassay-based diagnosis of Mycobacterium tuberculosis infection

    DEFF Research Database (Denmark)

    Brock, I; Weldingh, K; Leyten, EM

    2004-01-01

    Specific T-cell epitopes for immunoassay-based diagnosis of Mycobacterium tuberculosis infection.Brock I, Weldingh K, Leyten EM, Arend SM, Ravn P, Andersen P. Department of Infectious Disease Immunology, Statens Serum Institute, Artillerivej 5, DK-2300 Copenhagen S, Denmark. The currently used...... method for immunological detection of tuberculosis infection, the tuberculin skin test, has low specificity. Antigens specific for Mycobacterium tuberculosis to replace purified protein derivative are therefore urgently needed. We have performed a rigorous assessment of the diagnostic potential of four...... recently identified antigens (Rv2653, Rv2654, Rv3873, and Rv3878) from genomic regions that are lacking from the Mycobacterium bovis bacillus Calmette-Guerin (BCG) vaccine strains as well as from the most common nontuberculous mycobacteria. The fine specificity of potential epitopes in these molecules...

  8. Epitope design of L1 protein for vaccine production against Human Papilloma Virus types 16 and 18.

    Science.gov (United States)

    Baidya, Sunanda; Das, Rasel; Kabir, Md Golam; Arifuzzaman, Md

    2017-01-01

    Cervical cancer accounts for about two-thirds of all cancer cases linked etiologically to Human Papilloma Virus (HPV). 15 oncogenic HPV types can cause cervical cancer, of which HPV16 and HPV18 combinedly account for about 70% of it. So, effective epitope design for the clinically relevant HPV types 16 and 18 would be of major medical benefit. Here, a comprehensive analysis is carried out to predict the epitopes against HPV types 16 and 18 through "reverse vaccinology" approach. We attempted to identify the evolutionarily conserved regions of major capsid protein (L1) as well as minor capsid protein (L2) of HPV and designed epitopes within these regions. In this study, we analyzed about 49 and 27 sequences of HPV L2 and L1 proteins respectively. Since we found that the intertype variability of L2 is higher than for L1 proteins, our analysis was emphasized on epitopes of L1 of HPV types 16 and 18. We had selected HLA-A*0201, DRB1*1501, DQB1*0602, DRB1*0401 and DQB1*0301 alleles for the prediction of T cell epitopes of L1 of HPV 16 and 18. Finally, we reported that predicted epitope sequences EEYDLQFIFQLCKITLTA, and RHGEEYDLQFIFQLCKITLTA of L1 protein of HPV 16, and LPDPNKF, PETQRLVWAC, PVPGQYDA, YNPETQRLVWAC, DTGYGAMD, PVPGQYDATK, KQDIPKVSAYQYRVFRV, RDNVSVDYKQTQLCI and YSRHVEEYDLQFIF of L1 protein of HPV 18 could be therapeutic tools for vaccine design against HPV.

  9. Virus-Like Particles of Chimeric Recombinant Porcine Circovirus Type 2 as Antigen Vehicle Carrying Foreign Epitopes

    Directory of Open Access Journals (Sweden)

    Huawei Zhang

    2014-12-01

    Full Text Available Virus-like particles (VLPs of chimeric porcine circovirus type 2 (PCV2 were generated by replacing the nuclear localization signal (NLS; at 1–39 aa of PCV2 capsid protein (Cap with classical swine fever virus (CSFV T-cell epitope (1446–1460 aa, CSFV B-cell epitope (693–716 aa and CSFV T-cell epitope conjugated with B-cell epitope. The recombinant proteins were expressed using the baculovirus expression system and detected by immunoblotting and indirect immunofluorescence assay. The abilities to form PCV2 VLPs were confirmed by transmission electron microscopy. Immunogenicities of the three recombinant proteins were evaluated in mice. Our Results indicated that Cap protein NLS deletion or substitution with CSFV epitopes did not affect the VLPs assembly. Three chimeric Cap proteins could form VLPs and induce efficient humoral and cellular immunity against PCV2 and CSFV in mice. Results show that PCV2 VLPs can be used as an efficient antigen carrier for delivery of foreign epitopes, and a potential novel vaccine.

  10. Recombinant and epitope-based vaccines on the road to the market and implications for vaccine design and production.

    Science.gov (United States)

    Oyarzún, Patricio; Kobe, Bostjan

    2016-03-03

    Novel vaccination approaches based on rational design of B- and T-cell epitopes - epitope-based vaccines - are making progress in the clinical trial pipeline. The epitope-focused recombinant protein-based malaria vaccine (termed RTS,S) is a next-generation approach that successfully reached phase-III trials, and will potentially become the first commercial vaccine against a human parasitic disease. Progress made on methods such as recombinant DNA technology, advanced cell-culture techniques, immunoinformatics and rational design of immunogens are driving the development of these novel concepts. Synthetic recombinant proteins comprising both B- and T-cell epitopes can be efficiently produced through modern biotechnology and bioprocessing methods, and can enable the induction of large repertoires of immune specificities. In particular, the inclusion of appropriate CD4+ T-cell epitopes is increasingly considered a key vaccine component to elicit robust immune responses, as suggested by results coming from HIV-1 clinical trials. In silico strategies for vaccine design are under active development to address genetic variation in pathogens and several broadly protective "universal" influenza and HIV-1 vaccines are currently at different stages of clinical trials. Other methods focus on improving population coverage in target populations by rationally considering specificity and prevalence of the HLA proteins, though a proof-of-concept in humans has not been demonstrated yet. Overall, we expect immunoinformatics and bioprocessing methods to become a central part of the next-generation epitope-based vaccine development and production process.

  11. Recognition of Porphyromonas gingivalis gingipain epitopes by natural IgM binding to malondialdehyde modified low-density lipoprotein.

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    S Pauliina Turunen

    Full Text Available OBJECTIVE: Increased risk for atherosclerosis is associated with infectious diseases including periodontitis. Natural IgM antibodies recognize pathogen-associated molecular patterns on bacteria, and oxidized lipid and protein epitopes on low-density lipoprotein (LDL and apoptotic cells. We aimed to identify epitopes on periodontal pathogen Porphyromonas gingivalis recognized by natural IgM binding to malondialdehyde (MDA modified LDL. METHODS AND RESULTS: Mouse monoclonal IgM (MDmAb specific for MDA-LDL recognized epitopes on P. gingivalis on flow cytometry and chemiluminescence immunoassays. Immunization of C57BL/6 mice with P. gingivalis induced IgM, but not IgG, immune response to MDA-LDL and apoptotic cells. Immunization of LDLR(-/- mice with P. gingivalis induced IgM, but not IgG, immune response to MDA-LDL and diminished aortic lipid deposition. On Western blot MDmAb bound to P. gingivalis fragments identified as arginine-specific gingipain (Rgp by mass spectrometry. Recombinant domains of Rgp produced in E. coli were devoid of phosphocholine epitopes but contained epitopes recognized by MDmAb and human serum IgM. Serum IgM levels to P. gingivalis were associated with anti-MDA-LDL levels in humans. CONCLUSION: Gingipain of P. gingivalis is recognized by natural IgM and shares molecular identity with epitopes on MDA-LDL. These findings suggest a role for natural antibodies in the pathogenesis of two related inflammatory diseases, atherosclerosis and periodontitis.

  12. Specific immunotherapy modifies allergen-specific CD4+ T cell responses in an epitope-dependent manner

    Science.gov (United States)

    Wambre, Erik; DeLong, Jonathan H.; James, Eddie A.; Torres-Chinn, Nadia; Pfützner, Wolfgang; Möbs, Christian; Durham, Stephen R.; Till, Stephen J.; Robinson, David; Kwok, William W.

    2014-01-01

    Background Understanding the mechanisms by which the immune system induces and controls allergic inflammation at the T cell epitope level is critical for the design of new allergy vaccine strategies. Objective To characterize allergen-specific T cell responses linked with allergy or peripheral tolerance and to determine how CD4+ T cell responses to individual allergen-derived epitopes change over allergen-specific immunotherapy (ASIT). Methods Timothy grass pollen (TGP) allergy was used as a model for studying grass pollen allergies. The breadth, magnitude, epitope hierarchy and phenotype of the DR04:01-restricted TGP-specific T cell responses in ten grass pollen allergic, five non-atopic and six allergy vaccine-treated individuals was determined using an ex vivo pMHCII-tetramer approach. Results CD4+ T cells in allergic individuals are directed to a broad range of TGP epitopes characterized by defined immunodominance hierarchy patterns and with distinct functional profiles that depend on the epitope recognized. Epitopes that are restricted specifically to either TH2 or TH1/TR1 responses were identified. ASIT was associated with preferential deletion of allergen-specific TH2 cells and without significant change in frequency of TH1/TR1 cells. Conclusions Preferential allergen-specific TH2-cells deletion after repeated high doses antigen stimulation can be another independent mechanism to restore tolerance to allergen during immunotherapy. PMID:24373351

  13. Excavating the surface-associated and secretory proteome of Mycobacterium leprae for identifying vaccines and diagnostic markers relevant immunodominant epitopes.

    Science.gov (United States)

    Rana, Aarti; Thakur, Shweta; Bhardwaj, Nupur; Kumar, Devender; Akhter, Yusuf

    2016-12-01

    For centuries, Mycobacterium leprae, etiological agent of leprosy, has been afflicting mankind regardless of extensive use of live-attenuated vaccines and antibiotics. Surface-associated and secretory proteins (SASPs) are attractive targets against bacteria. We have integrated biological knowledge with computational approaches and present a proteome-wide identification of SASPs. We also performed computational assignment of immunodominant epitopes as coordinates of prospective antigenic candidates in most important class of SASPs, the outer membrane proteins (OMPs). Exploiting the known protein sequence and structural characteristics shared by the SASPs from bacteria, 17 lipoproteins, 11 secretory and 19 novel OMPs (including 4 essential proteins) were identified in M. leprae As OMPs represent the most exposed antigens on the cell surface, their immunoinformatics analysis showed that the identified 19 OMPs harbor T-cell MHC class I epitopes and class II epitopes against HLA-DR alleles (54), while 15 OMPs present potential T-cell class II epitopes against HLA-DQ alleles (6) and 7 OMPs possess T-cell class II epitopes against HLA-DP alleles (5) of humans. Additionally, 11 M. leprae OMPs were found to have B-cell epitopes and these may be considered as prime candidates for the development of new immunotherapeutics against M. leprae. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Identification of one B-cell epitope from NS1 protein of duck Tembusu virus with monoclonal antibodies.

    Directory of Open Access Journals (Sweden)

    Jinfeng Ti

    Full Text Available This study describes the identification of one linear B-cell epitope on TMUV NS1 protein with monoclonal antibody (mAb 3G2 by indirect enzyme-linked immunosorbent assay (ELISA. In this study, NS1 protein was expressed in prokaryotic expression system and purified. One mAb against NS1 protein was generated from Balb/c mice immunized with recombinant protein NS1. A set of 35 partially-overlapping polypeptides covering the entire NS1 protein was expressed with PGEX-6P-1 vector and screened with mAb 3G2. One polypeptide against the mAb was acquired and identified by indirect ELISA and western-blot. To map the epitope accurately, one or two amino acid residues were removed from the carboxy and amino terminal of polypeptide sequentially. A series of truncated oligopeptides were expressed and purified. The minimal determinant of the linear B cell epitope was recognized and identified with mAb 3G2. The accurate linear B-cell epitope was 269DEKEIV274 located in NS1 protein. Furthermore, sequence alignment showed that the epitope was highly conserved and specific among TMUV strains and other flavivirus respectively. The linear B-cell epitope of TMUV NS1 protein could benefit the development of new vaccines and diagnostic assays.

  15. Prediction of CD8+ Epitopes in Leishmania braziliensis Proteins Using EPIBOT: In Silico Search and In Vivo Validation.

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    Angelo Duarte

    Full Text Available Leishmaniasis is caused by intracellular Leishmania parasites that induce a T-cell mediated response associated with recognition of CD4+ and CD8+ T cell Line 1Lineepitopes. Identification of CD8+ antigenic determinants is crucial for vaccine and therapy development. Herein, we developed an open-source software dedicated to search and compile data obtained from currently available on line prediction algorithms.We developed a two-phase algorithm and implemented in an open source software called EPIBOT, that consolidates the results obtained with single prediction algorithms, generating a final output in which epitopes are ranked. EPIBOT was initially trained using a set of 831 known epitopes from 397 proteins from IEDB. We then screened 63 Leishmania braziliensis vaccine candidates with the EPIBOT trained tool to search for CD8+ T cell epitopes. A proof-of-concept experiment was conducted with the top eight CD8+ epitopes, elected by EPIBOT. To do this, the elected peptides were synthesized and validated for their in vivo cytotoxicity. Among the tested epitopes, three were able to induce lysis of pulsed-target cells.Our results show that EPIBOT can successfully search across existing prediction tools, generating a compiled list of candidate CD8+ epitopes. This software is fast and a simple search engine that can be customized to search over different MHC alleles or HLA haplotypes.

  16. Identification of a conserved B-cell epitope on the GapC protein of Streptococcus dysgalactiae.

    Science.gov (United States)

    Zhang, Limeng; Zhou, Xue; Fan, Ziyao; Tang, Wei; Chen, Liang; Dai, Jian; Wei, Yuhua; Zhang, Jianxin; Yang, Xuan; Yang, Xijing; Liu, Daolong; Yu, Liquan; Zhang, Hua; Wu, Zhijun; Yu, Yongzhong; Sun, Hunan; Cui, Yudong

    2015-01-01

    Streptococcus dysgalactiae (S. dysgalactia) GapC is a highly conserved surface dehydrogenase among the streptococcus spp., which is responsible for inducing protective antibody immune responses in animals. However, the B-cell epitope of S. dysgalactia GapC have not been well characterized. In this study, a monoclonal antibody 1F2 (mAb1F2) against S. dysgalactiae GapC was generated by the hybridoma technique and used to screen a phage-displayed 12-mer random peptide library (Ph.D.-12) for mapping the linear B-cell epitope. The mAb1F2 recognized phages displaying peptides with the consensus motif TRINDLT. Amino acid sequence of the motif exactly matched (30)TRINDLT(36) of the S. dysgalactia GapC. Subsequently, site-directed mutagenic analysis further demonstrated that residues R31, I32, N33, D34 and L35 formed the core of (30)TRINDLT(36), and this core motif was the minimal determinant of the B-cell epitope recognized by the mAb1F2. The epitope (30)TRINDLT(36) showed high homology among different streptococcus species. Overall, our findings characterized a conserved B-cell epitope, which will be useful for the further study of epitope-based vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. An Improved Model of Heat-Induced Hyperalgesia—Repetitive Phasic Heat Pain Causing Primary Hyperalgesia to Heat and Secondary Hyperalgesia to Pinprick and Light Touch

    Science.gov (United States)

    Henrich, Florian; Magerl, Walter; May, Arne

    2014-01-01

    This study tested a modified experimental model of heat-induced hyperalgesia, which improves the efficacy to induce primary and secondary hyperalgesia and the efficacy-to-safety ratio reducing the risk of tissue damage seen in other heat pain models. Quantitative sensory testing was done in eighteen healthy volunteers before and after repetitive heat pain stimuli (60 stimuli of 48°C for 6 s) to assess the impact of repetitive heat on somatosensory function in conditioned skin (primary hyperalgesia area) and in adjacent skin (secondary hyperalgesia area) as compared to an unconditioned mirror image control site. Additionally, areas of flare and secondary hyperalgesia were mapped, and time course of hyperalgesia determined. After repetitive heat pain conditioning we found significant primary hyperalgesia to heat, and primary and secondary hyperalgesia to pinprick and to light touch (dynamic mechanical allodynia). Acetaminophen (800 mg) reduced pain to heat or pinpricks only marginally by 11% and 8%, respectively (n.s.), and had no effect on heat hyperalgesia. In contrast, the areas of flare (−31%) and in particular of secondary hyperalgesia (−59%) as well as the magnitude of hyperalgesia (−59%) were significantly reduced (all pheat pain induces significant peripheral sensitization (primary hyperalgesia to heat) and central sensitization (punctate hyperalgesia and dynamic mechanical allodynia). These findings are relevant to further studies using this model of experimental heat pain as it combines pronounced peripheral and central sensitization, which makes a convenient model for combined pharmacological testing of analgesia and anti-hyperalgesia mechanisms related to thermal and mechanical input. PMID:24911787

  18. Viral Escape Mutant Epitope Maintains TCR Affinity for Antigen yet Curtails CD8 T Cell Responses.

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    Shayla K Shorter

    Full Text Available T cells have the remarkable ability to recognize antigen with great specificity and in turn mount an appropriate and robust immune response. Critical to this process is the initial T cell antigen recognition and subsequent signal transduction events. This antigen recognition can be modulated at the site of TCR interaction with peptide:major histocompatibility (pMHC or peptide interaction with the MHC molecule. Both events could have a range of effects on T cell fate. Though responses to antigens that bind sub-optimally to TCR, known as altered peptide ligands (APL, have been studied extensively, the impact of disrupting antigen binding to MHC has been highlighted to a lesser extent and is usually considered to result in complete loss of epitope recognition. Here we present a model of viral evasion from CD8 T cell immuno-surveillance by a lymphocytic choriomeningitis virus (LCMV escape mutant with an epitope for which TCR affinity for pMHC remains high but where the antigenic peptide binds sub optimally to MHC. Despite high TCR affinity for variant epitope, levels of interferon regulatory factor-4 (IRF4 are not sustained in response to the variant indicating differences in perceived TCR signal strength. The CD8+ T cell response to the variant epitope is characterized by early proliferation and up-regulation of activation markers. Interestingly, this response is not maintained and is characterized by a lack in IL-2 and IFNγ production, increased apoptosis and an abrogated glycolytic response. We show that disrupting the stability of peptide in MHC can effectively disrupt TCR signal strength despite unchanged affinity for TCR and can significantly impact the CD8+ T cell response to a viral escape mutant.

  19. Type II collagen C2C epitope in human synovial fluid and serum after knee injury

    DEFF Research Database (Denmark)

    Kumahashi, N; Swärd, P; Larsson, S

    2015-01-01

    PURPOSE: Investigate in a cross-sectional study time-dependent changes of synovial fluid type II collagen epitope C2C concentrations after knee injury and correlate to other joint injury biomarkers. METHODS: Synovial fluid samples were aspirated between 0 days and 7 years after injury (n = 235...... = 0.403, P type II collagen (r = 0.444, P = 0.003), ARGS-aggrecan (r = 0.337, P ... with an immediate and sustained local degradation of type II collagen....

  20. Exposed and hidden lectin-binding epitopes at the surface of Borrelia burgdorferi

    Czech Academy of Sciences Publication Activity Database

    Stoitsova, S. R.; Grubhoffer, Libor; Nebesářová, Jana

    2003-01-01

    Roč. 48, č. 5 (2003), s. 654-658 ISSN 0015-5632 R&D Projects: GA AV ČR IAA6022001 Grant - others:National Research Council at the Ministry of Education and Science(BG) K-709/97 Institutional research plan: CEZ:AV0Z6022909 Keywords : Borrelia burgdorferi * lectin-binding epitopes Subject RIV: EE - Microbiology, Virology Impact factor: 0.857, year: 2003

  1. Ineffective Degradation of Immunogenic Gluten Epitopes by Currently Available Digestive Enzyme Supplements

    Science.gov (United States)

    Janssen, George; Christis, Chantal; Kooy-Winkelaar, Yvonne; Edens, Luppo; Smith, Drew

    2015-01-01

    Background Due to the high proline content of gluten molecules, gastrointestinal proteases are unable to fully degrade them leaving large proline-rich gluten fragments intact, including an immunogenic 33-mer from α-gliadin and a 26-mer from γ-gliadin. These latter peptides can trigger pro-inflammatory T cell responses resulting in tissue remodeling, malnutrition and a variety of other complications. A strict lifelong gluten-free diet is currently the only available treatment to cope with gluten intolerance. Post-proline cutting enzymes have been shown to effectively degrade the immunogenic gluten peptides and have been proposed as oral supplements. Several existing digestive enzyme supplements also claim to aid in gluten degradation. Here we investigate the effectiveness of such existing enzyme supplements in comparison with a well characterized post-proline cutting enzyme, Prolyl EndoPeptidase from Aspergillus niger (AN-PEP). Methods Five commercially available digestive enzyme supplements along with purified digestive enzymes were subjected to 1) enzyme assays and 2) mass spectrometric identification. Gluten epitope degradation was monitored by 1) R5 ELISA, 2) mass spectrometric analysis of the degradation products and 3) T cell proliferation assays. Findings The digestive enzyme supplements showed comparable proteolytic activities with near neutral pH optima and modest gluten detoxification properties as determined by ELISA. Mass spectrometric analysis revealed the presence of many different enzymes including amylases and a variety of different proteases with aminopeptidase and carboxypeptidase activity. The enzyme supplements leave the nine immunogenic epitopes of the 26-mer and 33-mer gliadin fragments largely intact. In contrast, the pure enzyme AN-PEP effectively degraded all nine epitopes in the pH range of the stomach at much lower dose. T cell proliferation assays confirmed the mass spectrometric data. Conclusion Currently available digestive enzyme

  2. Ineffective degradation of immunogenic gluten epitopes by currently available digestive enzyme supplements.

    Directory of Open Access Journals (Sweden)

    George Janssen

    Full Text Available Due to the high proline content of gluten molecules, gastrointestinal proteases are unable to fully degrade them leaving large proline-rich gluten fragments intact, including an immunogenic 33-mer from α-gliadin and a 26-mer from γ-gliadin. These latter peptides can trigger pro-inflammatory T cell responses resulting in tissue remodeling, malnutrition and a variety of other complications. A strict lifelong gluten-free diet is currently the only available treatment to cope with gluten intolerance. Post-proline cutting enzymes have been shown to effectively degrade the immunogenic gluten peptides and have been proposed as oral supplements. Several existing digestive enzyme supplements also claim to aid in gluten degradation. Here we investigate the effectiveness of such existing enzyme supplements in comparison with a well characterized post-proline cutting enzyme, Prolyl EndoPeptidase from Aspergillus niger (AN-PEP.Five commercially available digestive enzyme supplements along with purified digestive enzymes were subjected to 1 enzyme assays and 2 mass spectrometric identification. Gluten epitope degradation was monitored by 1 R5 ELISA, 2 mass spectrometric analysis of the degradation products and 3 T cell proliferation assays.The digestive enzyme supplements showed comparable proteolytic activities with near neutral pH optima and modest gluten detoxification properties as determined by ELISA. Mass spectrometric analysis revealed the presence of many different enzymes including amylases and a variety of different proteases with aminopeptidase and carboxypeptidase activity. The enzyme supplements leave the nine immunogenic epitopes of the 26-mer and 33-mer gliadin fragments largely intact. In contrast, the pure enzyme AN-PEP effectively degraded all nine epitopes in the pH range of the stomach at much lower dose. T cell proliferation assays confirmed the mass spectrometric data.Currently available digestive enzyme supplements are ineffective in

  3. Adjuvant-Mediated Epitope Specificity and Enhanced Neutralizing Activity of Antibodies Targeting Dengue Virus Envelope Protein

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    Denicar Lina Nascimento Fabris Maeda

    2017-09-01

    Full Text Available The heat-labile toxins (LT produced by enterotoxigenic Escherichia coli display adjuvant effects to coadministered antigens, leading to enhanced production of serum antibodies. Despite extensive knowledge of the adjuvant properties of LT derivatives, including in vitro-generated non-toxic mutant forms, little is known about the capacity of these adjuvants to modulate the epitope specificity of antibodies directed against antigens. This study characterizes the role of LT and its non-toxic B subunit (LTB in the modulation of antibody responses to a coadministered antigen, the dengue virus (DENV envelope glycoprotein domain III (EDIII, which binds to surface receptors and mediates virus entry into host cells. In contrast to non-adjuvanted or alum-adjuvanted formulations, antibodies induced in mice immunized with LT or LTB showed enhanced virus-neutralization effects that were not ascribed to a subclass shift or antigen affinity. Nonetheless, immunosignature analyses revealed that purified LT-adjuvanted EDIII-specific antibodies display distinct epitope-binding patterns with regard to antibodies raised in mice immunized with EDIII or the alum-adjuvanted vaccine. Notably, the analyses led to the identification of a specific EDIII epitope located in the EF to FG loop, which is involved in the entry of DENV into eukaryotic cells. The present results demonstrate that LT and LTB modulate the epitope specificity of antibodies generated after immunization with coadministered antigens that, in the case of EDIII, was associated with the induction of neutralizing antibody responses. These results open perspectives for the more rational development of vaccines with enhanced protective effects against DENV infections.

  4. Expression of human apolipoprotein A-I epitopes in high density lipoproteins and in serum

    International Nuclear Information System (INIS)

    Marcel, Y.L.; Jewer, D.; Vezina, C.; Milthorp, P.; Weech, P.K.

    1987-01-01

    The expression and immunoreactivity of apolipoprotein (apo) A-I epitopes in high density lipoproteins (HDL) and serum has been investigated using two series of monoclonal antibodies (Mabs) which have been described elsewhere. Series 1 Mabs, identified as 3D4, 6B8, and 5G6, were obtained by immunization and screening with apoA-I, and series 2 Mabs, identified as 2F1, 4H1, 3G10, 4F7, and 5F6, were obtained by immunization and screening with HDL. These Mabs were characterized with respect to their binding to HDL particles in solution. In series 2 Mabs, 2F1, 3G10, and 4F7, which react with apoA-I CNBr-fragments 1 and 2, could precipitate 100% of 125 I-labeled HDL, while 4H1 and 5F6, which react with CNBr fragments 1 and 3, precipitated 90 and 60% of 125 I-labeled HDL, respectively. Therefore, three distinct epitopes mapped to CNBr fragments 1 and 2 have been identified which are expressed on all HDL particles, indicating that several antigenic do mains exist on apoA-I which have the same conformation on all apoA-I-containing lipoproteins. The Mabs reacting at these sites have significantly higher affinity constants for 125 I-labeled HDL than those that failed to precipitate 100% of HDL. This suggests that the high affinity Mabs react with apoA-I epitopes that are both expressed on all lipoproteins and located in thermo-dynamically stable regions of the molecules. All Mabs from series 1 precipitated 35% or less of 125 I-labeled HDL prepared from freshly collected serum, but the proportion of HDL particles expressing the epitopes for these Mabs doubled or more upon serum storage at 4 degrees C. The time course of the alteration of apoA-I antigen in vitro was measured in three normolipemic donors

  5. Epitope analysis of anti-myeloperoxidase antibodies in patients with ANCA-associated vasculitis.

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    Shen-Ju Gou

    Full Text Available OBJECTIVE: Increasing evidences have suggested the pathogenic role of anti-neutrophil cytoplasmic antibodies (ANCA directing myeloperoxidase (MPO in ANCA-associated vasculitis (AAV. The current study aimed to analyze the association between the linear epitopes of MPO-ANCA and clinicopathological features of patients with AAV. METHODS: Six recombinant linear fragments, covering the whole length amino acid sequence of a single chain of MPO, were produced from E.coli. Sera from 77 patients with AAV were collected at presentation. 13 out of the 77 patients had co-existence of serum anti-GBM antibodies. Ten patients also had sequential sera during follow up. The epitope specificities were detected by enzyme-linked immunosorbent assay using the recombinant fragments as solid phase ligands. RESULTS: Sera from 45 of the 77 (58.4% patients with AAV showed a positive reaction to one or more linear fragments of the MPO chain. The Birmingham Vasculitis Activity Scores and the sera creatinine were significantly higher in patients with positive binding to the light chain fragment than that in patients without the binding. The epitopes recognized by MPO-ANCA from patients with co-existence of serum anti-GBM antibodies were mainly located in the N-terminus of the heavy chain. In 5 out of the 6 patients, whose sera in relapse recognize linear fragments, the reactivity to linear fragments in relapse was similar to that of initial onset. CONCLUSION: The epitope specificities of MPO-ANCA were associated with disease activity and some clinicopathological features in patients with ANCA-associated vasculitis.

  6. Noncanonical Expression of a Murine Cytomegalovirus Early Protein CD8 T-Cell Epitope as an Immediate Early Epitope Based on Transcription from an Upstream Gene

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    Annette Fink

    2014-02-01

    Full Text Available Viral CD8 T-cell epitopes, represented by viral peptides bound to major histocompatibility complex class-I (MHC-I glycoproteins, are often identified by “reverse immunology”, a strategy not requiring biochemical and structural knowledge of the actual viral protein from which they are derived by antigen processing. Instead, bioinformatic algorithms predicting the probability of C-terminal cleavage in the proteasome, as well as binding affinity to the presenting MHC-I molecules, are applied to amino acid sequences deduced from predicted open reading frames (ORFs based on the genomic sequence. If the protein corresponding to an antigenic ORF is known, it is usually inferred that the kinetic class of the protein also defines the phase in the viral replicative cycle during which the respective antigenic peptide is presented for recognition by CD8 T cells. We have previously identified a nonapeptide from the predicted ORFm164 of murine cytomegalovirus that is presented by the MHC-I allomorph H-2 Dd and that is immunodominant in BALB/c (H-2d haplotype mice. Surprisingly, although the ORFm164 protein gp36.5 is expressed as an Early (E phase protein, the m164 epitope is presented already during the Immediate Early (IE phase, based on the expression of an upstream mRNA starting within ORFm167 and encompassing ORFm164.

  7. Future of an “Asymptomatic” T-cell Epitope-Based Therapeutic Herpes Simplex Vaccine

    Science.gov (United States)

    Dervillez, Xavier; Gottimukkala, Chetan; Kabbara, Khaled W.; Nguyen, Chelsea; Badakhshan, Tina; Kim, Sarah M.; Nesburn, Anthony B.; Wechsler, Steven L.; BenMohamed, Lbachir

    2012-01-01

    Summary Considering the limited success of the recent herpes clinical vaccine trial [1], new vaccine strategies are needed. Infections with herpes simplex virus type 1 and type 2 (HSV-1 & HSV-2) in the majority of men and women are usually asymptomatic and results in lifelong viral latency in neurons of sensory ganglia (SG). However, in a minority of men and women HSV spontaneous reactivation can cause recurrent disease (i.e., symptomatic individuals). Our recent findings show that T cells from symptomatic and asymptomatic men and women (i.e. those with and without recurrences, respectively) recognize different herpes epitopes. This finding breaks new ground and opens new doors to assess a new vaccine strategy: mucosal immunization with HSV-1 & HSV-2 epitopes that induce strong in vitro CD4 and CD8 T cell responses from PBMC derived from asymptomatic men and women (designated here as “asymptomatic” protective epitopes”) could boost local and systemic “natural” protective immunity, induced by wild-type infection. Here we highlight the rationale and the future of our emerging “asymptomatic” T cell epitope-based mucosal vaccine strategy to decrease recurrent herpetic disease. PMID:22701511

  8. Flow shear stress differentially regulates endothelial uptake of nanocarriers targeted to distinct epitopes of PECAM-1.

    Science.gov (United States)

    Han, Jingyan; Shuvaev, Vladimir V; Davies, Peter F; Eckmann, David M; Muro, Silvia; Muzykantov, Vladimir R

    2015-07-28

    Targeting nanocarriers (NC) to endothelial cell adhesion molecules including Platelet-Endothelial Cell Adhesion Molecule-1 (PECAM-1 or CD31) improves drug delivery and pharmacotherapy of inflammation, oxidative stress, thrombosis and ischemia in animal models. Recent studies unveiled that hydrodynamic conditions modulate endothelial endocytosis of NC targeted to PECAM-1, but the specificity and mechanism of effects of flow remain unknown. Here we studied the effect of flow on endocytosis by human endothelial cells of NC targeted by monoclonal antibodies Ab62 and Ab37 to distinct epitopes on the distal extracellular domain of PECAM. Flow in the range of 1-8dyn/cm(2), typical for venous vasculature, stimulated the uptake of spherical Ab/NC (~180nm diameter) carrying ~50 vs 200 Ab62 and Ab37 per NC, respectively. Effect of flow was inhibited by disruption of cholesterol-rich plasmalemma domains and deletion of PECAM-1 cytosolic tail. Flow stimulated endocytosis of Ab62/NC and Ab37/NC via eliciting distinct signaling pathways mediated by RhoA/ROCK and Src Family Kinases, respectively. Therefore, flow stimulates endothelial endocytosis of Ab/NC in a PECAM-1 epitope specific manner. Using ligands of binding to distinct epitopes on the same target molecule may enable fine-tuning of intracellular delivery based on the hemodynamic conditions in the vascular area of interest. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Determination of critical epitope of PcMab-47 against human podocalyxin

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    Shunsuke Itai

    2018-07-01

    Full Text Available Podocalyxin (PODXL is a type I transmembrane protein, which is highly glycosylated. PODXL is expressed in some types of human cancer tissues including oral, breast, and lung cancer tissues and may promote tumor growth, invasion, and metastasis. We previously produced PcMab-47, a novel anti-PODXL monoclonal antibody (mAb which reacts with endogenous PODXL-expressing cancer cell lines and normal cells independently of glycosylation in Western blot, flow cytometry, and immunohistochemical analysis. In this study, we used enzyme-linked immunosorbent assay (ELISA, flow cytometry, and immunohistochemical analysis to determine the epitope of PcMab-47. The minimum epitope of PcMab-47 was found to be Asp207, His208, Leu209, and Met210. A blocking peptide containing this minimum epitope completely neutralized PcMab-47 reaction against oral cancer cells by flow cytometry and immunohistochemical analysis. These findings could lead to the production of more functional anti-PODXL mAbs, which are advantageous for antitumor activities.

  10. Determination of critical epitope of PcMab-47 against human podocalyxin.

    Science.gov (United States)

    Itai, Shunsuke; Yamada, Shinji; Kaneko, Mika K; Kato, Yukinari

    2018-07-01

    Podocalyxin (PODXL) is a type I transmembrane protein, which is highly glycosylated. PODXL is expressed in some types of human cancer tissues including oral, breast, and lung cancer tissues and may promote tumor growth, invasion, and metastasis. We previously produced PcMab-47, a novel anti-PODXL monoclonal antibody (mAb) which reacts with endogenous PODXL-expressing cancer cell lines and normal cells independently of glycosylation in Western blot, flow cytometry, and immunohistochemical analysis. In this study, we used enzyme-linked immunosorbent assay (ELISA), flow cytometry, and immunohistochemical analysis to determine the epitope of PcMab-47. The minimum epitope of PcMab-47 was found to be Asp207, His208, Leu209, and Met210. A blocking peptide containing this minimum epitope completely neutralized PcMab-47 reaction against oral cancer cells by flow cytometry and immunohistochemical analysis. These findings could lead to the production of more functional anti-PODXL mAbs, which are advantageous for antitumor activities.

  11. Identification of linear B-cell epitopes on goose parvovirus non-structural protein.

    Science.gov (United States)

    Yu, Tian-Fei; Ma, Bo; Wang, Jun-Wei

    2016-10-15

    Goose parvovirus (GPV) infection can cause a highly contagious and lethal disease in goslings and muscovy ducklings which is widespread in all major goose (Anser anser) and Muscovy duck (Cairina moschata) farming countries, leading to a huge economic loss. Humoral immune responses play a major role in GPV immune protection during GPV infection. However, it is still unknown for the localization and immunological characteristics of B-cell epitopes on GPV non-structural protein (NSP). Therefore, in this study, the epitopes on the NSP of GPV were identified by means of overlapping peptides expressed in Escherichia coli in combination with Western blot. The results showed that the antigenic epitopes on the GPV NSP were predominantly localized in the C-terminal (aa 485-627), and especially, the fragment NS (498-532) was strongly positive. These results may facilitate future investigations on the function of NSP of GPV and the development of immunoassays for the diagnosis of GPV infection. Copyright © 2016. Published by Elsevier B.V.

  12. Mapping of Lol p I allergenic epitopes by using murine monoclonal antibodies.

    Science.gov (United States)

    Mourad, W; Bernier, D; Jobin, M; Hébert, J

    1989-11-01

    Murine monoclonal antibodies (MAbs) against three non-overlapping epitopes of Lol p I allergen were previously produced and subsequently used for purification of the allergen. In the present study, these MAbs were further characterized, and the biological activity of the purified allergen assessed. The three MAbs were of the IgG isotype and carried a kappa light chain. Their affinity constants were in the range of 7.4-15.1 x 10(-9) mol/l. Purified Lol p I kept its biological activity, as shown by its ability to induce histamine release by basophils of Lol p I-sensitive patients. The profiles of histamine release induced by either Lol p I or crude Lolium perenne extracts were comparable. This observation suggests that human IgE bound to basophils are polyspecific which has been confirmed by immunoblot and inhibition assay. Our data indicated also that Lol p I possesses a major allergenic epitope recognized by all human serum IgE tested. This epitope seems to be partially shared by those recognized by the three MAbs. Finally, preincubation of Lol p I with either one of the Mabs did not affect significantly the basophil-histamine release induced by the purified allergen. This suggests that Lol p I possesses allergenic sites other than the one shared by MAbs and IgE Abs.

  13. Generation of HER2 monoclonal antibodies using epitopes of a rabbit polyclonal antibody.

    Science.gov (United States)

    Hu, Francis Jingxin; Uhlen, Mathias; Rockberg, Johan

    2014-01-25

    One of the issues in using polyclonal antibodies is the limited amount of reagent available from an immunisation, leading to batch-to-batch variation and difficulties in obtaining the same antibody performance when the same antigen is re-immunised into several separate animals. This led to the development of hybridoma technology allowing, at least theoretically, for an unlimited production of a specific binder. Nevertheless, polyclonal antibodies are widely used in research and diagnostics and there exists a need for robust methods to convert a polyclonal antibody with good binding performance into a renewable monoclonal with identical or similar binding specificity. Here we have used precise information regarding the functional recognition sequence (epitope) of a rabbit polyclonal antibody with attractive binding characteristics as the basis for generation of a renewable mouse monoclonal antibody. First, the original protein fragment antigen was used for immunisation and generation of mouse hybridoma, without obtaining binders to the same epitope region. Instead a peptide designed using the functional epitope and structural information was synthesised and used for hybridoma production. Several of the monoclonal antibodies generated were found to have similar binding characteristics to those of the original polyclonal antibody. These monoclonal antibodies detected native HER2 on cell lines and were also able to stain HER2 in immunohistochemistry using xenografted mice, as well as human normal and cancer tissues. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Preparation and application of epitope magnetic molecularly imprinted polymers for enrichment of sulfonamide antibiotics in water.

    Science.gov (United States)

    Hu, Yufeng; Wang, Cheng; Li, Xiangdao; Liu, Lifen

    2017-10-01

    Sulfonamides, which are widely used synthetic antibiotics, are hydrophilic and stable. They can easily migrate into the environment and aquatic animals, and increase the risk of cancer, drug resistance, and allergic symptoms if consumed by humans. Here, we developed an epitope magnetic imprinting approach to enrich multiple sulfonamide antibiotics from a water sample. Epitope magnetic molecularly imprinted polymers (EMMIPs) were prepared by free-radical polymerization using vinyl-functioned Fe 3 O 4 as a core, sulfanilamide (SA) as a dummy template, methacrylic acid as a functional monomer, and ethylene glycol dimethacrylate as a cross-linker. The performance of the EMMIPs was first evaluated by rebinding SA, and then an adsorption experiment was conducted to assess the extraction of multiple sulfonamide antibiotics containing the SA group. The binding experiments showed that the EMMIPs reached adsorption equilibrium in only 5 min with adsorption of SA at 2040 μg/g, compared with just 462 μg/g for the epitope magnetic non-imprinted polymers. EMMIPs were combined with HPLC for the detection of six sulfonamide antibiotics in surface water samples. The recoveries ranged from 79.3 to 92.4% and the relative standard deviations from 0.9 to 7.3%. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Epitope Sequences in Dengue Virus NS1 Protein Identified by Monoclonal Antibodies

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    Leticia Barboza Rocha

    2017-10-01

    Full Text Available Dengue nonstructural protein 1 (NS1 is a multi-functional glycoprotein with essential functions both in viral replication and modulation of host innate immune responses. NS1 has been established as a good surrogate marker for infection. In the present study, we generated four anti-NS1 monoclonal antibodies against recombinant NS1 protein from dengue virus serotype 2 (DENV2, which were used to map three NS1 epitopes. The sequence 193AVHADMGYWIESALNDT209 was recognized by monoclonal antibodies 2H5 and 4H1BC, which also cross-reacted with Zika virus (ZIKV protein. On the other hand, the sequence 25VHTWTEQYKFQPES38 was recognized by mAb 4F6 that did not cross react with ZIKV. Lastly, a previously unidentified DENV2 NS1-specific epitope, represented by the sequence 127ELHNQTFLIDGPETAEC143, is described in the present study after reaction with mAb 4H2, which also did not cross react with ZIKV. The selection and characterization of the epitope, specificity of anti-NS1 mAbs, may contribute to the development of diagnostic tools able to differentiate DENV and ZIKV infections.

  16. Collaborative enhancement of antibody binding to distinct PECAM-1 epitopes modulates endothelial targeting.

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    Ann-Marie Chacko

    Full Text Available Antibodies to platelet endothelial cell adhesion molecule-1 (PECAM-1 facilitate targeted drug delivery to endothelial cells by "vascular immunotargeting." To define the targeting quantitatively, we investigated the endothelial binding of monoclonal antibodies (mAbs to extracellular epitopes of PECAM-1. Surprisingly, we have found in human and mouse cell culture models that the endothelial binding of PECAM-directed mAbs and scFv therapeutic fusion protein is increased by co-administration of a paired mAb directed to an adjacent, yet distinct PECAM-1 epitope. This results in significant enhancement of functional activity of a PECAM-1-targeted scFv-thrombomodulin fusion protein generating therapeutic activated Protein C. The "collaborative enhancement" of mAb binding is affirmed in vivo, as manifested by enhanced pulmonary accumulation of intravenously administered radiolabeled PECAM-1 mAb when co-injected with an unlabeled paired mAb in mice. This is the first demonstration of a positive modulatory effect of endothelial binding and vascular immunotargeting provided by the simultaneous binding a paired mAb to adjacent distinct epitopes. The "collaborative enhancement" phenomenon provides a novel paradigm for optimizing the endothelial-targeted delivery of therapeutic agents.

  17. Characterization of an Immunodominant Epitope in the Endodomain of the Coronavirus Membrane Protein

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    Hui Dong

    2016-12-01

    Full Text Available The coronavirus membrane (M protein acts as a dominant immunogen and is a major player in virus assembly. In this study, we prepared two monoclonal antibodies (mAbs; 1C3 and 4C7 directed against the transmissible gastroenteritis virus (TGEV M protein. The 1C3 and 4C7 mAbs both reacted with the native TGEV M protein in western blotting and immunofluorescence (IFA assays. Two linear epitopes, 243YSTEART249 (1C3 and 243YSTEARTDNLSEQEKLLHMV262 (4C7, were identified in the endodomain of the TGEV M protein. The 1C3 mAb can be used for the detection of the TGEV M protein in different assays. An IFA method for the detection of TGEV M protein was optimized using mAb 1C3. Furthermore, the ability of the epitope identified in this study to stimulate antibody production was also evaluated. An immunodominant epitope in the TGEV membrane protein endodomain was identified. The results of this study have implications for further research on TGEV replication.

  18. Selective memory retrieval can impair and improve retrieval of other memories.

    Science.gov (United States)

    Bäuml, Karl-Heinz T; Samenieh, Anuscheh

    2012-03-01

    Research from the past decades has shown that retrieval of a specific memory (e.g., retrieving part of a previous vacation) typically attenuates retrieval of other memories (e.g., memories for other details of the event), causing retrieval-induced forgetting. More recently, however, it has been shown that retrieval can both attenuate and aid recall of other memories (K.-H. T. Bäuml & A. Samenieh, 2010). To identify the circumstances under which retrieval aids recall, the authors examined retrieval dynamics in listwise directed forgetting, context-dependent forgetting, proactive interference, and in the absence of any induced memory impairment. They found beneficial effects of selective retrieval in listwise directed forgetting and context-dependent forgetting but detrimental effects in all the other conditions. Because context-dependent forgetting and listwise directed forgetting arguably reflect impaired context access, the results suggest that memory retrieval aids recall of memories that are subject to impaired context access but attenuates recall in the absence of such circumstances. The findings are consistent with a 2-factor account of memory retrieval and suggest the existence of 2 faces of memory retrieval. 2012 APA, all rights reserved

  19. Data Fusion in Information Retrieval

    CERN Document Server

    Wu, Shengli

    2012-01-01

    The technique of data fusion has been used extensively in information retrieval due to the complexity and diversity of tasks involved such as web and social networks, legal, enterprise, and many others. This book presents both a theoretical and empirical approach to data fusion. Several typical data fusion algorithms are discussed, analyzed and evaluated. A reader will find answers to the following questions, among others: -          What are the key factors that affect the performance of data fusion algorithms significantly? -          What conditions are favorable to data fusion algorithms? -          CombSum and CombMNZ, which one is better? and why? -          What is the rationale of using the linear combination method? -          How can the best fusion option be found under any given circumstances?

  20. Retrieval-practice task affects relationship between working memory capacity and retrieval-induced forgetting.

    Science.gov (United States)

    Storm, Benjamin C; Bui, Dung C

    2016-11-01

    Retrieving a subset of items from memory can cause forgetting of other items in memory, a phenomenon referred to as retrieval-induced forgetting (RIF). Individuals who exhibit greater amounts of RIF have been shown to also exhibit superior working memory capacity (WMC) and faster stop-signal reaction times (SSRTs), results which have been interpreted as suggesting that RIF reflects an inhibitory process that is mediated by the processes of executive control. Across four experiments, we sought to further elucidate this issue by manipulating the way in which participants retrieved items during retrieval practice and examining how the resulting effects of forgetting correlated with WMC (Experiments 1-3) and SSRT (Experiment 4). Significant correlations were observed when participants retrieved items from an earlier study phase (within-list retrieval practice), but not when participants generated items from semantic memory (extra-list retrieval practice). These results provide important new insight into the role of executive-control processes in RIF.