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Sample records for involves discrete epitopes

  1. Surface targeting of the dopamine transporter involves discrete epitopes in the distal C terminus but does not require canonical PDZ domain interactions

    DEFF Research Database (Denmark)

    Bjerggaard, Christian; Fog, Jacob U; Hastrup, Hanne

    2004-01-01

    are indispensable for proper targeting, PDZ domain interactions are not required. By progressive substitutions with beta2-adrenergic receptor sequence, and by triple-alanine substitutions in the hDAT C terminus, we examined the importance of epitopes preceding the LKV motif. Substitution of RHW(615...... deletion of this motif, hDAT was retained in the endoplasmic reticulum (ER) of human embryonic kidney (HEK) 293 and Neuro2A cells, suggesting that PDZ domain interactions might be critical for hDAT targeting. Nonetheless, substitution of LKV with SLL, the type 1 PDZ-binding sequence from the beta2......-adrenergic receptor, did not disrupt plasma membrane targeting. Moreover, the addition of an alanine to the hDAT C terminus (+Ala), resulting in an LKVA termination sequence, or substitution of LKV with alanines (3xAla_618-620) prevented neither plasma membrane targeting nor targeting into sprouting neurites...

  2. Targeting of the Dopamine Transporter Involves Discrete Epitopes in the Distal C Terminus But Does Not Require Canonical PDZ Domain Interactions

    DEFF Research Database (Denmark)

    Bjerggaard(Vægter), Christian; Fog, Jacob Ulrik; Hastrup, Hanne

    2004-01-01

    are indispensable for proper targeting, PDZ domain interactions are not required. By progressive substitutions with beta2-adrenergic receptor sequence, and by triple-alanine substitutions in the hDAT C terminus, we examined the importance of epitopes preceding the LKV motif. Substitution of RHW(615...... deletion of this motif, hDAT was retained in the endoplasmic reticulum (ER) of human embryonic kidney (HEK) 293 and Neuro2A cells, suggesting that PDZ domain interactions might be critical for hDAT targeting. Nonetheless, substitution of LKV with SLL, the type 1 PDZ-binding sequence from the beta2......-adrenergic receptor, did not disrupt plasma membrane targeting. Moreover, the addition of an alanine to the hDAT C terminus (+Ala), resulting in an LKVA termination sequence, or substitution of LKV with alanines (3xAla_618-620) prevented neither plasma membrane targeting nor targeting into sprouting neurites...

  3. Microbial transglutaminases generate T cell stimulatory epitopes involved in celiac disease

    NARCIS (Netherlands)

    Dekking, E.H.A.; Veelen, P.A. van; Ru, A. de; Kooy-Winkelaar, E.M.C.; Gröneveld, T.; Nieuwenhuizen, W.F.; Koning, F.

    2008-01-01

    Celiac disease (CD) is a permanent intolerance to gluten. In CD patients, gluten peptides cause an inflammation in the small intestine leading to tissue damage. Tissue transglutaminase (tTG) is an enzyme involved in the repair of damaged tissue by crosslinking of extracellular matrix proteins. Under

  4. Bifurcation and complex dynamics of a discrete-time predator-prey system involving group defense

    Directory of Open Access Journals (Sweden)

    S. M. Sohel Rana

    2015-09-01

    Full Text Available In this paper, we investigate the dynamics of a discrete-time predator-prey system involving group defense. The existence and local stability of positive fixed point of the discrete dynamical system is analyzed algebraically. It is shown that the system undergoes a flip bifurcation and a Neimark-Sacker bifurcation in the interior of R+2 by using bifurcation theory. Numerical simulation results not only show the consistence with the theoretical analysis but also display the new and interesting dynamical behaviors, including phase portraits, period-7, 20-orbits, attracting invariant circle, cascade of period-doubling bifurcation from period-20 leading to chaos, quasi-periodic orbits, and sudden disappearance of the chaotic dynamics and attracting chaotic set. The Lyapunov exponents are numerically computed to characterize the complexity of the dynamical behaviors.

  5. PERFORMANCE EVALUATION OF DISCRETE EVENT SYSTEMS INVOLVING HENSTOCK-KURZWEIL INTEGRAL

    Institute of Scientific and Technical Information of China (English)

    Calin CIUFUDEAN; Bianca SATCO

    2009-01-01

    This paper presents a study on the performance of flexible manufacturing systems (FMSs), by using discrete event system (DES) models, considering resource losses modelled by a parameter entitled coverage factor. We conclude that the resources cell loss distribution between the tasks of a FSM is a real function that cannot be integrated, in order to calculate its primitive, in the classical sense of Riemann or Lebesgue, but only in the sense of Henstock-Kurzweil integral. Our result allows one to study more general processes where highly oscillatory functions occur. The method used to deduce the function describing the resources cell loss distribution is compared with a classical method related in the literature, respectively rational interpolants. An example has been constructed to emphasize what we believe to be, new approaches.

  6. SOLUTIONS TO DISCRETE MULTIPARAMETER PERIODIC BOUNDARY VALUE PROBLEMS INVOLVING THE p-LAPLACIAN VIA CRITICAL POINT THEORY

    Institute of Scientific and Technical Information of China (English)

    高承华

    2014-01-01

    In this paper, we consider the existence of three nontrivial solutions for a discrete non-linear multiparameter periodic problem involving the p-Laplacian. By using the similar method for the Dirichlet boundary value problems in [G. Bonanno and P. Candito, Appl. Anal., 88(4) (2009), pp. 605-616], we construct two new strong maximum principles and obtain that the boundary value problem has three positive solutions for λ and µ in some suitable intervals. The approaches we use are the critical point theory.

  7. Discrete event simulation for petroleum transfers involving harbors, refineries and pipelines

    Energy Technology Data Exchange (ETDEWEB)

    Martins, Marcella S.R.; Lueders, Ricardo; Delgado, Myriam R.B.S. [Universidade Tecnologica Federal do Parana (UTFPR), Curitiba, PR (Brazil)

    2009-07-01

    Nowadays a great effort has been spent by companies to improve their logistics in terms of programming of events that affect production and distribution of products. In this case, simulation can be a valuable tool for evaluating different behaviors. The objective of this work is to build a discrete event simulation model for scheduling of operational activities in complexes containing one harbor and two refineries interconnected by a pipeline infrastructure. The model was developed in Arena package, based on three sub-models that control pier allocation, loading of tanks, and transfers to refineries through pipelines. Preliminary results obtained for a given control policy, show that profit can be calculated by taking into account many parameters such as oil costs on ships, pier using, over-stay of ships and interface costs. Such problem has already been considered in the literature but using different strategies. All these factors should be considered in a real-world operation where decision making tools are necessary to obtain high returns. (author)

  8. 葡萄膜炎自身抗原表位的研究%Studies on autoantigenic epitopes involving in the development of uveitis

    Institute of Scientific and Technical Information of China (English)

    赵长霖; 杨培增

    2008-01-01

    It has been proposed that a few kinds of autoantigens imitate the development of autoimmune uveitis while the immunodominant epitopes of these antigens have not been identified.Researches on retinal S-antigen and interphotoreceptor retinoid-binding protein as well as tyrosinase-related protein epitopes mapping have shown that each autoantigen contains several immunopathogenic epitopes and immunogenic epitopes and that the immunopathogenic sites ale not coincident with the immunogenic epitopes.The reactivity of peripheral blood mononucleal cells from uveitis patients against each autoantigenic epitopes displays high heterogeneity.Epitopes spreading phenomenon has been disclosed in human uveifis study and reinforced in animal experiments.Study on this epitope spreading may contribute to our understanding of immune tolerance induced by different epitopes in the treatment of autoimmune disease including uveifis.%多种抗原参与自身免疫性葡萄膜炎的发生发展,但是这些抗原的免疫优势表位尚不明确.针对视网膜S抗原等葡萄膜炎自身抗原免疫表位的研究显示,每种抗原蛋白均存在多个可诱导易感动物葡萄膜炎发作的致病位点,每种抗原均存在多个可诱导葡萄膜炎患者产生体外细胞免疫反应的免疫原性表位,同种抗原的致病表位和免疫原性表位不完全一致.葡萄膜炎患者对于各抗原表位肽的反应性显示出高度异质性,表现为不同患者对不同肽发生反应和同一例患者在不同时期对不同肽发生反应.由此,提出了葡萄膜炎表位扩展现象,并利用动物实验得以证实.表位扩展可能是自身免疫反应的防御现象,但是自身免疫反应的多样化同时又对抗原特异性耐受疗法提出了挑战.

  9. Involving patients in primary care consultations: assessing preferences using discrete choice experiments.

    NARCIS (Netherlands)

    Longo, M.F.; Cohen, D.R.; Hood, K.; Edwards, A.; Robling, M.; Elwyn, G.; Russell, I.T.

    2006-01-01

    BACKGROUND: Shared decision making (SDM) involves patients and doctors contributing as partners to treatment decisions. It is not known whether or to what extent SDM contributes to the welfare arising from a consultation, and how important this contribution is relative to other attributes of a consu

  10. A combinatorial mutagenesis approach for functional epitope mapping on phage-displayed target antigen: application to antibodies against epidermal growth factor.

    Science.gov (United States)

    Infante, Yanelys Cabrera; Pupo, Amaury; Rojas, Gertrudis

    2014-01-01

    Although multiple different procedures to characterize the epitopes recognized by antibodies have been developed, site-directed mutagenesis remains the method of choice to define the energetic contribution of antigen residues to binding. These studies are useful to identify critical residues and to delineate functional maps of the epitopes. However, they tend to underestimate the roles of residues that are not critical for binding on their own, but contribute to the formation of the target epitope in an additive, or even cooperative, way. Mapping antigenic determinants with a diffuse energetic landscape, which establish multiple individually weak interactions with the antibody paratope, resulting in high affinity and specificity recognition of the epitope as a whole, is thus technically challenging. The current work was aimed at developing a combinatorial strategy to overcome the limitations of site-directed mutagenesis, relying on comprehensive randomization of discrete antigenic regions within phage-displayed antigen libraries. Two model antibodies recognizing epidermal growth factor were used to validate the mapping platform. Abrogation of antibody recognition due to the introduction of simultaneous replacements was able to show the involvement of particular amino acid clusters in epitope formation. The abundance of some of the original residues (or functionally equivalent amino acids sharing their physicochemical properties) among the set of mutated antigen variants selected on a given antibody highlighted their contributions and allowed delineation of a detailed functional map of the corresponding epitope. The use of the combinatorial approach could be expanded to map the interactions between other antigens/antibodies.

  11. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site.

    Directory of Open Access Journals (Sweden)

    Ema T Crooks

    2015-05-01

    Full Text Available Eliciting broad tier 2 neutralizing antibodies (nAbs is a major goal of HIV-1 vaccine research. Here we investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit nAbs. Unusually potent nAb titers developed in 2 of 8 rabbits immunized with virus-like particles (VLPs expressing trimers (trimer VLP sera and in 1 of 20 rabbits immunized with DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. Specifically, trimer VLP sera took advantage of the unusual absence of a glycan at residue 197 (present in 98.7% of Envs. Intriguingly, removing the N197 glycan (with no loss of tier 2 phenotype rendered 50% or 16.7% (n = 18 of clade B tier 2 isolates sensitive to the two trimer VLP sera, showing broad neutralization via the surface masked by the N197 glycan. Neutralizing sera targeted epitopes that overlap with the CD4 binding site, consistent with the role of the N197 glycan in a putative "glycan fence" that limits access to this region. A bioinformatics analysis suggested shared features of one of the trimer VLP sera and monoclonal antibody PG9, consistent with its trimer-dependency. The neutralizing DNA trimer serum took advantage of the absence of a glycan at residue 230, also proximal to the CD4 binding site and suggesting an epitope similar to that of monoclonal antibody 8ANC195, albeit lacking tier 2 breadth. Taken together, our data show for the first time that strain-specific holes in the glycan fence can allow the development of tier 2 neutralizing antibodies to native spikes. Moreover, cross-neutralization can occur in the absence of protecting glycan. Overall, our observations provide new insights that may inform the future development of a neutralizing antibody vaccine.

  12. Intramolecular epitope spreading in Heymann nephritis.

    Science.gov (United States)

    Shah, Pallavi; Tramontano, Alfonso; Makker, Sudesh P

    2007-12-01

    Immunization with megalin induces active Heymann nephritis, which reproduces features of human idiopathic membranous glomerulonephritis. Megalin is a complex immunological target with four discrete ligand-binding domains (LBDs) that may contain epitopes to which pathogenic autoantibodies are directed. Recently, a 236-residue N-terminal fragment, termed "L6," that spans the first LBD was shown to induce autoantibodies and severe disease. We used this model to examine epitope-specific contributions to pathogenesis. Sera obtained from rats 4 weeks after immunization with L6 demonstrated reactivity only with the L6 fragment on Western blot, whereas sera obtained after 8 weeks demonstrated reactivity with all four recombinant fragments of interest (L6 and LBDs II, III, and IV). We demonstrated that the L6 immunogen does not contain the epitopes responsible for the reactivity to the LBD fragments. Therefore, the appearance of antibodies directed at LBD fragments several weeks after the primary immune response suggests intramolecular epitope spreading. In vivo, we observed a temporal association between increased proteinuria and the appearance of antibodies to LBD fragments. These data implicate B cell epitope spreading in antibody-mediated pathogenesis of active Heymann nephritis, a model that should prove valuable for further study of autoimmune dysregulation.

  13. Repeated epitope in the recombinant epitope-peptide could enhance ELDKWA-epitope-specific antibody response

    Institute of Scientific and Technical Information of China (English)

    LIU Zuqiang; WANG Zuguang; CHEN Yinghua

    2005-01-01

    Based on the hypothesis suggested by us that epitope-vaccine may be a new strategy against HIV mutation, we have studied several neutralizing epitopes on HIV envelope proteins. However we do not know whether a repeated epitope in a recombinant epitope-peptide can enhance epitope-specific antibody response or not. ELDKWA-epitope (aa669-674) on the C-domain of HIV-1 gp41 is a neutralizing epitope defined by the monoclonal antibody (mAb) 2F5 with broad neutralizing activity. In this study, we designed and prepared a series of the recombinant epitope-peptides bearing 1, 4 and 8 copies of ELDKWA-epitope respectively. In the comparison of the antisera induced by the three recombinant antigens, an obviously increased titre of ELDKWA-epitope-specific antibody was observed in the case of four and eight repeated epitopes. In flow cytometry analysis, the epitope-specific antibodies in both antisera showed stronger activity to bind the transfected CHO-WT cells that stably express HIV-1 envelope glycoprotein on the cell surfaces. These experimental results indicated that repeated epitope in the recombinant epitope-peptide could enhance ELDKWA-epitope-specific antibody response, which could contribute to designing an effective recombinant epitope-vaccine.

  14. The Immune Epitope Database: How Data Are Entered and Retrieved

    National Research Council Canada - National Science Library

    Ward Fleri; Kerrie Vaughan; Nima Salimi; Randi Vita; Bjoern Peters; Alessandro Sette

    2017-01-01

    .... It contains T cell, B cell, MHC binding, and MHC ligand elution experiments. Its data are curated primarily from the published literature and also include direct submissions from researchers involved in epitope discovery...

  15. Immune-driven adaptation of hepatitis B virus genotype D involves preferential alteration in B-cell epitopes and replicative attenuation--an insight from human immunodeficiency virus/hepatitis B virus coinfection.

    Science.gov (United States)

    Mondal, R K; Khatun, M; Ghosh, S; Banerjee, P; Datta, S; Sarkar, S; Saha, B; Santra, A; Banerjee, S; Chowdhury, A; Datta, S

    2015-07-01

    An important driving force behind the sequence diversity of hepatitis B virus (HBV) is viral adaptation to host immune responses. To gain an insight into the impact of host immunity on genetic diversification and properties of HBV, we characterized HBV of genotype D from treatment-naive hepatitis B e antigen-positive (EP) and hepatitis B e antigen-negative (EN) patients with chronic hepatitis B (CHB), where HBV is under stronger immune pressure, with that of HBV derived from human immunodeficiency virus (HIV)/HBV-coinfected individuals, where HIV infection has significantly weakened the immune system. Full-length sequence analysis showed that HBV heterogeneity was most extensive in EN-CHB followed by EP-CHB and HIV/HBV coinfection. The relative magnitude of non-synonymous changes within B-cell epitopes was greater than that in T-cell epitopes of HBV open reading frames (ORFs) in both EP-CHB and EN-CHB. Nine amino acid substitutions were identified in B-cell epitopes and one in a T-cell epitope of HBV in EN-CHB, most of which resulted in altered hydrophobicities, as determined using the Kyte and Doolittle method, relative to wild-type residues found in HBV from the HIV-positive group. Additionally, 19 substitutions occurred at significantly higher frequencies in non-epitope regions of HBV ORF-P in EN-CHB than HIV/HBV-coinfected patients. In vitro replication assay demonstrated that the substitutions, particularly in reverse transcriptase and RNaseH domains of ORF-P, resulted in a decline in replication capacity of HBV. Hence, our results indicate that HBV adapts to increasing immune pressure through preferential mutations in B-cell epitopes and by replicative attenuation. The viral epitopes linked to immune response identified in this study bear important implications for future HBV vaccine studies.

  16. Pearls of Discrete Mathematics

    CERN Document Server

    Erickson, Martin

    2009-01-01

    Presents methods for solving counting problems and other types of problems that involve discrete structures. This work illustrates the relationship of these structures to algebra, geometry, number theory and combinatorics. It addresses topics such as information and game theories

  17. Cocrystal Structures of Antibody N60-i3 and Antibody JR4 in Complex with gp120 Define More Cluster A Epitopes Involved in Effective Antibody-Dependent Effector Function against HIV-1.

    Science.gov (United States)

    Gohain, Neelakshi; Tolbert, William D; Acharya, Priyamvada; Yu, Lei; Liu, Tongyun; Zhao, Pingsen; Orlandi, Chiara; Visciano, Maria L; Kamin-Lewis, Roberta; Sajadi, Mohammad M; Martin, Loïc; Robinson, James E; Kwong, Peter D; DeVico, Anthony L; Ray, Krishanu; Lewis, George K; Pazgier, Marzena

    2015-09-01

    Accumulating evidence indicates a role for Fc receptor (FcR)-mediated effector functions of antibodies, including antibody-dependent cell-mediated cytotoxicity (ADCC), in prevention of human immunodeficiency virus type 1 (HIV-1) acquisition and in postinfection control of viremia. Consequently, an understanding of the molecular basis for Env epitopes that constitute effective ADCC targets is of fundamental interest for humoral anti-HIV-1 immunity and for HIV-1 vaccine design. A substantial portion of FcR effector function of potentially protective anti-HIV-1 antibodies is directed toward nonneutralizing, transitional, CD4-inducible (CD4i) epitopes associated with the gp41-reactive region of gp120 (cluster A epitopes). Our previous studies defined the A32-like epitope within the cluster A region and mapped it to the highly conserved and mobile layers 1 and 2 of the gp120 inner domain within the C1-C2 regions of gp120. Here, we elucidate additional cluster A epitope structures, including an A32-like epitope, recognized by human monoclonal antibody (MAb) N60-i3, and a hybrid A32-C11-like epitope, recognized by rhesus macaque MAb JR4. These studies define for the first time a hybrid A32-C11-like epitope and map it to elements of both the A32-like subregion and the seven-layered β-sheet of the gp41-interactive region of gp120. These studies provide additional evidence that effective antibody-dependent effector function in the cluster A region depends on precise epitope targeting--a combination of epitope footprint and mode of antibody attachment. All together these findings help further an understanding of how cluster A epitopes are targeted by humoral responses. HIV/AIDS has claimed the lives of over 30 million people. Although antiretroviral drugs can control viral replication, no vaccine has yet been developed to prevent the spread of the disease. Studies of natural HIV-1 infection, simian immunodeficiency virus (SIV)- or simian-human immunodeficiency virus (SHIV

  18. Discrete Mathematics

    DEFF Research Database (Denmark)

    Sørensen, John Aasted

    2011-01-01

    The objectives of Discrete Mathematics (IDISM2) are: The introduction of the mathematics needed for analysis, design and verification of discrete systems, including the application within programming languages for computer systems. Having passed the IDISM2 course, the student will be able...... to accomplish the following: -Understand and apply formal representations in discrete mathematics. -Understand and apply formal representations in problems within discrete mathematics. -Understand methods for solving problems in discrete mathematics. -Apply methods for solving problems in discrete mathematics......; construct a finite state machine for a given application. Apply these concepts to new problems. The teaching in Discrete Mathematics is a combination of sessions with lectures and students solving problems, either manually or by using Matlab. Furthermore a selection of projects must be solved and handed...

  19. Epitope prediction methods

    DEFF Research Database (Denmark)

    Karosiene, Edita

    on machine learning techniques. Several MHC class I binding prediction algorithms have been developed and due to their high accuracy they are used by many immunologists to facilitate the conventional experimental process of epitope discovery. However, the accuracy of these methods depends on data defining...... the NetMHCIIpan-3.0 predictor based on artificial neural networks, which is capable of giving binding affinities to any human MHC class II molecule. Chapter 4 of this thesis gives an overview of bioinformatics tools developed by the Immunological Bioinformatics group at Center for Biological Sequence...

  20. 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:MH...

  1. Discrete Breathers

    CERN Document Server

    Flach, S

    1998-01-01

    Nonlinear classical Hamiltonian lattices exhibit generic solutions in the form of discrete breathers. These solutions are time-periodic and (typically exponentially) localized in space. The lattices exhibit discrete translational symmetry. Discrete breathers are not confined to certain lattice dimensions. Necessary ingredients for their occurence are the existence of upper bounds on the phonon spectrum (of small fluctuations around the groundstate) of the system as well as the nonlinearity in the differential equations. We will present existence proofs, formulate necessary existence conditions, and discuss structural stability of discrete breathers. The following results will be also discussed: the creation of breathers through tangent bifurcation of band edge plane waves; dynamical stability; details of the spatial decay; numerical methods of obtaining breathers; interaction of breathers with phonons and electrons; movability; influence of the lattice dimension on discrete breather properties; quantum lattic...

  2. Discrete Stein characterizations and discrete information distances

    CERN Document Server

    Ley, Christophe

    2012-01-01

    We construct two different Stein characterizations of discrete distributions and use these to provide a natural connection between Stein characterizations for discrete distributions and discrete information functionals.

  3. Discrete Mathematics

    DEFF Research Database (Denmark)

    Sørensen, John Aasted

    2010-01-01

    The introduction of the mathematics needed for analysis, design and verification of discrete systems, including applications within programming languages for computer systems. Course sessions and project work. Semester: Spring 2010 Ectent: 5 ects Class size: 18......The introduction of the mathematics needed for analysis, design and verification of discrete systems, including applications within programming languages for computer systems. Course sessions and project work. Semester: Spring 2010 Ectent: 5 ects Class size: 18...

  4. Discrete Mathematics

    DEFF Research Database (Denmark)

    Sørensen, John Aasted

    2010-01-01

    The introduction of the mathematics needed for analysis, design and verification of discrete systems, including applications within programming languages for computer systems. Course sessions and project work. Semester: Autumn 2010 Ectent: 5 ects Class size: 15......The introduction of the mathematics needed for analysis, design and verification of discrete systems, including applications within programming languages for computer systems. Course sessions and project work. Semester: Autumn 2010 Ectent: 5 ects Class size: 15...

  5. Intact Transition Epitope Mapping (ITEM)

    Science.gov (United States)

    Yefremova, Yelena; Opuni, Kwabena F. M.; Danquah, Bright D.; Thiesen, Hans-Juergen; Glocker, Michael O.

    2017-08-01

    Intact transition epitope mapping (ITEM) enables rapid and accurate determination of protein antigen-derived epitopes by either epitope extraction or epitope excision. Upon formation of the antigen peptide-containing immune complex in solution, the entire mixture is electrosprayed to translate all constituents as protonated ions into the gas phase. There, ions from antibody-peptide complexes are separated from unbound peptide ions according to their masses, charges, and shapes either by ion mobility drift or by quadrupole ion filtering. Subsequently, immune complexes are dissociated by collision induced fragmentation and the ion signals of the "complex-released peptides," which in effect are the epitope peptides, are recorded in the time-of-flight analyzer of the mass spectrometer. Mixing of an antibody solution with a solution in which antigens or antigen-derived peptides are dissolved is, together with antigen proteolysis, the only required in-solution handling step. Simplicity of sample handling and speed of analysis together with very low sample consumption makes ITEM faster and easier to perform than other experimental epitope mapping methods.

  6. Discrete Chaos

    CERN Document Server

    Waelbroeck, H

    1999-01-01

    We propose a theory of deterministic chaos for discrete systems, based on their representations in symbolic history spaces Ømega. These are spaces of semi-infinite sequences, as the one-sided shift spaces, but endowed with a more general topology which we call a semicausal topology. We show that define metrical properties, including the correlation dimension of the attractor. Examples are considered: Asymmetric neural networks and random cellular automata are not chaotic. A neural network model with memory, on the other hand, does appear to be an example of discrete chaos.

  7. Discrete mechanics

    CERN Document Server

    Caltagirone, Jean-Paul

    2014-01-01

    This book presents the fundamental principles of mechanics to re-establish the equations of Discrete Mechanics. It introduces physics and thermodynamics associated to the physical modeling.  The development and the complementarity of sciences lead to review today the old concepts that were the basis for the development of continuum mechanics. The differential geometry is used to review the conservation laws of mechanics. For instance, this formalism requires a different location of vector and scalar quantities in space. The equations of Discrete Mechanics form a system of equations where the H

  8. Territorial discretion

    Directory of Open Access Journals (Sweden)

    Augusto Hernández Vidal

    2011-12-01

    Full Text Available In order to strengthen the concept of municipal autonomy, this essay proposes an extensive interpretation of administrative discretion. Discretion is the exercise of free judgment given by law to authorities for performing official acts. This legislative technique seems to be suitable whenever the legislative is intended to legislate over the essential core of municipal autonomy. This way, an eventual abuse of that autonomy could be avoided, for the disproportional restriction of the local faculty to oversee the local issues. This alternative is presented as a tool to provide with dynamism the performing of administrative activities as well, aiming to assimilate public administration new practices.

  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. Introductory discrete mathematics

    CERN Document Server

    Balakrishnan, V K

    2010-01-01

    This concise text offers an introduction to discrete mathematics for undergraduate students in computer science and mathematics. Mathematics educators consider it vital that their students be exposed to a course in discrete methods that introduces them to combinatorial mathematics and to algebraic and logical structures focusing on the interplay between computer science and mathematics. The present volume emphasizes combinatorics, graph theory with applications to some stand network optimization problems, and algorithms to solve these problems.Chapters 0-3 cover fundamental operations involv

  11. 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...

  12. Discrete Mathematics

    DEFF Research Database (Denmark)

    Sørensen, John Aasted

    2011-01-01

    examples on regular languages. Apply these concepts to new problems. Finite state machines: Define a finite state machine as a 6-tuble; describe simple finite state machines by tables and graphs; pattern recognition by finite state machines; minimizing the number of states in a finite state machine......The objectives of Discrete Mathematics (IDISM2) are: The introduction of the mathematics needed for analysis, design and verification of discrete systems, including the application within programming languages for computer systems. Having passed the IDISM2 course, the student will be able...... of natural numbers. Apply these concepts to new problems. Division and factorizing: Define a prime number and apply Euclid´s algorithm for factorizing an integer. Regular languages: Define a language from the elements of a set; define a regular language; form strings from a regular language; construct...

  13. Antibody protection reveals extended epitopes on the human TSH receptor.

    Directory of Open Access Journals (Sweden)

    Rauf Latif

    Full Text Available Stimulating, and some blocking, antibodies to the TSH receptor (TSHR have conformation-dependent epitopes reported to involve primarily the leucine rich repeat region of the ectodomain (LRD. However, successful crystallization of TSHR residues 22-260 has omitted important extracellular non-LRD residues including the hinge region which connects the TSHR ectodomain to the transmembrane domain and which is involved in ligand induced signal transduction. The aim of the present study, therefore, was to determine if TSHR antibodies (TSHR-Abs have non-LRD binding sites outside the LRD. To obtain this information we employed the method of epitope protection in which we first protected TSHR residues 1-412 with intact TSHR antibodies and then enzymatically digested the unprotected residues. Those peptides remaining were subsequently delineated by mass spectrometry. Fourteen out of 23 of the reported stimulating monoclonal TSHR-Ab crystal contact residues were protected by this technique which may reflect the higher binding energies of certain residues detected in this approach. Comparing the protected epitopes of two stimulating TSHR-Abs we found both similarities and differences but both antibodies also contacted the hinge region and the amino terminus of the TSHR following the signal peptide and encompassing cysteine box 1 which has previously been shown to be important for TSH binding and activation. A monoclonal blocking TSHR antibody revealed a similar pattern of binding regions but the residues that it contacted on the LRD were again distinct. These data demonstrated that conformationally dependent TSHR-Abs had epitopes not confined to the LRDs but also incorporated epitopes not revealed in the available crystal structure. Furthermore, the data also indicated that in addition to overlapping contact regions within the LRD, there are unique epitope patterns for each of the antibodies which may contribute to their functional heterogeneity.

  14. Epitope mapping by epitope excision, hydrogen/deuterium exchange, and peptide-panning techniques combined with in silico analysis.

    Science.gov (United States)

    Clementi, Nicola; Mancini, Nicasio; Criscuolo, Elena; Cappelletti, Francesca; Clementi, Massimo; Burioni, Roberto

    2014-01-01

    The fine characterization of protective B cell epitopes plays a pivotal role in the development of novel vaccines. The development of epitope-based vaccines, in fact, cannot be possible without a clear definition of the antigenic regions involved in the binding between the protective antibody (Ab) and its molecular target. To achieve this result, different epitope-mapping approaches have been widely described (Clementi et al. Drug Discov Today 18(9-10):464-471, 2013). Nowadays, the best way to characterize an Ab bound region is still the resolution of Ab-antigen (Ag) co-crystal structure. Unfortunately, the crystallization approaches are not always feasible. However, different experimental strategies aimed to predict Ab-Ag interaction and followed by in silico analysis of the results may be good surrogate approaches to achieve this result. Here, we review few experimental techniques followed by the use of "basic" informatics tools for the analysis of the results.

  15. Collection of phage-peptide probes for HIV-1 immunodominant loop-epitope.

    Science.gov (United States)

    Palacios-Rodríguez, Yadira; Gazarian, Tatiana; Rowley, Merrill; Majluf-Cruz, Abraham; Gazarian, Karlen

    2007-02-01

    Early diagnosis and prevention of human immunodeficiency virus type-1 (HIV-1) infection, which remains a serious public health threat, is inhibited by the lack of reagents that elicit antiviral responses in the immune system. To create mimotopes (peptide models of epitopes) of the most immunodominant epitope, CSGKLIC, that occurs as a loop on the envelope gp41 glycoprotein and is a key participant in infection, we used phage-display technology involving biopanning of large random libraries with IgG of HIV-1-infected patients. Under the conditions used, library screening with IgG from patient serum was directed to the CSGKLIC epitope. Three rounds of selection converted a 12 mer library of 10(9) sequences into a population in which up to 79% of phage bore a family of CxxKxxC sequences ("x" designates a non-epitope amino acid). Twenty-one phage clones displaying the most frequently selected peptides were obtained and were shown to display the principal structural (sequence and conformational), antigenic and immunogenic features of the HIV-1 immunodominant loop-epitope. Notably, when the mixture of the phage mimotopes was injected into mice, it induced 2- to 3-fold higher titers of antibody to the HIV-1 epitope than could be induced from individual mimotopes. The described approach could be applicable for accurately reproducing HIV-1 epitope structural and immunological patterns by generation of specialized viral epitope libraries for use in diagnosis and therapy.

  16. Discrete optimization

    CERN Document Server

    Parker, R Gary

    1988-01-01

    This book treats the fundamental issues and algorithmic strategies emerging as the core of the discipline of discrete optimization in a comprehensive and rigorous fashion. Following an introductory chapter on computational complexity, the basic algorithmic results for the two major models of polynomial algorithms are introduced--models using matroids and linear programming. Further chapters treat the major non-polynomial algorithms: branch-and-bound and cutting planes. The text concludes with a chapter on heuristic algorithms.Several appendixes are included which review the fundamental ideas o

  17. Discrete transforms

    CERN Document Server

    Firth, Jean M

    1992-01-01

    The analysis of signals and systems using transform methods is a very important aspect of the examination of processes and problems in an increasingly wide range of applications. Whereas the initial impetus in the development of methods appropriate for handling discrete sets of data occurred mainly in an electrical engineering context (for example in the design of digital filters), the same techniques are in use in such disciplines as cardiology, optics, speech analysis and management, as well as in other branches of science and engineering. This text is aimed at a readership whose mathematical background includes some acquaintance with complex numbers, linear differen­ tial equations, matrix algebra, and series. Specifically, a familiarity with Fourier series (in trigonometric and exponential forms) is assumed, and an exposure to the concept of a continuous integral transform is desirable. Such a background can be expected, for example, on completion of the first year of a science or engineering degree cour...

  18. Discrete torsion defects

    CERN Document Server

    Brunner, Ilka; Plencner, Daniel

    2014-01-01

    Orbifolding two-dimensional quantum field theories by a symmetry group can involve a choice of discrete torsion. We apply the general formalism of `orbifolding defects' to study and elucidate discrete torsion for topological field theories. In the case of Landau-Ginzburg models only the bulk sector had been studied previously, and we re-derive all known results. We also introduce the notion of `projective matrix factorisations', show how they naturally describe boundary and defect sectors, and we further illustrate the efficiency of the defect-based approach by explicitly computing RR charges. Roughly half of our results are not restricted to Landau-Ginzburg models but hold more generally, for any topological field theory. In particular we prove that for a pivotal bicategory, any two objects of its orbifold completion that have the same base are orbifold equivalent. Equivalently, from any orbifold theory (including those based on nonabelian groups) the original unorbifolded theory can be be obtained by orbifo...

  19. 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...

  20. Discretization of topological spaces

    OpenAIRE

    Amini, Massoud; Golestani, Nasser

    2014-01-01

    There are several compactification procedures in topology, but there is only one standard discretization, namely, replacing the original topology with the discrete topology. We give a notion of discretization which is dual (in categorical sense) to compactification and give examples of discretizations. Especially, a discretization functor from the category of $\\alpha$-scattered Stonean spaces to the category of discrete spaces is constructed which is the converse of the Stone-\\v{C}ech compact...

  1. Induction of multi-epitope specific antibodies against HIV-1 by multi-epitope vaccines

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Some neutralizing antibodies against HIV-1 envelope proteins were highly effective to inhibit the infection of different strains in vitro, and existed in the infected individuals with very low levels. We suggested multi-epitope-vaccine as a new strategy to increase levels of neutralizing antibodies and the abilities against HIV mutation in vivo. Two candidate multi-epitope-vaccines induced antibodies with predefined multi-epitope-specificity in rhesus macaque. These antibodies recognized corresponding neutralizing epitopes on epitope-peptides, gp41 peptides, V3 loop peptide, rsgp41 and rgp120. Besides, three candidate epitope-vaccines in combination (another kind of multi-epitopevaccines) showed similar potency to induce predefined multiple immune responses in rabbits. These results suggest that multi-epitope-vaccines may be a new strategy to induce multi-antiviral activities against HIV-1 infection and mutafions.

  2. Discrete Curvatures and Discrete Minimal Surfaces

    KAUST Repository

    Sun, Xiang

    2012-06-01

    This thesis presents an overview of some approaches to compute Gaussian and mean curvature on discrete surfaces and discusses discrete minimal surfaces. The variety of applications of differential geometry in visualization and shape design leads to great interest in studying discrete surfaces. With the rich smooth surface theory in hand, one would hope that this elegant theory can still be applied to the discrete counter part. Such a generalization, however, is not always successful. While discrete surfaces have the advantage of being finite dimensional, thus easier to treat, their geometric properties such as curvatures are not well defined in the classical sense. Furthermore, the powerful calculus tool can hardly be applied. The methods in this thesis, including angular defect formula, cotangent formula, parallel meshes, relative geometry etc. are approaches based on offset meshes or generalized offset meshes. As an important application, we discuss discrete minimal surfaces and discrete Koenigs meshes.

  3. 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

  4. 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.

  5. Characterization of Immunodominant BK Polyomavirus 9mer Epitope T Cell Responses

    Science.gov (United States)

    Cioni, M.; Leboeuf, C.; Comoli, P.; Ginevri, F.

    2016-01-01

    Uncontrolled BK polyomavirus (BKPyV) replication in kidney transplant recipients (KTRs) causes polyomavirus‐associated nephropathy and allograft loss. Reducing immunosuppression is associated with clearing viremia and nephropathy and increasing BKPyV‐specific T cell responses in most patients; however, current immunoassays have limited sensitivity, target mostly CD4+ T cells, and largely fail to predict onset and clearance of BKPyV replication. To characterize BKPyV‐specific CD8+ T cells, bioinformatics were used to predict 9mer epitopes in the early viral gene region (EVGR) presented by 14 common HLAs in Europe and North America. Thirty‐nine EVGR epitopes were experimentally confirmed by interferon‐γ enzyme‐linked immunospot assays in at least 30% of BKPyV IgG–seropositive healthy participants. Most 9mers clustered in domains, and some were presented by more than one HLA class I, as typically seen for immunodominant epitopes. Specific T cell binding using MHC class I streptamers was demonstrated for 21 of 39 (54%) epitopes. In a prospective cohort of 118 pediatric KTRs, 19 patients protected or recovering from BKPyV viremia were experimentally tested, and 13 epitopes were validated. Single HLA mismatches were not associated with viremia, suggesting that failing immune control likely involves multiple factors including maintenance immunosuppression. Combining BKPyV load and T cell assays using immunodominant epitopes may help in evaluating risk and reducing immunosuppression and may lead to safe adoptive T cell transfer. PMID:26663765

  6. Design of a heterosubtypic epitope-based peptide vaccine fused with hemokinin-1 against influenza viruses

    Institute of Scientific and Technical Information of China (English)

    Shahla; Shahsavandi; Mohammad; Majid; Ebrahimi; Kaveh; Sadeghi; Homayoon; Mahravani

    2015-01-01

    Influenza viruses continue to emerge and re-emerge, posing new threats for public health. Control and treatment of influenza depends mainly on vaccination and chemoprophylaxis with approved antiviral drugs. Identification of specific epitopes derived from influenza viruses has significantly advanced the development of epitope-based vaccines. Here, we explore the idea of using HLA binding data to design an epitope-based vaccine that can elicit heterosubtypic T-cell responses against circulating H7N9, H5N1, and H9N2 subtypes. The hemokinin-1(HK-1) peptide sequence was used to induce immune responses against the influenza viruses. Five conserved high score cytotoxic T lymphocyte(CTL) epitopes restricted to HLA-A*0201-binding peptides within the hemagglutinin(HA) protein of the viruses were chosen, and two HA CTL/HK-1 chimera protein models designed. Using in silico analysis, which involves interferon epitope scanning, protein structure prediction, antigenic epitope determination, and model quality evaluation, chimeric proteins were designed. The applicability of one of these proteins as a heterosubtypic epitopebased vaccine candidate was analyzed.

  7. Whole-exome sequencing predicted cancer epitope trees of 23 early cervical cancers in Chinese women.

    Science.gov (United States)

    Li, Xia; Huang, Hailiang; Guan, Yanfang; Gong, Yuhua; He, Cheng-Yi; Yi, Xin; Qi, Ming; Chen, Zhi-Ying

    2017-01-01

    Emerging evidence suggest that the heterogeneity of cancer limits the efficacy of immunotherapy. To search for optimal therapeutic targets for enhancing the efficacy, we used whole-exome sequencing data of 23 early cervical tumors from Chinese women to investigate the hierarchical structure of the somatic mutations and the neo-epitopes. The putative neo-epitopes were predicted based on the mutant peptides' strong binding with major histocompatibility complex class I molecules. We found that each tumor carried an average of 117 mutations and 61 putative neo-epitopes. Each patient displayed a unique phylogenetic tree in which almost all subclones harbored neo-epitopes, highlighting the importance of individual neo-epitope tree in determination of immunotherapeutic targets. The alterations in FBXW7 and PIK3CA, or other members of the significantly altered ubiquitin-mediated proteolysis and extracellular matrix receptor interaction related pathways, were proposed as the earliest changes triggering the malignant progression. The neo-epitopes involved in these pathways, and located at the top of the hierarchy tree, might become the optimal candidates for therapeutic targets, possessing the potential to mediate T-cell killing of the descendant cells. These findings expanded our understanding in early stage of cervical carcinogenesis and offered an important approach to assist optimizing the immunotherapeutic target selection.

  8. 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

    for predicting B-cell epitopes from antigen sequences. BepiPred-2.0 is based on a random forest algorithm trained on epitopes annotated from antibody-antigen protein structures. This new method was found to outperform other available tools for sequence-based epitope prediction both on epitope data derived from...

  9. Common antiviral cytotoxic t-lymphocyte epitope for diverse arenaviruses.

    Science.gov (United States)

    Oldstone, M B; Lewicki, H; Homann, D; Nguyen, C; Julien, S; Gairin, J E

    2001-07-01

    Members of the Arenaviridae family have been isolated from mammalian hosts in disparate geographic locations, leading to their grouping as Old World types (i.e., lymphocytic choriomeningitis virus [LCMV], Lassa fever virus [LFV], Mopeia virus, and Mobala virus) and New World types (i.e., Junin, Machupo, Tacaribe, and Sabia viruses) (C. J. Peters, M. J. Buchmeier, P. E. Rollin, and T. G. Ksiazek, p. 1521-1551, in B. N. Fields, D. M. Knipe, and P. M. Howley [ed.], Fields virology, 3rd ed., 1996; P. J. Southern, p. 1505-1519, in B. N. Fields, D. M. Knipe, and P. M. Howley [ed.], Fields virology, 3rd ed., 1996). Several types in both groups-LFV, Junin, Machupo, and Sabia viruses-cause severe and often lethal human diseases. By sequence comparison, we noted that eight Old World and New World arenaviruses share several amino acids with the nucleoprotein (NP) that consists of amino acids (aa) 118 to 126 (NP 118-126) (RPQASGVYM) of LCMV that comprise the immunodominant cytotoxic T-lymphocyte (CTL) epitope for H-2(d) mice (32). This L(d)-restricted epitope constituted >97% of the total bulk CTLs produced in the specific antiviral or clonal responses of H-2(d) BALB mice. NP 118-126 of the Old World arenaviruses LFV, Mopeia virus, and LCMV and the New World arenavirus Sabia virus bound at high affinity to L(d). The primary H-2(d) CTL anti-LCMV response as well as that of a CTL clone responsive to LCMV NP 118-126 recognized target cells coated with NP 118-126 peptides derived from LCMV, LFV, and Mopeia virus but not Sabia virus, indicating that a common functional NP epitope exists among Old World arenaviruses. Use of site-specific amino acid exchanges in the NP CTL epitope among these arenaviruses identified amino acids involved in major histocompatibility complex binding and CTL recognition.

  10. Groupoids, Discrete Mechanics, and Discrete Variation

    Institute of Scientific and Technical Information of China (English)

    GUO Jia-Feng; JIA Xiao-Yu; WU Ke; ZHAO Wei-Zhong

    2008-01-01

    After introducing some of the basic definitions and results from the theory of groupoid and Lie algebroid,we investigate the discrete Lagrangian mechanics from the viewpoint of groupoid theory and give the connection between groupoids variation and the methods of the first and second discrete variational principles.

  11. On discrete cosine transform

    CERN Document Server

    Zhou, Jianqin

    2011-01-01

    The discrete cosine transform (DCT), introduced by Ahmed, Natarajan and Rao, has been used in many applications of digital signal processing, data compression and information hiding. There are four types of the discrete cosine transform. In simulating the discrete cosine transform, we propose a generalized discrete cosine transform with three parameters, and prove its orthogonality for some new cases. A new type of discrete cosine transform is proposed and its orthogonality is proved. Finally, we propose a generalized discrete W transform with three parameters, and prove its orthogonality for some new cases.

  12. Mimetic discretization methods

    CERN Document Server

    Castillo, Jose E

    2013-01-01

    To help solve physical and engineering problems, mimetic or compatible algebraic discretization methods employ discrete constructs to mimic the continuous identities and theorems found in vector calculus. Mimetic Discretization Methods focuses on the recent mimetic discretization method co-developed by the first author. Based on the Castillo-Grone operators, this simple mimetic discretization method is invariably valid for spatial dimensions no greater than three. The book also presents a numerical method for obtaining corresponding discrete operators that mimic the continuum differential and

  13. Discrete mathematics, discrete physics and numerical methods

    Directory of Open Access Journals (Sweden)

    Felice Iavernaro

    2007-12-01

    Full Text Available Discrete mathematics has been neglected for a long time. It has been put in the shade by the striking success of continuous mathematics in the last two centuries, mainly because continuous models in physics proved very reliable, but also because of the greater difficulty in dealing with it. This perspective has been rapidly changing in the last years owing to the needs of the numerical analysis and, more recently, of the so called discrete physics. In this paper, starting from some sentences of Fichera about discrete and continuous world, we shall present some considerations about discrete phenomena which arise when designing numerical methods or discrete models for some classical physical problems.

  14. Functional characterization of a monoclonal antibody epitope using a lambda phage display-deep sequencing platform

    Science.gov (United States)

    Domina, Maria; Lanza Cariccio, Veronica; Benfatto, Salvatore; Venza, Mario; Venza, Isabella; Borgogni, Erica; Castellino, Flora; Midiri, Angelina; Galbo, Roberta; Romeo, Letizia; Biondo, Carmelo; Masignani, Vega; Teti, Giuseppe; Felici, Franco; Beninati, Concetta

    2016-01-01

    We have recently described a method, named PROFILER, for the identification of antigenic regions preferentially targeted by polyclonal antibody responses after vaccination. To test the ability of the technique to provide insights into the functional properties of monoclonal antibody (mAb) epitopes, we used here a well-characterized epitope of meningococcal factor H binding protein (fHbp), which is recognized by mAb 12C1. An fHbp library, engineered on a lambda phage vector enabling surface expression of polypeptides of widely different length, was subjected to massive parallel sequencing of the phage inserts after affinity selection with the 12C1 mAb. We detected dozens of unique antibody-selected sequences, the most enriched of which (designated as FrC) could largely recapitulate the ability of fHbp to bind mAb 12C1. Computational analysis of the cumulative enrichment of single amino acids in the antibody-selected fragments identified two overrepresented stretches of residues (H248-K254 and S140-G154), whose presence was subsequently found to be required for binding of FrC to mAb 12C1. Collectively, these results suggest that the PROFILER technology can rapidly and reliably identify, in the context of complex conformational epitopes, discrete “hot spots” with a crucial role in antigen-antibody interactions, thereby providing useful clues for the functional characterization of the epitope. PMID:27530334

  15. 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.

  16. Antigen epitope of Helicobacter pylorivacuolating cytotoxin A

    Institute of Scientific and Technical Information of China (English)

    Xiu-Li Liu; Shu-Qin Li; Chun-Jie Liu; Hao-Xia Tao; Zhao-Shan Zhang

    2004-01-01

    AIM: To construct and select antigen epitopes of vacuolating cytotoxin A (VacA) for nontoxic VacA vaccine against Helicobacter pylori (H pylori) infection.METHODS: Eleven VacA epitopes were predicted according to VacA antigenic bioinformatics. Three candidates of VacA epitope were constructed through different combined epitopes. The candidate was linked with E. coli heat-labile enterotoxin B (LTB) by a linker of 7 amino acids, and cloned into plasmid pQE-60 in which fusion LTB-VacA epitope was efficiently expressed. To test the antigencity of the candidate, 6 BALB/c mice were treated with the fusion LTB-VacA epitope through intraperitoneal injection. To explore the ability of inhibiting the toxicity of VacA, cantiserum against the candidate was used to counteract VacA that induced HeLa cells to produce cell vacuoles in vitro.RESULTS: Serum IgG against the candidate was induced in the BALB/c mice. In vitro, the three antisera against the candidate efficiently counteracted the toxicity of VacA, and decreased the number of cell vacuoles by 14.17%, 20.20%and 30.41% respectively.CONCLUSION: Two of the three candidates, LZ-VacA1and LZ-VacA2, can be used to further study the mechanism of vacuolating toxicity of VacA, and to construct nontoxic VacA vaccine against H pylori infection.

  17. Epitope specificity and V gene expression of cerebrospinal fluid T cells specific for intact versus cryptic epitopes of myelin basic protein.

    Science.gov (United States)

    Satyanarayana, K; Chou, Y K; Bourdette, D; Whitham, R; Hashim, G A; Offner, H; Vandenbark, A A

    1993-04-01

    Recent evidence supports the possible involvement of myelin basic protein (BP) as one of the target autoantigens in multiple sclerosis (MS), including elevated frequencies of MS blood and cerebrospinal fluid (CSF) T cells, and the presence in MS plaque tissue of V beta gene sequences and CDR3 motifs characteristic of BP-reactive T cells. Because of its proximity to the target organ, the CSF has long been thought to harbor T cells involved in the pathogenic process. In order to evaluate their frequency and response characteristics, BP-reactive T cells were isolated by limiting dilution from the CSF of patients with MS and other neurological diseases (OND) for quantitation and determination of epitope specificity and V alpha and V beta gene expression. In addition to isolates responsive to intact BP epitopes that were present at a significantly higher frequency in MS versus OND CSF, we here describe a second clonotype responsive to 'cryptic' BP epitopes that is present at approximately equal frequencies in MS and OND patients. In spite of their difference in recognition of intact versus 'cryptic' BP determinants, both clonotypes predominantly recognized epitopes in the N terminal half of human BP, using a similar V gene repertoire that included biased use of V alpha 2 and to a lesser degree V beta 7 and V beta 18. These V gene biases were not related to the epitope specificity of the T cells, indicating that V gene selection is not epitope-driven. These data suggest that there is differential recognition of intact versus 'cryptic' BP determinants in MS versus OND patients that may be related to the processing and presentation of BP to the immune system.

  18. Discrete Wigner function dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Klimov, A B; Munoz, C [Departamento de Fisica, Universidad de Guadalajara, Revolucion 1500, 44410, Guadalajara, Jalisco (Mexico)

    2005-12-01

    We study the evolution of the discrete Wigner function for prime and the power of prime dimensions using the discrete version of the star-product operation. Exact and semiclassical dynamics in the limit of large dimensions are considered.

  19. Discrete Pearson distributions

    Energy Technology Data Exchange (ETDEWEB)

    Bowman, K.O. [Oak Ridge National Lab., TN (United States); Shenton, L.R. [Georgia Univ., Athens, GA (United States); Kastenbaum, M.A. [Kastenbaum (M.A.), Basye, VA (United States)

    1991-11-01

    These distributions are generated by a first order recursive scheme which equates the ratio of successive probabilities to the ratio of two corresponding quadratics. The use of a linearized form of this model will produce equations in the unknowns matched by an appropriate set of moments (assumed to exist). Given the moments we may find valid solutions. These are two cases; (1) distributions defined on the non-negative integers (finite or infinite) and (2) distributions defined on negative integers as well. For (1), given the first four moments, it is possible to set this up as equations of finite or infinite degree in the probability of a zero occurrence, the sth component being a product of s ratios of linear forms in this probability in general. For (2) the equation for the zero probability is purely linear but may involve slowly converging series; here a particular case is the discrete normal. Regions of validity are being studied. 11 refs.

  20. Discrete Noether Currents

    CERN Document Server

    Seidl, Gerhart

    2014-01-01

    We present a simple generalization of Noether's theorem for discrete symmetries in relativistic continuum field theories. We calculate explicitly the conserved current for several discrete spacetime and internal symmetries. In addition, we formulate an analogue of the Ward-Takahashi identity for the Noether current associated with a discrete symmetry.

  1. Epitope predictions indicate the presence of two distinct types of epitope-antibody-reactivities determined by epitope profiling of intravenous immunoglobulins.

    Directory of Open Access Journals (Sweden)

    Mitja Luštrek

    Full Text Available Epitope-antibody-reactivities (EAR of intravenous immunoglobulins (IVIGs determined for 75,534 peptides by microarray analysis demonstrate that roughly 9% of peptides derived from 870 different human protein sequences react with antibodies present in IVIG. Computational prediction of linear B cell epitopes was conducted using machine learning with an ensemble of classifiers in combination with position weight matrix (PWM analysis. Machine learning slightly outperformed PWM with area under the curve (AUC of 0.884 vs. 0.849. Two different types of epitope-antibody recognition-modes (Type I EAR and Type II EAR were found. Peptides of Type I EAR are high in tyrosine, tryptophan and phenylalanine, and low in asparagine, glutamine and glutamic acid residues, whereas for peptides of Type II EAR it is the other way around. Representative crystal structures present in the Protein Data Bank (PDB of Type I EAR are PDB 1TZI and PDB 2DD8, while PDB 2FD6 and 2J4W are typical for Type II EAR. Type I EAR peptides share predicted propensities for being presented by MHC class I and class II complexes. The latter interaction possibly favors T cell-dependent antibody responses including IgG class switching. Peptides of Type II EAR are predicted not to be preferentially presented by MHC complexes, thus implying the involvement of T cell-independent IgG class switch mechanisms. The high extent of IgG immunoglobulin reactivity with human peptides implies that circulating IgG molecules are prone to bind to human protein/peptide structures under non-pathological, non-inflammatory conditions. A webserver for predicting EAR of peptide sequences is available at www.sysmed-immun.eu/EAR.

  2. Equivalent T cell epitope promiscuity in ecologically diverse human pathogens.

    Science.gov (United States)

    Wiens, Kirsten E; Swaminathan, Harish; Copin, Richard; Lun, Desmond S; Ernst, Joel D

    2013-01-01

    The HLA (human leukocyte antigen) molecules that present pathogen-derived epitopes to T cells are highly diverse. Correspondingly, many pathogens such as HIV evolve epitope variants in order to evade immune recognition. In contrast, another persistent human pathogen, Mycobacterium tuberculosis, has highly conserved epitope sequences. This raises the question whether there is also a difference in the ability of these pathogens' epitopes to bind diverse HLA alleles, referred to as an epitope's binding promiscuity. To address this question, we compared the in silico HLA binding promiscuity of T cell epitopes from pathogens with distinct infection strategies and outcomes of human exposure. We used computer algorithms to predict the binding affinity of experimentally-verified microbial epitope peptides to diverse HLA-DR, HLA-A and HLA-B alleles. We then analyzed binding promiscuity of epitopes derived from HIV and M. tuberculosis. We also analyzed promiscuity of epitopes from Streptococcus pyogenes, which is known to exhibit epitope diversity, and epitopes of Bacillus anthracis and Clostridium tetani toxins, as these bacteria do not depend on human hosts for their survival or replication, and their toxin antigens are highly immunogenic human vaccines. We found that B. anthracis and C. tetani epitopes were the most promiscuous of the group that we analyzed. However, there was no consistent difference or trend in promiscuity in epitopes contained in HIV, M. tuberculosis, and S. pyogenes. Our results show that human pathogens with distinct immune evasion strategies and epitope diversities exhibit equivalent levels of T cell epitope promiscuity. These results indicate that differences in epitope promiscuity do not account for the observed differences in epitope variation and conservation.

  3. Equivalent T cell epitope promiscuity in ecologically diverse human pathogens.

    Directory of Open Access Journals (Sweden)

    Kirsten E Wiens

    Full Text Available BACKGROUND: The HLA (human leukocyte antigen molecules that present pathogen-derived epitopes to T cells are highly diverse. Correspondingly, many pathogens such as HIV evolve epitope variants in order to evade immune recognition. In contrast, another persistent human pathogen, Mycobacterium tuberculosis, has highly conserved epitope sequences. This raises the question whether there is also a difference in the ability of these pathogens' epitopes to bind diverse HLA alleles, referred to as an epitope's binding promiscuity. To address this question, we compared the in silico HLA binding promiscuity of T cell epitopes from pathogens with distinct infection strategies and outcomes of human exposure. METHODS: We used computer algorithms to predict the binding affinity of experimentally-verified microbial epitope peptides to diverse HLA-DR, HLA-A and HLA-B alleles. We then analyzed binding promiscuity of epitopes derived from HIV and M. tuberculosis. We also analyzed promiscuity of epitopes from Streptococcus pyogenes, which is known to exhibit epitope diversity, and epitopes of Bacillus anthracis and Clostridium tetani toxins, as these bacteria do not depend on human hosts for their survival or replication, and their toxin antigens are highly immunogenic human vaccines. RESULTS: We found that B. anthracis and C. tetani epitopes were the most promiscuous of the group that we analyzed. However, there was no consistent difference or trend in promiscuity in epitopes contained in HIV, M. tuberculosis, and S. pyogenes. CONCLUSIONS: Our results show that human pathogens with distinct immune evasion strategies and epitope diversities exhibit equivalent levels of T cell epitope promiscuity. These results indicate that differences in epitope promiscuity do not account for the observed differences in epitope variation and conservation.

  4. Analysis of risk epitopes of anti-neutrophil antibody MPO-ANCA in vasculitis in Japanese population.

    Science.gov (United States)

    Suzuki, Kazuo; Kobayashi, Shigeto; Yamazaki, Kazushige; Gondo, Masaaki; Tomizawa, Kazuo; Arimura, Yoshihiro; Nakabayashi, Kimimasa; Ozaki, Shoichi; Yoshida, Masaharu; Yoshida, Toshiharu; Tsusaka, Norimasa; Muso, Eri; Okazaki, Tomio; Hashimoto, Hiroshi

    2007-01-01

    Autoantibodies to myeloperoxidase (MPO) are a subset of anti-neutrophil cytoplasmic antibody (ANCA, MPO-ANCA) detected in the sera of some patients with primary systemic vasculitis. The titer of MPO-ANCA does not always reflect disease activity and this inconsistency may be attributable to differences in epitopic specificity by MPO-ANCA among various patients with vasculitis. Epitope analysis may also explain the occurrence of MPO-ANCA in different vasculitic syndromes. We screened the sera of 148 MPO-ANCA positive patients from six vasculitic syndromes: rapidly progressive gromerulonephritis (RPGN), microscopic polyangiitis (MPA), idiopathic crescentic glomerulonephritis (I-CrGN), classic polyangiitis nodosa (cPAN), Churg-Strauss syndrome (CSS), Kawasaki disease (KD); and from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The sera were collected by the Intractable Vasculitis Research Project Group in Japan. No serum showed epitopes La and Lb of light chain of MPO, and sera with 68.6% of patients showed a positive reaction to one or more epitopes in heavy chain of MPO. Analysis of binding level showed that RPGN, I-CrGN and MPA sera mainly reacted to the Ha epitope at the N-termimus of the MPO heavy chain, CSS sera reacted to Ha and the Hf epitope close to the C-terminus of the MPO heavy chain, KD reacted mainly to Hf, while SLE and RA sera reacted to all epitopes. These results suggest that MPO-ANCA recognizing specific regions of the N-terminus of the MPO H-chain confer an increased risk of vasculitis RPGN, I-CrGN, MPA and CSS. Furthermore, the epitopic specificity of MPO-ANCA differentiates vasculitic from non-vasculitic syndromes associated with MPO-ANCA positivity and differentiates in the cirtain type of vasculitis from various vasculitic syndromes. In particular, vasculitic syndromes associated with kidney involvement had similar epitopic reactivity which suggests that this pattern confers an increased risk of vasculitis.

  5. Discrete implementations of scale transform

    Science.gov (United States)

    Djurdjanovic, Dragan; Williams, William J.; Koh, Christopher K.

    1999-11-01

    Scale as a physical quantity is a recently developed concept. The scale transform can be viewed as a special case of the more general Mellin transform and its mathematical properties are very applicable in the analysis and interpretation of the signals subject to scale changes. A number of single-dimensional applications of scale concept have been made in speech analysis, processing of biological signals, machine vibration analysis and other areas. Recently, the scale transform was also applied in multi-dimensional signal processing and used for image filtering and denoising. Discrete implementation of the scale transform can be carried out using logarithmic sampling and the well-known fast Fourier transform. Nevertheless, in the case of the uniformly sampled signals, this implementation involves resampling. An algorithm not involving resampling of the uniformly sampled signals has been derived too. In this paper, a modification of the later algorithm for discrete implementation of the direct scale transform is presented. In addition, similar concept was used to improve a recently introduced discrete implementation of the inverse scale transform. Estimation of the absolute discretization errors showed that the modified algorithms have a desirable property of yielding a smaller region of possible error magnitudes. Experimental results are obtained using artificial signals as well as signals evoked from the temporomandibular joint. In addition, discrete implementations for the separable two-dimensional direct and inverse scale transforms are derived. Experiments with image restoration and scaling through two-dimensional scale domain using the novel implementation of the separable two-dimensional scale transform pair are presented.

  6. ENDOGENOUS EXPRESSION AND HLA STABILIZATION ASSAY OF PLASMODIUM FALCIPARUM CTL EPITOPE MINIGENE IN HUMAN HLA-A2.1 AND HLA-B51 CELLS

    Institute of Scientific and Technical Information of China (English)

    唐玉阳; 王恒

    2001-01-01

    Objective. To evaluate the Plasmodium falciparum CTL epitope vaccines in HLA class I allele specific human cell lines that have high frequency among Chinese population. Methods. Synthesized oligonucleotides encoding for P.f. CTL epitope genes, constructed eukaryotic expression plasmids, transfected the minigenes into HLA class I allele specific human cell lines and identified endogenous expressing of the minigenes by RT-PCR and HLA stabilization assay. Results. Two mini-genes encoding Plasmodium falciparum CTL epitopes were designed and cloned, respectively, into an eukaryotic expressing vector to form TR26 which was restricted to HLA-B51, SH6 which was restricted to HLA-A2.1, and TS, which had the two aforementioned mini-genes fused in tandem. All of these CTL epitope genes were transfected and endogenously expressed in respective cell lines containing appropriate HLA molecules. The obviously increased expressions of HLA class I molecules were detected in the transfected cell lines. It was demonstrated that the two discrete Plasmodium falciparum epitope genes were effectively processed and presented, and the close proximity of the two epitope genes in one chain as in mini-gene TS did not interfere with the processing and presenting of each epitope gene in corresponding cell line. Conclusion. A successful expression and presentation of multiple CTL epitope mini-gene in MHC class I allele specific human cell lines were demonstrated by an in vitro assay, which could be corresponding to the vaccination of CTL vaccines in people with different MHC I molecules. This work also suggested the possibility of constructing a multiple CTL epitope plasmodium falciparum DNA vaccine that could cover most of Chinese population.

  7. 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...... of eight new tools were added, including two B-cell epitope prediction tools, four T-cell epitope prediction tools and two analysis tools....

  8. Statistical discrete geometry

    CERN Document Server

    Ariwahjoedi, Seramika; Kosasih, Jusak Sali; Rovelli, Carlo; Zen, Freddy Permana

    2016-01-01

    Following our earlier work, we construct statistical discrete geometry by applying statistical mechanics to discrete (Regge) gravity. We propose a coarse-graining method for discrete geometry under the assumptions of atomism and background independence. To maintain these assumptions, restrictions are given to the theory by introducing cut-offs, both in ultraviolet and infrared regime. Having a well-defined statistical picture of discrete Regge geometry, we take the infinite degrees of freedom (large n) limit. We argue that the correct limit consistent with the restrictions and the background independence concept is not the continuum limit of statistical mechanics, but the thermodynamical limit.

  9. Discrete mathematics, discrete physics and numerical methods

    OpenAIRE

    Felice Iavernaro; Donato Trigiante

    2007-01-01

    Discrete mathematics has been neglected for a long time. It has been put in the shade by the striking success of continuous mathematics in the last two centuries, mainly because continuous models in physics proved very reliable, but also because of the greater difficulty in dealing with it. This perspective has been rapidly changing in the last years owing to the needs of the numerical analysis and, more recently, of the so called discrete physics. In this paper, starting from some sentences o...

  10. Characterization of T cell epitopes in bovine α-lactalbumin

    NARCIS (Netherlands)

    Meulenbroek, Laura A P M; den Hartog Jager, Constance F; Lebens, Ans F M; Knulst, André C; Bruijnzeel-Koomen, Carla A F M; Garssen, Johan; Knippels, Léon M J; van Hoffen, Els

    2014-01-01

    BACKGROUND: Recent studies have indicated that peptides containing T cell epitopes may be used for immunotherapy. While for several cow's milk allergens the T cell epitopes have been described, the T cell epitopes in the major allergen α-lactalbumin (α-LAC) are unknown. Therefore, the aim of this st

  11. Modules for C-terminal epitope tagging of Tetrahymena genes

    Science.gov (United States)

    Kataoka, Kensuke; Schoeberl, Ursula E.; Mochizuki, Kazufumi

    2010-01-01

    Although epitope tagging has been widely used for analyzing protein function in many organisms, there are few genetic tools for epitope tagging in Tetrahymena. In this study, we describe several C-terminal epitope tagging modules that can be used to express tagged proteins in Tetrahymena cells by both plasmid- and PCR-based strategies. PMID:20624430

  12. Analysis of epitopes on dengue virus envelope protein recognized by monoclonal antibodies and polyclonal human sera by a high throughput assay.

    Directory of Open Access Journals (Sweden)

    Hong-En Lin

    2012-01-01

    Full Text Available BACKGROUND: The envelope (E protein of dengue virus (DENV is the major target of neutralizing antibodies and vaccine development. While previous studies on domain III or domain I/II alone have reported several epitopes of monoclonal antibodies (mAbs against DENV E protein, the possibility of interdomain epitopes and the relationship between epitopes and neutralizing potency remain largely unexplored. METHODOLOGY/PRINCIPAL FINDINGS: We developed a dot blot assay by using 67 alanine mutants of predicted surface-exposed E residues as a systematic approach to identify epitopes recognized by mAbs and polyclonal sera, and confirmed our findings using a capture-ELISA assay. Of the 12 mouse mAbs tested, three recognized a novel epitope involving residues (Q211, D215, P217 at the central interface of domain II, and three recognized residues at both domain III and the lateral ridge of domain II, suggesting a more frequent presence of interdomain epitopes than previously appreciated. Compared with mAbs generated by traditional protocols, the potent neutralizing mAbs generated by a new protocol recognized multiple residues in A strand or residues in C strand/CC' loop of DENV2 and DENV1, and multiple residues in BC loop and residues in DE loop, EF loop/F strand or G strand of DENV1. The predominant epitopes of anti-E antibodies in polyclonal sera were found to include both fusion loop and non-fusion residues in the same or adjacent monomer. CONCLUSIONS/SIGNIFICANCE: Our analyses have implications for epitope-specific diagnostics and epitope-based dengue vaccines. This high throughput method has tremendous application for mapping both intra and interdomain epitopes recognized by human mAbs and polyclonal sera, which would further our understanding of humoral immune responses to DENV at the epitope level.

  13. Development of an epitope conservancy analysis tool to facilitate the design of epitope-based diagnostics and vaccines

    Directory of Open Access Journals (Sweden)

    Fusseder Nicolas

    2007-09-01

    Full Text Available Abstract Background In an epitope-based vaccine setting, the use of conserved epitopes would be expected to provide broader protection across multiple strains, or even species, than epitopes derived from highly variable genome regions. Conversely, in a diagnostic and disease monitoring setting, epitopes that are specific to a given pathogen strain, for example, can be used to monitor responses to that particular infectious strain. In both cases, concrete information pertaining to the degree of conservancy of the epitope(s considered is crucial. Results To assist in the selection of epitopes with the desired degree of conservation, we have developed a new tool to determine the variability of epitopes within a given set of protein sequences. The tool was implemented as a component of the Immune Epitope Database and Analysis Resources (IEDB, and is directly accessible at http://tools.immuneepitope.org/tools/conservancy. Conclusion An epitope conservancy analysis tool was developed to analyze the variability or conservation of epitopes. The tool is user friendly, and is expected to aid in the design of epitope-based vaccines and diagnostics.

  14. Hairs of discrete symmetries and gravity

    Directory of Open Access Journals (Sweden)

    Kang Sin Choi

    2017-06-01

    Full Text Available Gauge symmetries are known to be respected by gravity because gauge charges carry flux lines, but global charges do not carry flux lines and are not conserved by gravitational interaction. For discrete symmetries, they are spontaneously broken in the Universe, forming domain walls. Since the realization of discrete symmetries in the Universe must involve the vacuum expectation values of Higgs fields, a string-like configuration (hair at the intersection of domain walls in the Higgs vacua can be realized. Therefore, we argue that discrete charges are also respected by gravity.

  15. Hairs of discrete symmetries and gravity

    Science.gov (United States)

    Choi, Kang Sin; Kim, Jihn E.; Kyae, Bumseok; Nam, Soonkeon

    2017-06-01

    Gauge symmetries are known to be respected by gravity because gauge charges carry flux lines, but global charges do not carry flux lines and are not conserved by gravitational interaction. For discrete symmetries, they are spontaneously broken in the Universe, forming domain walls. Since the realization of discrete symmetries in the Universe must involve the vacuum expectation values of Higgs fields, a string-like configuration (hair) at the intersection of domain walls in the Higgs vacua can be realized. Therefore, we argue that discrete charges are also respected by gravity.

  16. Dominant epitopes and allergic cross-reactivity

    DEFF Research Database (Denmark)

    Mirza, Osman Asghar; Henriksen, A; Ipsen, H

    2000-01-01

    The symptoms characteristic of allergic hypersensitivity are caused by the release of mediators, i.e., histamine, from effector cells such as basophils and mast cells. Allergens with more than one B cell epitope cross-link IgE Abs bound to high affinity FcepsilonRI receptors on mast cell surfaces...

  17. IgE-binding epitopes: a reappraisal

    NARCIS (Netherlands)

    R.C. Aalberse; R. Crameri

    2011-01-01

    Here, we discuss various questions related to IgE epitopes: What are the technical possibilities and pitfalls, what is currently known, how can we put this information into hypothetical frameworks and the unavoidable question: how useful is this information for patient care or allergenicity predicti

  18. Viral O-GalNAc peptide epitopes

    DEFF Research Database (Denmark)

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

    2016-01-01

    on a novel three-step procedure that identifies any reactive viral O-glycosyl peptide epitope with respect to (i) relevant peptide sequence, (ii) the reactive glycoform out of several possible glycopeptide isomers of that peptide sequence, and (iii) possibly tolerated carbohydrate or peptide structural...

  19. 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

    for pseudotypes to escape neutralization by the immune system in vivo. Previous reports have suggested that carbohydrate structures may be conserved neutralization epitopes on retroviruses. In this study, the neutralizing capacity of lectins and anti-carbohydrate monoclonal antibodies was found to block infection...... 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....

  20. Finite Discrete Gabor Analysis

    DEFF Research Database (Denmark)

    Søndergaard, Peter Lempel

    2007-01-01

    on the real line to be well approximated by finite and discrete Gabor frames. This method of approximation is especially attractive because efficient numerical methods exists for doing computations with finite, discrete Gabor systems. This thesis presents new algorithms for the efficient computation of finite...

  1. Discrete Mathematics Re "Tooled."

    Science.gov (United States)

    Grassl, Richard M.; Mingus, Tabitha T. Y.

    1999-01-01

    Indicates the importance of teaching discrete mathematics. Describes how the use of technology can enhance the teaching and learning of discrete mathematics. Explorations using Excel, Derive, and the TI-92 proved how preservice and inservice teachers experienced a new dimension in problem solving and discovery. (ASK)

  2. Discrete Quantum Mechanics

    CERN Document Server

    Chang, Lay Nam; Minic, Djordje; Takeuchi, Tatsu

    2012-01-01

    We construct a discrete quantum mechanics using a vector space over the Galois field GF(q). We find that the correlations in our model do not violate the Clauser-Horne-Shimony-Holt (CHSH) version of Bell's inequality, despite the fact that the predictions of this discrete quantum mechanics cannot be reproduced with any hidden variable theory.

  3. Epitope-Specific Suppression of IgG Responses by Passively Administered Specific IgG: Evidence of Epitope Masking

    Science.gov (United States)

    Bergström, Joakim J. E.; Xu, Hui; Heyman, Birgitta

    2017-01-01

    Specific IgG, passively administered together with particulate antigen, can completely prevent induction of antibody responses to this antigen. The ability of IgG to suppress antibody responses to sheep red blood cells (SRBCs) is intact in mice lacking FcγRs, complement factor 1q, C3, or complement receptors 1 and 2, suggesting that Fc-dependent effector functions are not involved. Two of the most widely discussed explanations for the suppressive effect are increased clearance of IgG–antigen complexes and/or that IgG “hides” the antigen from recognition by specific B cells, so-called epitope masking. The majority of data on how IgG induces suppression was obtained through studies of the effects on IgM-secreting single spleen cells during the first week after immunization. Here, we show that IgG also suppresses antigen-specific extrafollicular antibody-secreting cells, germinal center B-cells, long-lived plasma cells, long-term IgG responses, and induction of memory antibody responses. IgG anti-SRBC reduced the amount of SRBC in the spleens of wild-type, but not of FcγR-deficient mice. However, no correlation between suppression and the amount of SRBC in the spleen was observed, suggesting that increased clearance does not explain IgG-mediated suppression. Instead, we found compelling evidence for epitope masking because IgG anti-NP administered with NP-SRBC suppressed the IgG anti-NP, but not the IgG anti-SRBC response. Vice versa, IgG anti-SRBC administered with NP-SRBC, suppressed only the IgG anti-SRBC response. In conclusion, passively transferred IgG suppressed all measured parameters of an antigen-specific antibody/B cell response and an important mechanism of action is likely to be epitope masking.

  4. Discrete Control Systems

    CERN Document Server

    Lee, Taeyoung; McClamroch, N Harris

    2007-01-01

    Discrete control systems, as considered here, refer to the control theory of discrete-time Lagrangian or Hamiltonian systems. These discrete-time models are based on a discrete variational principle, and are part of the broader field of geometric integration. Geometric integrators are numerical integration methods that preserve geometric properties of continuous systems, such as conservation of the symplectic form, momentum, and energy. They also guarantee that the discrete flow remains on the manifold on which the continuous system evolves, an important property in the case of rigid-body dynamics. In nonlinear control, one typically relies on differential geometric and dynamical systems techniques to prove properties such as stability, controllability, and optimality. More generally, the geometric structure of such systems plays a critical role in the nonlinear analysis of the corresponding control problems. Despite the critical role of geometry and mechanics in the analysis of nonlinear control systems, non...

  5. Discrete Element Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Morris, J; Johnson, S

    2007-12-03

    The Distinct Element Method (also frequently referred to as the Discrete Element Method) (DEM) is a Lagrangian numerical technique where the computational domain consists of discrete solid elements which interact via compliant contacts. This can be contrasted with Finite Element Methods where the computational domain is assumed to represent a continuum (although many modern implementations of the FEM can accommodate some Distinct Element capabilities). Often the terms Discrete Element Method and Distinct Element Method are used interchangeably in the literature, although Cundall and Hart (1992) suggested that Discrete Element Methods should be a more inclusive term covering Distinct Element Methods, Displacement Discontinuity Analysis and Modal Methods. In this work, DEM specifically refers to the Distinct Element Method, where the discrete elements interact via compliant contacts, in contrast with Displacement Discontinuity Analysis where the contacts are rigid and all compliance is taken up by the adjacent intact material.

  6. Discrete control systems

    CERN Document Server

    Okuyama, Yoshifumi

    2014-01-01

    Discrete Control Systems establishes a basis for the analysis and design of discretized/quantized control systemsfor continuous physical systems. Beginning with the necessary mathematical foundations and system-model descriptions, the text moves on to derive a robust stability condition. To keep a practical perspective on the uncertain physical systems considered, most of the methods treated are carried out in the frequency domain. As part of the design procedure, modified Nyquist–Hall and Nichols diagrams are presented and discretized proportional–integral–derivative control schemes are reconsidered. Schemes for model-reference feedback and discrete-type observers are proposed. Although single-loop feedback systems form the core of the text, some consideration is given to multiple loops and nonlinearities. The robust control performance and stability of interval systems (with multiple uncertainties) are outlined. Finally, the monograph describes the relationship between feedback-control and discrete ev...

  7. Continuity in Discrete Sets

    CERN Document Server

    Burgin, Mark

    2010-01-01

    Continuous models used in physics and other areas of mathematics applications become discrete when they are computerized, e.g., utilized for computations. Besides, computers are controlling processes in discrete spaces, such as films and television programs. At the same time, continuous models that are in the background of discrete representations use mathematical technology developed for continuous media. The most important example of such a technology is calculus, which is so useful in physics and other sciences. The main goal of this paper is to synthesize continuous features and powerful technology of the classical calculus with the discrete approach of numerical mathematics and computational physics. To do this, we further develop the theory of fuzzy continuous functions and apply this theory to functions defined on discrete sets. The main interest is the classical Intermediate Value theorem. Although the result of this theorem is completely based on continuity, utilization of a relaxed version of contin...

  8. Expression and immunoreactivity of HCV/HBV epitopes

    Institute of Scientific and Technical Information of China (English)

    Xin-Yu Xiong; Xiao Liu; Yuan-Ding Chen

    2005-01-01

    AIM: To develop the epitope-based vaccines to prevent Hepatitis C virus (HCV)/Hepatitis B virus (HBV) infections.METHODS: The HCV core epitopes C1 STNPKPQRKTKRNTNRRPQD (residuals aa2-21) and C2 VKFPGGGQIVGGVYLLPRR (residuals aa22-40), envelope epitope E GHRMAWDMMMNWSP (residuals aa315-328) and HBsAg epitope S CTTPAQGNSMFPSCCCTKPTDGNC (residuals aa124-147) were displayed in five different sites of the flock house virus capsid protein as a vector, and expressed in E. coli cells (pET-3 system).Immunoreactivity of the epitopes with anti-HCV and anti-HBV antibodies in the serum from hepatitis C and hepatitis B patients were determined.RESULTS: The expressed chimeric protein carrying the HCV epitopes C1, C2, E (two times), L3C1-I2E-L1C2-L2E could react with anti-HCV antibodies. The expressed chimeric protein carrying the HBV epitopes S, I3S could react with anti-HBs antibodies. The expressed chimeric proteins carrying the HCV epitopes C1, C2, E plus HBV epitope S, L3C1-I2E-L1C2-L2E-I3S could react with antiHCV and anti-HBs antibodies.CONCLUSION: These epitopes have highly specific and sensitive immunoreaction and are useful in the development of epitope-based vaccines.

  9. B cell epitope spreading: mechanisms and contribution to autoimmune diseases.

    Science.gov (United States)

    Cornaby, Caleb; Gibbons, Lauren; Mayhew, Vera; Sloan, Chad S; Welling, Andrew; Poole, Brian D

    2015-01-01

    While a variety of factors act to trigger or initiate autoimmune diseases, the process of epitope spreading is an important contributor in their development. Epitope spreading is a diversification of the epitopes recognized by the immune system. This process happens to both T and B cells, with this review focusing on B cells. Such spreading can progress among multiple epitopes on a single antigen, or from one antigenic molecule to another. Systemic lupus erythematosus, multiple sclerosis, pemphigus, bullous pemphigoid and other autoimmune diseases, are all influenced by intermolecular and intramolecular B cell epitope spreading. Endocytic processing, antigen presentation, and somatic hypermutation act as molecular mechanisms that assist in driving epitope spreading and broadening the immune response in autoimmune diseases. The purpose of this review is to summarize our current understanding of B cell epitope spreading with regard to autoimmunity, how it contributes during the progression of various autoimmune diseases, and treatment options available.

  10. Identification of a novel B-cell epitope specific for avian leukosis virus subgroup J gp85 protein.

    Science.gov (United States)

    Li, Xiaofei; Zhu, Haibo; Wang, Qi; Sun, Jiashan; Gao, Yanni; Qi, Xiaole; Wang, Yongqiang; Gao, Honglei; Gao, Yulong; Wang, Xiaomei

    2015-04-01

    Avian leukosis virus subgroup J (ALV-J) is an avian oncogenic retrovirus that has caused severe economic losses in China. Gp85 protein is the main envelope protein and the most variable structural protein of ALV-J. It is also involved in virus neutralization. In this study, a specific monoclonal antibody, 4A3, was produced against the ALV-J gp85 protein. Immunofluorescence assays showed that 4A3 could react with different strains of ALV-J, including the British prototype isolate HPRS103, the American strains, an early Chinese broiler isolate, and layer isolates. A linear epitope on the gp85 protein was identified using a series of partially overlapping fragments spanning the gp85-encoding gene and subjecting them to western blot analysis. The results indicated that (134)AEAELRDFI(142) was the minimal linear epitope that could be recognized by mAb 4A3. Enzyme-linked immunosorbent assay (ELISA) revealed that chicken anti-ALV-J sera and mouse anti-ALV-J gp85 sera could also recognize the minimal linear epitope. Alignment analysis of amino acid sequences indicated that the epitope was highly conserved among 34 ALV-J strains. Furthermore, the epitope was not conserved among subgroup A and B of avian leukosis virus (ALV). Taken together, the mAb and the identified epitope may provide valuable tools for the development of new diagnostic methods for ALV-J.

  11. Identification of continuous human B-cell epitopes in the envelope glycoprotein of dengue virus type 3 (DENV-3.

    Directory of Open Access Journals (Sweden)

    Andréa N M Rangel da Silva

    Full Text Available BACKGROUND: Dengue virus infection is a growing global public health concern in tropical and subtropical regions of the world. Dengue vaccine development has been hampered by concerns that cross-reactive immunological memory elicited by a candidate vaccine could increase the risk of development of more severe clinical forms. One possible strategy to reduce risks associated with a dengue vaccine is the development of a vaccine composed of selected critical epitopes of each of the serotypes. METHODOLOGY/PRINCIPAL FINDINGS: Synthetic peptides were used to identify B-cell epitopes in the envelope (E glycoprotein of dengue virus type 3 (DENV-3. Eleven linear, immunodominant epitopes distributed in five regions at amino acid (aa positions: 51-65, 71-90, 131-170, 196-210 and 246-260 were identified by employing an enzyme- linked immunosorbent assay (ELISA, using a pool of human sera from dengue type 3 infected individuals. Peptides 11 (aa51-65, 27 and 28 (aa131-150 also reacted with dengue 1 (DENV-1 and dengue 2 (DENV-2 patient sera as analyzed through the ROC curves generated for each peptide by ELISA and might have serotype specific diagnostic potential. Mice immunized against each one of the five immunogenic regions showed epitopes 51-65, 131-170, 196-210 and 246-260 elicited the highest antibody response and epitopes131-170, 196-210 and 246-260, elicited IFN-gamma production and T CD4+ cell response, as evaluated by ELISA and ELISPOT assays respectively. CONCLUSIONS/SIGNIFICANCE: Our study identified several useful immunodominant IgG-specific epitopes on the envelope of DENV-3. They are important tools for understanding the mechanisms involved in antibody dependent enhancement and immunity. If proven protective and safe, in conjunction with others well-documented epitopes, they might be included into a candidate epitope-based vaccine.

  12. Continuum limit of discrete Sommerfeld problems on square lattice

    Indian Academy of Sciences (India)

    BASANT LAL SHARMA

    2017-05-01

    A low-frequency approximation of the discrete Sommerfeld diffraction problems, involving the scattering of a time harmonic lattice wave incident on square lattice by a discrete Dirichlet or a discrete Neumann half-plane, is investigated. It is established that the exact solution of the discrete model converges to the solution of the continuum model, i.e., the continuous Sommerfeld problem, in the discrete Sobolev space defined by Hackbusch. A proof of convergence has been provided for both types of boundary conditions when the imaginary part of incident wavenumber is positive.

  13. Torus Bifurcation Under Discretization

    Institute of Scientific and Technical Information of China (English)

    邹永魁; 黄明游

    2002-01-01

    Parameterized dynamical systems with a simple zero eigenvalue and a couple of purely imaginary eigenvalues are considered. It is proved that this type of eigen-structure leads to torns bifurcation under certain nondegenerate conditions. We show that the discrete systems, obtained by discretizing the ODEs using symmetric, eigen-structure preserving schemes, inherit the similar torus bifurcation properties. Fredholm theory in Banach spaces is applied to obtain the global torns bifurcation. Our results complement those on the study of discretization effects of global bifurcation.

  14. Discrete density of states

    Science.gov (United States)

    Aydin, Alhun; Sisman, Altug

    2016-03-01

    By considering the quantum-mechanically minimum allowable energy interval, we exactly count number of states (NOS) and introduce discrete density of states (DOS) concept for a particle in a box for various dimensions. Expressions for bounded and unbounded continua are analytically recovered from discrete ones. Even though substantial fluctuations prevail in discrete DOS, they're almost completely flattened out after summation or integration operation. It's seen that relative errors of analytical expressions of bounded/unbounded continua rapidly decrease for high NOS values (weak confinement or high energy conditions), while the proposed analytical expressions based on Weyl's conjecture always preserve their lower error characteristic.

  15. Discrete fractional calculus

    CERN Document Server

    Goodrich, Christopher

    2015-01-01

    This text provides the first comprehensive treatment of the discrete fractional calculus. Experienced researchers will find the text useful as a reference for discrete fractional calculus and topics of current interest. Students who are interested in learning about discrete fractional calculus will find this text to provide a useful starting point. Several exercises are offered at the end of each chapter and select answers have been provided at the end of the book. The presentation of the content is designed to give ample flexibility for potential use in a myriad of courses and for independent study. The novel approach taken by the authors includes a simultaneous treatment of the fractional- and integer-order difference calculus (on a variety of time scales, including both the usual forward and backwards difference operators). The reader will acquire a solid foundation in the classical topics of the discrete calculus while being introduced to exciting recent developments, bringing them to the frontiers of the...

  16. Compatible Spatial Discretizations for Partial Differential Equations

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, Douglas, N, ed.

    2004-11-25

    From May 11--15, 2004, the Institute for Mathematics and its Applications held a hot topics workshop on Compatible Spatial Discretizations for Partial Differential Equations. The numerical solution of partial differential equations (PDE) is a fundamental task in science and engineering. The goal of the workshop was to bring together a spectrum of scientists at the forefront of the research in the numerical solution of PDEs to discuss compatible spatial discretizations. We define compatible spatial discretizations as those that inherit or mimic fundamental properties of the PDE such as topology, conservation, symmetries, and positivity structures and maximum principles. A wide variety of discretization methods applied across a wide range of scientific and engineering applications have been designed to or found to inherit or mimic intrinsic spatial structure and reproduce fundamental properties of the solution of the continuous PDE model at the finite dimensional level. A profusion of such methods and concepts relevant to understanding them have been developed and explored: mixed finite element methods, mimetic finite differences, support operator methods, control volume methods, discrete differential forms, Whitney forms, conservative differencing, discrete Hodge operators, discrete Helmholtz decomposition, finite integration techniques, staggered grid and dual grid methods, etc. This workshop seeks to foster communication among the diverse groups of researchers designing, applying, and studying such methods as well as researchers involved in practical solution of large scale problems that may benefit from advancements in such discretizations; to help elucidate the relations between the different methods and concepts; and to generally advance our understanding in the area of compatible spatial discretization methods for PDE. Particular points of emphasis included: + Identification of intrinsic properties of PDE models that are critical for the fidelity of numerical

  17. The Discrete Wavelet Transform

    Science.gov (United States)

    1991-06-01

    focuses on bringing together two separately motivated implementations of the wavelet transform , the algorithm a trous and Mallat’s multiresolution...decomposition. These algorithms are special cases of a single filter bank structure, the discrete wavelet transform , the behavior of which is governed by...nonorthogonal multiresolution algorithm for which the discrete wavelet transform is exact. Moreover, we show that the commonly used Lagrange a trous

  18. Discrete computational structures

    CERN Document Server

    Korfhage, Robert R

    1974-01-01

    Discrete Computational Structures describes discrete mathematical concepts that are important to computing, covering necessary mathematical fundamentals, computer representation of sets, graph theory, storage minimization, and bandwidth. The book also explains conceptual framework (Gorn trees, searching, subroutines) and directed graphs (flowcharts, critical paths, information network). The text discusses algebra particularly as it applies to concentrates on semigroups, groups, lattices, propositional calculus, including a new tabular method of Boolean function minimization. The text emphasize

  19. Time domain analysis for discrete difference equation on discrete linear system controllable problem's research

    Institute of Scientific and Technical Information of China (English)

    DENG Shu-xian; DING Yu; GE Lei

    2008-01-01

    We usually describle a comparatively more complex control system, especially a multi-inputs and multioutputs system by time domation analytical procedure. While the system's controllability means whether the system is controllable according to certain requirements. It involves not only the system's outputs' controllability but also the controllability of the system's partial or total conditions. The movement is described by difference equation in the linear discrete-time system. Therefore, the problem of controllability of the linear discrete-time system has been converted into a problem of the controllability of discrete-time difference equation. The thesis makes out the determination method of the discrete-time system's controllability and puts forward the sufficient and necessary conditions to determine it's controllability by making a study on the controllability of the linear discrete-time equation.

  20. Fundamental approach to discrete mathematics

    CERN Document Server

    Acharjya, DP

    2009-01-01

    About the Book: The book `Fundamental Approach to Discrete Mathematics` is a required part of pursuing a computer science degree at most universities. It provides in-depth knowledge to the subject for beginners and stimulates further interest in the topic. The salient features of this book include: Strong coverage of key topics involving recurrence relation, combinatorics, Boolean algebra, graph theory and fuzzy set theory. Algorithms and examples integrated throughout the book to bring clarity to the fundamental concepts. Each concept and definition is followed by thoughtful examples.

  1. Sex influences on the penetrance of HLA shared-epitope genotypes for rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, J.M. [Virginia Commonwealth Univ., Richmond, VA (United States)] [and others

    1996-02-01

    The association between rheumatoid arthritis (RA) and HLA DRB1 alleles may arise through linkage disequilibrium with a disease locus or the direct involvement of HLA alleles in RA. In support of the latter possibility, the shared-epitope hypothesis has been postulated, stating that conformationally similar DR{beta} chains encoded by several DRB1 alleles confer disease susceptibility. To examine these alternative hypotheses of marker-disease association and to investigate gender differences in RA susceptibility, we analyzed the distributions of PCR-based DRB1 genotypes of 309 Caucasian RA patients and 283 Caucasian controls. Initially, the marker-association-segregation {chi}{sup 2} method was used to evaluate evidence for linkage disequilibrium and the direct involvement of markers DR4 Dw4, DR4 Dw14, and DR1 in RA susceptibility. Additional shared-epitope models that grouped DRB1 alleles into five classes (*0401, *0404/*0102, *0405/*0408/*0101, *1001, and all others) and postulated relationships between genotypes and RA susceptibility were also fitted to observed genotypic distributions by the method of minimal {chi}{sup 2}. For females, a linkage-disequilibrium model provided a good fit to the data, as did a shared-epitope model with RA most penetrant among individuals with the *0401, *0401 genotype. For males, the best model indicated highest RA penetrance among shared-epitope compound heterozygotes. Clinically, male RA patients had more subcutaneous nodules and greater use of slowly acting antirheumatic drugs, while female RA patients had earlier disease onset. This study therefore suggests that sex-related factors influence the RA penetrance associated with DRB1 shared-epitope genotypes and that DRB1 effects on RA prognosis and pathogenesis should be considered separately for men and women. 67 refs., 7 tabs.

  2. Discrete fractional Radon transforms and quadratic forms

    CERN Document Server

    Pierce, Lillian B

    2010-01-01

    We consider discrete analogues of fractional Radon transforms involving integration over paraboloids defined by positive definite quadratic forms. We prove sharp results for this class of discrete operators in all dimensions, providing necessary and sufficient conditions for them to extend to bounded operators from $\\ell^p$ to $\\ell^q$. The method involves an intricate spectral decomposition according to major and minor arcs, motivated by ideas from the circle method of Hardy and Littlewood. Techniques from harmonic analysis, in particular Fourier transform methods and oscillatory integrals, as well as the number theoretic structure of quadratic forms, exponential sums, and theta functions, play key roles in the proof.

  3. Identification of distinct antibody epitopes and mimotopes from a peptide array of 5520 randomly generated sequences.

    Science.gov (United States)

    Reineke, Ulrich; Ivascu, Claudia; Schlief, Marén; Landgraf, Christiane; Gericke, Seike; Zahn, Grit; Herzel, Hanspeter; Volkmer-Engert, Rudolf; Schneider-Mergener, Jens

    2002-09-01

    We used a relatively small library of 5520 randomly generated single 15-mer peptides prepared by SPOT synthesis as an array of 28.5x19.0 cm to identify epitopes for three distinct monoclonal antibodies, namely anti-p24 (human immunodeficiency virus (HIV)-1) monoclonal anibody (mab) CB4-1, anti-interleukin-10 (IL-10) mab CB/RS/13, and anti-transforming growth factor alpha (TGFalpha) mab Tab2. Initially identified peptide ligands mostly had very low affinities for the antibodies with dissociation constants around 10(-4) M. Subsequent identification of residues critical for the antibody interactions involved complete L-amino acid substitutional analyses. Several substitutions resulted in analogs with dissociation constants in the low micromolar and high nanomolar range. Specifically binding peptides with key residue patterns matching the wild-type epitopes were identified for all three antibodies. In addition, for antibody CB4-1 mimotopes that showed no homology to the known epitope were selected. Our results suggest that a very limited library diversity, although far from covering the entire sequence repertoire, can suffice to rapidly and economically select peptidic antibody epitopes and mimotopes.

  4. 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.

  5. Identification of immunodominant epitopes in Trypanosoma cruzi trypomastigote surface antigen-1 protein that mask protective epitopes.

    Science.gov (United States)

    Wrightsman, R A; Dawson, B D; Fouts, D L; Manning, J E

    1994-10-01

    The gene that encodes trypomastigote surface Ag-1 (TSA-1), a major surface Ag of the bloodstream trypomastigote stage of Trypanosoma cruzi, was expressed in a baculovirus expression system. To determine the epitope(s) in TSA-1 that was recognized during T. cruzi infection and after immunization with TSA-1, subregions of the TSA-1 gene were expressed in a bacterial expression system. As seen by Western blotting, both mice and rabbits immunized with recombinant TSA-1 protein, as well as T. cruzi-infected mice, developed strong immune responses to the carboxyl-proximal region of TSA-1, but show no reaction to the amino-proximal portion of TSA-1. When mice were immunized with either recombinant TSA-1 protein or the carboxyl-proximal region of TSA-1, they did not survive challenge with 10(3) bloodstream trypomastigotes. However, 70% of the mice immunized with the amino-proximal portion of TSA-1 survived challenge with 10(3) bloodstream trypomastigotes. Thus, the immune responses elicited by recombinant TSA-1 or the carboxyl-proximal portion of TSA-1 are nonprotective during T. cruzi infection. In contrast, vaccination with the amino proximal region of TSA-1 elicits a protective immune response. These results suggest that responses to immunodominant epitope(s) within the carboxyl-proximal portion of TSA-1 mask epitopes within the amino-proximal portion that are capable of stimulating host-protective immune responses. It is suggested that immunodominant regions in surface molecules such as TSA-1 may provide a mechanism for the parasite to evade the host immune response by directing the response away from epitopes that have the potential to elicit a reaction that is damaging to the parasite.

  6. Advances of Bioinformatics Tools Applied in Virus Epitopes Prediction

    Institute of Scientific and Technical Information of China (English)

    Ping Chen; Simon Rayner; Kang-hong Hu

    2011-01-01

    In recent years, the in silico epitopes prediction tools have facilitated the progress of vaccines development significantly and many have been applied to predict epitopes in viruses successfully. Herein, a general overview of different tools currently available, including T cell and B cell epitopes prediction tools, is presented. And the principles of different prediction algorithms are reviewed briefly. Finally, several examples are present to illustrate the application of the prediction tools.

  7. Atomic-level mapping of antibody epitopes on a GPCR.

    Science.gov (United States)

    Paes, Cheryl; Ingalls, Jada; Kampani, Karan; Sulli, Chidananda; Kakkar, Esha; Murray, Meredith; Kotelnikov, Valery; Greene, Tiffani A; Rucker, Joseph B; Doranz, Benjamin J

    2009-05-27

    Epitopes that define the immunodominant regions of conformationally complex integral membrane proteins have been difficult to reliably delineate. Here, a high-throughput approach termed shotgun mutagenesis was used to map the binding epitopes of five different monoclonal antibodies targeting the GPCR CCR5. The amino acids, and in some cases the atoms, that comprise the critical contact points of each epitope were identified, defining the immunodominant structures of this GPCR and their physicochemistry.

  8. Molecular fingerprinting of complex grass allergoids: size assessments reveal new insights in epitope repertoires and functional capacities.

    Science.gov (United States)

    Starchenka, S; Bell, A J; Mwange, J; Skinner, M A; Heath, M D

    2017-01-01

    Subcutaneous allergen immunotherapy (SCIT) is a well-documented treatment for allergic disease which involves injections of native allergen or modified (allergoid) extracts. The use of allergoid vaccines is a growing sector of the allergy immunotherapy market, associated with shorter-course therapy. The aim of this study was the structural and immunological characterisation of group 1 (Lol p 1) IgG-binding epitopes within a complex mix grass allergoid formulation containing rye grass. HP-SEC was used to resolve a mix grass allergoid preparation of high molecular weight into several distinct fractions with defined molecular weight and elution profiles. Allergen verification of the HP-SEC allergoid fractions was confirmed by mass spectrometry analysis. IgE and IgG immunoreactivity of the allergoid preparations was explored and Lol p 1 specific IgG-binding epitopes mapped by SPOT synthesis technology (PepSpot™) with structural analysis based on a Lol p 1 homology model. Grass specific IgE reactivity of the mix grass modified extract (allergoid) was diminished in comparison with the mix grass native extract. A difference in IgG profiles was observed between an intact mix grass allergoid preparation and HP-SEC allergoid fractions, which indicated enhancement of accessible reactive IgG epitopes across size distribution profiles of the mix grass allergoid formulation. Detailed analysis of the epitope specificity showed retention of six Lol p 1 IgG-binding epitopes in the mix grass modified extract. The structural and immunological changes which take place following the grass allergen modification process was further unravelled revealing distinct IgG immunological profiles. All epitopes were mapped on the solvent exposed area of Lol p 1 homology model accessible for IgG binding. One of the epitopes was identified as an 'immunodominant' Lol p 1 IgG-binding epitope (62-IFKDGRGCGSCFEIK-76) and classified as a novel epitope. The results from this study support the concept

  9. Discrete-Event Simulation

    Directory of Open Access Journals (Sweden)

    Prateek Sharma

    2015-04-01

    Full Text Available Abstract Simulation can be regarded as the emulation of the behavior of a real-world system over an interval of time. The process of simulation relies upon the generation of the history of a system and then analyzing that history to predict the outcome and improve the working of real systems. Simulations can be of various kinds but the topic of interest here is one of the most important kind of simulation which is Discrete-Event Simulation which models the system as a discrete sequence of events in time. So this paper aims at introducing about Discrete-Event Simulation and analyzing how it is beneficial to the real world systems.

  10. Discrete Anderson Speckle

    CERN Document Server

    Kondakci, H Esat; Saleh, Bahaa E A

    2016-01-01

    When a disordered array of coupled waveguides is illuminated with an extended coherent optical field, discrete speckle develops: partially coherent light with a granular intensity distribution on the lattice sites. The same paradigm applies to a variety of other settings in photonics, such as imperfectly coupled resonators or fibers with randomly coupled cores. Through numerical simulations and analytical modeling, we uncover a set of surprising features that characterize discrete speckle in one- and two-dimensional lattices known to exhibit transverse Anderson localization. Firstly, the fingerprint of localization is embedded in the fluctuations of the discrete speckle and is revealed in the narrowing of the spatial coherence function. Secondly, the transverse coherence length (or speckle grain size) is frozen during propagation. Thirdly, the axial coherence depth is independent of the axial position, thereby resulting in a coherence voxel of fixed volume independently of position. We take these unique featu...

  11. Discrete systems and integrability

    CERN Document Server

    Hietarinta, J; Nijhoff, F W

    2016-01-01

    This first introductory text to discrete integrable systems introduces key notions of integrability from the vantage point of discrete systems, also making connections with the continuous theory where relevant. While treating the material at an elementary level, the book also highlights many recent developments. Topics include: Darboux and Bäcklund transformations; difference equations and special functions; multidimensional consistency of integrable lattice equations; associated linear problems (Lax pairs); connections with Padé approximants and convergence algorithms; singularities and geometry; Hirota's bilinear formalism for lattices; intriguing properties of discrete Painlevé equations; and the novel theory of Lagrangian multiforms. The book builds the material in an organic way, emphasizing interconnections between the various approaches, while the exposition is mostly done through explicit computations on key examples. Written by respected experts in the field, the numerous exercises and the thoroug...

  12. Discrete Classical Electromagnetic Fields

    CERN Document Server

    De Souza, M M

    1997-01-01

    The classical electromagnetic field of a spinless point electron is described in a formalism with extended causality by discrete finite transverse point-vector fields with discrete and localized point interactions. These fields are taken as a classical representation of photons, ``classical photons". They are all transversal photons; there are no scalar nor longitudinal photons as these are definitely eliminated by the gauge condition. The angular distribution of emitted photons coincides with the directions of maximum emission in the standard formalism. The Maxwell formalism and its standard field are retrieved by the replacement of these discrete fields by their space-time averages, and in this process scalar and longitudinal photons are necessarily created and added. Divergences and singularities are by-products of this averaging process. This formalism enlighten the meaning and the origin of the non-physical photons, the ones that violate the Lorentz condition in manifestly covariant quantization methods.

  13. Discrete breathers in crystals

    Science.gov (United States)

    Dmitriev, S. V.; Korznikova, E. A.; Baimova, Yu A.; Velarde, M. G.

    2016-05-01

    It is well known that periodic discrete defect-containing systems, in addition to traveling waves, support vibrational defect-localized modes. It turned out that if a periodic discrete system is nonlinear, it can support spatially localized vibrational modes as exact solutions even in the absence of defects. Since the nodes of the system are all on equal footing, it is only through the special choice of initial conditions that a group of nodes can be found on which such a mode, called a discrete breather (DB), will be excited. The DB frequency must be outside the frequency range of the small-amplitude traveling waves. Not resonating with and expending no energy on the excitation of traveling waves, a DB can theoretically conserve its vibrational energy forever provided no thermal vibrations or other perturbations are present. Crystals are nonlinear discrete systems, and the discovery in them of DBs was only a matter of time. It is well known that periodic discrete defect-containing systems support both traveling waves and vibrational defect-localized modes. It turns out that if a periodic discrete system is nonlinear, it can support spatially localized vibrational modes as exact solutions even in the absence of defects. Because the nodes of the system are all on equal footing, only a special choice of the initial conditions allows selecting a group of nodes on which such a mode, called a discrete breather (DB), can be excited. The DB frequency must be outside the frequency range of small-amplitude traveling waves. Not resonating with and expending no energy on the excitation of traveling waves, a DB can theoretically preserve its vibrational energy forever if no thermal vibrations or other perturbations are present. Crystals are nonlinear discrete systems, and the discovery of DBs in them was only a matter of time. Experimental studies of DBs encounter major technical difficulties, leaving atomistic computer simulations as the primary investigation tool. Despite

  14. Discrete and computational geometry

    CERN Document Server

    Devadoss, Satyan L

    2011-01-01

    Discrete geometry is a relatively new development in pure mathematics, while computational geometry is an emerging area in applications-driven computer science. Their intermingling has yielded exciting advances in recent years, yet what has been lacking until now is an undergraduate textbook that bridges the gap between the two. Discrete and Computational Geometry offers a comprehensive yet accessible introduction to this cutting-edge frontier of mathematics and computer science. This book covers traditional topics such as convex hulls, triangulations, and Voronoi diagrams, as well a

  15. Deformed discrete symmetries

    Science.gov (United States)

    Arzano, Michele; Kowalski-Glikman, Jerzy

    2016-09-01

    We construct discrete symmetry transformations for deformed relativistic kinematics based on group valued momenta. We focus on the specific example of κ-deformations of the Poincaré algebra with associated momenta living on (a sub-manifold of) de Sitter space. Our approach relies on the description of quantum states constructed from deformed kinematics and the observable charges associated with them. The results we present provide the first step towards the analysis of experimental bounds on the deformation parameter κ to be derived via precision measurements of discrete symmetries and CPT.

  16. Babesia bigemina: identification of B cell epitopes associated with parasitized erythrocytes.

    Science.gov (United States)

    Vidotto, O; McElwain, T F; Machado, R Z; Perryman, L E; Suarez, C E; Palmer, G H

    1995-12-01

    Rhoptries are involved in host cell invasion and rhoptry polypeptides, including the Babesia bigemina rhoptry-associated protein-1 (RAP-1), are targets for protective immune responses. Polyclonal antisera produced against isolated rhoptries is directed predominantly against RAP-1 and reacts with both the merozoite and the membrane of parasitized erythrocytes. To determine whether these B cell epitopes associated with the parasitized erythrocyte are derived from RAP-1 or, alternatively, from previously undetected merozoite polypeptides, monoclonal antibodies (mAbs) were generated from mice immunized with rhoptries isolated from the JG-29 clone of the Mexico strain. The anti-RAP-1 mAbs bound only merozoites in a punctate immunofluorescence pattern. A second group of four mAbs, none of which were reactive with RAP-1, bound the parasitized erythrocyte. Two of these latter mAbs, 64/44.17.3 and 64/05.7.2, reacted only with parasitized erythrocytes that had been permeabilized. MAb 64/44.17.3 bound a 54-kDa merozoite polypeptide while 64/05.7.2 bound a > or = 225-kDa merozoite polypeptide. MAbs 64/32.8.5 and 64/38.5.3 recognized epitopes on 17.5- and 76-kDa polypeptides exposed on the external surface of intact parasitized erythrocytes. The results indicate that the identified RAP-1 epitopes are not associated with the erythrocyte cytoskeleton or membrane and that anti-RAP-1 immunity is most likely generated against the free merozoite. All new mAbs reacted with every B. bigemina strain tested (Mexico, Puerto Rico, St. Croix, Texcoco, Jaboticabal). The conservation of RAP-1 epitopes among these strains supports the continued testing of RAP-1 as a vaccine component. In addition, the identification of epitopes expressed on the surface of erythrocytes infected with all five strains provides new candidate immunogens.

  17. 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.

  18. Epitope DNA vaccines against tuberculosis: spacers and ubiquitin modulates cellular immune responses elicited by epitope DNA vaccine

    Institute of Scientific and Technical Information of China (English)

    Wang QM; Sun SH; Hu ZL; Zhou FJ; Yin M; Xiao CJ; Zhang JC

    2005-01-01

    Cell-mediated immune responses are crucial in the protection against tuberculosis. In this study, we constructed epitope DNA vaccines (p3-M-38) encoding cytotoxic T lymphocyte (CTL) epitopes of MPT64 and 38 kDa proteins of Mycobacterium tuberculosis. In order to observe the influence of spacer sequence (Ala-Ala-Tyr) or ubiquitin (UbGR) on the efficacy of the two CTL epitopes, we also constructed DNA vaccines, p3-M-S(spacer)-38, p3-Ub (UbGR)-M-S-38 and p3-Ub-M-38. The immune responses elicited by the four DNA vaccines were tested in C57BL/6 (H-2b) mice. The cytotoxicity of T cells was detected by LDH-release method and by enzyme-linked immunospot assay for epitope-specific cells secreting interferon-gamma. The results showed that DNA immunization with p3-M-38 vaccine could induce epitope-specific CD8+ CTL response and that the spacer sequence (AAY) only enhanced M epitope presentation. The protein-targeting sequence (UbGR) enhanced the immunogenicity of the two epitopes. The finding that defined spacer sequences at C-terminus and protein-targeting degradation modulated the immune response of epitope string DNA vaccines will be of importance for the further development of multi-epitope DNA vaccines against tuberculosis.

  19. Discrete variable representation for singular Hamiltonians

    DEFF Research Database (Denmark)

    Schneider, B. I.; Nygaard, Nicolai

    2004-01-01

    We discuss the application of the discrete variable representation (DVR) to Schrodinger problems which involve singular Hamiltonians. Unlike recent authors who invoke transformations to rid the eigenvalue equation of singularities at the cost of added complexity, we show that an approach based...

  20. Cuspidal discrete series for projective hyperbolic spaces

    DEFF Research Database (Denmark)

    Andersen, Nils Byrial; Flensted-Jensen, Mogens

    2013-01-01

    Abstract. We have in [1] proposed a definition of cusp forms on semisimple symmetric spaces G/H, involving the notion of a Radon transform and a related Abel transform. For the real non-Riemannian hyperbolic spaces, we showed that there exists an infinite number of cuspidal discrete series, and a...

  1. Within-Epitope Interactions Can Bias CTL Escape Estimation in Early HIV Infection

    Directory of Open Access Journals (Sweden)

    Victor Garcia

    2017-05-01

    Full Text Available As human immunodeficiency virus (HIV begins to replicate within hosts, immune responses are elicited against it. Escape mutations in viral epitopes—immunogenic peptide parts presented on the surface of infected cells—allow HIV to partially evade these responses, and thus rapidly go to fixation. The faster they go to fixation, i.e., the higher their escape rate, the larger the selective pressure exerted by the immune system is assumed to be. This relation underpins the rationale for using escapes to assess the strength of immune responses. However, escape rate estimates are often obtained by employing an aggregation procedure, where several mutations that affect the same epitope are aggregated into a single, composite epitope mutation. The aggregation procedure thus rests upon the assumption that all within-epitope mutations have indistinguishable effects on immune recognition. In this study, we investigate how violation of this assumption affects escape rate estimates. To this end, we extend a previously developed simulation model of HIV that accounts for mutation, selection, and recombination to include different distributions of fitness effects (DFEs and inter-mutational genomic distances. We use this discrete time Wright–Fisher based model to simulate early within-host evolution of HIV for DFEs and apply standard estimation methods to infer the escape rates. We then compare true with estimated escape rate values. We also compare escape rate values obtained by applying the aggregation procedure with values estimated without use of that procedure. We find that across the DFEs analyzed, the aggregation procedure alters the detectability of escape mutations: large-effect mutations are overrepresented while small-effect mutations are concealed. The effect of the aggregation procedure is similar to extracting the largest-effect mutation appearing within an epitope. Furthermore, the more pronounced the over-exponential decay of the DFEs, the

  2. The discrete Feynman integral

    NARCIS (Netherlands)

    Dorlas, T. C.; Thomas, E. G. F.

    2008-01-01

    We construct a genuine Radon measure with values in B(l(2)(Z(d))) on the set of paths in Z(d) representing Feynman's integral for the discrete Laplacian on l(2)(Z(d)), and we prove the Feynman integral formula for the solutions of the Schrodinger equation with Hamiltonian H=-1/2 Delta+ V, where Delt

  3. Discrete time process algebra

    NARCIS (Netherlands)

    Bergstra, J.A.; Baeten, J.C.M.

    1996-01-01

    The axiom system ACP of [BeK84a] was extended with real time features in [BaB91]. Here we proceed to define a discrete time extension of ACP, along the lines of ATP [NiS94]. We present versions based on relative timing and on absolute timing. Both approaches are integrated using parametric timing. T

  4. Discrete gauge theories

    NARCIS (Netherlands)

    de Wild Propitius, M.D.F.; Bais, F.A.

    1999-01-01

    In these lectures, we present a self-contained treatment of planar gauge theories broken down to some finite residual gauge group $H$ via the Higgs mechanism. The main focus is on the discrete $H$ gauge theory describing the long distance physics of such a model. The spectrum features global $H$ cha

  5. The molecular relationship between antigenic domains and epitopes on hCG.

    Science.gov (United States)

    Berger, Peter; Lapthorn, Adrian J

    2016-08-01

    CGβŁ1+3 (aa 20-25+64+68-81) and hCGαŁ1 (aa 13-22; Pro16, Phe17, Phe18) plus hCGαŁ3 (Met71, Phe74), respectively, have been identified in the two "ISOBM Tissue Differentiation-7 Workshops on hCG and Related Molecules" and in other studies. These Abs recognize distinct but overlapping epitopes with slightly different specificity profiles and affinities. Heterodimeric-specific epitopes involve neighboring αŁ1 plus βŁ2 (hCGβ44/45 and 47/48). Diagnostically important Abs recognize the middle of the molecule, the ck (aa Arg10, Arg60 and possibly Gln89) and the linear hCGβCTP "tail" (aa 135-145; Asp139, Pro144, Gln145), respectively. Identification of antigenic domains and of specific epitopes is essential for harmonization of Abs in methods that are used for reliable and robust hCG measurements for the management of pregnancy, pregnancy-related disease and tumors.

  6. 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 epitope...... that is specifically associated with a plant cell separation process that results in complete cell detachment....

  7. Quantum dynamical entropies for discrete classical systems: a comparison

    Energy Technology Data Exchange (ETDEWEB)

    Cappellini, Valerio [Dipartimento di Fisica Teorica, Universita di Trieste, Strada Costiera 11, 34014 Trieste (Italy)

    2005-08-05

    On a family of classical dynamical systems on the 2-torus, we perform a discretization procedure similar to the anti-Wick quantization. Such a discretization is performed by using a particular class of states, fulfilling an appropriate dynamical localization property, typical of quantum coherent states. The same set of states is involved in the construction of a quantum entropy, that we test on the discrete approximants; a correspondence with the classical metric entropy of Kolmogorov-Sinai is found only over time scales that are logarithmic in the discretization parameter.

  8. Autoantibody recognition mechanisms of p53 epitopes

    Science.gov (United States)

    Phillips, J. C.

    2016-06-01

    There is an urgent need for economical blood based, noninvasive molecular biomarkers to assist in the detection and diagnosis of cancers in a cost-effective manner at an early stage, when curative interventions are still possible. Serum autoantibodies are attractive biomarkers for early cancer detection, but their development has been hindered by the punctuated genetic nature of the ten million known cancer mutations. A landmark study of 50,000 patients (Pedersen et al., 2013) showed that a few p53 15-mer epitopes are much more sensitive colon cancer biomarkers than p53, which in turn is a more sensitive cancer biomarker than any other protein. The function of p53 as a nearly universal "tumor suppressor" is well established, because of its strong immunogenicity in terms of not only antibody recruitment, but also stimulation of autoantibodies. Here we examine dimensionally compressed bioinformatic fractal scaling analysis for identifying the few sensitive epitopes from the p53 amino acid sequence, and show how it could be used for early cancer detection (ECD). We trim 15-mers to 7-mers, and identify specific 7-mers from other species that could be more sensitive to aggressive human cancers, such as liver cancer. Our results could provide a roadmap for ECD.

  9. High-Throughput Tools for Characterization of Antibody Epitopes

    DEFF Research Database (Denmark)

    Christiansen, Anders

    , it is important to characterize antibodies thoroughly. In parallel to the characterization of antibodies, it is also important to characterize the binding area that is recognized by the antibody, known as an epitope. With the development of new technologies, such as high-throughput sequencing (HTS....... 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...... multiple years. Taken together, the presented studies demonstrated new applications for the investigated techniques focusing on their utilization in epitope mapping. In the process, new insights were obtained into how antibodies recognize their targets in a major disease, i.e. food allergy....

  10. Analysis of cytotoxic T cell epitopes in relation to cancer

    DEFF Research Database (Denmark)

    Stranzl, Thomas

    kill the infected cells. The focus of my PhD project has been on improving a method for CTL epitope pathway prediction, on analyzing the epitope density in the alternative cancer exome, and on a study investigating minor histocompatibility antigens (mHags) associated with leukemia. Part I......CTL methods, the experimental effort to identify 90% of new epitopes can be reduced by 15% and 40%, respectively. Part III reports the results of an analysis investigating how the alternatively spliced cancer exome differs from the exome of normal tissue in terms of containing predicted MHC class I binding...... epitopes. We show that peptides unique to cancer splice variants comprise significantly fewer predicted HLA class I epitopes than peptides unique to spliced transcripts in normal tissue. We furthermore find that hydrophilic amino acids are significantly enriched in the unique carcinoma sequences, which...

  11. Discrete geometric structures for architecture

    KAUST Repository

    Pottmann, Helmut

    2010-06-13

    The emergence of freeform structures in contemporary architecture raises numerous challenging research problems, most of which are related to the actual fabrication and are a rich source of research topics in geometry and geometric computing. The talk will provide an overview of recent progress in this field, with a particular focus on discrete geometric structures. Most of these result from practical requirements on segmenting a freeform shape into planar panels and on the physical realization of supporting beams and nodes. A study of quadrilateral meshes with planar faces reveals beautiful relations to discrete differential geometry. In particular, we discuss meshes which discretize the network of principal curvature lines. Conical meshes are among these meshes; they possess conical offset meshes at a constant face/face distance, which in turn leads to a supporting beam layout with so-called torsion free nodes. This work can be generalized to a variety of multilayer structures and laid the ground for an adapted curvature theory for these meshes. There are also efforts on segmenting surfaces into planar hexagonal panels. Though these are less constrained than planar quadrilateral panels, this problem is still waiting for an elegant solution. Inspired by freeform designs in architecture which involve circles and spheres, we present a new kind of triangle mesh whose faces\\' in-circles form a packing, i.e., the in-circles of two triangles with a common edge have the same contact point on that edge. These "circle packing (CP) meshes" exhibit an aesthetic balance of shape and size of their faces. They are closely tied to sphere packings on surfaces and to various remarkable structures and patterns which are of interest in art, architecture, and design. CP meshes constitute a new link between architectural freeform design and computational conformal geometry. Recently, certain timber structures motivated us to study discrete patterns of geodesics on surfaces. This

  12. Broad epitope coverage of a human in vitro antibody library

    Science.gov (United States)

    Sivasubramanian, Arvind; Lynaugh, Heather; Yu, Yao; Miles, Adam; Eckman, Josh; Schutz, Kevin; Piffath, Crystal; Boland, Nadthakarn; Durand, Stéphanie; Boland, Todd; Vásquez, Maximiliano; Xu, Yingda; Abdiche, Yasmina

    2017-01-01

    ABSTRACT Successful discovery of therapeutic antibodies hinges on the identification of appropriate affinity binders targeting a diversity of molecular epitopes presented by the antigen. Antibody campaigns that yield such broad “epitope coverage” increase the likelihood of identifying candidates with the desired biological functions. Accordingly, epitope binning assays are employed in the early discovery stages to partition antibodies into epitope families or “bins” and prioritize leads for further characterization and optimization. The collaborative program described here, which used hen egg white lysozyme (HEL) as a model antigen, combined 3 key capabilities: 1) access to a diverse panel of antibodies selected from a human in vitro antibody library; 2) application of state-of-the-art high-throughput epitope binning; and 3) analysis and interpretation of the epitope binning data with reference to an exhaustive set of published antibody:HEL co-crystal structures. Binning experiments on a large merged panel of antibodies containing clones from the library and the literature revealed that the inferred epitopes for the library clones overlapped with, and extended beyond, the known structural epitopes. Our analysis revealed that nearly the entire solvent-exposed surface of HEL is antigenic, as has been proposed for protein antigens in general. The data further demonstrated that synthetic antibody repertoires provide as wide epitope coverage as those obtained from animal immunizations. The work highlights molecular insights contributed by increasingly higher-throughput binning methods and their broad utility to guide the discovery of therapeutic antibodies representing a diverse set of functional epitopes. PMID:27748644

  13. B Epitope Multiplicity and B/T Epitope Orientation Influence Immunogenicity of Foot-and-Mouth Disease Peptide Vaccines

    Directory of Open Access Journals (Sweden)

    Esther Blanco

    2013-01-01

    Full Text Available Synthetic peptides incorporating protective B- and T-cell epitopes are candidates for new safer foot-and-mouth disease (FMD vaccines. We have reported that dendrimeric peptides including four copies of a B-cell epitope (VP1 136 to 154 linked to a T-cell epitope (3A 21 to 35 of FMD virus (FMDV elicit potent B- and T-cell specific responses and confer protection to viral challenge, while juxtaposition of these epitopes in a linear peptide induces less efficient responses. To assess the relevance of B-cell epitope multivalency, dendrimers bearing two (B2T or four (B4T copies of the B-cell epitope from type O FMDV (a widespread circulating serotype were tested in CD1 mice and showed that multivalency is advantageous over simple B-T-epitope juxtaposition, resulting in efficient induction of neutralizing antibodies and optimal release of IFNγ. Interestingly, the bivalent B2T construction elicited similar or even better B- and T-cell specific responses than tetravalent B4T. In addition, the presence of the T-cell epitope and its orientation were shown to be critical for the immunogenicity of the linear juxtaposed monovalent peptides analyzed in parallel. Taken together, our results provide useful insights for a more accurate design of FMD subunit vaccines.

  14. EPITOPE MAPPING OF SCLC-CLUSTER-2 MABS AND GENERATION OF ANTIBODIES DIRECTED AGAINST NEW EGP-2 EPITOPES

    NARCIS (Netherlands)

    HELFRICH, W; KONING, PW; THE, TH; DELEIJ, L

    1994-01-01

    Western blot analysis proved that all cluster-2 MAbs recognize identical or overlapping disulfide-bond-dependent epitopes, indicating the presence of a disulfide-bond-stabilized EGP-2 domain carrying highly immunodominant non-linear epitopes. The apparent immunodominance of this domain makes it diff

  15. Is Fitts' law continuous in discrete aiming?

    Directory of Open Access Journals (Sweden)

    Rita Sleimen-Malkoun

    Full Text Available The lawful continuous linear relation between movement time and task difficulty (i.e., index of difficulty; ID in a goal-directed rapid aiming task (Fitts' law has been recently challenged in reciprocal performance. Specifically, a discontinuity was observed at critical ID and was attributed to a transition between two distinct dynamic regimes that occurs with increasing difficulty. In the present paper, we show that such a discontinuity is also present in discrete aiming when ID is manipulated via target width (experiment 1 but not via target distance (experiment 2. Fitts' law's discontinuity appears, therefore, to be a suitable indicator of the underlying functional adaptations of the neuro-muscular-skeletal system to task properties/requirements, independently of reciprocal or discrete nature of the task. These findings open new perspectives to the study of dynamic regimes involved in discrete aiming and sensori-motor mechanisms underlying the speed-accuracy trade-off.

  16. Discrete mathematics with applications

    CERN Document Server

    Koshy, Thomas

    2003-01-01

    This approachable text studies discrete objects and the relationsips that bind them. It helps students understand and apply the power of discrete math to digital computer systems and other modern applications. It provides excellent preparation for courses in linear algebra, number theory, and modern/abstract algebra and for computer science courses in data structures, algorithms, programming languages, compilers, databases, and computation.* Covers all recommended topics in a self-contained, comprehensive, and understandable format for students and new professionals * Emphasizes problem-solving techniques, pattern recognition, conjecturing, induction, applications of varying nature, proof techniques, algorithm development and correctness, and numeric computations* Weaves numerous applications into the text* Helps students learn by doing with a wealth of examples and exercises: - 560 examples worked out in detail - More than 3,700 exercises - More than 150 computer assignments - More than 600 writing projects*...

  17. Discrete Variational Optimal Control

    CERN Document Server

    Jimenez, Fernando; de Diego, David Martin

    2012-01-01

    This paper develops numerical methods for optimal control of mechanical systems in the Lagrangian setting. It extends the theory of discrete mechanics to enable the solutions of optimal control problems through the discretization of variational principles. The key point is to solve the optimal control problem as a variational integrator of a specially constructed higher-dimensional system. The developed framework applies to systems on tangent bundles, Lie groups, underactuated and nonholonomic systems with symmetries, and can approximate either smooth or discontinuous control inputs. The resulting methods inherit the preservation properties of variational integrators and result in numerically robust and easily implementable algorithms. Several theoretical and a practical examples, e.g. the control of an underwater vehicle, will illustrate the application of the proposed approach.

  18. Discrete Variational Optimal Control

    Science.gov (United States)

    Jiménez, Fernando; Kobilarov, Marin; Martín de Diego, David

    2013-06-01

    This paper develops numerical methods for optimal control of mechanical systems in the Lagrangian setting. It extends the theory of discrete mechanics to enable the solutions of optimal control problems through the discretization of variational principles. The key point is to solve the optimal control problem as a variational integrator of a specially constructed higher dimensional system. The developed framework applies to systems on tangent bundles, Lie groups, and underactuated and nonholonomic systems with symmetries, and can approximate either smooth or discontinuous control inputs. The resulting methods inherit the preservation properties of variational integrators and result in numerically robust and easily implementable algorithms. Several theoretical examples and a practical one, the control of an underwater vehicle, illustrate the application of the proposed approach.

  19. Discrete dynamical models

    CERN Document Server

    Salinelli, Ernesto

    2014-01-01

    This book provides an introduction to the analysis of discrete dynamical systems. The content is presented by an unitary approach that blends the perspective of mathematical modeling together with the ones of several discipline as Mathematical Analysis, Linear Algebra, Numerical Analysis, Systems Theory and Probability. After a preliminary discussion of several models, the main tools for the study of linear and non-linear scalar dynamical systems are presented, paying particular attention to the stability analysis. Linear difference equations are studied in detail and an elementary introduction of Z and Discrete Fourier Transform is presented. A whole chapter is devoted to the study of bifurcations and chaotic dynamics. One-step vector-valued dynamical systems are the subject of three chapters, where the reader can find the applications to positive systems, Markov chains, networks and search engines. The book is addressed mainly to students in Mathematics, Engineering, Physics, Chemistry, Biology and Economic...

  20. Time Discretization Techniques

    KAUST Repository

    Gottlieb, S.

    2016-10-12

    The time discretization of hyperbolic partial differential equations is typically the evolution of a system of ordinary differential equations obtained by spatial discretization of the original problem. Methods for this time evolution include multistep, multistage, or multiderivative methods, as well as a combination of these approaches. The time step constraint is mainly a result of the absolute stability requirement, as well as additional conditions that mimic physical properties of the solution, such as positivity or total variation stability. These conditions may be required for stability when the solution develops shocks or sharp gradients. This chapter contains a review of some of the methods historically used for the evolution of hyperbolic PDEs, as well as cutting edge methods that are now commonly used.

  1. Linearity stabilizes discrete breathers

    Indian Academy of Sciences (India)

    T R Krishna Mohan; Surajit Sen

    2011-11-01

    The study of the dynamics of 1D chains with both harmonic and nonlinear interactions, as in the Fermi–Pasta–Ulam (FPU) and related problems, has played a central role in efforts to identify the broad consequences of nonlinearity in these systems. Here we study the dynamics of highly localized excitations, or discrete breathers, which are known to be initiated by the quasistatic stretching of bonds between adjacent particles. We show via dynamical simulations that acoustic waves introduced by the harmonic term stabilize the discrete breather by suppressing the breather’s tendency to delocalize and disperse. We conclude that the harmonic term, and hence acoustic waves, are essential for the existence of localized breathers in these systems.

  2. Lectures on discrete geometry

    CERN Document Server

    2002-01-01

    Discrete geometry investigates combinatorial properties of configurations of geometric objects. To a working mathematician or computer scientist, it offers sophisticated results and techniques of great diversity and it is a foundation for fields such as computational geometry or combinatorial optimization. This book is primarily a textbook introduction to various areas of discrete geometry. In each area, it explains several key results and methods, in an accessible and concrete manner. It also contains more advanced material in separate sections and thus it can serve as a collection of surveys in several narrower subfields. The main topics include: basics on convex sets, convex polytopes, and hyperplane arrangements; combinatorial complexity of geometric configurations; intersection patterns and transversals of convex sets; geometric Ramsey-type results; polyhedral combinatorics and high-dimensional convexity; and lastly, embeddings of finite metric spaces into normed spaces. Jiri Matousek is Professor of Com...

  3. Steerable Discrete Cosine Transform

    OpenAIRE

    Fracastoro, Giulia; Fosson, Sophie; Magli, Enrico

    2017-01-01

    In image compression, classical block-based separable transforms tend to be inefficient when image blocks contain arbitrarily shaped discontinuities. For this reason, transforms incorporating directional information are an appealing alternative. In this paper, we propose a new approach to this problem, namely, a discrete cosine transform (DCT) that can be steered in any chosen direction. Such transform, called steerable DCT (SDCT), allows to rotate in a flexible way pairs of basis vectors, an...

  4. Discrete Quantum Mechanics

    OpenAIRE

    Odake, Satoru; Sasaki, Ryu

    2011-01-01

    A comprehensive review of the discrete quantum mechanics with the pure imaginary shifts and the real shifts is presented in parallel with the corresponding results in the ordinary quantum mechanics. The main subjects to be covered are the factorised Hamiltonians, the general structure of the solution spaces of the Schroedinger equation (Crum's theorem and its modification), the shape invariance, the exact solvability in the Schroedinger picture as well as in the Heisenberg picture, the creati...

  5. Quantum evolution by discrete measurements

    Energy Technology Data Exchange (ETDEWEB)

    Roa, L [Center for Quantum Optics and Quantum Information, Departamento de Fisica, Universidad de Concepcion, Casilla 160-C, Concepcion (Chile); Guevara, M L Ladron de [Departamento de Fisica, Universidad Catolica del Norte, Casilla 1280, Antofagasta (Chile); Delgado, A [Center for Quantum Optics and Quantum Information, Departamento de Fisica, Universidad de Concepcion, Casilla 160-C, Concepcion (Chile); Olivares-RenterIa, G [Center for Quantum Optics and Quantum Information, Departamento de Fisica, Universidad de Concepcion, Casilla 160-C, Concepcion (Chile); Klimov, A B [Departamento de Fisica, Universidad de Guadalajara, Revolucion 1500, 44420 Guadalajara, Jalisco (Mexico)

    2007-10-15

    In this article we review two ways of driving a quantum system to a known pure state via a sequence discrete of von Neumann measurements. The first of them assumes that the initial state of the system is unknown, and the evolution is attained only with the help of two non-commuting observables. For this method, the overall success probability is maximized when the eigentstates of the involved observables constitute mutually unbiased bases. The second method assumes the initial state is known and it uses N observables which are consecutively measured to make the state of the system approach the target state. The probability of success of this procedure converges to 1 as the number of observables increases.

  6. Identification of Autoantigen Epitopes in Alopecia Areata.

    Science.gov (United States)

    Wang, Eddy H C; Yu, Mei; Breitkopf, Trisia; Akhoundsadegh, Noushin; Wang, Xiaojie; Shi, Feng-Tao; Leung, Gigi; Dutz, Jan P; Shapiro, Jerry; McElwee, Kevin J

    2016-08-01

    Alopecia areata (AA) is believed to be a cell-mediated autoimmune hair loss disease. Both CD4 and cytotoxic CD8 T cells (CTLs) are important for the onset and progression of AA. Hair follicle (HF) keratinocyte and/or melanocyte antigen epitopes are suspected potential targets of autoreactive CTLs, but the specific epitopes have not yet been identified. We investigated the potential for a panel of known epitopes, expressed by HF keratinocytes and melanocytes, to induce activation of CTL populations in peripheral blood mononuclear cells. Specific synthetic epitopes derived from HF antigens trichohyalin and tyrosinase-related protein-2 induced significantly higher frequencies of response in AA CTLs compared with healthy controls (IFN-gamma secretion). Apoptosis assays revealed conditioned media from AA peripheral blood mononuclear cells stimulated with trichohyalin peptides elevated the expression of apoptosis markers in primary HF keratinocytes. A cytokine array revealed higher expression of IL-13 and chemokine ligand 5 (CCL5, RANTES) from AA peripheral blood mononuclear cells stimulated with trichohyalin peptides compared with controls. The data indicate that AA affected subjects present with an increased frequency of CTLs responsive to epitopes originating from keratinocytes and melanocytes; the activated CTLs secreted soluble factors that induced apoptosis in HF keratinocytes. Potentially, CTL response to self-antigen epitopes, particularly trichohyalin epitopes, could be a prognostic marker for human AA.

  7. In situ localization of epidermal stem cells using a novel multi epitope ligand cartography approach.

    Science.gov (United States)

    Ruetze, Martin; Gallinat, Stefan; Wenck, Horst; Deppert, Wolfgang; Knott, Anja

    2010-06-01

    Precise knowledge of the frequency and localization of epidermal stem cells within skin tissue would further our understanding of their role in maintaining skin homeostasis. As a novel approach we used the recently developed method of multi epitope ligand cartography, applying a set of described putative epidermal stem cell markers. Bioinformatic evaluation of the data led to the identification of several discrete basal keratinocyte populations, but none of them displayed the complete stem cell marker set. The distribution of the keratinocyte populations within the tissue was remarkably heterogeneous, but determination of distance relationships revealed a population of quiescent cells highly expressing p63 and the integrins alpha(6)/beta(1) that represent origins of a gradual differentiation lineage. This population comprises about 6% of all basal cells, shows a scattered distribution pattern and could also be found in keratinocyte holoclone colonies. The data suggest that this population identifies interfollicular epidermal stem cells.

  8. B Cell Epitope-Based Vaccination Therapy

    Directory of Open Access Journals (Sweden)

    Yoshie Kametani

    2015-08-01

    Full Text Available Currently, many peptide vaccines are undergoing clinical studies. Most of these vaccines were developed to activate cytotoxic T cells; however, the response is not robust. Unlike vaccines, anti-cancer antibodies based on passive immunity have been approved as a standard treatment. Since passive immunity is more effective in tumor treatment, the evidence suggests that limited B cell epitope-based peptide vaccines may have similar activity. Nevertheless, such peptide vaccines have not been intensively developed primarily because humoral immunity is thought to be preferable to cancer progression. B cells secrete cytokines, which suppress immune functions. This review discusses the possibility of therapeutic antibody induction by a peptide vaccine and the role of active and passive B cell immunity in cancer patients. We also discuss the use of humanized mice as a pre-clinical model. The necessity of a better understanding of the activity of B cells in cancer is also discussed.

  9. Comprehensive mapping infection-enhancing epitopes of dengue pr protein using polyclonal antibody against prM.

    Science.gov (United States)

    Luo, Yayan; Guo, Xiaolan; Yan, Huijun; Fang, Danyun; Zeng, Gucheng; Zhou, Junmei; Jiang, Lifang

    2015-07-01

    Dengue vaccine development is considered a global public health priority, but the antibody-dependent enhancement (ADE) issues have critically restricted vaccine development. Recent findings have demonstrated that pre-membrane (prM) protein was involved in dengue virus (DENV) infection enhancement. Although the importance of prM antibodies have been well characterized, only a few epitopes in DENV prM protein have ever been identified. In this study, we screened five potential linear epitopes located at positions pr1 (1-16aa), pr3 (13-28aa), pr4 (19-34aa), pr9 (49-64aa), and pr10 (55-70aa) in pr protein using peptide scanning and comprehensive bioinformatics analysis. Then, we found that only pr4 (19-34aa) could elicit high-titer antibodies in Balb/c mice, and this epitope could react with sera from DENV2-infected patients, suggesting that specific antibodies against epitope peptide pr4 were elicited in both DENV-infected mice and human. In addition, our data demonstrated that anti-pr4 sera showed limited neutralizing activity but significant ADE activity toward standard DENV serotypes and imDENV. Hence, it seems responsible to hypothesize that anti-pr4 serum was infection-enhancing antibody and pr4 was infection-enhancing epitope. In conclusion, we characterized a novel infection-enhancing epitope on dengue pr protein, a finding that may provide new insight into the pathogenesis of DENV infection and contribute to dengue vaccine design.

  10. Immune control in the absence of immunodominant epitopes: implications for immunotherapy of cytomegalovirus infection with antiviral CD8 T cells.

    Science.gov (United States)

    Ebert, Stefan; Lemmermann, Niels A W; Thomas, Doris; Renzaho, Angélique; Reddehase, Matthias J; Holtappels, Rafaela

    2012-11-01

    Adoptive transfer of virus-specific donor-derived CD8 T cells is a therapeutic option to prevent cytomegalovirus (CMV) disease in recipients of hematopoietic cell transplantation. Due to their high coding capacity, human as well as animal CMVs have the potential to encode numerous CD8 T cell epitopes. Although the CD8 T cell response to CMVs is indeed broadly specific in that it involves epitopes derived from almost every open reading frame when tested for cohorts of immune CMV carriers representing the polymorphic MHC/HLA distribution in the population, the response in any one individual is directed against relatively few epitopes selected by the private combination of MHC/HLA alleles. Of this individually selected set of epitopes, few epitopes are 'immunodominant' in terms of magnitude of the response directed against them, while others are 'subdominant' according to this definition. In the assumption that 'immunodominance' indicates 'relevance' in antiviral control, research interest was focused on the immunodominant epitopes (IDEs) and their potential use in immunotherapy and in vaccines. The murine model has provided 'proof of concept' for the efficacy of CD8 T cell therapy of CMV infection. By experimental modulation of the CD8 T cell 'immunome' of murine CMV constructing an IDE deletion mutant, we have used this established cytoimmunotherapy model (a) for evaluating the actual contribution of IDEs to the control of infection and (b) for answering the question whether antigenicity-determining codon polymorphisms in IDE-encoding genes of CMV strains impact on the efficacy of CD8 T cell immunotherapy in case the donor and the recipient harbor different CMV strains.

  11. Prediction of epitopes using neural network based methods

    DEFF Research Database (Denmark)

    Lundegaard, Claus; Lund, Ole; Nielsen, Morten

    2011-01-01

    been evaluated to be among the very best performing MHC:peptide binding predictors available. Here we describe the background for these methods, and the rationale behind the different optimization steps implemented in the methods. We go through the practical use of the methods, which are publicly...... available in the form of relatively fast and simple web interfaces. Furthermore, we will review results obtained in actual epitope discovery projects where previous implementations of the described methods have been used in the initial selection of potential epitopes. Selected potential epitopes were all...

  12. Discrete epidemic models.

    Science.gov (United States)

    Brauer, Fred; Feng, Zhilan; Castillo-Chavez, Carlos

    2010-01-01

    The mathematical theory of single outbreak epidemic models really began with the work of Kermack and Mackendrick about decades ago. This gave a simple answer to the long-standing question of why epidemics woould appear suddenly and then disappear just as suddenly without having infected an entire population. Therefore it seemed natural to expect that theoreticians would immediately proceed to expand this mathematical framework both because the need to handle recurrent single infectious disease outbreaks has always been a priority for public health officials and because theoreticians often try to push the limits of exiting theories. However, the expansion of the theory via the inclusion of refined epidemiological classifications or through the incorporation of categories that are essential for the evaluation of intervention strategies, in the context of ongoing epidemic outbreaks, did not materialize. It was the global threat posed by SARS in that caused theoreticians to expand the Kermack-McKendrick single-outbreak framework. Most recently, efforts to connect theoretical work to data have exploded as attempts to deal with the threat of emergent and re-emergent diseases including the most recent H1N1 influenza pandemic, have marched to the forefront of our global priorities. Since data are collected and/or reported over discrete units of time, developing single outbreak models that fit collected data naturally is relevant. In this note, we introduce a discrete-epidemic framework and highlight, through our analyses, the similarities between single-outbreak comparable classical continuous-time epidemic models and the discrete-time models introduced in this note. The emphasis is on comparisons driven by expressions for the final epidemic size.

  13. Discrete Dynamics Lab

    Science.gov (United States)

    Wuensche, Andrew

    DDLab is interactive graphics software for creating, visualizing, and analyzing many aspects of Cellular Automata, Random Boolean Networks, and Discrete Dynamical Networks in general and studying their behavior, both from the time-series perspective — space-time patterns, and from the state-space perspective — attractor basins. DDLab is relevant to research, applications, and education in the fields of complexity, self-organization, emergent phenomena, chaos, collision-based computing, neural networks, content addressable memory, genetic regulatory networks, dynamical encryption, generative art and music, and the study of the abstract mathematical/physical/dynamical phenomena in their own right.

  14. 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.

  15. Design and Characterization of Epitope-Scaffold Immunogens That Present the Motavizumab Epitope from Respiratory Syncytial Virus

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-06-28

    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 {angstrom} 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.

  16. De Novo Transcriptome Analysis of Allium cepa L. (Onion Bulb to Identify Allergens and Epitopes.

    Directory of Open Access Journals (Sweden)

    Hemalatha Rajkumar

    Full Text Available Allium cepa (onion is a diploid plant with one of the largest nuclear genomes among all diploids. Onion is an example of an under-researched crop which has a complex heterozygous genome. There are no allergenic proteins and genomic data available for onions. This study was conducted to establish a transcriptome catalogue of onion bulb that will enable us to study onion related genes involved in medicinal use and allergies. Transcriptome dataset generated from onion bulb using the Illumina HiSeq 2000 technology showed a total of 99,074,309 high quality raw reads (~20 Gb. Based on sequence homology onion genes were categorized into 49 different functional groups. Most of the genes however, were classified under 'unknown' in all three gene ontology categories. Of the categorized genes, 61.2% showed metabolic functions followed by cellular components such as binding, cellular processes; catalytic activity and cell part. With BLASTx top hit analysis, a total of 2,511 homologous allergenic sequences were found, which had 37-100% similarity with 46 different types of allergens existing in the database. From the 46 contigs or allergens, 521 B-cell linear epitopes were identified using BepiPred linear epitope prediction tool. This is the first comprehensive insight into the transcriptome of onion bulb tissue using the NGS technology, which can be used to map IgE epitopes and prediction of structures and functions of various proteins.

  17. Transcriptome analysis of Solanum melongena L. (eggplant) fruit to identify putative allergens and their epitopes.

    Science.gov (United States)

    Ramesh, Kumar Ramagoni; Hemalatha, R; Vijayendra, Chary Anchoju; Arshi, Uz Zaman Syed; Dushyant, Singh Baghel; Dinesh, Kumar Bharadwaj

    2016-01-15

    Eggplant is the third most important Solanaceae crop after tomato and potato, particularly in India and China. A transcriptome analysis of eggplant's fruit was performed to study genes involved in medicinal importance and allergies. Illumina HiSeq 2000 system generated 89,763,638 raw reads (~18 Gb) from eggplant. High quality reads (59,039,694) obtained after trimming process, were assembled into a total of 149,224 non redundant set of transcripts. Out of 80,482 annotated sequences of eggplant fruit (BLASTx results against nr-green plant database), 40,752 transcripts showed significant similarity with predicted proteins of Solanum tuberosum (51%) followed by Solanum lycopersicum (34%) and other sequenced plant genomes. With BLASTx top hit analysis against existing allergens, a total of 1986 homologous allergen sequences were found, which had >37% similarity with 48 different allergens existing in the database. From the 48 putative allergens, 526 B-cell linear epitopes were identified using BepiPred linear epitope prediction tool. Transcript sequences generated from this study can be used to map epitopes of monoclonal antibodies and polyclonal sera from patients. With the support of this whole transcriptome catalogue of eggplant fruit, complete list of genes can be predicted based on which secondary structures of proteins may be modeled.

  18. De Novo Transcriptome Analysis of Allium cepa L. (Onion) Bulb to Identify Allergens and Epitopes.

    Science.gov (United States)

    Rajkumar, Hemalatha; Ramagoni, Ramesh Kumar; Anchoju, Vijayendra Chary; Vankudavath, Raju Naik; Syed, Arshi Uz Zaman

    2015-01-01

    Allium cepa (onion) is a diploid plant with one of the largest nuclear genomes among all diploids. Onion is an example of an under-researched crop which has a complex heterozygous genome. There are no allergenic proteins and genomic data available for onions. This study was conducted to establish a transcriptome catalogue of onion bulb that will enable us to study onion related genes involved in medicinal use and allergies. Transcriptome dataset generated from onion bulb using the Illumina HiSeq 2000 technology showed a total of 99,074,309 high quality raw reads (~20 Gb). Based on sequence homology onion genes were categorized into 49 different functional groups. Most of the genes however, were classified under 'unknown' in all three gene ontology categories. Of the categorized genes, 61.2% showed metabolic functions followed by cellular components such as binding, cellular processes; catalytic activity and cell part. With BLASTx top hit analysis, a total of 2,511 homologous allergenic sequences were found, which had 37-100% similarity with 46 different types of allergens existing in the database. From the 46 contigs or allergens, 521 B-cell linear epitopes were identified using BepiPred linear epitope prediction tool. This is the first comprehensive insight into the transcriptome of onion bulb tissue using the NGS technology, which can be used to map IgE epitopes and prediction of structures and functions of various proteins.

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

    Directory of Open Access Journals (Sweden)

    Somsri Wiwanitkit

    2017-01-01

    Full Text Available 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 transplacental infection and result in congenital neurological defect. To prevent this infection, 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.

  20. Epitopemap: a web application for integrated whole proteome epitope prediction.

    Science.gov (United States)

    Farrell, Damien; Gordon, Stephen V

    2015-07-14

    Predictions of MHC binding affinity are commonly used in immunoinformatics for T cell epitope prediction. There are multiple available methods, some of which provide web access. However there is currently no convenient way to access the results from multiple methods at the same time or to execute predictions for an entire proteome at once. We designed a web application that allows integration of multiple epitope prediction methods for any number of proteins in a genome. The tool is a front-end for various freely available methods. Features include visualisation of results from multiple predictors within proteins in one plot, genome-wide analysis and estimates of epitope conservation. We present a self contained web application, Epitopemap, for calculating and viewing epitope predictions with multiple methods. The tool is easy to use and will assist in computational screening of viral or bacterial genomes.

  1. Difference Discrete Variational Principle in Discrete Mechanics and Symplectic Algorithm

    Institute of Scientific and Technical Information of China (English)

    LUO Xu-Dong; GUO Han-Ying; LI Yu-Qi; WU Ke

    2004-01-01

    We propose the difference discrete variational principle in discrete mechanics and symplectic algorithmwith variable step-length of time in finite duration based upon a noncommutative differential calculus established inthis paper. This approach keeps both symplecticity and energy conservation discretely. We show that there exists thediscrete version of the Euler-Lagrange cohomology in these discrete systems. We also discuss the solution existencein finite time-length and its site density in continuous limit, and apply our approach to the pendulum with periodicperturbation. The numerical results are satisfactory.

  2. Discrete Exterior Calculus Discretization of Incompressible Navier-Stokes Equations

    KAUST Repository

    Mohamed, Mamdouh S.

    2017-05-23

    A conservative discretization of incompressible Navier-Stokes equations over surface simplicial meshes is developed using discrete exterior calculus (DEC). Numerical experiments for flows over surfaces reveal a second order accuracy for the developed scheme when using structured-triangular meshes, and first order accuracy otherwise. The mimetic character of many of the DEC operators provides exact conservation of both mass and vorticity, in addition to superior kinetic energy conservation. The employment of barycentric Hodge star allows the discretization to admit arbitrary simplicial meshes. The discretization scheme is presented along with various numerical test cases demonstrating its main characteristics.

  3. 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

  4. Continuous versus discrete for interacting carbon nanostructures

    Science.gov (United States)

    Hilder, Tamsyn A.; Hill, James M.

    2007-04-01

    Intermolecular forces between two interacting nanostructures can be obtained by either summing over all the individual atomic interactions or by using a continuum or continuous approach, where the number of atoms situated at discrete locations is averaged over the surface of each molecule. This paper aims to undertake a limited comparison of the continuum approach, the discrete atom-atom formulation and a hybrid discrete-continuum formulation for a range of molecular interactions involving a carbon nanotube, including interactions with another carbon nanotube and the fullerenes C60, C70 and C80. In the hybrid approach only one of the interacting molecules is discretized and the other is considered to be continuous. The hybrid discrete-continuum formulation would enable non-regular shaped molecules to be described, particularly useful for drug delivery systems which employ carbon nanotubes as carriers. The present investigation is important to obtain a rough estimate of the anticipated percentage errors which may occur between the various approaches in any specific application. Although our investigation is by no means comprehensive, overall we show that typically the interaction energies for these three approaches differ on average by at most 10% and the forces by 5%, with the exception of the C80 fullerene. For the C80 fullerene, while the intermolecular forces and the suction energies are in reasonable overall agreement, the point-wise energies can be significantly different. This may in part be due to differences in modelling the geometry of the C80 fullerene, but also the suction energies involve integrals of the energy, and therefore any errors or discrepancies in the point-wise energy tend to be smoothed out to give reasonable overall agreement for the former quantities.

  5. Poisson hierarchy of discrete strings

    Energy Technology Data Exchange (ETDEWEB)

    Ioannidou, Theodora, E-mail: ti3@auth.gr [Faculty of Civil Engineering, School of Engineering, Aristotle University of Thessaloniki, 54249, Thessaloniki (Greece); Niemi, Antti J., E-mail: Antti.Niemi@physics.uu.se [Department of Physics and Astronomy, Uppsala University, P.O. Box 803, S-75108, Uppsala (Sweden); Laboratoire de Mathematiques et Physique Theorique CNRS UMR 6083, Fédération Denis Poisson, Université de Tours, Parc de Grandmont, F37200, Tours (France); Department of Physics, Beijing Institute of Technology, Haidian District, Beijing 100081 (China)

    2016-01-28

    The Poisson geometry of a discrete string in three dimensional Euclidean space is investigated. For this the Frenet frames are converted into a spinorial representation, the discrete spinor Frenet equation is interpreted in terms of a transfer matrix formalism, and Poisson brackets are introduced in terms of the spinor components. The construction is then generalised, in a self-similar manner, into an infinite hierarchy of Poisson algebras. As an example, the classical Virasoro (Witt) algebra that determines reparametrisation diffeomorphism along a continuous string, is identified as a particular sub-algebra, in the hierarchy of the discrete string Poisson algebra. - Highlights: • Witt (classical Virasoro) algebra is derived in the case of discrete string. • Infinite dimensional hierarchy of Poisson bracket algebras is constructed for discrete strings. • Spinor representation of discrete Frenet equations is developed.

  6. Advances in discrete differential geometry

    CERN Document Server

    2016-01-01

    This is one of the first books on a newly emerging field of discrete differential geometry and an excellent way to access this exciting area. It surveys the fascinating connections between discrete models in differential geometry and complex analysis, integrable systems and applications in computer graphics. The authors take a closer look at discrete models in differential geometry and dynamical systems. Their curves are polygonal, surfaces are made from triangles and quadrilaterals, and time is discrete. Nevertheless, the difference between the corresponding smooth curves, surfaces and classical dynamical systems with continuous time can hardly be seen. This is the paradigm of structure-preserving discretizations. Current advances in this field are stimulated to a large extent by its relevance for computer graphics and mathematical physics. This book is written by specialists working together on a common research project. It is about differential geometry and dynamical systems, smooth and discrete theories, ...

  7. Kinetics of antigen expression and epitope presentation during virus infection.

    Directory of Open Access Journals (Sweden)

    Nathan P Croft

    2013-01-01

    Full Text Available Current knowledge about the dynamics of antigen presentation to T cells during viral infection is very poor despite being of fundamental importance to our understanding of anti-viral immunity. Here we use an advanced mass spectrometry method to simultaneously quantify the presentation of eight vaccinia virus peptide-MHC complexes (epitopes on infected cells and the amounts of their source antigens at multiple times after infection. The results show a startling 1000-fold range in abundance as well as strikingly different kinetics across the epitopes monitored. The tight correlation between onset of protein expression and epitope display for most antigens provides the strongest support to date that antigen presentation is largely linked to translation and not later degradation of antigens. Finally, we show a complete disconnect between the epitope abundance and immunodominance hierarchy of these eight epitopes. This study highlights the complexity of viral antigen presentation by the host and demonstrates the weakness of simple models that assume total protein levels are directly linked to epitope presentation and immunogenicity.

  8. Strategic Use of Epitope Matching to Improve Outcomes.

    Science.gov (United States)

    Wiebe, Chris; Nickerson, Peter

    2016-10-01

    Understanding the events leading to allorecognition and the subsequent effector pathways engaged is key for the development of strategies to prolong graft survival. Optimizing patient outcomes will require 2 major advancements: (1) minimizing premature death with a functioning graft in the patients with stable graft function, and (2) maximizing graft survival by avoiding the aforementioned allorecognition. This necessitates personalized immunosuppression to avoid known metabolic side effects, risk for infection, and malignancy, while holding the alloimmune system in check. Since the beginning of transplant a key strategy to achieve this goal is to minimize HLA mismatching between donor and recipient. What has not evolved is any refinement in our evaluation of HLA relatedness between donor and recipient when HLA mismatch exists. Donor-recipient HLA mismatch at the amino acid level can now be determined. These mismatches serve as potential epitopes for de novo donor specific antibody development and correlate with late rejection and graft loss. It is in this context that HLA epitope analysis is considered as a strategy to permit safe immunosuppression minimization to improve patient outcomes through: (1) improved allocation schemes that favor donor-recipient pairs with a low HLA epitope mismatch load (especially at the class II loci) or avoiding specific epitope mismatches known to be highly immunogenic and (2) immunosuppressive minimization in patients with low epitope mismatch loads or without highly immunogenic epitope mismatches.

  9. 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.

  10. HLA-A*0201-restricted CD8+ T-cell epitopes identified in dengue viruses

    Directory of Open Access Journals (Sweden)

    Duan Zhi-Liang

    2012-11-01

    Full Text Available Abstract Background All four dengue virus (DV serotypes (D1V, D2V, D3V and D4V can cause a series of disorders, ranging from mild dengue fever (DF to severe dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS. Previous studies have revealed that DV serotype-specific CD8+ T cells are involved in controlling DV infection. Serotype cross-reactive CD8+ T-cells may contribute to the immunopathogenesis of DHF/DSS. The aim of the study was to identify HLA-A*0201-binding peptides from four DV serotypes. We then examined their immunogenicity in vivo and cross-reactivity within heterologous peptides. Methods D1V-derived candidate CD8+ T-cell epitopes were synthesized and evaluated for their affinity to the HLA-A*0201 molecule. Variant peptides representing heterologous D2V, D3V, D4V serotypes were synthesized. The immunogenicity of the high-affinity peptides were evaluated in HLA-A*0201 transgenic mice. Results Of the seven D1V-derived candidate epitopes [D1V-NS4a56–64(MLLALIAVL, D1V-C46–54(LVMAFMAFL, D1V-NS4b562–570(LLATSIFKL, D1V-NS2a169–177(AMVLSIVSL, D1V-NS4a140–148(GLLFMILTV, D1V-NS2a144–152(QLWAALLSL and D1V-NS4b183–191(LLMRTTWAL], three peptides [D1V-NS4a140–148, D1V-NS2a144–152 and D1V-NS4b183–191] had a high affinity for HLA-A*0201 molecules. Moreover, their variant peptides for D2V, D3V and D4V [D2V-NS4a140–148(AILTVVAAT, D3V-NS4a140-148(GILTLAAIV, D4V-NS4a140-148(TILTIIGLI, D2V-NS2a144–152(QLAVTIMAI, D3V-NS2a144–152(QLWTALVSL, D4V-NS2a143–151(QVGTLALSL, D2V-NS4b182–190(LMMRTTWAL, D3V-NS4b182–190 (LLMRTSWAL and D4V-NS4b179–187(LLMRTTWAF] also had a high affinity for HLA-A*0201 molecules. Furthermore, CD8+ T cells directed to these twelve peptides were induced in HLA-A*0201 transgenic mice following immunization with these peptides. Additionally, cross-reactivity within four peptides (D1V-NS4b183–191, D2V-NS4b182–190, D3V-NS4b182–190 and D4V-NS4b179–187 was observed. Conclusions Two novel serotype

  11. Discrete R Symmetries and Anomalies

    OpenAIRE

    Michael Dine(Santa Cruz Institute for Particle Physics and Department of Physics, Santa Cruz CA 95064, U.S.A.); Angelo Monteux(Santa Cruz Institute for Particle Physics, University of California Santa Cruz, 1156 High Street, Santa Cruz, U.S.A.)

    2012-01-01

    We comment on aspects of discrete anomaly conditions focussing particularly on $R$ symmetries. We review the Green-Schwarz cancellation of discrete anomalies, providing a heuristic explanation why, in the heterotic string, only the "model-independent dilaton" transforms non-linearly under discrete symmetries; this argument suggests that, in other theories, multiple fields might play a role in anomaly cancellations, further weakening any anomaly constraints at low energies. We provide examples...

  12. Epitope Mapping of Avian Influenza M2e Protein: Different Species Recognise Various Epitopes.

    Directory of Open Access Journals (Sweden)

    Noor Haliza Hasan

    Full Text Available A common approach for developing diagnostic tests for influenza virus detection is the use of mouse or rabbit monoclonal and/or polyclonal antibodies against a target antigen of the virus. However, comparative mapping of the target antigen using antibodies from different animal sources has not been evaluated before. This is important because identification of antigenic determinants of the target antigen in different species plays a central role to ensure the efficiency of a diagnostic test, such as competitive ELISA or immunohistochemistry-based tests. Interest in the matrix 2 ectodomain (M2e protein of avian influenza virus (AIV as a candidate for a universal vaccine and also as a marker for detection of virus infection in vaccinated animals (DIVA is the rationale for the selection of this protein for comparative mapping evaluation. This study aimed to map the epitopes of the M2e protein of avian influenza virus H5N1 using chicken, mouse and rabbit monoclonal or monospecific antibodies. Our findings revealed that rabbit antibodies (rAbs recognized epitope 6EVETPTRN13 of the M2e, located at the N-terminal of the protein, while mouse (mAb and chicken antibodies (cAbs recognized epitope 10PTRNEWECK18, located at the centre region of the protein. The findings highlighted the difference between the M2e antigenic determinants recognized by different species that emphasized the importance of comparative mapping of antibody reactivity from different animals to the same antigen, especially in the case of multi-host infectious agents such as influenza. The findings are of importance for antigenic mapping, as well as diagnostic test and vaccine development.

  13. Diversity of T cell epitopes in Plasmodium falciparum circumsporozoite protein likely due to protein-protein interactions.

    Directory of Open Access Journals (Sweden)

    Nagesh R Aragam

    Full Text Available Circumsporozoite protein (CS is a leading vaccine antigen for falciparum malaria, but is highly polymorphic in natural parasite populations. The factors driving this diversity are unclear, but non-random assortment of the T cell epitopes TH2 and TH3 has been observed in a Kenyan parasite population. The recent publication of the crystal structure of the variable C terminal region of the protein allows the assessment of the impact of diversity on protein structure and T cell epitope assortment. Using data from the Gambia (55 isolates and Malawi (235 isolates, we evaluated the patterns of diversity within and between epitopes in these two distantly-separated populations. Only non-synonymous mutations were observed with the vast majority in both populations at similar frequencies suggesting strong selection on this region. A non-random pattern of T cell epitope assortment was seen in Malawi and in the Gambia, but structural analysis indicates no intramolecular spatial interactions. Using the information from these parasite populations, structural analysis reveals that polymorphic amino acids within TH2 and TH3 colocalize to one side of the protein, surround, but do not involve, the hydrophobic pocket in CS, and predominately involve charge switches. In addition, free energy analysis suggests residues forming and behind the novel pocket within CS are tightly constrained and well conserved in all alleles. In addition, free energy analysis shows polymorphic residues tend to be populated by energetically unfavorable amino acids. In combination, these findings suggest the diversity of T cell epitopes in CS may be primarily an evolutionary response to intermolecular interactions at the surface of the protein potentially counteracting antibody-mediated immune recognition or evolving host receptor diversity.

  14. Steerable Discrete Cosine Transform

    Science.gov (United States)

    Fracastoro, Giulia; Fosson, Sophie M.; Magli, Enrico

    2017-01-01

    In image compression, classical block-based separable transforms tend to be inefficient when image blocks contain arbitrarily shaped discontinuities. For this reason, transforms incorporating directional information are an appealing alternative. In this paper, we propose a new approach to this problem, namely a discrete cosine transform (DCT) that can be steered in any chosen direction. Such transform, called steerable DCT (SDCT), allows to rotate in a flexible way pairs of basis vectors, and enables precise matching of directionality in each image block, achieving improved coding efficiency. The optimal rotation angles for SDCT can be represented as solution of a suitable rate-distortion (RD) problem. We propose iterative methods to search such solution, and we develop a fully fledged image encoder to practically compare our techniques with other competing transforms. Analytical and numerical results prove that SDCT outperforms both DCT and state-of-the-art directional transforms.

  15. Discrete Thermodynamics of Lasers

    CERN Document Server

    Zilbergleyt, B

    2007-01-01

    The paper offers a discrete thermodynamic model of lasers. Laser is an open system; its equilibrium is based on a balance of two thermodynamic forces, one related to the incoming pumping power and another to the emitted light. The basic expression for such equilibrium is a logistic map, graphical solutions to which are pitchfork bifurcation diagrams. As pumping force increases, the relative populations on the ground and lasing branches tend to zero and unity correspondingly. An interesting feature of this model is the line spectrum of the up and down transitions between the branches beyond bifurcation point. Even in a simple case of 2-level laser with only 2 possible transition types (up and down), the spectra look like sets of the line packets, starting well before the population inversion. This effect is an independent confirmation of the Einstein's prohibition on practical realization of 2-level laser. Multilevel lasers may be approached by employing the idea of thermodynamic activity for the emitting atom...

  16. Discrete anti-gravity

    Science.gov (United States)

    Noyes, H. Pierre; Starson, Scott

    1991-03-01

    Discrete physics, because it replaces time evolution generated by the energy operator with a global bit-string generator (program universe) and replaces fields with the relativistic Wheeler-Feynman action at a distance, allows the consistent formulation of the concept of signed gravitational charge for massive particles. The resulting prediction made by this version of the theory is that free anti-particles near the surface of the earth will fall up with the same acceleration that the corresponding particles fall down. So far as we can see, no current experimental information is in conflict with this prediction of our theory. The experiment crusis will be one of the anti-proton or anti-hydrogen experiments at CERN. Our prediction should be much easier to test than the small effects which those experiments are currently designed to detect or bound.

  17. Discrete anti-gravity

    Energy Technology Data Exchange (ETDEWEB)

    Noyes, H.P. (Stanford Linear Accelerator Center, Menlo Park, CA (USA)); Starson, S. (STARSON Corp. (USA))

    1991-03-01

    Discrete physics, because it replaces time evolution generated by the energy operator with a global bit-string generator (program universe) and replaces fields'' with the relativistic Wheeler-Feynman action at a distance,'' allows the consistent formulation of the concept of signed gravitational charge for massive particles. The resulting prediction made by this version of the theory is that free anti-particles near the surface of the earth will fall'' up with the same acceleration that the corresponding particles fall down. So far as we can see, no current experimental information is in conflict with this prediction of our theory. The experiment crusis will be one of the anti-proton or anti-hydrogen experiments at CERN. Our prediction should be much easier to test than the small effects which those experiments are currently designed to detect or bound. 23 refs.

  18. Immigration and Prosecutorial Discretion.

    Science.gov (United States)

    Apollonio, Dorie; Lochner, Todd; Heddens, Myriah

    Immigration has become an increasingly salient national issue in the US, and the Department of Justice recently increased federal efforts to prosecute immigration offenses. This shift, however, relies on the cooperation of US attorneys and their assistants. Traditionally federal prosecutors have enjoyed enormous discretion and have been responsive to local concerns. To consider how the centralized goal of immigration enforcement may have influenced federal prosecutors in regional offices, we review their prosecution of immigration offenses in California using over a decade's worth of data. Our findings suggest that although centralizing forces influence immigration prosecutions, individual US attorneys' offices retain distinct characteristics. Local factors influence federal prosecutors' behavior in different ways depending on the office. Contrary to expectations, unemployment rates did not affect prosecutors' willingness to pursue immigration offenses, nor did local popular opinion about illegal immigration.

  19. A discrete, finite multiverse

    CERN Document Server

    McKenzie, Alan

    2016-01-01

    The Many Worlds Interpretation (MWI) famously avoids the issue of wave function collapse. Different MWI trees representing the same quantum events can have different topologies, depending upon the observer. However, they are all isomorphic to the group of block universes containing all of the outcomes of all of the events, and so, in that sense, the group of block universes is a more fundamental representation. Different branches of the MWI tree, representing different universes in MWI, ultimately share the same quantum state in a common ancestor branch. This branching topology is incompatible with that of the Minkowski block universe; the resolution is to replace the branches with discrete, parallel block universes, each of which extends from the trunk to the outermost twigs. The number of universes in a branch is proportional to its thickness which, in turn, depends upon the absolute square of the probability amplitude for the state in that branch. Every quantum event may be represented by a kernel of unive...

  20. Thermodynamics of discrete quantum processes

    Science.gov (United States)

    Anders, Janet; Giovannetti, Vittorio

    2013-03-01

    We define thermodynamic configurations and identify two primitives of discrete quantum processes between configurations for which heat and work can be defined in a natural way. This allows us to uncover a general second law for any discrete trajectory that consists of a sequence of these primitives, linking both equilibrium and non-equilibrium configurations. Moreover, in the limit of a discrete trajectory that passes through an infinite number of configurations, i.e. in the reversible limit, we recover the saturation of the second law. Finally, we show that for a discrete Carnot cycle operating between four configurations one recovers Carnot's thermal efficiency.

  1. Principles of discrete time mechanics

    CERN Document Server

    Jaroszkiewicz, George

    2014-01-01

    Could time be discrete on some unimaginably small scale? Exploring the idea in depth, this unique introduction to discrete time mechanics systematically builds the theory up from scratch, beginning with the historical, physical and mathematical background to the chronon hypothesis. Covering classical and quantum discrete time mechanics, this book presents all the tools needed to formulate and develop applications of discrete time mechanics in a number of areas, including spreadsheet mechanics, classical and quantum register mechanics, and classical and quantum mechanics and field theories. A consistent emphasis on contextuality and the observer-system relationship is maintained throughout.

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

    Science.gov (United States)

    Alderete, J F; Neace, Calvin J

    2013-01-01

    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.

  3. 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

  4. T cell epitope-based allergy vaccines.

    Science.gov (United States)

    Larché, Mark

    2011-01-01

    Specific immunotherapy (SIT) with extracts containing intact allergen molecules is clinically efficacious, but associated with frequent adverse events related to the allergic sensitization of the patient. As a result, treatment is initiated in an incremental dose fashion which ultimately achieves a plateau (maintenance dose) that may be continued for several years. Reduction of allergic adverse events may allow safer and more rapid treatment Thus, many groups have developed and evaluated strategies to reduce allergenicity whilst maintaining immunogenicity, the latter being required to achieve specific modulation of the immune response. Peptide immunotherapy can be used to target T and/or B cells in an antigen-specific manner. To date, only approaches that target T cells have been clinically evaluated. Short, synthetic peptides representing immunodominant T cell epitopes of major allergens are able to modulate allergen-specific T cell responses in the absence of IgE cross linking and activation of effector cells. Here we review clinical and mechanistic studies associated with peptide immunotherapy targeting allergy to cats or to bee venom. 

  5. Molecular characterization of HIV-1 CRF01_AE in Mekong Delta, Vietnam, and impact of T-cell epitope mutations on HLA recognition (ANRS 12159.

    Directory of Open Access Journals (Sweden)

    Estibaliz Lazaro

    Full Text Available BACKGROUND: To date, 11 HIV-1 subtypes and 48 circulating recombinant forms have been described worldwide. The underlying reason why their distribution is so heterogeneous is not clear. Host genetic factors could partly explain this distribution. The aim of this study was to describe HIV-1 strains circulating in an unexplored area of Mekong Delta, Vietnam, and to assess the impact of optimal epitope mutations on HLA binding. METHODS: We recruited 125 chronically antiretroviral-naive HIV-1-infected subjects from five cities in the Mekong Delta. We performed high-resolution DNA typing of HLA class I alleles, sequencing of Gag and RT-Prot genes and phylogenetic analysis of the strains. Epitope mutations were analyzed in patients bearing the HLA allele restricting the studied epitope. Optimal wild-type epitopes from the Los Alamos database were used as reference. T-cell epitope recognition was predicted using the immune epitope database tool according to three different scores involved in antigen processing (TAP and proteasome scores and HLA binding (MHC score. RESULTS: All sequences clustered with CRF01_AE. HLA class I genotyping showed the predominance of Asian alleles as A*11:01 and B*46:01 with a Vietnamese specificity held by two different haplotypes. The percentage of homology between Mekong and B consensus HIV-1 sequences was above 85%. Divergent epitopes had TAP and proteasome scores comparable with wild-type epitopes. MHC scores were significantly lower in divergent epitopes with a mean of 2.4 (±0.9 versus 2 (±0.7 in non-divergent ones (p<0.0001. CONCLUSIONS: Our study confirms the wide predominance of CRF01_AE in the Mekong Delta where patients harbor a specific HLA pattern. Moreover, it demonstrates the lower MHC binding affinity among divergent epitopes. This weak immune pressure combined with a narrow genetic diversity favors immune escape and could explain why CRF01_AE is still predominant in Vietnam, particularly in the Mekong area.

  6. Discretization of partial differential equations preserving their physical symmetries

    Energy Technology Data Exchange (ETDEWEB)

    Valiquette, F; Winternitz, P [Centre de Recherches Mathematiques, Universite de Montreal, C.P. 6128, succ. Centre-ville, Montreal, QC, H3C 3J7 (Canada)

    2005-11-11

    A procedure for obtaining a 'minimal' discretization of a partial differential equation, preserving all of its Lie point symmetries, is presented. 'Minimal' in this case means that the differential equation is replaced by a partial difference scheme involving N difference equations, where N is the number of independent and dependent variables. We restrict ourselves to one scalar function of two independent variables. As examples, invariant discretizations of the heat, Burgers and Korteweg-de Vries equations are presented. Some exact solutions of the discrete schemes are obtained.

  7. Energy Criterion for the Spectral Stability of Discrete Breathers

    Science.gov (United States)

    Kevrekidis, Panayotis G.; Cuevas-Maraver, Jesús; Pelinovsky, Dmitry E.

    2016-08-01

    Discrete breathers are ubiquitous structures in nonlinear anharmonic models ranging from the prototypical example of the Fermi-Pasta-Ulam model to Klein-Gordon nonlinear lattices, among many others. We propose a general criterion for the emergence of instabilities of discrete breathers analogous to the well-established Vakhitov-Kolokolov criterion for solitary waves. The criterion involves the change of monotonicity of the discrete breather's energy as a function of the breather frequency. Our analysis suggests and numerical results corroborate that breathers with increasing (decreasing) energy-frequency dependence are generically unstable in soft (hard) nonlinear potentials.

  8. Discrete dynamics versus analytic dynamics

    DEFF Research Database (Denmark)

    Toxværd, Søren

    2014-01-01

    For discrete classical Molecular dynamics obtained by the “Verlet” algorithm (VA) with the time increment h there exists a shadow Hamiltonian H˜ with energy E˜(h) , for which the discrete particle positions lie on the analytic trajectories for H˜ . Here, we proof that there, independent...

  9. Discretization error of Stochastic Integrals

    CERN Document Server

    Fukasawa, Masaaki

    2010-01-01

    Asymptotic error distribution for approximation of a stochastic integral with respect to continuous semimartingale by Riemann sum with general stochastic partition is studied. Effective discretization schemes of which asymptotic conditional mean-squared error attains a lower bound are constructed. Two applications are given; efficient delta hedging strategies with transaction costs and effective discretization schemes for the Euler-Maruyama approximation are constructed.

  10. Discrete Mathematics and Its Applications

    Science.gov (United States)

    Oxley, Alan

    2010-01-01

    The article gives ideas that lecturers of undergraduate Discrete Mathematics courses can use in order to make the subject more interesting for students and encourage them to undertake further studies in the subject. It is possible to teach Discrete Mathematics with little or no reference to computing. However, students are more likely to be…

  11. Discretization and implicit mapping dynamics

    CERN Document Server

    Luo, Albert C J

    2015-01-01

    This unique book presents the discretization of continuous systems and implicit mapping dynamics of periodic motions to chaos in continuous nonlinear systems. The stability and bifurcation theory of fixed points in discrete nonlinear dynamical systems is reviewed, and the explicit and implicit maps of continuous dynamical systems are developed through the single-step and multi-step discretizations. The implicit dynamics of period-m solutions in discrete nonlinear systems are discussed. The book also offers a generalized approach to finding analytical and numerical solutions of stable and unstable periodic flows to chaos in nonlinear systems with/without time-delay. The bifurcation trees of periodic motions to chaos in the Duffing oscillator are shown as a sample problem, while the discrete Fourier series of periodic motions and chaos are also presented. The book offers a valuable resource for university students, professors, researchers and engineers in the fields of applied mathematics, physics, mechanics,...

  12. Identification of Melanoma-specific Peptide Epitopes by HLA-A2.1-restricted Cytotoxic T Lymphocytes

    Institute of Scientific and Technical Information of China (English)

    Hai-Liang GE; Ying WANG; Shu-Jun WANG; Yong ZHANG

    2006-01-01

    HLA-A2.1-associated peptides, extracted from human melanoma cells, were used to study epitopes for melanoma-specific HLA-A2.1-restricted cytotoxic T lymphocytes (CTLs) by epitope reconstitution, active peptide sequence characterization and synthetic peptide verification. CTL were generated from tumor-involved nodes by in vitro stimulation, initially with autologous melanoma cells and subsequently with allogeneic HLA-A2.1 positive melanoma cells. The CTLs could lyse autologous and allogeneic HLA-A2.1 positive melanomas, but not HLA-A2.1 negative melanomas or HLA-A2.1 positive non-melanomas. The lysis of melanomas could be inhibited by anti-CD3, anti-HLA class Ⅰ and anti-HLA-A2.1 monoclonal antibodies.HLA-A2.1 molecules were purified from detergent-solubilized human melanoma cells by immunoaffinity column chromatography and further fractionated by reversed phase high performance liquid chromatography.The fractions were assessed for their ability to reconstitute melanoma-specific epitopes with HLA-A2.1 positive antigen-processing mutant T2 cells. Three reconstitution peaks were observed in lactate dehydrogenase release assay. Mass spectrometry and ion-exchange high performance liquid chromatography analysis were used to identify peptide epitopes. Peptides with a mass-to-charge ratio of 948 usually consist of nine amino acid residues. The data from reconstitution experiments confirmed that the synthetic peptides contained epitopes and that the peptides associated with HLA-A2.1 and recognized by melanoma-specific CTL were present in these different melanoma cells. These peptides could be potentially exploited in novel peptide-based antitumor vaccines in immunotherapy for CTL.

  13. An immunoinformatic approach for identification of Trypanosoma cruzi HLA-A2-restricted CD8+ T cell epitopes

    Science.gov (United States)

    Eickhoff, Christopher S; Van Aartsen, Daniel; Terry, Frances E; Meymandi, Sheba K; Traina, Mahmoud M; Hernandez, Salvador; Martin, William D; Moise, Leonard; De Groot, Annie S; Hoft, Daniel F

    2015-01-01

    Chagas disease is a major neglected tropical disease caused by persistent chronic infection with the protozoan parasite Trypanosoma cruzi. An estimated 8 million people are infected with T. cruzi, however only 2 drugs are approved for treatment and no vaccines are available. Thus there is an urgent need to develop vaccines and new drugs to prevent and treat Chagas disease. In this work, we identify T cell targets relevant for human infection with T. cruzi. The trans-sialidase (TS) gene family is a large family of homologous genes within the T. cruzi genome encoding over 1,400 members. There are 12 highly conserved TS gene family members which encode enzymatically active TS (functional TS; F-TS), while the remaining TS family genes are less conserved, enzymatically inactive and have been hypothesized to be involved in immune evasion (non-functional TS; NF-TS). We utilized immunoinformatic tools to identify HLA-A2-restricted CD8+ T cell epitopes conserved within F-TS family members and NF-TS gene family members. We also utilized a whole-genome approach to identify T cell epitopes present within genes which have previously been shown to be expressed in life stages relevant for human infection (Non-TS genes). Thirty immunogenic HLA-A2-restricted CD8+ T cell epitopes were identified using IFN-γ ELISPOT assays after vaccination of humanized HLA-A2 transgenic mice with mature dendritic cells pulsed with F-TS, NF-TS, and Non-TS peptide pools. The immunogenic HLA-A2-restricted T cell epitopes identified in this work may serve as potential components of an epitope-based T cell targeted vaccine for Chagas disease. PMID:26107442

  14. 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.

  15. 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.

  16. Alterations in expression of Cat-315 epitope of perineuronal nets during normal ageing, and its modulation by an open-channel NMDA receptor blocker, memantine.

    Science.gov (United States)

    Yamada, Jun; Ohgomori, Tomohiro; Jinno, Shozo

    2017-03-08

    The perineuronal net (PNN), a specialized aggregate of the extracellular matrix, is involved in neuroprotection against oxidative stress, which is now recognized as a major contributor to age-related decline in brain functions. In this study, we investigated the age-related molecular changes of PNNs using monoclonal antibody Cat-315, which recognizes human natural killer-1 (HNK-1) glycan on aggrecan-based PNNs. Western blot analysis showed that the expression levels of Cat-315 epitope in the hippocampus were higher in middle-aged (MA, 12-month-old) mice than in young adult (YA, 2-month-old) mice. Although there were no differences in the expression levels of Cat-315 epitope between old age (OA, 20-month-old) and MA mice, Cat-315 immunoreactivity was also detected in astrocytes of OA mice. To focus on Cat-315 epitope in PNNs, we used YA and MA mice in the following experiments. Optical disector analysis showed that there were no differences in the numbers of Cat-315-positive (Cat-315(+) ) PNNs between YA and MA mice. Fluorescence intensity analysis indicated that Cat-315 immunoreactivity in PNNs increased with age in the dorsal hippocampus, which is mainly involved in cognitive functions. Administration of an open-channel blocker of NMDA receptor, memantine, reduced the expression levels of Cat-315 epitope in the hippocampus. Furthermore, the numbers of glutamatergic and GABAergic terminals colocalized with Cat-315 epitope around parvalbumin-positive neurons were decreased by memantine. These findings provide novel insight into the involvement of PNNs in normal brain ageing, and suggest that memantine may counteract the age-related alterations in expression levels of Cat-315 epitope via regulation of its subcellular localization. This article is protected by copyright. All rights reserved.

  17. Discrete Darboux transformation for discrete polynomials of hypergeometric type

    Science.gov (United States)

    Bangerezako, Gaspard

    1998-03-01

    The Darboux transformation, well known in second-order differential operator theory, is applied to the difference equations satisfied by the discrete hypergeometric polynomials (Charlier, Meixner-Kravchuk, Hahn).

  18. The origin of discrete particles

    CERN Document Server

    Bastin, T

    2009-01-01

    This book is a unique summary of the results of a long research project undertaken by the authors on discreteness in modern physics. In contrast with the usual expectation that discreteness is the result of mathematical tools for insertion into a continuous theory, this more basic treatment builds up the world from the discrimination of discrete entities. This gives an algebraic structure in which certain fixed numbers arise. As such, one agrees with the measured value of the fine-structure constant to one part in 10,000,000 (10 7 ). Sample Chapter(s). Foreword (56 KB). Chapter 1: Introduction

  19. 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.

  20. Common food allergens and their IgE-binding epitopes.

    Science.gov (United States)

    Matsuo, Hiroaki; Yokooji, Tomoharu; Taogoshi, Takanori

    2015-10-01

    Food allergy is an adverse immune response to certain kinds of food. Although any food can cause allergic reactions, chicken egg, cow's milk, wheat, shellfish, fruit, and buckwheat account for 75% of food allergies in Japan. Allergen-specific immunoglobulin E (IgE) antibodies play a pivotal role in the development of food allergy. Recent advances in molecular biological techniques have enabled the efficient analysis of food allergens. As a result, many food allergens have been identified, and their molecular structure and IgE-binding epitopes have also been identified. Studies of allergens have demonstrated that IgE antibodies specific to allergen components and/or the peptide epitopes are good indicators for the identification of patients with food allergy, prediction of clinical severity and development of tolerance. In this review, we summarize our current knowledge regarding the allergens and IgE epitopes in the well-researched allergies to chicken egg, cow's milk, wheat, shrimp, and peanut.

  1. Phage displaying epitope of Candida albicans HSP90 and serodiagnosis

    Institute of Scientific and Technical Information of China (English)

    杨琼; 王丽; 卢大宁; 邢沈阳; 尹东; 朱筱娟

    2004-01-01

    @@ Recently, the frequent use of immunosuppressants and chemotherapeutic drugs for cancers has caused an increase in the frequency of life-threatening systemic candidiasis.1 Studies by Matthews et al2 indicated HSP90 fragments are major targets for the immune system in infection due to C. albicans, and anti-epitope LKVIRK of HSP90 antibody is a serological marker for diagnosis of invasive candidiasis. Cloning and sequencing HSP90 antigen revealed that the linear epitope LKVIRK, localized near the C-terminus of the 47 kDa protein which circulates in the sera of patients with invasive candidiasis, as a heat-stable breakdown product of large more heat-labile antigen HSP90.2 In this study, epitope LKVIRK was displayed on the surface of phage fd to develop a new serological test for systemic candidiasis.

  2. 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....

  3. 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....

  4. Branched peptide amphiphiles, related epitope compounds and self assembled structures thereof

    Science.gov (United States)

    Stupp, Samuel I.; Guler, Mustafa O.

    2008-11-18

    Branched peptide amphiphilic compounds incorporating one or residues providing a pendant amino group for coupling one or more epitope sequences thereto, such compounds and related compositions for enhanced epitope presentation.

  5. 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

    BACKGROUND: Current immunological bioinformatic approaches focus on the prediction of allele-specific epitopes capable of triggering immunogenic activity. The prediction of major histocompatibility complex (MHC) class I epitopes is well studied, and various software solutions exist for this purpo...

  6. 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....

  7. Analysis of a subclass-restricted HIV-1 gp41 epitope by omission peptides.

    Science.gov (United States)

    Mathiesen, T; Chiodi, F; Broliden, P A; Albert, J; Houghten, R A; Utter, G; Wahren, B; Norrby, E

    1989-01-01

    To define the amino acids involved in IgG subclass reactivity to two overlapping HIV-1 gp41 (E34/32; amino acid positions 582-613) peptides, sera from 18 HIV-infected individuals were studied. Peptides mimicking E34 but with single amino acid deletions or glycine substitutions were used to define the amino acid residues necessary for antibody binding. Two dominating immunogenic epitopes, containing highly hydrophilic amino acids, were found on the original peptide. Further analysis was undertaken with two corresponding omission sets of dodecapeptides representing halves of the complete E34 plus a terminal cystein peptide. The subclass reactivities usually differed between the patients with regard to the epitopes with which the different IgG subclasses reacted and also to the importance of different amino acids in antibody binding. The 600 glycine and the 601 lysine were involved in the binding of all IgG1, 2 and 4 and most IgG3. The development of E34/32-reactive IgM and IgG subclasses showed different patterns in four patients with primary HIV infections, contradicting the existence of a general pattern for the development of IgG subclasses to this peptide. The findings suggest that different progenitor clones are selected for synthesis of the different subclasses. PMID:2472353

  8. Discrete geodesics and cellular automata

    CERN Document Server

    Arrighi, Pablo

    2015-01-01

    This paper proposes a dynamical notion of discrete geodesics, understood as straightest trajectories in discretized curved spacetime. The notion is generic, as it is formulated in terms of a general deviation function, but readily specializes to metric spaces such as discretized pseudo-riemannian manifolds. It is effective: an algorithm for computing these geodesics naturally follows, which allows numerical validation---as shown by computing the perihelion shift of a Mercury-like planet. It is consistent, in the continuum limit, with the standard notion of timelike geodesics in a pseudo-riemannian manifold. Whether the algorithm fits within the framework of cellular automata is discussed at length. KEYWORDS: Discrete connection, parallel transport, general relativity, Regge calculus.

  9. Exact analysis of discrete data

    CERN Document Server

    Hirji, Karim F

    2005-01-01

    Researchers in fields ranging from biology and medicine to the social sciences, law, and economics regularly encounter variables that are discrete or categorical in nature. While there is no dearth of books on the analysis and interpretation of such data, these generally focus on large sample methods. When sample sizes are not large or the data are otherwise sparse, exact methods--methods not based on asymptotic theory--are more accurate and therefore preferable.This book introduces the statistical theory, analysis methods, and computation techniques for exact analysis of discrete data. After reviewing the relevant discrete distributions, the author develops the exact methods from the ground up in a conceptually integrated manner. The topics covered range from univariate discrete data analysis, a single and several 2 x 2 tables, a single and several 2 x K tables, incidence density and inverse sampling designs, unmatched and matched case -control studies, paired binary and trinomial response models, and Markov...

  10. Causal Dynamics of Discrete Surfaces

    Directory of Open Access Journals (Sweden)

    Pablo Arrighi

    2014-03-01

    Full Text Available We formalize the intuitive idea of a labelled discrete surface which evolves in time, subject to two natural constraints: the evolution does not propagate information too fast; and it acts everywhere the same.

  11. Discrete Event Programming with Simkit

    OpenAIRE

    Buss, Arnold

    2001-01-01

    This paper is a brief introduction to the use of Simkit, a software package for implementing Discrete Event Simulation (DES) models. Simkit is written in Java (for any operating system with Java 2TM ).

  12. Police investigations: discretion denied yet undeniably exercised

    Science.gov (United States)

    Belur, J.; Tilley, N.; Osrin, D.; Daruwalla, N.; Kumar, M.; Tiwari, V.

    2014-01-01

    Police investigations involve determining whether a crime has been committed, and if so what type of crime, who has committed it and whether there is the evidence to charge the perpetrators. Drawing on fieldwork in Delhi and Mumbai, this paper explores how police investigations unfolded in the specific context of women’s deaths by burning in India. In particular, it focuses on the use of discretion despite its denial by those exercising it. In India, there are distinctive statutes relating to women’s suspicious deaths, reflecting the widespread expectation that the bride’s family will pay a dowry to the groom’s family and the tensions to which this may on occasion give rise in the early years of a marriage. Often, there are conflicting claims influencing how the woman’s death is classified. These in turn affect police investigation. The nature and direction of police discretion in investigating women’s deaths by burning reflect in part the unique nature of the legislation and the particular sensitivities in relation to these types of death. They also highlight processes that are liable to be at work in any crime investigation. It was found that police officers exercised unacknowledged discretion at seven specific points in the investigative process, with potentially significant consequences for the achievement of just outcomes: first response, recording the victim’s ‘dying declaration’, inquest, registering of the ‘First Information Report’, collecting evidence, arrest and framing of the charges. PMID:26376482

  13. Multiscale expansions in discrete world

    Indian Academy of Sciences (India)

    Ömer Ünsal; Filiz Taşcan; Mehmet Naci Özer

    2014-07-01

    In this paper, we show the attainability of KdV equation from some types of nonlinear Schrödinger equation by using multiscale expansions discretely. The power of this manageable method is confirmed by applying it to two selected nonlinear Schrödinger evolution equations. This approach can also be applied to other nonlinear discrete evolution equations. All the computations have been made with Maple computer packet program.

  14. Discrete solitons in graphene metamaterials

    OpenAIRE

    Bludov, Yuliy V.; Smirnova, Daria A.; Kivshar, Yuri S.; Peres, N. M. R.; Vasilevskiy, Mikhail

    2014-01-01

    We study nonlinear properties of multilayer metamaterials created by graphene sheets separated by dielectric layers. We demonstrate that such structures can support localized nonlinear modes described by the discrete nonlinear Schr\\"{o}dinger equation and that its solutions are associated with stable discrete plasmon solitons. We also analyze the nonlinear surface modes in truncated graphene metamaterials being a nonlinear analog of surface Tamm states. Fundação para a Ciência e a Tecnolog...

  15. Discrete solitons in graphene metamaterials

    Science.gov (United States)

    Bludov, Yu. V.; Smirnova, D. A.; Kivshar, Yu. S.; Peres, N. M. R.; Vasilevskiy, M. I.

    2015-01-01

    We study nonlinear properties of multilayer metamaterials created by graphene sheets separated by dielectric layers. We demonstrate that such structures can support localized nonlinear modes described by the discrete nonlinear Schrödinger equation and that its solutions are associated with stable discrete plasmon solitons. We also analyze the nonlinear surface modes in truncated graphene metamaterials being a nonlinear analog of surface Tamm states.

  16. 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 ...

  17. 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 ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Pan.05.Epitope_tags.AllCell mm9 TFs and others Epitope tags Pancreas SRX747491,...SRX747492 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Pan.05.Epitope_tags.AllCell.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Gon.50.Epitope_tags.AllCell mm9 TFs and others Epitope tags Gonad SRX153153,SRX...153152,SRX153151 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Gon.50.Epitope_tags.AllCell.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.YSt.10.Epitope_tags.AllCell sacCer3 TFs and others Epitope tags Yeast strain SR...1370,SRX493939,SRX211371 http://dbarchive.biosciencedbc.jp/kyushu-u/sacCer3/assembled/Oth.YSt.10.Epitope_tags.AllCell.bed ...

  1. 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 ...

  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.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 ...

  4. 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 ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Unc.05.Epitope_tags.AllCell hg19 TFs and others Epitope tags Unclassified SRX88...9798 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Unc.05.Epitope_tags.AllCell.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.CDV.50.Epitope_tags.AllCell mm9 TFs and others Epitope tags Cardiovascular SRX1...304813 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.CDV.50.Epitope_tags.AllCell.bed ...

  7. 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 ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Kid.20.Epitope_tags.AllCell hg19 TFs and others Epitope tags Kidney SRX065541,S...RX644727,SRX644719,SRX644723 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Kid.20.Epitope_tags.AllCell.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Myo.50.Epitope_tags.AllCell hg19 TFs and others Epitope tags Muscle SRX1470542,...SRX1470544 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Myo.50.Epitope_tags.AllCell.bed ...

  10. 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 ...

  11. 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 ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Liv.10.Epitope_tags.AllCell hg19 TFs and others Epitope tags Liver SRX1165095,S...RX1165103,SRX1165100,SRX1165096,SRX1165104,SRX1165101,SRX1165090,SRX1165102,SRX1165091 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Liv.10.Epitope_tags.AllCell.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.CeL.05.Epitope_tags.AllCell dm3 TFs and others Epitope tags Cell line SRX330995...099636 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Oth.CeL.05.Epitope_tags.AllCell.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.NoD.05.Epitope_tags.AllCell sacCer3 TFs and others Epitope tags No description ...http://dbarchive.biosciencedbc.jp/kyushu-u/sacCer3/assembled/Oth.NoD.05.Epitope_tags.AllCell.bed ...

  15. File list: Oth.YSt.05.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.YSt.05.Epitope_tags.AllCell sacCer3 TFs and others Epitope tags Yeast strain SR...1370,SRX211371,SRX493939 http://dbarchive.biosciencedbc.jp/kyushu-u/sacCer3/assembled/Oth.YSt.05.Epitope_tags.AllCell.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Oth.50.Epitope_tags.AllCell mm9 TFs and others Epitope tags Others SRX228677,SR...X228679,SRX228676,SRX228678 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Oth.50.Epitope_tags.AllCell.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Utr.50.Epitope_tags.AllCell hg19 TFs and others Epitope tags Uterus SRX188854,S...,SRX210703,SRX968127,SRX610673,SRX610674,SRX610672,SRX095386 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Utr.50.Epitope_tags.AllCell.bed ...

  18. 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 ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Oth.05.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.05.Epitope_tags.AllCell.bed ...

  20. High frequency of T cells specific for cryptic epitopes in melanoma patients

    DEFF Research Database (Denmark)

    Andersen, Rikke Sick; Andersen, Sofie Ramskov; Hjortsø, Mads Duus

    2013-01-01

    A number of cytotoxic T-cell epitopes are cryptic epitopes generated from non-conventional sources. These include epitopes that are encoded by alternative open reading frames or in generally non-coding genomic regions, such as introns. We have previously observed a frequent recognition of cryptic...

  1. 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

    could be relevant to the pathogenesis of CD. In A20 B cells transduced with TG2-specific B-cell receptor, epitope 2-expressing cells had poorer uptake of TG2-gluten complexes and were less efficient in gluten epitope presentation to T cells than cells expressing an epitope 1 receptor. Thus, the ability...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Neu.50.Epitope_tags.AllCell hg19 TFs and others Epitope tags Neural SRX367452,S...RX367451 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Neu.50.Epitope_tags.AllCell.bed ...

  3. 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 ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Gon.50.Epitope_tags.AllCell hg19 TFs and others Epitope tags Gonad SRX204898,SR...X204899 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Gon.50.Epitope_tags.AllCell.bed ...

  5. 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 ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Brs.20.Epitope_tags.AllCell hg19 TFs and others Epitope tags Breast SRX667411,S...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Brs.20.Epitope_tags.AllCell.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.NoD.20.Epitope_tags.AllCell hg19 TFs and others Epitope tags No description htt...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.NoD.20.Epitope_tags.AllCell.bed ...

  8. File list: Oth.Kid.05.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Kid.05.Epitope_tags.AllCell hg19 TFs and others Epitope tags Kidney SRX065541,S...RX644719,SRX527876,SRX644723 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Kid.05.Epitope_tags.AllCell.bed ...

  9. 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 ...

  10. 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 ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.EmF.20.Epitope_tags.AllCell mm9 TFs and others Epitope tags Embryonic fibroblas...RX255459,SRX255462,SRX255460,SRX204643,SRX204642 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.EmF.20.Epitope_tags.AllCell.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Utr.20.Epitope_tags.AllCell hg19 TFs and others Epitope tags Uterus SRX188854,S...,SRX210703,SRX679119,SRX095385,SRX210702,SRX968127,SRX095386 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Utr.20.Epitope_tags.AllCell.bed ...

  13. 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 ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.CeL.50.Epitope_tags.AllCell dm3 TFs and others Epitope tags Cell line SRX099638...099636 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Oth.CeL.50.Epitope_tags.AllCell.bed ...

  15. 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 ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Prs.10.Epitope_tags.AllCell hg19 TFs and others Epitope tags Prostate SRX084528...,SRX084527,SRX084524 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Prs.10.Epitope_tags.AllCell.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Myo.20.Epitope_tags.AllCell mm9 TFs and others Epitope tags Muscle SRX344965,SR...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Myo.20.Epitope_tags.AllCell.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Unc.50.Epitope_tags.AllCell hg19 TFs and others Epitope tags Unclassified SRX88...9798 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Unc.50.Epitope_tags.AllCell.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.CeL.10.Epitope_tags.AllCell dm3 TFs and others Epitope tags Cell line SRX099635...099636 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Oth.CeL.10.Epitope_tags.AllCell.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.05.Epitope_tags.AllCell mm9 TFs and others Epitope tags Blood SRX180156,SRX...,SRX180155,SRX695808 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.05.Epitope_tags.AllCell.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.20.Epitope_tags.AllCell sacCer3 TFs and others Epitope tags All cell types ...211371,SRX493939,SRX381289 http://dbarchive.biosciencedbc.jp/kyushu-u/sacCer3/assembled/Oth.ALL.20.Epitope_tags.AllCell.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Gon.05.Epitope_tags.AllCell hg19 TFs and others Epitope tags Gonad SRX204899,SR...X204898 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Gon.05.Epitope_tags.AllCell.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Epd.50.Epitope_tags.AllCell hg19 TFs and others Epitope tags Epidermis SRX71842...0,SRX512368,SRX512366,SRX807621,SRX512367,SRX512372,SRX512373,SRX807620 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Epd.50.Epitope_tags.AllCell.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Unc.20.Epitope_tags.AllCell sacCer3 TFs and others Epitope tags Unclassified ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/sacCer3/assembled/Oth.Unc.20.Epitope_tags.AllCell.bed ...

  5. 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 ...

  6. File list: Oth.Unc.50.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Unc.50.Epitope_tags.AllCell sacCer3 TFs and others Epitope tags Unclassified ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/sacCer3/assembled/Oth.Unc.50.Epitope_tags.AllCell.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Adl.10.Epitope_tags.AllCell dm3 TFs and others Epitope tags Adult SRX181427,SRX...ttp://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Oth.Adl.10.Epitope_tags.AllCell.bed ...

  8. File list: Oth.Prs.05.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Prs.05.Epitope_tags.AllCell hg19 TFs and others Epitope tags Prostate SRX084528...,SRX084527,SRX084524 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Prs.05.Epitope_tags.AllCell.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.PSC.20.Epitope_tags.AllCell hg19 TFs and others Epitope tags Pluripotent stem c...ell SRX555489 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.PSC.20.Epitope_tags.AllCell.bed ...

  10. 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 ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Brs.10.Epitope_tags.AllCell hg19 TFs and others Epitope tags Breast SRX667411,S...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Brs.10.Epitope_tags.AllCell.bed ...

  12. 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 ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.50.Epitope_tags.AllCell sacCer3 TFs and others Epitope tags All cell types ...493939 http://dbarchive.biosciencedbc.jp/kyushu-u/sacCer3/assembled/Oth.ALL.50.Epitope_tags.AllCell.bed ...

  14. File list: Oth.Bld.50.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.50.Epitope_tags.AllCell mm9 TFs and others Epitope tags Blood SRX718015,SRX...,SRX180155,SRX695808 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.50.Epitope_tags.AllCell.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.05.Epitope_tags.AllCell dm3 TFs and others Epitope tags Embryo SRX066244,SR...X815533,SRX066245,SRX815531,SRX066247 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Oth.Emb.05.Epitope_tags.AllCell.bed ...

  16. 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 ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.10.Epitope_tags.AllCell dm3 TFs and others Epitope tags Embryo SRX066244,SR...X815533,SRX066245,SRX815531,SRX066247 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Oth.Emb.10.Epitope_tags.AllCell.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Neu.20.Epitope_tags.AllCell mm9 TFs and others Epitope tags Neural SRX275807,SR...SRX691799,SRX691794,SRX759286,SRX691798,SRX691797,SRX275809,SRX275811,SRX691795,SRX022866 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.20.Epitope_tags.AllCell.bed ...

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

    Lifescience Database Archive (English)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    Lifescience Database Archive (English)

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

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

    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.20.Epitope_tags.AllCell hg19 TFs and others Epitope tags All cell types SRX...322539,SRX170374,SRX644727,SRX644719,SRX644723 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.ALL.20.Epitope_tags.AllCell.bed ...

  20. File list: Oth.Neu.50.Epitope_tags.AllCell [Chip-atlas[Archive

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  1. File list: Oth.Pan.50.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Pan.50.Epitope_tags.AllCell mm9 TFs and others Epitope tags Pancreas SRX747491,...SRX747492 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Pan.50.Epitope_tags.AllCell.bed ...

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

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

    Lifescience Database Archive (English)

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

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

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

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

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

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

    Lifescience Database Archive (English)

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

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

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

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

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

    Lifescience Database Archive (English)

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

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

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

    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

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

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

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

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

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

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

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

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

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  7. 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 ...

  8. Applied discrete-time queues

    CERN Document Server

    Alfa, Attahiru S

    2016-01-01

    This book introduces the theoretical fundamentals for modeling queues in discrete-time, and the basic procedures for developing queuing models in discrete-time. There is a focus on applications in modern telecommunication systems. It presents how most queueing models in discrete-time can be set up as discrete-time Markov chains. Techniques such as matrix-analytic methods (MAM) that can used to analyze the resulting Markov chains are included. This book covers single node systems, tandem system and queueing networks. It shows how queues with time-varying parameters can be analyzed, and illustrates numerical issues associated with computations for the discrete-time queueing systems. Optimal control of queues is also covered. Applied Discrete-Time Queues targets researchers, advanced-level students and analysts in the field of telecommunication networks. It is suitable as a reference book and can also be used as a secondary text book in computer engineering and computer science. Examples and exercises are includ...

  9. Immunolocalization of cell wall carbohydrate epitopes in seaweeds: presence of land plant epitopes in Fucus vesiculosus L. (Phaeophyceae).

    Science.gov (United States)

    Raimundo, Sandra Cristina; Avci, Utku; Hopper, Christina; Pattathil, Sivakumar; Hahn, Michael G; Popper, Zoë A

    2016-02-01

    Land plant cell wall glycan epitopes are present in Fucus vesiculosus. RG-I/AG mAbs recognize distinct glycan epitopes in structurally different galactans, and 3-linked glucans are also present in the cell walls. Cell wall-directed monoclonal antibodies (mAbs) have given increased knowledge of fundamental land plant processes but are not extensively used to study seaweeds. We profiled the brown seaweed Fucus vesiculosus glycome employing 155 mAbs that recognize predominantly vascular plant cell wall glycan components. The resulting profile was used to inform in situ labeling studies. Several of the mAbs recognized and bound to epitopes present in different thallus parts of Fucus vesiculosus. Antibodies recognizing arabinogalactan epitopes were divided into four groups based on their immunolocalization patterns. Group 1 bound to the stipe, blade, and receptacles. Group 2 bound to the antheridia, oogonia and paraphyses. Group 3 recognized antheridia cell walls and Group 4 localized on the antheridia inner wall and oogonia mesochite. This study reveals that epitopes present in vascular plant cell walls are also present in brown seaweeds. Furthermore, the diverse in situ localization patterns of the RG-I/AG clade mAbs suggest that these mAbs likely detect distinct epitopes present in structurally different galactans. In addition, 3-linked glucans were also detected throughout the cell walls of the algal tissues, using the β-glucan-directed LAMP mAb. Our results give insights into cell wall evolution, and diversify the available tools for the study of brown seaweed cell walls.

  10. Identification of two major conformational aquaporin-4 epitopes for neuromyelitis optica autoantibody binding.

    Science.gov (United States)

    Pisani, Francesco; Mastrototaro, Mauro; Rossi, Andrea; Nicchia, Grazia Paola; Tortorella, Carla; Ruggieri, Maddalena; Trojano, Maria; Frigeri, Antonio; Svelto, Maria

    2011-03-18

    Neuromyelitis optica (NMO) is an autoimmune demyelinating disease characterized by the presence of anti-aquaporin-4 (AQP4) antibodies in the patient sera. We recently reported that these autoantibodies are able to bind AQP4 when organized in the supramolecular structure called the orthogonal array of particles (OAP). To map the antigenic determinants, we produced a series of AQP4 mutants based on multiple alignment sequence analysis between AQP4 and other OAP-forming AQPs. Mutations were introduced in the three extracellular loops (A, C, and E), and the binding capacity of NMO sera was tested on AQP4 mutants. Results indicate that one group of sera was able to recognize a limited portion of loop C containing the amino acid sequence (146)GVT(T/M)V(150). A second group of sera was characterized by a predominant role of loop A. Deletion of four AQP4-specific amino acids ((61)G(S/T)E(N/K)(64)) in loop A substantially affected the binding of this group of sera. However, the binding capacity was further reduced when amino acids in loop A were mutated together with those in loop E or when those in loop C were mutated in combination with loop E. Finally, a series of AQP0 mutants were produced in which the extracellular loops were progressively changed to make them identical to AQP4. Results showed that none of the mutants was able to reproduce in AQP0 the NMO-IgG epitopes, indicating that the extracellular loop sequence by itself was not sufficient to determine the rearrangement required to create the epitopes. Although our data highlight the complexity of the disease, this study identifies key immunodominant epitopes and provides direct evidence that the transition from AQP4 tetramers to AQP4-OAPs involves conformational changes of the extracellular loops.

  11. Epitope Mapping of Dengue-Virus-Enhancing Monoclonal-Antibody Using Phage Display Peptide Library

    Directory of Open Access Journals (Sweden)

    Chung-I Rai

    2008-01-01

    Full Text Available The Antibody-Dependent Enhancement (ADE hypothesis has been proposed to explain why more severe manifestations of Dengue Hemorrhagic Fever and Dengue Shock Syndrome (DHF/DSS occur predominantly during secondary infections of Dengue Virus (DV with different serotypes. However, the epitopes recognized by these enhancing antibodies are unclear. Recently, anti-pre-M monoclonal antibody (mAb 70-21, which recognized all DV serotypes without neutralizing activity, were generated and demonstrated as an enhancing antibody for DV infection. In the present study, the epitope recognized by mAb 70-21 was identified using a phage-displayed random-peptide library. After three rounds of biopanning, ELISA showed that immunopositive phage clones specifically bound to mAb 70-21 but not to serum or purified IgG from naive mice. DNA sequencing of these phage clones showed a consensus sequence, QNNLGPR. Like mAb70-21, these phage-induced antisera also enhanced the DV infection of cells. In addition, indirect fluorescent assays showed phage-induced antisera bound to human rhabdomyosarcoma or Vero cells. Western blotting and immunoprecipitation analysis showed that phage-induced antisera recognized hsp 60 in BHK cell lysate. Moreover, the sera levels of antibodies against the synthetic peptide QNNLGPR correlated with the disease severity of dengue patients. Taken together, these results suggest that antibodies which recognized epitopes shared by pre-M of DV and hsp 60 of host cells may enhance DV infection and be involved in the development of DHF or DSS.

  12. Finite Volumes Discretization of Topology Optimization Problems

    DEFF Research Database (Denmark)

    Evgrafov, Anton; Gregersen, Misha Marie; Sørensen, Mads Peter

    such a mature and versatile technique for discretiz- ing partial dierential equations in the form of conservation laws of varying types. Advantages of FVMs include the simplicity of implementation, their local conservation properties, and the ease of coupling various PDEs in a multi-physics setting. In fact...... attractive, as all involved PDEs on a given domain are discretized using the same and the low- est possible number of degrees of freedom. In spite of their numerous favourable advantages, FVMs have seen very little adoption within the topology optimization community, where the absolute majority of numerical...

  13. Improved method for linear B-cell epitope prediction using antigen's primary sequence.

    Directory of Open Access Journals (Sweden)

    Harinder Singh

    Full Text Available One of the major challenges in designing a peptide-based vaccine is the identification of antigenic regions in an antigen that can stimulate B-cell's response, also called B-cell epitopes. In the past, several methods have been developed for the prediction of conformational and linear (or continuous B-cell epitopes. However, the existing methods for predicting linear B-cell epitopes are far from perfection. In this study, an attempt has been made to develop an improved method for predicting linear B-cell epitopes. We have retrieved experimentally validated B-cell epitopes as well as non B-cell epitopes from Immune Epitope Database and derived two types of datasets called Lbtope_Variable and Lbtope_Fixed length datasets. The Lbtope_Variable dataset contains 14876 B-cell epitope and 23321 non-epitopes of variable length where as Lbtope_Fixed length dataset contains 12063 B-cell epitopes and 20589 non-epitopes of fixed length. We also evaluated the performance of models on above datasets after removing highly identical peptides from the datasets. In addition, we have derived third dataset Lbtope_Confirm having 1042 epitopes and 1795 non-epitopes where each epitope or non-epitope has been experimentally validated in at least two studies. A number of models have been developed to discriminate epitopes and non-epitopes using different machine-learning techniques like Support Vector Machine, and K-Nearest Neighbor. We achieved accuracy from ∼54% to 86% using diverse s features like binary profile, dipeptide composition, AAP (amino acid pair profile. In this study, for the first time experimentally validated non B-cell epitopes have been used for developing method for predicting linear B-cell epitopes. In previous studies, random peptides have been used as non B-cell epitopes. In order to provide service to scientific community, a web server LBtope has been developed for predicting and designing B-cell epitopes (http://crdd.osdd.net/raghava/lbtope/.

  14. An epitope delivery system for use with recombinant mycobacteria

    NARCIS (Netherlands)

    Hetzel, C.; Janssen, R.; Ely, S.J.; Kristensen, N.M.; Bunting, K.; Cooper, J.B.; Lamb, J.R.; Young, D.B.; Thole, J.E.R.

    1998-01-01

    We have developed a novel epitope delivery system based on the insertion of peptides within a permissive loop of a bacterial superoxide dismutase molecule. This system allowed high-level expression of heterologous peptides in two mycobacterial vaccine strains, Mycobacterium bovis bacille Calmette- G

  15. 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....

  16. 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.

  17. An epitope delivery system for use with recombinant mycobacteria

    NARCIS (Netherlands)

    Hetzel, C.; Janssen, R.; Ely, S.J.; Kristensen, N.M.; Bunting, K.; Cooper, J.B.; Lamb, J.R.; Young, D.B.; Thole, J.E.R.

    1998-01-01

    We have developed a novel epitope delivery system based on the insertion of peptides within a permissive loop of a bacterial superoxide dismutase molecule. This system allowed high-level expression of heterologous peptides in two mycobacterial vaccine strains, Mycobacterium bovis bacille Calmette- G

  18. Discrete Curvature Theories and Applications

    KAUST Repository

    Sun, Xiang

    2016-08-25

    Discrete Di erential Geometry (DDG) concerns discrete counterparts of notions and methods in di erential geometry. This thesis deals with a core subject in DDG, discrete curvature theories on various types of polyhedral surfaces that are practically important for free-form architecture, sunlight-redirecting shading systems, and face recognition. Modeled as polyhedral surfaces, the shapes of free-form structures may have to satisfy di erent geometric or physical constraints. We study a combination of geometry and physics { the discrete surfaces that can stand on their own, as well as having proper shapes for the manufacture. These proper shapes, known as circular and conical meshes, are closely related to discrete principal curvatures. We study curvature theories that make such surfaces possible. Shading systems of freeform building skins are new types of energy-saving structures that can re-direct the sunlight. From these systems, discrete line congruences across polyhedral surfaces can be abstracted. We develop a new curvature theory for polyhedral surfaces equipped with normal congruences { a particular type of congruences de ned by linear interpolation of vertex normals. The main results are a discussion of various de nitions of normality, a detailed study of the geometry of such congruences, and a concept of curvatures and shape operators associated with the faces of a triangle mesh. These curvatures are compatible with both normal congruences and the Steiner formula. In addition to architecture, we consider the role of discrete curvatures in face recognition. We use geometric measure theory to introduce the notion of asymptotic cones associated with a singular subspace of a Riemannian manifold, which is an extension of the classical notion of asymptotic directions. We get a simple expression of these cones for polyhedral surfaces, as well as convergence and approximation theorems. We use the asymptotic cones as facial descriptors and demonstrate the

  19. Non-enzymatic glucosylation induced neo-epitopes on human serum albumin: A concentration based study

    Science.gov (United States)

    Neelofar, Km; Arif, Zarina; Ahmad, Jamal; Alam, Khursheed

    2017-01-01

    Hyperglycaemia induced non enzymatic glycation is accelerated in diabetic patients and aggressively involved in diabetes progression. Human serum albumin (HSA) is the most abundant protein in blood circulation. In hyperglycaemia, it undergoes fast glycation and results in the impairment of structure. Our previous study has demonstrated structural alterations in Amadori-albumin modified with different glucose concentrations from physiological to pathophysiological range. Here, we focused on immunological characterization of Amadori-albumin. Immunogenicity of Amadori-albumin was analysed by direct binding and competitive ELISA. Amadori-albumin was found to be highly immunogenic (expect albumin modified with 5mM) and induced high titre antibodies depending upon the extent of modification. Very high titre antibodies were obtained with albumin modified with 75mM glucose as compared to native albumin. Anti-Amadori-albumin-IgG from rabbit sera exhibited increased recognition of Amadori-albumin than native albumin in competitive immunoassay. Alteration induced in albumin after glucosylation has made it highly immunogenic. Induced antibodies were quite specific for respective immunogens but showed cross-reaction with other Amadori/native proteins. It suggests that glucosylation has generated highly immunogenic epitopes on albumin. Formation of high molecular weight immune complex with retarded mobility further supports specificity of anti-Amadori-albumin-IgG towards Amadori-albumin. It may be concluded that due to early glycation, an array of modification occurred in HSA structure. Such gross structural changes might favour polymerization of most of the native epitopes into potent immunogenic neo-epitopes, but some original epitopes were still active and has contributed in the immunogenicity. It could be concluded that induction of anti-Amadori-albumin antibodies may be due to protection of glucose modified albumin from protiolytic breakdown. We assumed that this type of

  20. B- and T-cell epitope mapping of human sapovirus capsid protein: an immunomics approach.

    Science.gov (United States)

    Amin, M Ruhul; Siddiqui, Mohammad S; Ahmed, Dilruba; Ahmed, Firoz; Hossain, Anowar

    2011-01-01

    Human sapovirus is one of the major causes of viral gastroenteritis. Although the capsid protein (VP1) confers antigenic cross-reactivity, immunity against sapovirus is still unclear. Using immunoinformatics approach, we defined putative T- and B-cell epitopes of VP1 and mapped on to its predicted three-dimensional structure. Identified five putative T-cell epitopes also occupied the putative B-cell epitope region. These putative epitopes were conserved in all existing serotypes. Predicted epitopes can be generated through proteasome cleavage and may be useful in designing peptide-based subunit vaccine to confer both humoral and cell-mediated immunity.

  1. MIMOX: a web tool for phage display based epitope mapping

    Directory of Open Access Journals (Sweden)

    Honda Wataru

    2006-10-01

    Full Text Available Abstract Background Phage display is widely used in basic research such as the exploration of protein-protein interaction sites and networks, and applied research such as the development of new drugs, vaccines, and diagnostics. It has also become a promising method for epitope mapping. Research on new algorithms that assist and automate phage display based epitope mapping has attracted many groups. Most of the existing tools have not been implemented as an online service until now however, making it less convenient for the community to access, utilize, and evaluate them. Results We present MIMOX, a free web tool that helps to map the native epitope of an antibody based on one or more user supplied mimotopes and the antigen structure. MIMOX was coded in Perl using modules from the Bioperl project. It has two sections. In the first section, MIMOX provides a simple interface for ClustalW to align a set of mimotopes. It also provides a simple statistical method to derive the consensus sequence and embeds JalView as a Java applet to view and manage the alignment. In the second section, MIMOX can map a single mimotope or a consensus sequence of a set of mimotopes, on to the corresponding antigen structure and search for all of the clusters of residues that could represent the native epitope. NACCESS is used to evaluate the surface accessibility of the candidate clusters; and Jmol is embedded to view them interactively in their 3D context. Initial case studies show that MIMOX can reproduce mappings from existing tools such as FINDMAP and 3DEX, as well as providing novel, rational results. Conclusion A web-based tool called MIMOX has been developed for phage display based epitope mapping. As a publicly available online service in this area, it is convenient for the community to access, utilize, and evaluate, complementing other existing programs. MIMOX is freely available at http://web.kuicr.kyoto-u.ac.jp/~hjian/mimox.

  2. Analysis of Discrete Mittag - Leffler Functions

    Directory of Open Access Journals (Sweden)

    N. Shobanadevi

    2015-03-01

    Full Text Available Discrete Mittag - Leffler functions play a major role in the development of the theory of discrete fractional calculus. In the present article, we analyze qualitative properties of discrete Mittag - Leffler functions and establish sufficient conditions for convergence, oscillation and summability of the infinite series associated with discrete Mittag - Leffler functions.

  3. Two highly similar LAEDDTNAQKT and LTDKIGTEI epitopes in G glycoprotein may be useful for effective epitope based vaccine design against pathogenic Henipavirus.

    Science.gov (United States)

    Parvege, Md Masud; Rahman, Monzilur; Nibir, Yead Morshed; Hossain, Mohammad Shahnoor

    2016-04-01

    Nipah virus and Hendra virus, two members of the genus Henipavirus, are newly emerging zoonotic pathogens which cause acute respiratory illness and severe encephalitis in human. Lack of the effective antiviral therapy endorses the urgency for the development of vaccine against these deadly viruses. In this study, we employed various computational approaches to identify epitopes which has the potential for vaccine development. By analyzing the immune parameters of the conserved sequences of G glycoprotein using various databases and bioinformatics tools, we identified two potential epitopes which may be used as peptide vaccines. Using different B cell epitope prediction servers, four highly similar B cell epitopes were identified. Immunoinformatics analyses revealed that LAEDDTNAQKT is a highly flexible and accessible B-cell epitope to antibody. Highly similar putative CTL epitopes were analyzed for their binding with the HLA-C 12*03 molecule. Docking simulation assay revealed that LTDKIGTEI has significantly lower binding energy, which bolstered its potential as epitope-based vaccine design. Finally, cytotoxicity analysis has also justified their potential as promising epitope-based vaccine candidate. In sum, our computational analysis indicates that either LAEDDTNAQKT or LTDKIGTEI epitope holds a promise for the development of universal vaccine against all kinds of pathogenic Henipavirus. Further in vivo and in vitro studies are necessary to validate the obtained findings.

  4. A novel multi-epitope vaccine from MMSA-1 and DKK1 for multiple myeloma immunotherapy.

    Science.gov (United States)

    Lu, Chenyang; Meng, Shan; Jin, Yanxia; Zhang, Wanggang; Li, Zongfang; Wang, Fang; Wang-Johanning, Feng; Wei, Yongchang; Liu, Hailing; Tu, Honglei; Su, Dan; He, Aili; Cao, Xingmei; Zhou, Fuling

    2017-08-01

    The identification of novel tumour-associated antigens is urgently needed to improve the efficacy of immunotherapy for multiple myeloma (MM). In this study, we identified a membrane protein MMSA-1 (multiple myeloma special antigen-1) that was specifically expressed in MM and exhibited significantly positive correlation with MM. We then identified HLA-A*0201-restricted MMSA-1 epitopes and tested their cytotoxic T lymphocyte (CTL) response. The MMSA-1 epitope SLSLLTIYV vaccine was shown to induce an obvious CTL response in vitro. To improve the immunotherapy, we constructed a multi-epitope peptide vaccine by combining epitopes derived from MMSA-1 and Dickkopf-1 (DKK1). The effector T cells induced by multi-epitope peptide vaccine-loaded dendritic cells lysed U266 cells more effectively than MMSA-1/DKK1 single-epitope vaccine. In myeloma-bearing severe combined immunodeficient mice, the multi-epitope vaccine improved the survival rate significantly compared with single-epitope vaccine. Consistently, multi-epitope vaccine decreased the tumour volume greatly and alleviated bone destruction. The frequencies of CD4(+) and CD8(+) T cells was significantly increased in mouse blood induced by the multi-epitope vaccine, indicating that it inhibits myeloma growth by changing T cell subsets and alleviating immune paralysis. This study identified a novel peptide from MMSA-1 and the multi-epitope vaccine will be used to establish appropriate individualized therapy for MM. © 2017 John Wiley & Sons Ltd.

  5. 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.

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

    Science.gov (United States)

    Ramanathan, Babu; Poh, Chit Laa; Kirk, Kristin; McBride, William John Hannan; Aaskov, John; Grollo, Lara

    2016-01-01

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

    Science.gov (United States)

    Poh, Chit Laa; Kirk, Kristin; McBride, William John Hannan; Aaskov, John; Grollo, Lara

    2016-01-01

    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. PMID:27223692

  8. Epitope-specific antibody levels in tuberculosis: biomarkers of protection, disease and response to treatment.

    Directory of Open Access Journals (Sweden)

    Graham H Bothamley

    2014-06-01

    Full Text Available Monoclonal antibodies restricted to Mycobacterium tuberculosis can measure epitope-specific antibody levels in a competition assay. Immunodominant epitopes were defined from clinical samples and related to the clinical spectrum of disease. Antibody to the immunodominant epitopes was associated with HLA-DR15. Occupational exposure showed a different response and was consistent with recognition of dormancy related proteins and protection despite exposure to tuberculosis. Studies in leprosy revealed the importance of immune deviation and the relationships between T and B cell epitopes. During treatment, antibody levels increased, epitope spreading occurred, but the affinity constants remained the same after further antigen exposure, suggesting constraints on the process of epitope selection. Epitope-specific antibody levels have a potential role as biomarkers for new vaccines which might prevent the progression of latent to active tuberculosis and as tools to measure treatment effects on subpopulations of tubercle bacilli.

  9. Optimization of Operations Resources via Discrete Event Simulation Modeling

    Science.gov (United States)

    Joshi, B.; Morris, D.; White, N.; Unal, R.

    1996-01-01

    The resource levels required for operation and support of reusable launch vehicles are typically defined through discrete event simulation modeling. Minimizing these resources constitutes an optimization problem involving discrete variables and simulation. Conventional approaches to solve such optimization problems involving integer valued decision variables are the pattern search and statistical methods. However, in a simulation environment that is characterized by search spaces of unknown topology and stochastic measures, these optimization approaches often prove inadequate. In this paper, we have explored the applicability of genetic algorithms to the simulation domain. Genetic algorithms provide a robust search strategy that does not require continuity and differentiability of the problem domain. The genetic algorithm successfully minimized the operation and support activities for a space vehicle, through a discrete event simulation model. The practical issues associated with simulation optimization, such as stochastic variables and constraints, were also taken into consideration.

  10. Maturation-induced cloaking of neutralization epitopes on HIV-1 particles.

    Directory of Open Access Journals (Sweden)

    Amanda S Joyner

    2011-09-01

    Full Text Available To become infectious, HIV-1 particles undergo a maturation process involving proteolytic cleavage of the Gag and Gag-Pol polyproteins. Immature particles contain a highly stable spherical Gag lattice and are impaired for fusion with target cells. The fusion impairment is relieved by truncation of the gp41 cytoplasmic tail (CT, indicating that an interaction between the immature viral core and gp41 within the particle represses HIV-1 fusion by an unknown mechanism. We hypothesized that the conformation of Env on the viral surface is regulated allosterically by interactions with the HIV-1 core during particle maturation. To test this, we quantified the binding of a panel of monoclonal antibodies to mature and immature HIV-1 particles by immunofluorescence imaging. Surprisingly, immature particles exhibited markedly enhanced binding of several gp41-specific antibodies, including two that recognize the membrane proximal external region (MPER and neutralize diverse HIV-1 strains. Several of the differences in epitope exposure on mature and immature particles were abolished by truncation of the gp41 CT, thus linking the immature HIV-1 fusion defect with altered Env conformation. Our results suggest that perturbation of fusion-dependent Env conformational changes contributes to the impaired fusion of immature particles. Masking of neutralization-sensitive epitopes during particle maturation may contribute to HIV-1 immune evasion and has practical implications for vaccine strategies targeting the gp41 MPER.

  11. Identification and characterization of human eosinophil cationic protein by an epitope-specific antibody.

    Science.gov (United States)

    Boix, E; Carreras, E; Nikolovski, Z; Cuchillo, C M; Nogués, M V

    2001-06-01

    The eosinophil cationic protein (ECP) is a basic secretion protein involved in the immune response system. ECP levels in biological fluids are an indicator of eosinophil-specific activation and degranulation and are currently used for the clinical monitoring and diagnosis of inflammatory disorders. A polyclonal epitope-specific antibody has been obtained by immunizing rabbits with a conjugated synthetic peptide. A sequence corresponding to a large exposed loop in the human ECP three-dimensional structure (D115-Y122) was selected as a putative antigenic epitope. The antibody was purified on an affinity column using recombinant ECP (rECP) as antigen. The antibody (D112-P123 Ab) specifically recognizes rECP and its native glycosylated and nonglycosylated forms in plasma, granulocytes, and sputum. The antibody detects as little as 1 ng of rECP, can be used both in reducing and nonreducing conditions, and does not cross-react with the highly homologous eosinophil-derived neurotoxin or other proteins of the pancreatic ribonuclease superfamily.

  12. Minisuperspace models of discrete systems

    CERN Document Server

    Baytaş, Bekir

    2016-01-01

    A discrete quantum spin system is presented in which several modern methods of canonical quantum gravity can be tested with promising results. In particular, features of interacting dynamics are analyzed with an emphasis on homogeneous configurations and the dynamical building-up and stability of long-range correlations. Different types of homogeneous minisuperspace models are introduced for the system, including one based on condensate states, and shown to capture different aspects of the discrete system. They are evaluated with effective methods and by means of continuum limits, showing good agreement with operator calculations whenever the latter are available. As a possibly quite general result, it is concluded that an analysis of the building-up of long-range correlations in discrete systems requires non-perturbative solutions of the dynamical equations. Some questions related to stability can be analyzed perturbatively, but suggest that matter couplings may be relevant for this question in the context o...

  13. Interference in discrete Wigner functions

    CERN Document Server

    Cormick, C; Cormick, Cecilia; Paz, Juan Pablo

    2006-01-01

    We analyse some features of the class of discrete Wigner functions that was recently introduced by Gibbons et al. to represent quantum states of systems with power-of-prime dimensional Hilbert spaces [Phys. Rev. A 70, 062101 (2004)]. We consider "cat" states obtained as coherent superpositions of states with positive Wigner function; for such states we show that the oscillations of the discrete Wigner function typically spread over the entire discrete phase-space (including the regions where the two interfering states are localized). This is a generic property which is in sharp contrast with the usual attributes of Wigner functions that make them useful candidates to display the existence of quantum coherence through oscillations. However, it is possible to find subsets of cat states with a natural phase-space representation, in which the oscillatory regions remain localized. We show that this can be done for interesting families of stabilizer states used in quantum error-correcting codes, and illustrate this...

  14. On discrete control of nonlinear systems with applications to robotics

    Science.gov (United States)

    Eslami, Mansour

    1989-01-01

    Much progress has been reported in the areas of modeling and control of nonlinear dynamic systems in a continuous-time framework. From implementation point of view, however, it is essential to study these nonlinear systems directly in a discrete setting that is amenable for interfacing with digital computers. But to develop discrete models and discrete controllers for a nonlinear system such as robot is a nontrivial task. Robot is also inherently a variable-inertia dynamic system involving additional complications. Not only the computer-oriented models of these systems must satisfy the usual requirements for such models, but these must also be compatible with the inherent capabilities of computers and must preserve the fundamental physical characteristics of continuous-time systems such as the conservation of energy and/or momentum. Preliminary issues regarding discrete systems in general and discrete models of a typical industrial robot that is developed with full consideration of the principle of conservation of energy are presented. Some research on the pertinent tactile information processing is reviewed. Finally, system control methods and how to integrate these issues in order to complete the task of discrete control of a robot manipulator are also reviewed.

  15. Geometry of discrete quantum computing

    Science.gov (United States)

    Hanson, Andrew J.; Ortiz, Gerardo; Sabry, Amr; Tai, Yu-Tsung

    2013-05-01

    Conventional quantum computing entails a geometry based on the description of an n-qubit state using 2n infinite precision complex numbers denoting a vector in a Hilbert space. Such numbers are in general uncomputable using any real-world resources, and, if we have the idea of physical law as some kind of computational algorithm of the universe, we would be compelled to alter our descriptions of physics to be consistent with computable numbers. Our purpose here is to examine the geometric implications of using finite fields Fp and finite complexified fields \\mathbf {F}_{p^2} (based on primes p congruent to 3 (mod4)) as the basis for computations in a theory of discrete quantum computing, which would therefore become a computable theory. Because the states of a discrete n-qubit system are in principle enumerable, we are able to determine the proportions of entangled and unentangled states. In particular, we extend the Hopf fibration that defines the irreducible state space of conventional continuous n-qubit theories (which is the complex projective space \\mathbf {CP}^{2^{n}-1}) to an analogous discrete geometry in which the Hopf circle for any n is found to be a discrete set of p + 1 points. The tally of unit-length n-qubit states is given, and reduced via the generalized Hopf fibration to \\mathbf {DCP}^{2^{n}-1}, the discrete analogue of the complex projective space, which has p^{2^{n}-1} (p-1)\\,\\prod _{k=1}^{n-1} ( p^{2^{k}}+1) irreducible states. Using a measure of entanglement, the purity, we explore the entanglement features of discrete quantum states and find that the n-qubit states based on the complexified field \\mathbf {F}_{p^2} have pn(p - 1)n unentangled states (the product of the tally for a single qubit) with purity 1, and they have pn + 1(p - 1)(p + 1)n - 1 maximally entangled states with purity zero.

  16. DISCRETE ROTATIONS AND CELLULAR AUTOMATA

    OpenAIRE

    Nouvel, Bertrand

    2006-01-01

    In a discrete space, such as the set of integer-coordinate points, the modelization of isotropy may lead to noticeable theoretical difficulties. At this time, we do not know any gerometric theory on $\\ZZ^n$ that would be suitable to describe the isotropy the same way it is perceived by Euclidean geometry. With respect to this problematic, our aim is to describe some algorithms that would give to the discrete rotations some properties that would be similar to the properties of the Euclidean ro...

  17. Stable discrete surface light bullets.

    Science.gov (United States)

    Mihalache, Dumitru; Mazilu, Dumitru; Lederer, Falk; Kivshar, Yuri S

    2007-01-22

    We analyze spatiotemporal light localization near the edge of a semi-infinite array of weakly coupled nonlinear optical waveguides and demonstrate the existence of a novel class of continuous-discrete spatiotemporal solitons, the so-called discrete surface light bullets. We show that their properties are strongly affected by the presence of the surface. To this end the crossover between surface and quasi-bulk bullets is studied by analyzing the families of solitons propagating at different distances from the edge of the waveguide array.

  18. Discrete Hamiltonian for General Relativity

    CERN Document Server

    Ziprick, Jonathan

    2015-01-01

    Beginning from canonical general relativity written in terms of Ashtekar variables, we derive a discrete phase space with a physical Hamiltonian for gravity. The key idea is to define the gravitational fields within a complex of three-dimensional cells such that the dynamics is completely described by discrete boundary variables, and the full theory is recovered in the continuum limit. Canonical quantization is attainable within the loop quantum gravity framework, and we believe this will lead to a promising candidate for quantum gravity.

  19. IL-7 Induces an Epitope Masking of γc Protein in IL-7 Receptor Signaling Complex

    Directory of Open Access Journals (Sweden)

    Tae Sik Goh

    2017-01-01

    Full Text Available IL-7 signaling via IL-7Rα and common γ-chain (γc is necessary for the development and homeostasis of T cells. Although the delicate mechanism in which IL-7Rα downregulation allows the homeostasis of T cell with limited IL-7 has been well known, the exact mechanism behind the interaction between IL-7Rα and γc in the absence or presence of IL-7 remains unclear. Additionally, we are still uncertain as to how only IL-7Rα is separately downregulated by the binding of IL-7 from the IL-7Rα/γc complex. We demonstrate here that 4G3, TUGm2, and 3E12 epitope masking of γc protein are induced in the presence of IL-7, indicating that the epitope alteration is induced by IL-7 binding to the preassembled receptor core. Moreover, the epitope masking of γc protein is inversely correlated with the expression of IL-7Rα upon IL-7 binding, implying that the structural alteration of γc might be involved in the regulation of IL-7Rα expression. The conformational change in γc upon IL-7 binding may contribute not only to forming the functional IL-7 signaling complex but also to optimally regulating the expression of IL-7Rα.

  20. Engineering Recombinant Reoviruses To Display gp41 Membrane-Proximal External-Region Epitopes from HIV-1

    Science.gov (United States)

    Boehme, Karl W.; Ikizler, Mine'; Iskarpatyoti, Jason A.; Wetzel, J. Denise; Willis, Jordan; Crowe, James E.; LaBranche, Celia C.; Montefiori, David C.

    2016-01-01

    . Antibodies that neutralize genetically diverse strains of HIV-1 bind to discrete regions of the envelope glycoproteins, including the gp41 MPER. We engineered recombinant reoviruses that displayed MPER epitopes in attachment protein σ1 (REO-MPER vectors). The REO-MPER vectors replicated with wild-type efficiency, were genetically stable, and retained native antigenicity. However, we did not detect HIV-1-specific immune responses following inoculation of the REO-MPER vectors into small animals. This work provides proof of principle for engineering reovirus to express antigenic epitopes and illustrates the difficulty in eliciting MPER-specific immune responses. PMID:27303748

  1. Automated Detection of Conformational Epitopes Using Phage Display Peptide Sequences

    Directory of Open Access Journals (Sweden)

    Surendra S Negi

    2009-01-01

    Full Text Available Background: Precise determination of conformational epitopes of neutralizing antibodies represents a key step in the rational design of novel vaccines. A powerful experimental method to gain insights on the physical chemical nature of conformational epitopes is the selection of linear peptides that bind with high affinities to a monoclonal antibody of interest by phage display technology. However, the structural characterization of conformational epitopes from these mimotopes is not straightforward, and in the past the interpretation of peptide sequences from phage display experiments focused on linear sequence analysis to find a consensus sequence or common sequence motifs.Results: We present a fully automated search method, EpiSearch that predicts the possible location of conformational epitopes on the surface of an antigen. The algorithm uses peptide sequences from phage display experiments as input, and ranks all surface exposed patches according to the frequency distribution of similar residues in the peptides and in the patch. We have tested the performance of the EpiSearch algorithm for six experimental data sets of phage display experiments, the human epidermal growth factor receptor-2 (HER-2/neu, the antibody mAb Bo2C11 targeting the C2 domain of FVIII, antibodies mAb 17b and mAb b12 of the HIV envelope protein gp120, mAb 13b5 targeting HIV-1 capsid protein and 80R of the SARS coronavirus spike protein. In all these examples the conformational epitopes as determined by the X-ray crystal structures of the antibody-antigen complexes, were found within the highest scoring patches of EpiSearch, covering in most cases more than 50% residues of experimental observed conformational epitopes. Input options of the program include mapping of a single peptide or a set of peptides on the antigen structure, and the results of the calculation can be visualized on our interactive web server.Availability: Users can access the EpiSearch from our web

  2. Celiac disease T-cell epitopes from gamma-gliadins: immunoreactivity depends on the genome of origin, transcript frequency, and flanking protein variation

    Directory of Open Access Journals (Sweden)

    Salentijn Elma MJ

    2012-06-01

    Full Text Available Abstract Background Celiac disease (CD is caused by an uncontrolled immune response to gluten, a heterogeneous mixture of wheat storage proteins. The CD-toxicity of these proteins and their derived peptides is depending on the presence of specific T-cell epitopes (9-mer peptides; CD epitopes that mediate the stimulation of HLA-DQ2/8 restricted T-cells. Next to the thoroughly characterized major T-cell epitopes derived from the α-gliadin fraction of gluten, γ-gliadin peptides are also known to stimulate T-cells of celiac disease patients. To pinpoint CD-toxic γ-gliadins in hexaploid bread wheat, we examined the variation of T-cell epitopes involved in CD in γ-gliadin transcripts of developing bread wheat grains. Results A detailed analysis of the genetic variation present in γ-gliadin transcripts of bread wheat (T. aestivum, allo-hexaploid, carrying the A, B and D genome, together with genomic γ-gliadin sequences from ancestrally related diploid wheat species, enabled the assignment of sequence variants to one of the three genomic γ-gliadin loci, Gli-A1, Gli-B1 or Gli-D1. Almost half of the γ-gliadin transcripts of bread wheat (49% was assigned to locus Gli-D1. Transcripts from each locus differed in CD epitope content and composition. The Gli-D1 transcripts contained the highest frequency of canonical CD epitope cores (on average 10.1 per transcript followed by the Gli-A1 transcripts (8.6 and the Gli-B1 transcripts (5.4. The natural variants of the major CD epitope from γ-gliadins, DQ2-γ-I, showed variation in their capacity to induce in vitro proliferation of a DQ2-γ-I specific and HLA-DQ2 restricted T-cell clone. Conclusions Evaluating the CD epitopes derived from γ-gliadins in their natural context of flanking protein variation, genome specificity and transcript frequency is a significant step towards accurate quantification of the CD toxicity of bread wheat. This approach can be used to predict relative levels of CD toxicity of

  3. On Weakly Singular Versions of Discrete Nonlinear Inequalities and Applications

    Directory of Open Access Journals (Sweden)

    Kelong Cheng

    2014-01-01

    Full Text Available Some new weakly singular versions of discrete nonlinear inequalities are established, which generalize some existing weakly singular inequalities and can be used in the analysis of nonlinear Volterra type difference equations with weakly singular kernels. A few applications to the upper bound and the uniqueness of solutions of nonlinear difference equations are also involved.

  4. System for Automatic Generation of Examination Papers in Discrete Mathematics

    Science.gov (United States)

    Fridenfalk, Mikael

    2013-01-01

    A system was developed for automatic generation of problems and solutions for examinations in a university distance course in discrete mathematics and tested in a pilot experiment involving 200 students. Considering the success of such systems in the past, particularly including automatic assessment, it should not take long before such systems are…

  5. Dissection of a circadian oscillation into discrete domains

    NARCIS (Netherlands)

    Merrow, Martha W.; Garceau, Norman Y.; Dunlap, Jay C.; Giles, Norman H.

    1997-01-01

    The circadian oscillator in Neurospora is a negative feedback loop involving as principal players the products of the frequency (frq) locus. frq encodes multiple forms of its protein product FRQ, which act to depress the amounts of frq transcript. In this scheme there are two discrete and separable

  6. Some discrete multiple orthogonal polynomials

    Science.gov (United States)

    Arvesú, J.; Coussement, J.; van Assche, W.

    2003-04-01

    In this paper, we extend the theory of discrete orthogonal polynomials (on a linear lattice) to polynomials satisfying orthogonality conditions with respect to r positive discrete measures. First we recall the known results of the classical orthogonal polynomials of Charlier, Meixner, Kravchuk and Hahn (T.S. Chihara, An Introduction to Orthogonal Polynomials, Gordon and Breach, New York, 1978; R. Koekoek and R.F. Swarttouw, Reports of the Faculty of Technical Mathematics and Informatics No. 98-17, Delft, 1998; A.F. Nikiforov et al., Classical Orthogonal Polynomials of a Discrete Variable, Springer, Berlin, 1991). These polynomials have a lowering and raising operator, which give rise to a Rodrigues formula, a second order difference equation, and an explicit expression from which the coefficients of the three-term recurrence relation can be obtained. Then we consider r positive discrete measures and define two types of multiple orthogonal polynomials. The continuous case (Jacobi, Laguerre, Hermite, etc.) was studied by Van Assche and Coussement (J. Comput. Appl. Math. 127 (2001) 317-347) and Aptekarev et al. (Multiple orthogonal polynomials for classical weights, manuscript). The families of multiple orthogonal polynomials (of type II) that we will study have a raising operator and hence a Rodrigues formula. This will give us an explicit formula for the polynomials. Finally, there also exists a recurrence relation of order r+1 for these multiple orthogonal polynomials of type II. We compute the coefficients of the recurrence relation explicitly when r=2.

  7. Solving discrete zero point problems

    NARCIS (Netherlands)

    van der Laan, G.; Talman, A.J.J.; Yang, Z.F.

    2004-01-01

    In this paper an algorithm is proposed to .nd a discrete zero point of a function on the collection of integral points in the n-dimensional Euclidean space IRn.Starting with a given integral point, the algorithm generates a .nite sequence of adjacent integral simplices of varying dimension and termi

  8. A nonlocal discretization of fields

    CERN Document Server

    Campos, R G; Pimentel, L O; Campos, Rafael G.; Tututi, Eduardo S.

    2001-01-01

    A nonlocal method to obtain discrete classical fields is presented. This technique relies on well-behaved matrix representations of the derivatives constructed on a non--equispaced lattice. The drawbacks of lattice theory like the fermion doubling or the breaking of chiral symmetry for the massless case, are absent in this method.

  9. Discrete breathers in Josephson ladders

    NARCIS (Netherlands)

    Trias, E.; Mazo, J.J.; Brinkman, A.; Orlando, T.P.

    2001-01-01

    We present a study of nonlinear localized excitations called discrete breathers in a superconducting array. These localized solutions were recently observed in Josephson-junction ladder arrays by two different experimental groups [Phys. Rev. Lett. 84 (2000) 741; Phys. Rev. Lett. 84 (2000) 745; Phys.

  10. Epitope mapping porcine reproductive and respiratory syndrome virus by phage display: the nsp2 fragment of the replicase polyprotein contains a cluster of B-cell epitopes

    DEFF Research Database (Denmark)

    Oleksiewicz, M.B.; Bøtner, Anette; Toft, P.;

    2001-01-01

    We screened phage display libraries of porcine reproductive and respiratory syndrome virus (PRRSV) protein fragments with sera from experimentally infected pigs to identify linear B-cell epitopes that are commonly recognized during infection in vivo. We identified 10 linear epitope sites (ES) 11...

  11. Quantum cosmology based on discrete Feynman paths

    Energy Technology Data Exchange (ETDEWEB)

    Chew, Geoffrey F.

    2002-10-10

    Although the rules for interpreting local quantum theory imply discretization of process, Lorentz covariance is usually regarded as precluding time quantization. Nevertheless a time-discretized quantum representation of redshifting spatially-homogeneous universe may be based on discrete-step Feynman paths carrying causal Lorentz-invariant action--paths that not only propagate the wave function but provide a phenomenologically-promising elementary-particle Hilbert-space basis. In a model under development, local path steps are at Planck scale while, at a much larger ''wave-function scale'', global steps separate successive wave-functions. Wave-function spacetime is but a tiny fraction of path spacetime. Electromagnetic and gravitational actions are ''at a distance'' in Wheeler-Feynman sense while strong (color) and weak (isospin) actions, as well as action of particle motion, are ''local'' in a sense paralleling the action of local field theory. ''Nonmaterial'' path segments and ''trivial events'' collaborate to define energy and gravity. Photons coupled to conserved electric charge enjoy privileged model status among elementary fermions and vector bosons. Although real path parameters provide no immediate meaning for ''measurement'', the phase of the complex wave function allows significance for ''information'' accumulated through ''gentle'' electromagnetic events involving charged matter and ''soft'' photons. Through its soft-photon content the wave function is an ''information reservoir''.

  12. Anti-epitope antibody,a novel site-directed antibody against human acetylcholinesterase

    Institute of Scientific and Technical Information of China (English)

    Xing-mei ZHANG; Gang LIU; Man-ji SUN

    2004-01-01

    AIM: To construct synthetic antigens using the epitope of human brain acetylcholinesterase (hbAChE) for induction and detection of the specific antibody against the epitope, and to analyse the immunogenicity of the antibody.METHODS: The epitope (RTVLVSMNYR, amino acids 143-152) of hbAChE was chemically synthesized, coupled with the carrier protein keyhole limpet hemocyanin (KLH) to construct an artificial immunogen (KLH-epitope), and injected into rabbits to raise antibody. The epitope conjugated with bovine serum albumin (BSA) was used as the detection antigen. The specificity of the antibody was tested by enzyme-linked immunosorbent assay (ELISA) and Western blotting. The immunoreaction between the anti-recombinant human butyrylcholinesterase (rhBChE)polyclonal antibody and the biotinylated-epitope was examined by indirect ELISA. RESULTS: The erythrocyte AChE, the hbAChE, rhBChE and the BSA-epitope all immunoreacted with the anti-epitope antibody against the epitope (143-152) of hbAChE, whereas the torpedo AChE did not. CONCLUSION: The hbAChE, the human erythrocyte AChE and hBChE share the conservative antigenic epitope RTVLVSMNYR, hence they can all immunoreact with the anti-epitope antibody. Since the epitope of hbAChE is less similar with the aligned amino acid sequences of AChE of Torpedo californica or Torpedo marmorata, there is not any immunoreactivity between them. The R, M, and N residues in the epitope seem to be necessary radicals for the conservation of antigenicity.

  13. Three Candidate Epitope-Vaccines in Combination Inducing High Levels of Multiantibodies Against HIV-1

    Institute of Scientific and Technical Information of China (English)

    刘祖强; 田海军; 王颖; 陈应华

    2003-01-01

    HIV-1 mutation results in immune evasion, which presents a serious challenge for conventional strategies for developing effective vaccines.So far, much experimental evidence indicates that HIV-1 particles in the blood of patients can be cleaned principally by neutralizing antibodies.Based on these facts, we prepared triple combination of epitope-vaccines with the objective of inducing antibodies with predefined multi-epitope-specificity against HIV-1.According to the sequences of three neutralizing epitopes (RILAVERYLKD, ELDKWA and GPGRAFY, designated E1, E2, and E3, respectively) on HIV-1 envelope proteins, three epitope-peptides ((E1)2: C-(RILAVERYLKDG)2; (E2)4: C-(ELDKWAG)4; and (E3)2: C-(GPGRAFY)2) were synthesized and then conjugated with carrier protein keyhole limpet hemocyanin (KLH) or bovine serum albumin (BSA), and used for immunizing rabbits.After the vaccine course, the triple combination of epitope-vaccines induced high levels of predefined multi-epitope-specific antibodies.An immunoblotting-analysis demonstrated that the antibodies could recognize the native epitopes on both gp41 protein and V3 loop peptide.Furthermore, we compared the immune responses of three doses of epitope-peptides in the candidate epitope-vaccine.Strong antibody responses to three epitopes were observed in a dose dependent manner, with increasing dose raising the immune response.This result indicated that immunotolerance did not occur using an epitope vaccine dose of 80 μg.Thus, our results demonstrate that epitope-vaccines in combination can synchronously induce high levels of antibodies with predefined multi-epitope-specificity against HIV-1, and may be used to develop effective vaccines against HIV as a new strategy.

  14. Construction and immunogenicity prediction of Plasmodium falciparum CTL epitope minigene vaccine

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The minigenes encoding Plasmodium falciparum CTL epitopesrestricted to human MHC class I molecular HLA-A2 and HLA-B51, which were both at high frequency among Chinese population, were constructed as mono-epitope CTL vaccines named pcDNA3.1/tr and pcDNA3.1/ sh. The minigenes of the two epitopes were then tandem linked to form a dimeric CTL epitope minigene recombinant vaccine. After DNA transfection, the epitope minigenes were expressed respectively in two human cell lines, each bearing one MHC class I molecule named CIR/HLA-A2.1 and K562/HLA-B51. The intracellular expression of the CTL epitope minigenes not only enhanced the stability of HLA-A2.1 and HLA-B51 molecules but also increased the assemblage of MHC class I molecules on cell surfaces, which testified the specific process and presentation of those endogenous expressed epitopes. For the cells transfected with the dimeric minigene encoding two tandem linked epitopes, the expression and presentation of each epitope were also detected on cell membranes that bore different MHC class I molecules. It meant that the adjacency of the two CTL epitopes did not interfere with the specific process and presentation of each epitope. Compared with the ordinary CTL studies that inoculated synthesized epitope peptides with peripheral blood cells, this work aimed to process the epitopes directly inside HLA class I allele specific human cells, and thus theoretically imitated the same procedure in vivo. It was also an economical way to predict the immunogenicity of CTL epitopes at an early stage especially in laboratories with limited financial resource.

  15. Identification of an epitope of SARS-coronavirus nucleocapsid protein

    Institute of Scientific and Technical Information of China (English)

    YING LIN; JIN WANG; HONG XIA WANG; HUA LIANG JIANG; JIAN HUA SHEN; YOU HUA XIE; YUAN WANG; GANG PEI; BEI FEN SHEN; JIA RUI WU; BING SUN; XU SHEN; RUI FU YANG; YI XUE LI; YONG YONG JI; YOU YU HE; MUDE SHI; WEI LU; TIE LIU SHI

    2003-01-01

    The nucleocapsid (N) protein of severe acute respiratory syndrome-coronavirus (SARS-CoV) is a majorvirion structural protein. In this study, two epitopes (N1 and N2) of the N protein of SARS-CoV werepredicted by bioinformatics analysis. After immunization with two peptides, the peptides-specific antibodieswere isolated from the immunized rabbits. The further experiments demonstrated that N1 peptide-inducedpolyclonal antibodies had a high affinity to bind to E. coli expressed N protein of SARS-CoV. Furthermore, itwas confirmed that N1 peptide-specific IgG antibodies were detectable in the sera of severe acute respiratorysyndrome (SARS) patients. The results indicated that an epitope of the N protein has been identified andN protein specific Abs were produced by peptide immunization, which will be useful for the study of SARS-CoV.

  16. Preparation and epitope characterization of monoclonal antibodies against firefly luciferase

    Institute of Scientific and Technical Information of China (English)

    徐沁; 丁建芳; 胡红雨; 许根俊

    1999-01-01

    The 6-His tagged firefly luciferase was highly expressed in E. coli and purified to homogeneity by affinity chromatography and gel filtration. After immunizing Balb/c mice with the antigen, 6 hybridomas clones were found to secrete monoelonal antibodies (mAbs) and the mAbs were also purified separately. The competitive binding experiments show that 2 mAbs can bind heat-denatured antigen or its proteolytic fragments but not the native lueiferase, suggesting that their epitopes might be accommodated in the internal segments of the protein. On the other hand, the other 4 mAbs are capable of binding both native and denatured antigens. It infers that their epitopes locate in the segments on the protein surface. The results also suggest that the six mAbs are all sequence-specific.

  17. FRED--a framework for T-cell epitope detection.

    Science.gov (United States)

    Feldhahn, Magdalena; Dönnes, Pierre; Thiel, Philipp; Kohlbacher, Oliver

    2009-10-15

    Over the last decade, immunoinformatics has made significant progress. Computational approaches, in particular the prediction of T-cell epitopes using machine learning methods, are at the core of modern vaccine design. Large-scale analyses and the integration or comparison of different methods become increasingly important. We have developed FRED, an extendable, open source software framework for key tasks in immunoinformatics. In this, its first version, FRED offers easily accessible prediction methods for MHC binding and antigen processing as well as general infrastructure for the handling of antigen sequence data and epitopes. FRED is implemented in Python in a modular way and allows the integration of external methods. FRED is freely available for download at http://www-bs.informatik.uni-tuebingen.de/Software/FRED.

  18. '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

  19. Discrete Multiscale Analysis: A Biatomic Lattice System

    CERN Document Server

    Contra, G A Cassatella; 10.1142/S1402925110000957

    2010-01-01

    We discuss a discrete approach to the multiscale reductive perturbative method and apply it to a biatomic chain with a nonlinear interaction between the atoms. This system is important to describe the time evolution of localized solitonic excitations. We require that also the reduced equation be discrete. To do so coherently we need to discretize the time variable to be able to get asymptotic discrete waves and carry out a discrete multiscale expansion around them. Our resulting nonlinear equation will be a kind of discrete Nonlinear Schr\\"odinger equation. If we make its continuum limit, we obtain the standard Nonlinear Schr\\"odinger differential equation.

  20. Identification of a new epitope in uPAR as a target for the cancer therapeutic monoclonal antibody ATN-658, a structural homolog of the uPAR binding integrin CD11b (αM.

    Directory of Open Access Journals (Sweden)

    Xiang Xu

    Full Text Available The urokinase plasminogen activator receptor (uPAR plays a role in tumor progression and has been proposed as a target for the treatment of cancer. We recently described the development of a novel humanized monoclonal antibody that targets uPAR and has anti-tumor activity in multiple xenograft animal tumor models. This antibody, ATN-658, does not inhibit ligand binding (i.e. uPA and vitronectin to uPAR and its mechanism of action remains unclear. As a first step in understanding the anti-tumor activity of ATN-658, we set out to identify the epitope on uPAR to which ATN-658 binds. Guided by comparisons between primate and human uPAR, epitope mapping studies were performed using several orthogonal techniques. Systematic site directed and alanine scanning mutagenesis identified the region of aa 268-275 of uPAR as the epitope for ATN-658. No known function has previously been attributed to this epitope Structural insights into epitope recognition were obtained from structural studies of the Fab fragment of ATN-658 bound to uPAR. The structure shows that the ATN-658 binds to the DIII domain of uPAR, close to the C-terminus of the receptor, corroborating the epitope mapping results. Intriguingly, when bound to uPAR, the complementarity determining region (CDR regions of ATN-658 closely mimic the binding regions of the integrin CD11b (αM, a previously identified uPAR ligand thought to be involved in leukocyte rolling, migration and complement fixation with no known role in tumor progression of solid tumors. These studies reveal a new functional epitope on uPAR involved in tumor progression and demonstrate a previously unrecognized strategy for the therapeutic targeting of uPAR.

  1. Combinatorial Contextualization of Peptidic Epitopes for Enhanced Cellular Immunity

    Science.gov (United States)

    Ito, Masaki; Hayashi, Kazumi; Adachi, Eru; Minamisawa, Tamiko; Homma, Sadamu; Koido, Shigeo; Shiba, Kiyotaka

    2014-01-01

    Invocation of cellular immunity by epitopic peptides remains largely dependent on empirically developed protocols, such as interfusion of aluminum salts or emulsification using terpenoids and surfactants. To explore novel vaccine formulation, epitopic peptide motifs were co-programmed with structural motifs to produce artificial antigens using our “motif-programming” approach. As a proof of concept, we used an ovalbumin (OVA) system and prepared an artificial protein library by combinatorially polymerizing MHC class I and II sequences from OVA along with a sequence that tends to form secondary structures. The purified endotoxin-free proteins were then examined for their ability to activate OVA-specific T-cell hybridoma cells after being processed within dendritic cells. One clone, F37A (containing three MHC I and two MHC II OVA epitopes), possessed a greater ability to evoke cellular immunity than the native OVA or the other artificial antigens. The sensitivity profiles of drugs that interfered with the F37A uptake differed from those of the other artificial proteins and OVA, suggesting that alteration of the cross-presentation pathway is responsible for the enhanced immunogenicity. Moreover, F37A, but not an epitopic peptide, invoked cellular immunity when injected together with monophosphoryl lipid A (MPL), and retarded tumor growth in mice. Thus, an artificially synthesized protein antigen induced cellular immunity in vivo in the absence of incomplete Freund's adjuvant or aluminum salts. The method described here could be potentially used for developing vaccines for such intractable ailments as AIDS, malaria and cancer, ailments in which cellular immunity likely play a crucial role in prevention and treatment. PMID:25343355

  2. A General Method to Discover Epitopes from Sera.

    Directory of Open Access Journals (Sweden)

    Kurt Whittemore

    Full Text Available Antigen-antibody complexes are central players in an effective immune response. However, finding those interactions relevant to a particular disease state can be arduous. Nonetheless many paths to discovery have been explored since deciphering these interactions can greatly facilitate the development of new diagnostics, therapeutics, and vaccines. In silico B cell epitope mapping approaches have been widely pursued, though success has not been consistent. Antibody mixtures in immune sera have been used as handles for biologically relevant antigens, but these and other experimental approaches have proven resource intensive and time consuming. In addition, these methods are often tailored to individual diseases or a specific proteome, rather than providing a universal platform. Most of these methods are not able to identify the specific antibody's epitopes from unknown antigens, such as un-annotated neo antigens in cancer. Alternatively, a peptide library comprised of sequences unrestricted by naturally-found protein space provides for a universal search for mimotopes of an antibody's epitope. Here we present the utility of such a non-natural random sequence library of 10,000 peptides physically addressed on a microarray for mimotope discovery without sequence information of the specific antigen. The peptide arrays were probed with serum from an antigen-immunized rabbit, or alternatively probed with serum pre-absorbed with the same immunizing antigen. With this positive and negative screening scheme, we identified the library-peptides as the mimotopes of the antigen. The unique library peptides were successfully used to isolate antigen-specific antibodies from complete immune serum. Sequence analysis of these peptides revealed the epitopes in the immunized antigen. We present this method as an inexpensive, efficient method for identifying mimotopes of any antibody's targets. These mimotopes should be useful in defining both components of the

  3. Elicitation of structure-specific antibodies by epitope scaffolds

    OpenAIRE

    2010-01-01

    Elicitation of antibodies against targets that are immunorecessive, cryptic, or transient in their native context has been a challenge for vaccine design. Here we demonstrate the elicitation of structure-specific antibodies against the HIV-1 gp41 epitope of the broadly neutralizing antibody 2F5. This conformationally flexible region of gp41 assumes mostly helical conformations but adopts a kinked, extended structure when bound by antibody 2F5. Computational techniques were employed to transpl...

  4. Engineering applications of discrete-time optimal control

    DEFF Research Database (Denmark)

    Vidal, Rene Victor Valqui; Ravn, Hans V.

    1990-01-01

    of some well-known and new results in discrete time optimal control methods applicable to practical problem solving within engineering. Emphasis is placed on dynamic programming, the classical maximum principle and generalized versions of the maximum principle for optimal control of discrete time systems......Many problems of design and operation of engineering systems can be formulated as optimal control problems where time has been discretisized. This is also true even if 'time' is not involved in the formulation of the problem, but rather another one-dimensional parameter. This paper gives a review...

  5. Engineering applications of discrete-time optimal control

    DEFF Research Database (Denmark)

    Vidal, Rene Victor Valqui; Ravn, Hans V.

    1990-01-01

    Many problems of design and operation of engineering systems can be formulated as optimal control problems where time has been discretisized. This is also true even if 'time' is not involved in the formulation of the problem, but rather another one-dimensional parameter. This paper gives a review...... of some well-known and new results in discrete time optimal control methods applicable to practical problem solving within engineering. Emphasis is placed on dynamic programming, the classical maximum principle and generalized versions of the maximum principle for optimal control of discrete time systems...

  6. 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.

  7. Common food allergens and their IgE-binding epitopes

    Directory of Open Access Journals (Sweden)

    Hiroaki Matsuo

    2015-10-01

    Full Text Available Food allergy is an adverse immune response to certain kinds of food. Although any food can cause allergic reactions, chicken egg, cow's milk, wheat, shellfish, fruit, and buckwheat account for 75% of food allergies in Japan. Allergen-specific immunoglobulin E (IgE antibodies play a pivotal role in the development of food allergy. Recent advances in molecular biological techniques have enabled the efficient analysis of food allergens. As a result, many food allergens have been identified, and their molecular structure and IgE-binding epitopes have also been identified. Studies of allergens have demonstrated that IgE antibodies specific to allergen components and/or the peptide epitopes are good indicators for the identification of patients with food allergy, prediction of clinical severity and development of tolerance. In this review, we summarize our current knowledge regarding the allergens and IgE epitopes in the well-researched allergies to chicken egg, cow's milk, wheat, shrimp, and peanut.

  8. Analysis of the effects of polymorphism on pollen profilin structural functionality and the generation of conformational, T- and B-cell epitopes.

    Directory of Open Access Journals (Sweden)

    Jose C Jimenez-Lopez

    Full Text Available An extensive polymorphism analysis of pollen profilin, a fundamental regulator of the actin cytoskeleton dynamics, has been performed with a major focus in 3D-folding maintenance, changes in the 2-D structural elements, surface residues involved in ligands-profilin interactions and functionality, and the generation of conformational and lineal B- and T-cell epitopes variability. Our results revealed that while the general fold is conserved among profilins, substantial structural differences were found, particularly affecting the special distribution and length of different 2-D structural elements (i.e. cysteine residues, characteristic loops and coils, and numerous micro-heterogeneities present in fundamental residues directly involved in the interacting motifs, and to some extension these residues nearby to the ligand-interacting areas. Differential changes as result of polymorphism might contribute to generate functional variability among the plethora of profilin isoforms present in the olive pollen from different genetic background (olive cultivars, and between plant species, since biochemical interacting properties and binding affinities to natural ligands may be affected, particularly the interactions with different actin isoforms and phosphoinositides lipids species. Furthermore, conspicuous variability in lineal and conformational epitopes was found between profilins belonging to the same olive cultivar, and among different cultivars as direct implication of sequences polymorphism. The variability of the residues taking part of IgE-binding epitopes might be the final responsible of the differences in cross-reactivity among olive pollen cultivars, among pollen and plant-derived food allergens, as well as between distantly related pollen species, leading to a variable range of allergy reactions among atopic patients. Identification and analysis of commonly shared and specific epitopes in profilin isoforms is essential to gain knowledge

  9. Discrete Gauge Symmetries in Discrete MSSM-like Orientifolds

    CERN Document Server

    Ibanez, L E; Uranga, A M

    2012-01-01

    Motivated by the necessity of discrete Z_N symmetries in the MSSM to insure baryon stability, we study the origin of discrete gauge symmetries from open string sector U(1)'s in orientifolds based on rational conformal field theory. By means of an explicit construction, we find an integral basis for the couplings of axions and U(1) factors for all simple current MIPFs and orientifolds of all 168 Gepner models, a total of 32990 distinct cases. We discuss how the presence of discrete symmetries surviving as a subgroup of broken U(1)'s can be derived using this basis. We apply this procedure to models with MSSM chiral spectrum, concretely to all known U(3)xU(2)xU(1)xU(1) and U(3)xSp(2)xU(1)xU(1) configurations with chiral bi-fundamentals, but no chiral tensors, as well as some SU(5) GUT models. We find examples of models with Z_2 (R-parity) and Z_3 symmetries that forbid certain B and/or L violating MSSM couplings. Their presence is however relatively rare, at the level of a few percent of all cases.

  10. Discrete gauge symmetries in discrete MSSM-like orientifolds

    Science.gov (United States)

    Ibáñez, L. E.; Schellekens, A. N.; Uranga, A. M.

    2012-12-01

    Motivated by the necessity of discrete ZN symmetries in the MSSM to insure baryon stability, we study the origin of discrete gauge symmetries from open string sector U(1)'s in orientifolds based on rational conformal field theory. By means of an explicit construction, we find an integral basis for the couplings of axions and U(1) factors for all simple current MIPFs and orientifolds of all 168 Gepner models, a total of 32 990 distinct cases. We discuss how the presence of discrete symmetries surviving as a subgroup of broken U(1)'s can be derived using this basis. We apply this procedure to models with MSSM chiral spectrum, concretely to all known U(3)×U(2)×U(1)×U(1) and U(3)×Sp(2)×U(1)×U(1) configurations with chiral bi-fundamentals, but no chiral tensors, as well as some SU(5) GUT models. We find examples of models with Z2 (R-parity) and Z3 symmetries that forbid certain B and/or L violating MSSM couplings. Their presence is however relatively rare, at the level of a few percent of all cases.

  11. Analysis of discretization errors in LES

    Science.gov (United States)

    Ghosal, Sandip

    1995-01-01

    All numerical simulations of turbulence (DNS or LES) involve some discretization errors. The integrity of such simulations therefore depend on our ability to quantify and control such errors. In the classical literature on analysis of errors in partial differential equations, one typically studies simple linear equations (such as the wave equation or Laplace's equation). The qualitative insight gained from studying such simple situations is then used to design numerical methods for more complex problems such as the Navier-Stokes equations. Though such an approach may seem reasonable as a first approximation, it should be recognized that strongly nonlinear problems, such as turbulence, have a feature that is absent in linear problems. This feature is the simultaneous presence of a continuum of space and time scales. Thus, in an analysis of errors in the one dimensional wave equation, one may, without loss of generality, rescale the equations so that the dependent variable is always of order unity. This is not possible in the turbulence problem since the amplitudes of the Fourier modes of the velocity field have a continuous distribution. The objective of the present research is to provide some quantitative measures of numerical errors in such situations. Though the focus of this work is LES, the methods introduced here can be just as easily applied to DNS. Errors due to discretization of the time-variable are neglected for the purpose of this analysis.

  12. Identification of an HLA-A*0201 restricted Bcl2-derived epitope expressed on tumors

    DEFF Research Database (Denmark)

    Wang, Mingjun; Johansen, Britta; Nissen, Mogens H

    2006-01-01

    A large number of human tumor-associated antigen-derived peptides have been identified that are recognized by CTLs in a MHC-I restricted fashion. The apoptosis inhibitory protein Bcl2 is overexpressed in many human cancers as part of their neoplastic phenotype. Since inhibition or loss of Bcl2...... expression might impair tumor growth and survival, this protein may serve as a rational target for vaccine-induced CTL responses. By Western blot technique, we screened a panel of established human tumor cell lines for proteins involved in the apoptotic process. Two of eight tumor cell lines, a B lymphoma...... (Loukes) and a colon carcinoma (CCL220) cell line showed increased Bcl2 protein expression whereas the majority of tumor cell lines expressed proapoptotic proteins. Neither fibroblasts nor peripheral blood mononuclear cells showed Bcl2 expression. An HLA-A*0201 restricted CTL epitope was deduced in silica...

  13. Broadening the repertoire of melanoma-associated T-cell epitopes

    DEFF Research Database (Denmark)

    Frøsig, Thomas Mørch; Lyngaa, Rikke Birgitte; Met, Özcan;

    2015-01-01

    Immune therapy has provided a significant breakthrough in the treatment of metastatic melanoma. Despite the remarkable clinical efficacy and established involvement of effector CD8 T cells, the knowledge of the exact peptide-MHC complexes recognized by T cells on the tumor cell surface is limited....... Many melanoma-associated T-cell epitopes have been described, but this knowledge remains largely restricted to HLA-A2, and we lack understanding of the T-cell recognition in the context of other HLA molecules. We selected six melanoma-associated antigens (MAGE-A3, NY-ESO-1, gp100, Mart1, tyrosinase......-based enrichment of peripheral blood from 39 melanoma patients and 10 healthy donors. To dissect the T-cell reactivity against this large peptide library, we used combinatorial-encoded MHC multimers and observed the T-cell responses against 17 different peptide-MHC complexes in the patient group and four...

  14. Intein-mediated peptide arrays for epitope mapping and kinase/phosphatase assays.

    Science.gov (United States)

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

    2007-01-01

    Synthetic peptides are widely used for production and analysis of antibodies as well as in the study of protein modification enzymes. To circumvent the technical challenges of the existing techniques regarding peptide quantization and normalization, a new method of producing peptide arrays has been developed. This approach utilizes intein-mediated protein ligation that involves linkage of a carrier protein possessing a reactive carboxyl-terminal thioester to a peptide with an amino-terminal cysteine through a native peptide bond. Ligated protein substrates or enzyme-treated samples are arrayed on nitrocellulose membranes with a standard dot-blot apparatus and analyzed by immunoassay. This technique has improved sensitivity and reproducibility, and is suitable for various peptide-based applications. In this report, several experimental procedures including epitope mapping and the study of protein modifications were described.

  15. Characterization of a cashew allergen, 11S globulin (Ana o 2), conformational epitope.

    Science.gov (United States)

    Robotham, Jason M; Xia, Lixin; Willison, LeAnna N; Teuber, Suzanne S; Sathe, Shridhar K; Roux, Kenneth H

    2010-05-01

    Both linear and conformational epitopes likely contribute to the allergenicity of tree nut allergens, yet, due largely to technical issues, few conformational epitopes have been characterized. Using the well studied recombinant cashew allergen, Ana o 2, an 11S globulin or legumin, we identified a murine monoclonal antibody which recognizes a conformational epitope and competes with patient IgE Ana o 2-reactive antibodies. This epitope is expressed on the large subunit of Ana o 2, but only when associated with an 11S globulin small subunit. Both Ana o 2 and the homologous soybean Gly m 6 small subunits can foster epitope expression, even when the natural N-terminal to C-terminal subunit order is reversed in chimeric molecules. The epitope, which is also expressed on native Ana o 2, is readily susceptible to destruction by physical and chemical denaturants.

  16. Identification and Phylogeny of the First T Cell Epitope Identified from a Human Gut Bacteroides Species.

    Science.gov (United States)

    Perez-Muñoz, Maria Elisa; Joglekar, Payal; Shen, Yi-Ju; Shen, Yi-Ji; Chang, Kuan Y; Peterson, Daniel A

    2015-01-01

    Host T cell reactivity toward gut bacterial epitopes has been recognized as part of disease pathogenesis. However, the specificity of T cells that recognize this vast number of epitopes has not yet been well described. After colonizing a C57BL/6J germ-free mouse with the human gut symbiotic bacteria Bacteroides thetaiotaomicron, we isolated a T cell that recognized these bacteria in vitro. Using this T cell, we mapped the first known non-carbohydrate T cell epitope within the phylum Bacteroidetes. The T cell also reacted to two other additional Bacteroides species. We identified the peptide that stimulated the T cell by using a genetic approach. Genomic data from the epitope-positive and epitope-negative bacteria explain the cross-reactivity of the T cell to multiple species. This epitope degeneracy should shape our understanding of the T cell repertoire stimulated by the complex microbiome residing in the gastrointestinal tract in both healthy and disease states.

  17. Limitations of homology searching for identification of T-cell antigens with library derived mimicry epitopes.

    Science.gov (United States)

    Hiemstra, H S; van Veelen, P A; Geluk, A; Schloot, N C; de Vries, R R; Ottenhoff, T H; Roep, B O; Drijfhout, J W

    1999-09-01

    Mimicry epitopes that are recognized by T-cells can be identified through screening of synthetic peptide libraries. We have shown that these mimicry epitopes share sequence similarity with the corresponding natural epitopes and that mimicry sequences can be used for the definition of protein derived T-cell epitopes from databases. This can be done by either homology searching or pattern searching. Here we discuss the advantages and disadvantages of homology searching as an alternative for the generally applicable recognition pattern approach. We show that only for part of the library derived mimicry epitopes, the degree of similarity to the natural epitope may be high enough for successful homology searching in small databases.

  18. High-order algorithms for solving eigenproblems over discrete surfaces

    CERN Document Server

    Chen, Sheng-Gwo; Wu, Jyh-Yang

    2013-01-01

    The eigenvalue problem of the Laplace-Beltrami operators on curved surfaces plays an essential role in the convergence analysis of the numerical simulations of some important geometric partial differential equations which involve this operator. In this note we shall combine the local tangential lifting (LTL) method with the configuration equation to develop a new effective and convergent algorithm to solve the eigenvalue problems of the Laplace-Beltrami operators acting on functions over discrete surfaces. The convergence rates of our algorithms of discrete Laplace-Beltrami operators over surfaces is $O(r^n)$, $n \\geq 1$, where $r$ represents the size of the mesh of discretization of the surface. The problem of high-order accuracies will also be discussed and used to compute geometric invariants of the underlying surfaces. Some convergence tests and eigenvalue computations on the sphere, tori and a dumbbell are presented.

  19. Social Work Discretion between Professionalism and Managerialism in Denmark

    DEFF Research Database (Denmark)

    Skals, Anette

    2014-01-01

    Professionalism and managerialism are important and conflicting concepts in the study of professionals working in public service organizations. By focusing on street-level social workers and social work discretion, it is possible to see how welfare-to-work policies are practiced as well as how...... organizational articulations opens or closes for discretion in social work. This paper seeks on an empirical basis to account for how management organizes, supervises and seeks control over social work discretion and, consequently, influences the discretionary powers of social workers in a Danish municipality...... working with clients who are unfit for work or work market as a result of ill health. In Denmark the local municipal Job Centre is the primary service delivery involved in welfare-to-work. Here values, interest and policies, transformed into rules and regulation, meet the concrete practices of welfare...

  20. Discrete post-processing of total cloud cover ensemble forecasts

    Science.gov (United States)

    Hemri, Stephan; Haiden, Thomas; Pappenberger, Florian

    2017-04-01

    This contribution presents an approach to post-process ensemble forecasts for the discrete and bounded weather variable of total cloud cover. Two methods for discrete statistical post-processing of ensemble predictions are tested. The first approach is based on multinomial logistic regression, the second involves a proportional odds logistic regression model. Applying them to total cloud cover raw ensemble forecasts from the European Centre for Medium-Range Weather Forecasts improves forecast skill significantly. Based on station-wise post-processing of raw ensemble total cloud cover forecasts for a global set of 3330 stations over the period from 2007 to early 2014, the more parsimonious proportional odds logistic regression model proved to slightly outperform the multinomial logistic regression model. Reference Hemri, S., Haiden, T., & Pappenberger, F. (2016). Discrete post-processing of total cloud cover ensemble forecasts. Monthly Weather Review 144, 2565-2577.

  1. Revival of the identification of cytotoxic T-lymphocyte epitopes for immunological diagnosis, therapy and vaccine development.

    Science.gov (United States)

    Liu, Jun; Zhang, Shihong; Tan, Shuguang; Zheng, Beiwen; Gao, George F

    2011-03-01

    Immunogenic T-cell epitopes have a central role in the cellular immunity against pathogens and tumors. However, in the early stage of cellular immunity studies, it was complicated and time-consuming to identify and characterize T-cell epitopes. Currently, the epitope screening is experiencing renewed enthusiasm due to advances in novel techniques and theories. Moreover, the application of T-cell epitope-based diagnoses for tuberculosis and new data on epitope-based vaccine development have also revived the field. There is a growing knowledge on the emphasis of epitope-stimulated T-cell immune responses in the elimination of pathogens and tumors. In this review, we outline the significance of the identification and characterization of T-cell epitopes. We also summarize the methods and strategies for epitope definition and, more importantly, address the relevance of cytotoxic T-lymphocyte epitopes to clinical diagnoses, therapy and vaccine development.

  2. Discretizing a backward stochastic differential equation

    OpenAIRE

    Yinnan Zhang; Weian Zheng

    2002-01-01

    We show a simple method to discretize Pardoux-Peng's nonlinear backward stochastic differential equation. This discretization scheme also gives a numerical method to solve a class of semi-linear PDEs.

  3. Discrete and Continuous Linearizable Equations

    CERN Document Server

    Lafortune, S; Ramani, A

    1998-01-01

    We study the projective systems in both continuous and discrete settings. These systems are linearizable by construction and thus, obviously, integrable. We show that in the continuous case it is possible to eliminate all variables but one and reduce the system to a single differential equation. This equation is of the form of those singled-out by Painlevé in his quest for integrable forms. In the discrete case, we extend previous results of ours showing that, again by elimination of variables, the general projective system can be written as a mapping for a single variable. We show that this mapping is a member of the family of multilinear systems (which is not integrable in general). The continuous limit of multilinear mappings is also discussed.

  4. Discrete mathematics using a computer

    CERN Document Server

    Hall, Cordelia

    2000-01-01

    Several areas of mathematics find application throughout computer science, and all students of computer science need a practical working understanding of them. These core subjects are centred on logic, sets, recursion, induction, relations and functions. The material is often called discrete mathematics, to distinguish it from the traditional topics of continuous mathematics such as integration and differential equations. The central theme of this book is the connection between computing and discrete mathematics. This connection is useful in both directions: • Mathematics is used in many branches of computer science, in applica­ tions including program specification, datastructures,design and analysis of algorithms, database systems, hardware design, reasoning about the correctness of implementations, and much more; • Computers can help to make the mathematics easier to learn and use, by making mathematical terms executable, making abstract concepts more concrete, and through the use of software tools su...

  5. Discrete Scalar Quantum Field Theory

    CERN Document Server

    Gudder, Stan

    2016-01-01

    We begin with a description of spacetime by a 4-dimensional cubic lattice $\\sscript$. It follows from this framework that the the speed of light is the only nonzero instantaneous speed for a particle. The dual space $\\sscripthat$ corresponds to a cubic lattice of energy-momentum. This description implies that there is a discrete set of possible particle masses. We then define discrete scalar quantum fields on $\\sscript$. These fields are employed to define interaction Hamiltonians and scattering operators. Although the scattering operator $S$ cannot be computed exactly, approximations are possible. Whether $S$ is unitary is an unsolved problem. Besides the definitions of these operators, our main assumption is conservation of energy-momentum for a scattering process. This article concludes with various examples of perturbation approximations. These include simplified versions of electron-electron and electron-proton scattering as well as simple decay processes. We also define scattering cross-sections, decay ...

  6. Discrete fields on the lightcone

    CERN Document Server

    De Souza, M M

    1997-01-01

    We introduce a classical field theory based on a concept of extended causality that mimics the causality of a point- particle Classical Mechanics by imposing constraints that are equivalent to a particle initial position and velocity. It results on a description of discrete (pointwise) interactions in terms of localized particle-like fields. We find the propagators of these particle-like fields and discuss their physical meaning, properties and consequences. They are conformally invariant, singularity-free, and describing a manifestly covariant $(1+1)$-dimensional dynamics in a $(3+1)$ spacetime. Remarkably this conformal symmetry remains even for the propagation of a massive field in four spacetime dimensions. The standard formalism with its distributed fields is retrieved in terms of spacetime average of the discrete fields. Singularities are the by-products of the averaging proccess. This new formalism enlighten the meaning and the problems of field theory, and may allow a softer transition to a quantum th...

  7. Applied geometry and discrete mathematics

    CERN Document Server

    Sturm; Gritzmann, Peter; Sturmfels, Bernd

    1991-01-01

    This volume, published jointly with the Association for Computing Machinery, comprises a collection of research articles celebrating the occasion of Victor Klee's sixty-fifth birthday in September 1990. During his long career, Klee has made contributions to a wide variety of areas, such as discrete and computational geometry, convexity, combinatorics, graph theory, functional analysis, mathematical programming and optimization, and theoretical computer science. In addition, Klee made important contributions to mathematics education, mathematical methods in economics and the decision sciences, applications of discrete mathematics in the biological and social sciences, and the transfer of knowledge from applied mathematics to industry. In honor of Klee's achievements, this volume presents more than forty papers on topics related to Klee's research. While the majority of the papers are research articles, a number of survey articles are also included. Mirroring the breadth of Klee's mathematical contributions, th...

  8. Discrete symmetries in the MSSM

    Energy Technology Data Exchange (ETDEWEB)

    Schieren, Roland

    2010-12-02

    The use of discrete symmetries, especially abelian ones, in physics beyond the standard model of particle physics is discussed. A method is developed how a general, abelian, discrete symmetry can be obtained via spontaneous symmetry breaking. In addition, anomalies are treated in the path integral approach with special attention to anomaly cancellation via the Green-Schwarz mechanism. All this is applied to the minimal supersymmetric standard model. A unique Z{sup R}{sub 4} symmetry is discovered which solves the {mu}-problem as well as problems with proton decay and allows to embed the standard model gauge group into a simple group, i.e. the Z{sup R}{sub 4} is compatible with grand unification. Also the flavor problem in the context of minimal flavor violation is addressed. Finally, a string theory model is presented which exhibits the mentioned Z{sup R}{sub 4} symmetry and other desirable features. (orig.)

  9. Discrete mathematics: methods and challenges

    OpenAIRE

    Alon, Noga

    2002-01-01

    Combinatorics is a fundamental mathematical discipline as well as an essential component of many mathematical areas, and its study has experienced an impressive growth in recent years. One of the main reasons for this growth is the tight connection between Discrete Mathematics and Theoretical Computer Science, and the rapid development of the latter. While in the past many of the basic combinatorial results were obtained mainly by ingenuity and detailed reasoning, the modern theory has grown ...

  10. The remarkable discreteness of being

    Indian Academy of Sciences (India)

    Bahram Houchmandzadeh

    2014-04-01

    Life is a discrete, stochastic phenomenon: for a biological organism, the time of the two most important events of its life (reproduction and death) is random and these events change the number of individuals of the species by single units. These facts can have surprising, counterintuitive consequences. I review here three examples where these facts play, or could play, important roles: the spatial distribution of species, the structuring of biodiversity and the (Darwinian) evolution of altruistic behaviour.

  11. Manpower Analysis Using Discrete Simulation

    Science.gov (United States)

    2015-12-01

    Course STA-21 Seaman to Admiral (21st century) SQL Structured Query Language TOS Time on Station xiv THIS PAGE INTENTIONALLY LEFT BLANK...using Simkit—a widely available library based in the Java programming language for building Discrete Event Simulation (DES) models. By overriding...intervals (i.e., quarterly), while holding attrition negligible. For the purposes of modeling each new accession to the system, the Arrival

  12. Invariants of broken discrete symmetries

    CERN Document Server

    Kalozoumis, P; Diakonos, F K; Schmelcher, P

    2014-01-01

    The parity and Bloch theorems are generalized to the case of broken global symmetry. Local inversion or translation symmetries are shown to yield invariant currents that characterize wave propagation. These currents map the wave function from an arbitrary spatial domain to any symmetry-related domain. Our approach addresses any combination of local symmetries, thus applying in particular to acoustic, optical and matter waves. Nonvanishing values of the invariant currents provide a systematic pathway to the breaking of discrete global symmetries.

  13. The remarkable discreteness of being

    CERN Document Server

    Houchmandzadeh, Bahram

    2013-01-01

    Life is a discrete, stochastic phenomena : for a biological organism, the time of the two most important events of its life (reproduction and death) is random and these events change the number of individuals of the species by single units. These facts can have surprising, counter-intuitive consequences. I review here three examples where these facts play, or could play, important roles : the spatial distribution of species, the biodiversity and the (Darwinian) evolution of altruistic behavior.

  14. Discretized configurations and partial partitions

    CERN Document Server

    Abrams, Aaron; Hower, Valerie

    2010-01-01

    We show that the discretized configuration space of $k$ points in the $n$-simplex is homotopy equivalent to a wedge of spheres of dimension $n-k+1$. This space is homeomorphic to the order complex of the poset of ordered partial partitions of $\\{1,\\...,n+1\\}$ with exactly $k$ parts. We also compute the Euler characteristic in two different ways, thereby obtaining a topological proof of a combinatorial recurrence satisfied by the Stirling numbers of the second kind.

  15. Observability of discretized partial differential equations

    Science.gov (United States)

    Cohn, Stephen E.; Dee, Dick P.

    1988-01-01

    It is shown that complete observability of the discrete model used to assimilate data from a linear partial differential equation (PDE) system is necessary and sufficient for asymptotic stability of the data assimilation process. The observability theory for discrete systems is reviewed and applied to obtain simple observability tests for discretized constant-coefficient PDEs. Examples are used to show how numerical dispersion can result in discrete dynamics with multiple eigenvalues, thereby detracting from observability.

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

    OpenAIRE

    Babu Ramanathan; Chit Laa Poh; Kristin Kirk; William John Hannan McBride; John Aaskov; Lara Grollo

    2016-01-01

    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 app...

  17. Vaccine Focusing to Cross-Subtype HIV-1 gp120 Variable Loop Epitopes

    OpenAIRE

    Cardozo, Timothy; Wang, Shixia; Jiang, Xunqing; Kong, Xiang-Peng; Hioe, Catarina; Krachmarov, Chavdar

    2014-01-01

    We designed synthetic, epitope-focused immunogens that preferentially display individual neutralization epitopes targeted by cross-subtype anti-HIV V3 loop neutralizing monoclonal antibodies (mAbs). Vaccination of rabbits with these immunogens resulted in the elicitation of distinct polyclonal serum Abs that exhibit cross-subtype neutralization specificities mimicking the mAbs that guided the design. Our results prove the principle that a predictable range of epitope-specific polyclonal cross...

  18. Vaccine Design for H5N1 Based on B- and T-cell Epitope Predictions.

    Science.gov (United States)

    Tambunan, Usman Sumo Friend; Sipahutar, Feimmy Ruth Pratiwi; Parikesit, Arli Aditya; Kerami, Djati

    2016-01-01

    From 2003 to 2013, Indonesia had the highest number of avian influenza A cases in humans, with 192 cases and 160 fatalities. Avian influenza is caused by influenza virus type A, such as subtype H5N1. This virus has two glycoproteins: hemagglutinin and neuraminidase, which will become the primary target to be neutralized by vaccine. Vaccine is the most effective immunologic intervention. In this study, we use the epitope-based vaccine design from hemagglutinin and neuraminidase of H5N1 Indonesian strain virus by using immunoinformatics approach in order to predict the binding of B-cell and T-cell epitopes (class I and class II human leukocyte antigen [HLA]). BCPREDS was used to predict the B-cell epitope. Propred, Propred I, netMHCpan, and netMHCIIpan were used to predict the T-cell epitope. Two B-cell epitopes of hemagglutinin candidates and one B-cell epitope of neuraminidase candidates were obtained to bind T-cell CD4(+) (class II HLA), and also five T-cell epitope hemagglutinin and four T-cell epitope neuraminidase were obtained to bind T-cell CD8(+) (class I HLA). The visualization of epitopes was done using MOE 2008.10. It shows that the binding affinity of epitope-HLA was based on minimum binding free energy (ΔG binding). Based on this result, visualization, and dynamic simulation, four hemagglutinin epitopes (MEKIVLLLA, CPYLGSPSF, KCQTPMGAI, and IGTSTLNQR) and two neuraminidase epitopes (NPNQKIITI and CYPDAGEIT) were computed as having the best binding affinity from HLA ligand. The results mentioned above are from in silico experiments and need to be validated using wet experiment.

  19. Reactive oxygen species expose cryptic epitopes associated with autoimmune goodpasture syndrome.

    Science.gov (United States)

    Kalluri, R; Cantley, L G; Kerjaschki, D; Neilson, E G

    2000-06-30

    Goodpasture syndrome is an autoimmune disease of the kidneys and lungs mediated by antibodies and T-cells directed to cryptic epitopes hidden within basement membrane hexamers rich in alpha3 non-collagenous globular (NC1) domains of type IV collagen. These epitopes are normally invisible to the immune system, but this privilege can be obviated by chemical modification. Endogenous drivers of immune activation consequent to the loss of privilege have long been suspected. We have examined the ability of reactive oxygen species (ROS) to expose Goodpasture epitopes buried within NC1 hexamers obtained from renal glomeruli abundant in alpha3(IV) NC1 domains. For some hexameric epitopes, like the Goodpasture epitopes, exposure to ROS specifically enhanced recognition by Goodpasture antibodies in a sequential and time-dependent fashion; control binding of epitopes to alpha3(IV) alloantibodies from renal transplant recipients with Alport syndrome was decreased, whereas epitope binding to heterologous antibodies recognizing all alpha3 NC1 epitopes remained the same. Inhibitors of hydrogen peroxide and hydroxyl radical scavengers were capable of attenuating the effects of ROS in cells and kidney by 30-50%, respectively, thereby keeping the Goodpasture epitopes largely concealed when compared with a 70% maximum inhibition by iron chelators. Hydrogen peroxide administration to rodents was sufficient to expose Goodpasture epitope in vivo and initiate autoantibody production. Our findings collectively suggest that ROS can alter the hexameric structure of type IV collagen to expose or destroy selectively immunologic epitopes embedded in basement membrane. The reasons for autoimmunity in Goodpasture syndrome may lie in an age-dependent deterioration in inhibitor function modulating oxidative damage to structural molecules. ROS therefore may play an important role in shaping post-translational epitope diversity or neoantigen formation in organ tissues.

  20. An Approach to Discrete Variable Structure Control System

    Institute of Scientific and Technical Information of China (English)

    FalahE.Alsaqre; YUANBaozong

    2003-01-01

    Variable structure control (VSC) systems consist of a set of subsystems referred to as structures and supplied with appropriate switching functions. The most common approach used for variable structure in continu-ous or discrete time systems is sliding mode. In this paper,a new scheme to design a discrete variable structure con-trol (DVSC) for an nth-order type one system is presented.First, a set of discrete subsystems is constructed relying on the assumption that every system is considered as a vari-able structure system when its poles can be assignment to other locations. The adopted method for constructing dif-ferent discrete structures involves switching alternatively two zero-order hold (ZOH) devices, having different char-acteristics. Second, a suitable switching function is devised based on minimizing a quadratic sum of discrete error sig-nal criterion, to perform one switching without chattering.New advantageous properties are carried out via compos-ing a desired performance from parts of performances of the constructed structures. Simulation results are made to illustrate the quality of control being achieved.

  1. Comparative study on mode split discrete choice models

    Institute of Scientific and Technical Information of China (English)

    Xianlong Chen; Xiaoqian Liu; Fazhi Li

    2013-01-01

    Discrete choice model acts as one of the most important tools for studies involving mode split in the context of transport demand forecast. As different types of discrete choice models display their merits and restrictions diversely, how to properly select the specific type among discrete choice models for realistic application still remains to be a tough problem. In this article, five typical discrete choice models for transport mode split are, respectively, discussed, which includes multinomial logit model, nested logit model (NL), heteroscedastic extreme value model, multinominal probit model and mixed multinomial logit model (MMNL). The theoretical basis and application attributes of these five models are especially analysed with great attention, and they are also applied to a realistic intercity case of mode split forecast, which results indi-cating that NL model does well in accommodating simi-larity and heterogeneity across alternatives, while MMNL model serves as the most effective method for mode choice prediction since it shows the highest reliability with the least significant prediction errors and even outperforms the other four models in solving the heterogeneity and similarity problems. This study indicates that conclusions derived from a single discrete choice model are not reli-able, and it is better to choose the proper model based on its characteristics.

  2. Aggregation patterns from nonlocal interactions: Discrete stochastic and continuum modeling

    KAUST Repository

    Hackett-Jones, Emily J.

    2012-04-17

    Conservation equations governed by a nonlocal interaction potential generate aggregates from an initial uniform distribution of particles. We address the evolution and formation of these aggregating steady states when the interaction potential has both attractive and repulsive singularities. Currently, no existence theory for such potentials is available. We develop and compare two complementary solution methods, a continuous pseudoinverse method and a discrete stochastic lattice approach, and formally show a connection between the two. Interesting aggregation patterns involving multiple peaks for a simple doubly singular attractive-repulsive potential are determined. For a swarming Morse potential, characteristic slow-fast dynamics in the scaled inverse energy is observed in the evolution to steady state in both the continuous and discrete approaches. The discrete approach is found to be remarkably robust to modifications in movement rules, related to the potential function. The comparable evolution dynamics and steady states of the discrete model with the continuum model suggest that the discrete stochastic approach is a promising way of probing aggregation patterns arising from two- and three-dimensional nonlocal interaction conservation equations. © 2012 American Physical Society.

  3. Discrete Space-Time: History and Recent Developments

    Science.gov (United States)

    Crouse, David

    2017-01-01

    Discussed in this work is the long history and debate of whether space and time are discrete or continuous. Starting from Zeno of Elea and progressing to Heisenberg and others, the issues with discrete space are discussed, including: Lorentz contraction (time dilation) of the ostensibly smallest spatial (temporal) interval, maintaining isotropy, violations of causality, and conservation of energy and momentum. It is shown that there are solutions to all these issues, such that discrete space is a viable model, yet the solution require strict non-absolute space (i.e., Mach's principle) and a re-analysis of the concept of measurement and the foundations of special relativity. In developing these solutions, the long forgotten but important debate between Albert Einstein and Henri Bergson concerning time will be discussed. Also discussed is the resolution to the Weyl tile argument against discrete space; however, the solution involves a modified version of the typical distance formula. One example effect of discrete space is then discussed, namely how it necessarily imposes order upon Wheeler's quantum foam, changing the foam into a gravity crystal and yielding crystalline properties of bandgaps, Brilluoin zones and negative inertial mass for astronomical bodies.

  4. Discretization of Preisach hysteresis model

    Institute of Scientific and Technical Information of China (English)

    安凯; 蔡国平

    2015-01-01

    In order to reduce the partial derivative errors in Preisach hysteresis model caused by inaccurate experimental data, the concept and correlative method of discretization of Preisach hysteresis model are proposed, the essential of which is to centralize the distribution density of Preisach hysteresis model in local region as an integral, which is defined as the weight of a certain point in that region. For the input composed of an ascending segment and a descending segment, a method to determine the initial weights together with an additional method to determine present weights is given according to the number of input ascending segments. If the number of input ascending segments increases, the weights of the corresponding points in updating rectangle are updated by adding the initial weights of corresponding points. A prominent advantage of discrete Preisach hysteresis model is its memory efficiency. Another advantage of discrete Preisach hysteresis model is that there is no function in the model, and thus, it can be expediently operated using a computer. By generalizing the above updating rectangle method to the continuous Preisach hysteresis model, identification method of distribution density can be given as well.

  5. Modelling Mobility: A Discrete Revolution

    CERN Document Server

    Clementi, Andrea; Silvestri, Riccardo

    2010-01-01

    We introduce a new approach to model and analyze \\emph{Mobility}. It is fully based on discrete mathematics and yields a class of mobility models, called the \\emph{Markov Trace} Model. This model can be seen as the discrete version of the \\emph{Random Trip} Model including all variants of the \\emph{Random Way-Point} Model \\cite{L06}. We derive fundamental properties and \\emph{explicit} analytical formulas for the \\emph{stationary distributions} yielded by the Markov Trace Model. Such results can be exploited to compute formulas and properties for concrete cases of the Markov Trace Model by just applying counting arguments. We apply the above general results to the discrete version of the \\emph{Manhattan Random Way-Point} over a square of bounded size. We get formulas for the total stationary distribution and for two important \\emph{conditional} ones: the agent spatial and destination distributions. Our method makes the analysis of complex mobile systems a feasible task. As a further evidence of this important...

  6. In silico vaccine design based on molecular simulations of rhinovirus chimeras presenting HIV-1 gp41 epitopes.

    Science.gov (United States)

    Lapelosa, Mauro; Gallicchio, Emilio; Arnold, Gail Ferstandig; Arnold, Eddy; Levy, Ronald M

    2009-01-16

    A cluster of promising epitopes for the development of human immunodeficiency virus (HIV) vaccines is located in the membrane-proximal external region (MPER) of the gp41 subunit of the HIV envelope spike structure. The crystal structure of the peptide corresponding to the so-called ELDKWA epitope (HIV-1 HxB2 gp41 residues 662-668), in complex with the corresponding broadly neutralizing human monoclonal antibody 2F5, provides a target for structure-based vaccine design strategies aimed at finding macromolecular carriers that are able to present this MPER-derived epitope with optimal antigenic activity. To this end, a series of replica exchange molecular dynamics computer simulations was conducted to characterize the distributions of conformations of ELDKWA-based epitopes inserted into a rhinovirus carrier and to identify those with the highest fraction of conformations that are able to bind 2F5. The length, hydrophobic character, and precise site of insertion were found to be critical for achieving structural similarity to the target crystal structure. A construct with a high degree of complementarity to the corresponding determinant region of 2F5 was obtained. This construct was employed to build a high-resolution structural model of the complex between the 2F5 antibody and the chimeric human rhinovirus type 14:HIV-1 ELDKWA virus particle. Additional simulations, which were conducted to study the conformational propensities of the ELDKWA region in solution, confirm the hypothesis that the ELDKWA region of gp41 is highly flexible and capable of assuming helical conformations (as in the postfusion helical bundle structure) and beta-turn conformations (as in the complex with the 2F5 antibody). These results also suggest that the ELDKWA epitope can be involved in intramolecular--and likely intermolecular--hydrophobic interactions. This tendency offers an explanation for the observation that mutations decreasing the hydrophobic character of the MPER in many cases result

  7. Discrete and Continuous Models for Partitioning Problems

    KAUST Repository

    Lellmann, Jan

    2013-04-11

    Recently, variational relaxation techniques for approximating solutions of partitioning problems on continuous image domains have received considerable attention, since they introduce significantly less artifacts than established graph cut-based techniques. This work is concerned with the sources of such artifacts. We discuss the importance of differentiating between artifacts caused by discretization and those caused by relaxation and provide supporting numerical examples. Moreover, we consider in depth the consequences of a recent theoretical result concerning the optimality of solutions obtained using a particular relaxation method. Since the employed regularizer is quite tight, the considered relaxation generally involves a large computational cost. We propose a method to significantly reduce these costs in a fully automatic way for a large class of metrics including tree metrics, thus generalizing a method recently proposed by Strekalovskiy and Cremers (IEEE conference on computer vision and pattern recognition, pp. 1905-1911, 2011). © 2013 Springer Science+Business Media New York.

  8. Discrete port-Hamiltonian systems : mixed interconnections

    NARCIS (Netherlands)

    Talasila, Viswanath; Clemente-Gallardo, J.; Schaft, A.J. van der

    2005-01-01

    Either from a control theoretic viewpoint or from an analysis viewpoint it is necessary to convert smooth systems to discrete systems, which can then be implemented on computers for numerical simulations. Discrete models can be obtained either by discretizing a smooth model, or by directly modeling

  9. 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...... from highly conserved open reading frames from seven complete vaccinia and variola genomes using EpiMatrix. Over 100 epitopes bearing low human sequence homology were selected and assessed in HLA binding assays and in T-cell antigenicity assays using PBMCs isolated from Dryvax-immunized subjects...

  10. Influenza A HA's conserved epitopes and broadly neutralizing antibodies: a prediction method.

    Science.gov (United States)

    Ren, Jing; Ellis, John; Li, Jinyan

    2014-10-01

    A conserved epitope is an epitope retained by multiple strains of influenza as the key target of a broadly neutralizing antibody. Identification of conserved epitopes is of strong interest to help design broad-spectrum vaccines against influenza. Conservation score measures the evolutionary conservation of an amino acid position in a protein based on the phylogenetic relationships observed amongst homologous sequences. Here, Average Amino Acid Conservation Score (AAACS) is proposed as a method to identify HA's conserved epitopes. Our analysis shows that there is a clear distinction between conserved epitopes and nonconserved epitopes in terms of AAACS. This method also provides an excellent classification performance on an independent dataset. In contrast, alignment-based comparison methods do not work well for this problem, because conserved epitopes to the same broadly neutralizing antibody are usually not identical or similar. Location-based methods are not successful either, because conserved epitopes are located at both the less-conserved globular head (HA1) and the more-conserved stem (HA2). As a case study, two conserved epitopes on HA are predicted for the influenza A virus H7N9: One should match the broadly neutralizing antibodies CR9114 or FI6v3, while the other is new and requires validation by wet-lab experiments.

  11. 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...

  12. Immunogenicity of multiple antigen peptides containing Plasmodium vivax CS epitopes in BALB/c mice

    Directory of Open Access Journals (Sweden)

    Myriam A. Herrera

    1994-01-01

    Full Text Available Multiple antigen peptide systems (MAPs allow the incorporation of various epitopes in to a single synthetic peptide immunogen. We have characterized the immune response of BALB/c mice to a series of MAPs assembled with different B and T cell epitopes derived from the Plasmodium vivax circumsporozoite (CS protein. A B-cell epitope from the central repeat domain and two T-cell epitopes from the amino and carboxyl flanking regions were used to assembled eight different MAPs. An additional universal T cell epitope (ptt-30 from tetanus toxin protein was included. Immunogenicity in terms of antibody responses and in vitro T lymphocyte proliferation was evaluated. MAPs containing B and T cell epitopes induced high titers of anti-peptides antibodies, which recognized the native protein on sporozoites as determined by IFAT. The antibody specificity was also determined by a competitive inhibition assay with different MAPs. A MAP containing the B cell epitope (p11 and the universal epitope ptt-30 together with another composed of p11 and the promiscuous T cell epitope (p25 proved to be the most immunogenic. The strong antibody response and specificity for the cognate protein indicates that further studies designed to assess the potential of these proteins as human malaria vaccine candidates are warranted.

  13. Optimization and immune recognition of multiple novel conserved HLA-A2, human immunodeficiency virus type 1-specific CTL epitopes

    DEFF Research Database (Denmark)

    Corbet, Sylvie; Nielsen, Henrik Vedel; Vinner, Lasse

    2003-01-01

    and more conserved. Such epitope peptides were anchor-optimized to improve immunogenicity and further increase the number of potential vaccine epitopes. About 67 % of anchor-optimized vaccine epitopes induced immune responses against the corresponding non-immunogenic naturally occurring epitopes....... This study demonstrates the potency of ANNs for identifying putative virus CTL epitopes, and the new HIV-1 CTL epitopes identified should have significant implications for HIV-1 vaccine development. As a novel vaccine approach, it is proposed to increase the coverage of HIV variants by including multiple...

  14. 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.

  15. Construction and characterization of an HCV-derived multi-epitope peptide antigen containing B-cell HVR1 mimotopes and T-cell conserved epitopes

    Institute of Scientific and Technical Information of China (English)

    GAO; Jun; GONG; Yuping; ZHAO; Ping; ZHU; Qing; YANG; Xiaoping; QI; Zhongtian

    2006-01-01

    Hepatitis C (HCV) genome is highly variable, particularly in the hypervariable region 1(HVR1) of its E2 envelope gene. The variability of HCV genome has been a major obstacle for developing HCV vaccines. Due to B-cell HVR1 mimotopes mimicking the antigenicity of natural HVR1 epitopes and some T-cell epitopes from the consensus sequence of HCV genes conserving among the different HCV genotypes, we synthesized an minigene of HCV-derived multi-epitope peptide antigen (CMEP), which contains 9 B-cell HVR1 mimotopes in E2, 2 conserved CTL epitopes in C, 1conserved CTL epitope in NS3 and 1 conserved Th epitope in NS3. This minigene was cloned into a GST expression vector to generate a fusion protein GST-CMER The immunogenic properties of CEMP were characterized by HCV infected patients' sera, and found that the reactivity frequency reached 75%. The cross reactivity of anti-CEMP antibody with different natural HVR1 variants was up to 90%. Meanwhile, we constructed an HCV DNA vaccine candidate, plasmid pVAX1.0-st-CMEP carrying the recombinant gene (st) of a secretion signal peptide and PADRE universal Th cell epitope sequence in front of the CMEP minigene. Immunization of rabbits with pVAX1.0-st-CMEP resulted in the production of antibody, which was of the same cross reactivity as the fusion protein GST-CMEP.Our findings indicate that the HCV-derived multi-epitope peptide antigen in some degree possessed the characteristics of neutralizing HCV epitopes, and would be of the value as a candidate for the development of HCV vaccines.

  16. Geometry and Hamiltonian mechanics on discrete spaces

    OpenAIRE

    Talasila, V.; Clemente-Gallardo, J.; van der Schaft, A. J.

    2004-01-01

    Numerical simulation is often crucial for analysing the behaviour of many complex systems which do not admit analytic solutions. To this end, one either converts a ‘smooth’ model into a discrete (in space and time) model, or models systems directly at a discrete level. The goal of this paper is to provide a discrete analogue of differential geometry, and to define on these discrete models a formal discrete Hamiltonian structure—in doing so we try to bring together various fundamental concepts...

  17. In vivo immunogenicity of Tax(11-19) epitope in HLA-A2/DTR transgenic mice: implication for dendritic cell-based anti-HTLV-1 vaccine.

    Science.gov (United States)

    Sagar, Divya; Masih, Shet; Schell, Todd; Jacobson, Steven; Comber, Joseph D; Philip, Ramila; Wigdahl, Brian; Jain, Pooja; Khan, Zafar K

    2014-05-30

    Viral oncoprotein Tax plays key roles in transformation of human T-cell leukemia virus (HTLV-1)-infected T cells leading to adult T-cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate CD8 T-cell immune response against this epitope in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR hybrid mouse strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T-cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund's adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly hybrid mouse strain could be used for investigating DC involvement in human class-I-restricted immune responses.

  18. Characterizing the interactions between a naturally primed immunoglobulin A and its conserved Bacteroides thetaiotaomicron species-specific epitope in gnotobiotic mice.

    Science.gov (United States)

    Peterson, Daniel A; Planer, Joseph D; Guruge, Janaki L; Xue, Lai; Downey-Virgin, Whitt; Goodman, Andrew L; Seedorf, Henning; Gordon, Jeffrey I

    2015-05-15

    The adaptive immune response to the human gut microbiota consists of a complex repertoire of antibodies interacting with a broad range of taxa. Fusing intestinal lamina propria lymphocytes from mice monocolonized with Bacteroides thetaiotaomicron to a myeloma fusion partner allowed us to recover hybridomas that captured naturally primed, antigen-specific antibody responses representing multiple isotypes, including IgA. One of these hybridomas, 260.8, produced a monoclonal antibody that recognizes an epitope specific for B. thetaiotaomicron isolates in a large panel of hospital- and community-acquired Bacteroides. Whole genome transposon mutagenesis revealed a 19-gene locus, involved in LPS O-antigen polysaccharide synthesis and conserved among multiple B. thetaiotaomicron isolates, that is required for 260.8 epitope expression. Mutants in this locus exhibited marked fitness defects in vitro during growth in rich medium and in gnotobiotic mice colonized with defined communities of human gut symbionts. Expression of the 260.8 epitope was sustained during 10 months of daily passage in vitro and during 14 months of monocolonization of gnotobiotic wild-type, Rag1-/-, or Myd88-/- mice. Comparison of gnotobiotic Rag1-/- mice with and without subcutaneous 260.8 hybridomas disclosed that this IgA did not affect B. thetaiotaomicron population density or suppress 260.8 epitope production but did affect bacterial gene expression in ways emblematic of a diminished host innate immune response. Our study illustrates an approach for (i) generating diagnostic antibodies, (ii) characterizing IgA responses along a continuum of specificity/degeneracy that defines the IgA repertoire to gut symbionts, and (iii) identifying immunogenic epitopes that affect competitiveness and help maintain host-microbe mutualism. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Characterizing the Interactions between a Naturally Primed Immunoglobulin A and Its Conserved Bacteroides thetaiotaomicron Species-specific Epitope in Gnotobiotic Mice*

    Science.gov (United States)

    Peterson, Daniel A.; Planer, Joseph D.; Guruge, Janaki L.; Xue, Lai; Downey-Virgin, Whitt; Goodman, Andrew L.; Seedorf, Henning; Gordon, Jeffrey I.

    2015-01-01

    The adaptive immune response to the human gut microbiota consists of a complex repertoire of antibodies interacting with a broad range of taxa. Fusing intestinal lamina propria lymphocytes from mice monocolonized with Bacteroides thetaiotaomicron to a myeloma fusion partner allowed us to recover hybridomas that captured naturally primed, antigen-specific antibody responses representing multiple isotypes, including IgA. One of these hybridomas, 260.8, produced a monoclonal antibody that recognizes an epitope specific for B. thetaiotaomicron isolates in a large panel of hospital- and community-acquired Bacteroides. Whole genome transposon mutagenesis revealed a 19-gene locus, involved in LPS O-antigen polysaccharide synthesis and conserved among multiple B. thetaiotaomicron isolates, that is required for 260.8 epitope expression. Mutants in this locus exhibited marked fitness defects in vitro during growth in rich medium and in gnotobiotic mice colonized with defined communities of human gut symbionts. Expression of the 260.8 epitope was sustained during 10 months of daily passage in vitro and during 14 months of monocolonization of gnotobiotic wild-type, Rag1−/−, or Myd88−/− mice. Comparison of gnotobiotic Rag1−/− mice with and without subcutaneous 260.8 hybridomas disclosed that this IgA did not affect B. thetaiotaomicron population density or suppress 260.8 epitope production but did affect bacterial gene expression in ways emblematic of a diminished host innate immune response. Our study illustrates an approach for (i) generating diagnostic antibodies, (ii) characterizing IgA responses along a continuum of specificity/degeneracy that defines the IgA repertoire to gut symbionts, and (iii) identifying immunogenic epitopes that affect competitiveness and help maintain host-microbe mutualism. PMID:25795776

  20. Identification and characterization of CD4⁺ T-cell epitopes on GapC protein of Streptococcus dysgalactiae.

    Science.gov (United States)

    Yao, Di; Zhang, Hua; Wang, Xintong; Yu, Simiao; Wei, Yuhua; Liu, Wei; Wang, Jiannan; Chen, Xiaoting; Zhang, Zhenghai; Sun, Hunan; Yu, Liquan; Ma, Jinzhu; Tong, Chunyu; Song, Baifen; Cui, Yudong

    2016-02-01

    The GapC protein is highly conserved surface dehydrogenase among Streptococcus dysgalactiae (S. dysgalactiae) and is shown to be involved in bacterial virulence. Immunization of GapC protein can induce specific CD4(+) T-cell immune responses and protect against S. dysgalactiae infection. However, there are no studies to identify immunodominant CD4(+) T-cell epitopes on GapC protein. In this study, in silico MHC affinity measurement method was firstly used to predict potential CD4(+) T-cell epitopes on GapC protein. Six predictive 15-mer peptides were synthesized and two novel GapC CD4(+) T-cell epitopes, GapC63-77 and GapC96-110, were for the first time identified using CD4(+) T-cells obtained from GapC-immunized BALB/c (H-2(d)) and C57BL/6 (H-2(b)) mice spleen based on cell proliferation and cytokines response. The results showed that peptides containing 63-77 and 96-110 induced significant antigen-specific CD4(+) T-cells proliferation response in vivo. At the same time, high levels of IFN-γ and IL-17A, as well as moderate levels of IL-10 and IL-4 were detected in CD4(+) T-cells isolated from both GapC and peptide-immunized mice in vivo, suggesting that GapC63-77 and GapC96-110 preferentially elicited polarized Th1/Th17-type responses. The characterization of GapC CD4(+) T-cell epitopes not only helps us understand its protective immunity, but also contributes to design effective T-cell epitope-based vaccine against S. dysgalactiae infection.

  1. A Discrete Equivalent of the Logistic Equation

    Directory of Open Access Journals (Sweden)

    Petropoulou EugeniaN

    2010-01-01

    Full Text Available A discrete equivalent and not analogue of the well-known logistic differential equation is proposed. This discrete equivalent logistic equation is of the Volterra convolution type, is obtained by use of a functional-analytic method, and is explicitly solved using the -transform method. The connection of the solution of the discrete equivalent logistic equation with the solution of the logistic differential equation is discussed. Also, some differences of the discrete equivalent logistic equation and the well-known discrete analogue of the logistic equation are mentioned. It is hoped that this discrete equivalent of the logistic equation could be a better choice for the modelling of various problems, where different versions of known discrete logistic equations are used until nowadays.

  2. A strategy for eliciting antibodies against cryptic, conserved, conformationally dependent epitopes of HIV envelope glycoprotein.

    Directory of Open Access Journals (Sweden)

    Hanna C Kelker

    Full Text Available BACKGROUND: Novel strategies are needed for the elicitation of broadly neutralizing antibodies to the HIV envelope glycoprotein, gp120. Experimental evidence suggests that combinations of antibodies that are broadly neutralizing in vitro may protect against challenge with HIV in nonhuman primates, and a small number of these antibodies have been selected by repertoire sampling of B cells and by the fractionation of antiserum from some patients with prolonged disease. Yet no additional strategies for identifying conserved epitopes, eliciting antibodies to these epitopes, and determining whether these epitopes are accessible to antibodies have been successful to date. The defining of additional conserved, accessible epitopes against which one can elicit antibodies will increase the probability that some may be the targets of broadly neutralizing antibodies. METHODOLOGY/PRINCIPAL FINDINGS: We postulate that additional cryptic epitopes of gp120 are present, against which neutralizing antibodies might be elicited even though these antibodies are not elicited by gp120, and that many of these epitopes may be accessible to antibodies should they be formed. We demonstrate a strategy for eliciting antibodies in mice against selected cryptic, conformationally dependent conserved epitopes of gp120 by immunizing with multiple identical copies of covalently linked peptides (MCPs. This has been achieved with MCPs representing 3 different domains of gp120. We show that some cryptic epitopes on gp120 are accessible to the elicited antibodies, and some epitopes in the CD4 binding region are not accessible. The antibodies bind to gp120 with relatively high affinity, and bind to oligomeric gp120 on the surface of infected cells. CONCLUSIONS/SIGNIFICANCE: Immunization with MCPs comprised of selected peptides of HIV gp120 is able to elicit antibodies against conserved, conformationally dependent epitopes of gp120 that are not immunogenic when presented as gp120. Some

  3. Plasmodium vivax Promiscuous T-Helper Epitopes Defined and Evaluated as Linear Peptide Chimera Immunogens

    Science.gov (United States)

    Caro-Aguilar, Ivette; Rodríguez, Alexandra; Calvo-Calle, J. Mauricio; Guzmán, Fanny; De la Vega, Patricia; Elkin Patarroyo, Manuel; Galinski, Mary R.; Moreno, Alberto

    2002-01-01

    Clinical trials of malaria vaccines have confirmed that parasite-derived T-cell epitopes are required to elicit consistent and long-lasting immune responses. We report here the identification and functional characterization of six T-cell epitopes that are present in the merozoite surface protein-1 of Plasmodium vivax (PvMSP-1) and bind promiscuously to four different HLA-DRB1∗ alleles. Each of these peptides induced lymphoproliferative responses in cells from individuals with previous P. vivax infections. Furthermore, linear-peptide chimeras containing the promiscuous PvMSP-1 T-cell epitopes, synthesized in tandem with the Plasmodium falciparum immunodominant circumsporozoite protein (CSP) B-cell epitope, induced high specific antibody titers, cytokine production, long-lasting immune responses, and immunoglobulin G isotype class switching in BALB/c mice. A linear-peptide chimera containing an allele-restricted P. falciparum T-cell epitope with the CSP B-cell epitope was not effective. Two out of the six promiscuous T-cell epitopes exhibiting the highest anti-peptide response also contain B-cell epitopes. Antisera generated against these B-cell epitopes recognize P. vivax merozoites in immunofluorescence assays. Importantly, the anti-peptide antibodies generated to the CSP B-cell epitope inhibited the invasion of P. falciparum sporozoites into human hepatocytes. These data and the simplicity of design of the chimeric constructs highlight the potential of multimeric, multistage, and multispecies linear-peptide chimeras containing parasite promiscuous T-cell epitopes for malaria vaccine development. PMID:12065487

  4. Human Antibodies that Recognize Novel Immunodominant Quaternary Epitopes on the HIV-1 Env Protein

    Science.gov (United States)

    Hicar, Mark D.; Chen, Xuemin; Sulli, Chidananda; Barnes, Trevor; Goodman, Jason; Sojar, Hakimuddin; Briney, Bryan; Willis, Jordan; Chukwuma, Valentine U.; Kalams, Spyros A.; Doranz, Benjamin J.; Spearman, Paul; Crowe, James E.

    2016-01-01

    Numerous broadly neutralizing antibodies (Abs) target epitopes that are formed or enhanced during mature HIV envelope formation (i.e. quaternary epitopes). Generally, it is thought that Env epitopes that induce broadly neutralizing Abs are difficult to access and poorly immunogenic because of the characteristic oligomerization, conformational flexibility, sequence diversity and extensive glycosylation of Env protein. To enhance for isolation of quaternary epitope-targeting Abs (QtAbs), we previously used HIV virus-like particles (VLPs) to bind B cells from long-term non-progressor subjects to identify a panel of monoclonal Abs. When expressed as recombinant full-length Abs, a subset of these novel Abs exhibited the binding profiles of QtAbs, as they either failed to bind to monomeric Env protein or showed much higher affinity for Env trimers and VLPs. These QtAbs represented a significant proportion of the B-cell response identified with VLPs. The Ab genes of these clones were highly mutated, but they did not neutralize common HIV strains. We sought to further define the epitopes targeted by these QtAbs. Competition-binding and mapping studies revealed these Abs targeted four separate epitopes; they also failed to compete for binding by Abs to known major neutralizing epitopes. Detailed epitope mapping studies revealed that two of the four epitopes were located in the gp41 subunit of Env. These QtAbs bound pre-fusion forms of antigen and showed differential binding kinetics depending on whether oligomers were produced as recombinant gp140 trimers or as full-length Env incorporated into VLPs. Antigenic regions within gp41 present unexpectedly diverse structural epitopes, including these QtAb epitopes, which may be targeted by the naturally occurring Ab response to HIV infection. PMID:27411063

  5. Human Antibodies that Recognize Novel Immunodominant Quaternary Epitopes on the HIV-1 Env Protein.

    Directory of Open Access Journals (Sweden)

    Mark D Hicar

    Full Text Available Numerous broadly neutralizing antibodies (Abs target epitopes that are formed or enhanced during mature HIV envelope formation (i.e. quaternary epitopes. Generally, it is thought that Env epitopes that induce broadly neutralizing Abs are difficult to access and poorly immunogenic because of the characteristic oligomerization, conformational flexibility, sequence diversity and extensive glycosylation of Env protein. To enhance for isolation of quaternary epitope-targeting Abs (QtAbs, we previously used HIV virus-like particles (VLPs to bind B cells from long-term non-progressor subjects to identify a panel of monoclonal Abs. When expressed as recombinant full-length Abs, a subset of these novel Abs exhibited the binding profiles of QtAbs, as they either failed to bind to monomeric Env protein or showed much higher affinity for Env trimers and VLPs. These QtAbs represented a significant proportion of the B-cell response identified with VLPs. The Ab genes of these clones were highly mutated, but they did not neutralize common HIV strains. We sought to further define the epitopes targeted by these QtAbs. Competition-binding and mapping studies revealed these Abs targeted four separate epitopes; they also failed to compete for binding by Abs to known major neutralizing epitopes. Detailed epitope mapping studies revealed that two of the four epitopes were located in the gp41 subunit of Env. These QtAbs bound pre-fusion forms of antigen and showed differential binding kinetics depending on whether oligomers were produced as recombinant gp140 trimers or as full-length Env incorporated into VLPs. Antigenic regions within gp41 present unexpectedly diverse structural epitopes, including these QtAb epitopes, which may be targeted by the naturally occurring Ab response to HIV infection.

  6. 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.

  7. 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.

  8. Immunoproteasome LMP2 60HH variant alters MBP epitope generation and reduces the risk to develop multiple sclerosis in Italian female population.

    Directory of Open Access Journals (Sweden)

    Michele Mishto

    Full Text Available BACKGROUND: Albeit several studies pointed out the pivotal role that CD4+T cells have in Multiple Sclerosis, the CD8+ T cells involvement in the pathology is still in its early phases of investigation. Proteasome degradation is the key step in the production of MHC class I-restricted epitopes and therefore its activity could be an important element in the activation and regulation of autoreactive CD8+ T cells in Multiple Sclerosis. METHODOLOGY/PRINCIPAL FINDINGS: Immunoproteasomes and PA28-alphabeta regulator are present in MS affected brain area and accumulated in plaques. They are expressed in cell types supposed to be involved in MS development such as neurons, endothelial cells, oligodendrocytes, macrophages/macroglia and lymphocytes. Furthermore, in a genetic study on 1262 Italian MS cases and 845 controls we observed that HLA-A*02+ female subjects carrying the immunoproteasome LMP2 codon 60HH variant have a reduced risk to develop MS. Accordingly, immunoproteasomes carrying the LMP2 60H allele produce in vitro a lower amount of the HLA-A*0201 restricted immunodominant epitope MBP(111-119. CONCLUSION/SIGNIFICANCE: The immunoproteasome LMP2 60HH variant reduces the risk to develop MS amongst Italian HLA-A*02+ females. We propose that such an effect is mediated by the altered proteasome-dependent production of a specific MBP epitope presented on the MHC class I. Our observations thereby support the hypothesis of an involvement of immunoproteasome in the MS pathogenesis.

  9. Comparative Multi-Epitope-Ligand-Cartography reveals essential immunological alterations in Barrett's metaplasia and esophageal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Bertram Wiedenmann

    2010-07-01

    Full Text Available Abstract Background Barrett's esophagus (BE is caused by gastroesophageal reflux with consecutive mucosal inflammation, predisposing patients to the development of esophageal adenocarcinoma (EAC. We investigated changes in T cell-related mucosal combinatorial molecular protein patterns in both diseases using the novel Multi-Epitope-Ligand-Cartography, a unique robotic whole-cell imaging technology that simultaneously visualizes dozens of proteins in structurally intact tissues and correlates cellular localization of proteins with function. Results Biopsies were taken during endoscopy from BE, EAC, and normal control tissue, and proteomic microscopy was performed on 32 different epitopes. When the significance level was set to p For example, the number of activated apoptotic naïve and memory T cells was significantly increased only in BE, whereas the number of activated apoptotic helper and regulatory T cells was significantly elevated in BE and EAC. In contrast, the number of activated apoptotic cytotoxic T cells was significantly elevated only in EAC. Confirming different pathways in BE and EAC, the number of T lymphocytes with p53 expression and downregulation of bcl2 expression (CD3+p53+Bcl2-NfkB- was significantly increased in EAC compared to BE and controls. Interestingly, the number of precursor T cells (CD7+ was significantly elevated only in EAC. These cells lack Bax and caspase-8, suggesting impaired apoptosis in the early stages of T cell differentiation. Conclusion Proteomic analysis showed for the first time that proteins, which are critically involved in the mucosal immune system of the esophagus, are distinctly expressed in BE and EAC, whereas others are comparably altered in both diseases, suggesting that many pathogenic events might be shared by both diseases. Topological proteomic analysis, therefore, helps us to understand the different pathogenic events in the underlying disease pathways.

  10. Distribution of conserved and specific epitopes on the VP8 subunit of rotavirus VP4.

    Science.gov (United States)

    Larralde, G; Gorziglia, M

    1992-01-01

    Three cDNA clones comprising the VP8 subunit of the VP4 of human rotavirus strain KU (VP7 serotype G1; VP4 serotype P1A) G1 were constructed. The corresponding encoded peptides were designated according to their locations in the VP8 subunit as A (amino acids 1 to 102), B (amino acids 84 to 180), and C (amino acids 150 to 246 plus amino acids 247 to 251 from VP5). In addition, cDNA clones encoding peptide B of the VP8 subunit of the VP4 gene from human rotavirus strains DS-1 (G2; P1B) and 1076 (G2; P2) were also constructed. These DNA fragments were inserted into plasmid pGEMEX-1 and expressed in Escherichia coli. Western immunoblot analysis using antisera to rotavirus strains KU (P1A), Wa (P1A), DS-1 (P1B), 1076 (P2), and M37 (P2) demonstrated that peptides A and C cross-reacted with heterotypic human rotavirus VP4 antisera, suggesting that these two peptides represent conserved epitopes in the VP8 subunit. In contrast, peptide B appears to be involved in the VP4 serotype and subtype specificities, because it reacted only with the corresponding serotype- and subtype-specific antiserum. Antiserum raised against peptide A, B, or C of strain KU contained a lower level of neutralizing activity than did that induced by the entire VP8 subunit. In addition, the serotype-specific neutralizing activity of anti-KU VP8 serum was ablated after adsorption with the KU VP8 protein but not with a mixture of peptides A, B, and C of strain KU, suggesting that most of the serotype-specific epitopes in the VP8 subunit are conformational and are dependent on the entire amino acid sequence of VP8. Images PMID:1279204

  11. Comparative Multi-Epitope-Ligand-Cartography reveals essential immunological alterations in Barrett's metaplasia and esophageal adenocarcinoma.

    Science.gov (United States)

    Berndt, Uta; Philipsen, Lars; Bartsch, Sebastian; Hu, Yuqin; Röcken, Christoph; Bertram, Wiedenmann; Hämmerle, Marcus; Rösch, Thomas; Sturm, Andreas

    2010-07-06

    Barrett's esophagus (BE) is caused by gastroesophageal reflux with consecutive mucosal inflammation, predisposing patients to the development of esophageal adenocarcinoma (EAC). We investigated changes in T cell-related mucosal combinatorial molecular protein patterns in both diseases using the novel Multi-Epitope-Ligand-Cartography, a unique robotic whole-cell imaging technology that simultaneously visualizes dozens of proteins in structurally intact tissues and correlates cellular localization of proteins with function. Biopsies were taken during endoscopy from BE, EAC, and normal control tissue, and proteomic microscopy was performed on 32 different epitopes. When the significance level was set to p < 0.0005 and the search depth to five antibody combinations, controls and BE can be differentiated by 63, controls and EAC by 3222, and BE from EAC by 1521 distinct protein combinations.For example, the number of activated apoptotic naïve and memory T cells was significantly increased only in BE, whereas the number of activated apoptotic helper and regulatory T cells was significantly elevated in BE and EAC. In contrast, the number of activated apoptotic cytotoxic T cells was significantly elevated only in EAC. Confirming different pathways in BE and EAC, the number of T lymphocytes with p53 expression and downregulation of bcl2 expression (CD3+p53+Bcl2-NfkB-) was significantly increased in EAC compared to BE and controls. Interestingly, the number of precursor T cells (CD7+) was significantly elevated only in EAC. These cells lack Bax and caspase-8, suggesting impaired apoptosis in the early stages of T cell differentiation. Proteomic analysis showed for the first time that proteins, which are critically involved in the mucosal immune system of the esophagus, are distinctly expressed in BE and EAC, whereas others are comparably altered in both diseases, suggesting that many pathogenic events might be shared by both diseases. Topological proteomic analysis

  12. Discrete Torsion and Symmetric Products

    CERN Document Server

    Dijkgraaf, R

    1999-01-01

    In this note we point out that a symmetric product orbifold CFT can be twisted by a unique nontrivial two-cocycle of the permutation group. This discrete torsion changes the spins and statistics of corresponding second-quantized string theory making it essentially ``supersymmetric.'' The long strings of even length become fermionic (or ghosts), those of odd length bosonic. The partition function and elliptic genus can be described by a sum over stringy spin structures. The usual cubic interaction vertex is odd and nilpotent, so this construction gives rise to a DLCQ string theory with a leading quartic interaction.

  13. Radiative transfer on discrete spaces

    CERN Document Server

    Preisendorfer, Rudolph W; Stark, M; Ulam, S

    1965-01-01

    Pure and Applied Mathematics, Volume 74: Radiative Transfer on Discrete Spaces presents the geometrical structure of natural light fields. This book describes in detail with mathematical precision the radiometric interactions of light-scattering media in terms of a few well established principles.Organized into four parts encompassing 15 chapters, this volume begins with an overview of the derivations of the practical formulas and the arrangement of formulas leading to numerical solution procedures of radiative transfer problems in plane-parallel media. This text then constructs radiative tran

  14. Invariants of Broken Discrete Symmetries

    Science.gov (United States)

    Kalozoumis, P. A.; Morfonios, C.; Diakonos, F. K.; Schmelcher, P.

    2014-08-01

    The parity and Bloch theorems are generalized to the case of broken global symmetry. Local inversion or translation symmetries in one dimension are shown to yield invariant currents that characterize wave propagation. These currents map the wave function from an arbitrary spatial domain to any symmetry-related domain. Our approach addresses any combination of local symmetries, thus applying, in particular, to acoustic, optical, and matter waves. Nonvanishing values of the invariant currents provide a systematic pathway to the breaking of discrete global symmetries.

  15. Discrete low-discrepancy sequences

    CERN Document Server

    Angel, Omer; Martin, James B; Propp, James

    2009-01-01

    Holroyd and Propp used Hall's marriage theorem to show that, given a probability distribution pi on a finite set S, there exists an infinite sequence s_1,s_2,... in S such that for all integers k >= 1 and all s in S, the number of i in [1,k] with s_i = s differs from k pi(s) by at most 1. We prove a generalization of this result using a simple explicit algorithm. A special case of this algorithm yields an extension of Holroyd and Propp's result to the case of discrete probability distributions on infinite sets.

  16. Discrete and finite General Relativity

    CERN Document Server

    De Souza, M M; Souza, Manoelito M. de; Silveira, Robson N.

    1999-01-01

    We develop the General Theory of Relativity in a formalism with extended causality that describes physical interaction through discrete, transversal and localized pointlike fields. The homogeneous field equations are then solved for a finite, singularity-free, point-like field that we associate to a ``classical graviton". The standard Einstein's continuous formalism is retrieved by means of an averaging process, and its continuous solutions are determined by the chsosen imposed symetry. The Schwarzschild metric is obtained by the imposition of spherical symmetry on the averaged field.

  17. Discrete gravity from statistical mechanics

    CERN Document Server

    Romano, Antonio Enea

    2011-01-01

    We show how to construct space time lattices with a Regge action proportional to the energy of a given Ising or Potts model macrostate. This allows to take advantage of the existence of exact solutions for these models to calculate the quantum wave function of the universe using the sum over the histories approach to quantum gravity. Motivated by this isomorphism we show how the Regge equations, i.e. the discrete equivalent of the vacuum Einstein equations, can be derived using statistical mechanics under the assumption that the energy of a given space time geometry is proportional to the Regge action.

  18. Identification of cross-reacting T-cell epitopes in structural and non-structural proteins of swine and pandemic H1N1 influenza A virus strains in pigs

    DEFF Research Database (Denmark)

    Baratelli, Massimiliano; Pedersen, Lasse Eggers; Trebbien, Ramona

    2017-01-01

    Heterologous protection against swine influenza viruses (SwIVs) of different lineages is an important concern for the pig industry. Cross-protection between 'avian-like' H1N1 and 2009 pandemic H1N1 lineages has been observed previously, indicating the involvement of cross-reacting T-cells. Here......, tetramer specific T-cell populations were identified. The majority of the identified T-cell epitopes were conserved between the examined lineages, suggesting that targeting cross-reactive T-cell epitopes could be used to improve vaccines against SwIV in SLA-1*0702-positive pigs....

  19. 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

  20. Entwinement in discretely gauged theories

    Science.gov (United States)

    Balasubramanian, V.; Bernamonti, A.; Craps, B.; De Jonckheere, T.; Galli, F.

    2016-12-01

    We develop the notion of "entwinement" to characterize the amount of quantum entanglement between internal, discretely gauged degrees of freedom in a quantum field theory. This concept originated in the program of reconstructing spacetime from entanglement in holographic duality. We define entwinement formally in terms of a novel replica method which uses twist operators charged in a representation of the discrete gauge group. In terms of these twist operators we define a non-local, gauge-invariant object whose expectation value computes entwinement in a standard replica limit. We apply our method to the computation of entwinement in symmetric orbifold conformal field theories in 1+1 dimensions, which have an S N gauging. Such a theory appears in the weak coupling limit of the D1-D5 string theory which is dual to AdS3 at strong coupling. In this context, we show how certain kinds of entwinement measure the lengths, in units of the AdS scale, of non-minimal geodesics present in certain excited states of the system which are gravitationally described as conical defects and the M = 0 BTZ black hole. The possible types of entwinement that can be computed define a very large new class of quantities characterizing the fine structure of quantum wavefunctions.

  1. Supervised Discrete Hashing With Relaxation.

    Science.gov (United States)

    Gui, Jie; Liu, Tongliang; Sun, Zhenan; Tao, Dacheng; Tan, Tieniu

    2016-12-29

    Data-dependent hashing has recently attracted attention due to being able to support efficient retrieval and storage of high-dimensional data, such as documents, images, and videos. In this paper, we propose a novel learning-based hashing method called ''supervised discrete hashing with relaxation'' (SDHR) based on ''supervised discrete hashing'' (SDH). SDH uses ordinary least squares regression and traditional zero-one matrix encoding of class label information as the regression target (code words), thus fixing the regression target. In SDHR, the regression target is instead optimized. The optimized regression target matrix satisfies a large margin constraint for correct classification of each example. Compared with SDH, which uses the traditional zero-one matrix, SDHR utilizes the learned regression target matrix and, therefore, more accurately measures the classification error of the regression model and is more flexible. As expected, SDHR generally outperforms SDH. Experimental results on two large-scale image data sets (CIFAR-10 and MNIST) and a large-scale and challenging face data set (FRGC) demonstrate the effectiveness and efficiency of SDHR.

  2. Entwinement in discretely gauged theories

    CERN Document Server

    Balasubramanian, V; Craps, B; De Jonckheere, T; Galli, F

    2016-01-01

    We develop the notion of entwinement to characterize the amount of quantum entanglement between internal, discretely gauged degrees of freedom in a quantum field theory. This concept originated in the program of reconstructing spacetime from entanglement in holographic duality. We define entwinement formally in terms of a novel replica method which uses twist operators charged in a representation of the discrete gauge group. In terms of these twist operators we define a non-local, gauge-invariant object whose expectation value computes entwinement in a standard replica limit. We apply our method to the computation of entwinement in symmetric orbifold conformal field theories in 1+1 dimensions, which have an $S_N$ gauging. Such a theory appears in the weak coupling limit of the D1-D5 string theory which is dual to AdS$_3$ at strong coupling. In this context, we show how certain kinds of entwinement measure the lengths, in units of the AdS scale, of non-minimal geodesics present in certain excited states of the...

  3. Discrete auroras and magnetotail processes.

    Science.gov (United States)

    Lyons, L. R.

    Important information about magnetospheric phenomena associated with auroras and substorms can be inferred from low-altitude auroral observations. Satellite observations have shown that discrete auroral arcs lie within a boundary plasma sheet (BPS) region that is outside the central plasma sheet (CPS). The observations imply that arcs are generated along BPS field lines by magnetospheric processes that form large, perpendicular electric field structures. The BPS and the arc generation processes apparently lie along field lines that are in the vicinity of the boundary between open and closed field lines and cross the tail (or magnetopause) current sheet. Ground-based observations show that the first indication of a substorm onset is the brightening of a quiet, discrete arc. This suggests that substorms are initiated along the BPS field lines associated with arc generation, and not within the CPS. Finally, auroral observations have shown that the area of open, polar-cap field lines varies considerably during periods of geomagnetic activity. Expansion of the polar cap has the potential for releasing trapped plasma sheet particles along freshly open field lines. The resulting evacuation of field lines has the potential for being an important loss process for the plasma sheet and for being a source of tailward flows and energetic particle bursts in the tail.

  4. Neisseria lactamica and Neisseria meningitidis share lipooligosaccharide epitopes but lack common capsular and class 1, 2, and 3 protein epitopes.

    Science.gov (United States)

    Kim, J J; Mandrell, R E; Griffiss, J M

    1989-02-01

    Neisseria lactamica, a common human pharyngeal commensal, contributes to acquired immunity to Neisseria meningitidis. To define the surface antigens shared between these two species, we used monoclonal antibodies (MAbs) to study 35 N. lactamica strains isolated in various parts of the world for cross-reactivity with meningococcal capsules, outer membrane proteins, and lipooligosaccharides (LOS). No N. lactamica strain reacted significantly with MAbs specific for capsular group A, B, C, Y, or W, and we were unable to extract capsular polysaccharide from them. Only 2 of 33 strains reacted weakly with MAbs against class 2 serotype proteins P2b and P2c. None reacted with MAbs specific for meningococcal class 1 protein P1.2 or P1.16 or class 2/3 serotype protein P2a or P15. Most N. lactamica strains (30 of 35) bound one or more of seven LOS-specific MAbs. Two LOS epitopes, defined by MAbs O6B4 and 3F11, that are commonly found on pathogenic Neisseria species were found on 25 of 35 N. lactamica. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting showed that the LOS of N. lactamica are composed of multiple components that are physically and antigenically similar to the LOS of pathogenic Neisseria species. Among four other commensal neisserial species, only Neisseria cinerea shared LOS epitopes defined by MAbs O6B4 and 3F11. Previous studies have shown that pharyngeal colonization with N. lactamica induces bactericidal antibodies against the meningococcus. We postulate that shared N. lactamica and meningococcal LOS epitopes may play an important role in the development of natural immunity to the meningococcus.

  5. Modeling the Role of Epitope Arrangement on Antibody Binding Stoichiometry in Flaviviruses.

    Science.gov (United States)

    Ripoll, Daniel R; Khavrutskii, Ilja; Wallqvist, Anders; Chaudhury, Sidhartha

    2016-10-18

    Cryo-electron-microscopy (cryo-EM) structures of flaviviruses reveal significant variation in epitope occupancy across different monoclonal antibodies that have largely been attributed to epitope-level differences in conformation or accessibility that affect antibody binding. The consequences of these variations for macroscopic properties such as antibody binding and neutralization are the results of the law of mass action-a stochastic process of innumerable binding and unbinding events between antibodies and the multiple binding sites on the flavivirus in equilibrium-that cannot be directly imputed from structure alone. We carried out coarse-grained spatial stochastic binding simulations for nine flavivirus antibodies with epitopes defined by cryo-EM or x-ray crystallography to assess the role of epitope spatial arrangement on antibody-binding stoichiometry, occupancy, and neutralization. In our simulations, all epitopes were equally competent for binding, representing the upper limit of binding stoichiometry that results from epitope spatial arrangement alone. Surprisingly, our simulations closely reproduced the relative occupancy and binding stoichiometry observed in cryo-EM, without having to account for differences in epitope accessibility or conformation, suggesting that epitope spatial arrangement alone may be sufficient to explain differences in binding occupancy and stoichiometry between antibodies. Furthermore, we found that there was significant heterogeneity in binding configurations even at saturating antibody concentrations, and that bivalent antibody binding may be more common than previously thought. Finally, we propose a structure-based explanation for the stoichiometric threshold model of neutralization. Published by Elsevier Inc.

  6. 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...

  7. 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 enzym...

  8. 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

    A B-cell epitope is the three-dimensional structure within an antigen that can be bound to the variable region of an antibody. The prediction of B-cell epitopes is highly desirable for various immunological applications, but has presented a set of unique challenges to the bioinformatics and immun...

  9. Approaching rational epitope vaccine design for hepatitis C virus with meta-server and multivalent scaffolding

    Science.gov (United States)

    He, Linling; Cheng, Yushao; Kong, Leopold; Azadnia, Parisa; Giang, Erick; Kim, Justin; Wood, Malcolm R.; Wilson, Ian A.; Law, Mansun; Zhu, Jiang

    2015-08-01

    Development of a prophylactic vaccine against hepatitis C virus (HCV) has been hampered by the extraordinary viral diversity and the poor host immune response. Scaffolding, by grafting an epitope onto a heterologous protein scaffold, offers a possible solution to epitope vaccine design. In this study, we designed and characterized epitope vaccine antigens for the antigenic sites of HCV envelope glycoproteins E1 (residues 314-324) and E2 (residues 412-423), for which neutralizing antibody-bound structures are available. We first combined six structural alignment algorithms in a “scaffolding meta-server” to search for diverse scaffolds that can structurally accommodate the HCV epitopes. For each antigenic site, ten scaffolds were selected for computational design, and the resulting epitope scaffolds were analyzed using structure-scoring functions and molecular dynamics simulation. We experimentally confirmed that three E1 and five E2 epitope scaffolds bound to their respective neutralizing antibodies, but with different kinetics. We then investigated a “multivalent scaffolding” approach by displaying 24 copies of an epitope scaffold on a self-assembling nanoparticle, which markedly increased the avidity of antibody binding. Our study thus demonstrates the utility of a multi-scale scaffolding strategy in epitope vaccine design and provides promising HCV immunogens for further assessment in vivo.

  10. Computational prediction of neutralization epitopes targeted by human anti-V3 HIV monoclonal antibodies.

    Directory of Open Access Journals (Sweden)

    Evgeny Shmelkov

    Full Text Available The extreme diversity of HIV-1 strains presents a formidable challenge for HIV-1 vaccine design. Although antibodies (Abs can neutralize HIV-1 and potentially protect against infection, antibodies that target the immunogenic viral surface protein gp120 have widely variable and poorly predictable cross-strain reactivity. Here, we developed a novel computational approach, the Method of Dynamic Epitopes, for identification of neutralization epitopes targeted by anti-HIV-1 monoclonal antibodies (mAbs. Our data demonstrate that this approach, based purely on calculated energetics and 3D structural information, accurately predicts the presence of neutralization epitopes targeted by V3-specific mAbs 2219 and 447-52D in any HIV-1 strain. The method was used to calculate the range of conservation of these specific epitopes across all circulating HIV-1 viruses. Accurately identifying an Ab-targeted neutralization epitope in a virus by computational means enables easy prediction of the breadth of reactivity of specific mAbs across the diversity of thousands of different circulating HIV-1 variants and facilitates rational design and selection of immunogens mimicking specific mAb-targeted epitopes in a multivalent HIV-1 vaccine. The defined epitopes can also be used for the purpose of epitope-specific analyses of breakthrough sequences recorded in vaccine clinical trials. Thus, our study is a prototype for a valuable tool for rational HIV-1 vaccine design.

  11. B-Cell Receptor Epitope Recognition Correlates With the Clinical Course of Chronic Lymphocytic Leukemia

    NARCIS (Netherlands)

    Binder, Mascha; Mueller, Fabian; Jackst, Antje; Lechenne, Barbara; Pantic, Milena; Bacher, Ulrike; Eulenburg, Christine Zu; Veelken, Hendrik; Mertelsmann, Roland; Pasqualini, Renata; Arap, Wadih; Trepel, Martin

    2011-01-01

    BACKGROUND: B-cell receptors (BCRs) and their recognition of specific epitopes may play a pivotal role in the development and progression of chronic lymphocytic leukemia (CLL). In this study, the authors set up a model system to explore epitope reactivity and its clinical relevance in CLL. METHODS:

  12. 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

    Cytotoxic T lymphocytes (CTLs) are critical for the control of human immunodeficiency virus, but containment of virus replication can be undermined by mutations in CTL epitopes that lead to virus escape. We analyzed the evolution in vivo of an immunodominant, HLA-A2-restricted CTL epitope and fou...

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

    NARCIS (Netherlands)

    Hosono-Fukao, T.; Ohtake-Niimi, S.; Nishitsuji, K.; Hossain, M.M.; Kuppevelt, A.H.M.S.M. van; Michikawa, M.; Uchimura, K.

    2011-01-01

    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 cytok

  14. Structural analysis of B-cell epitopes in antibody:protein complexes

    DEFF Research Database (Denmark)

    Kringelum, Jens Vindahl; Nielsen, Morten; Padkjær, Søren Berg;

    2013-01-01

    developed a novel framework for comparing and superimposing B-cell epitopes and applied it on a dataset of 107 non-similar antigen:antibody structures extracted from the PDB database. With the presented framework, we were able to describe the general B-cell epitope as a flat, oblong, oval shaped volume...

  15. Identification of novel helper epitope peptides of Survivin cancer-associated antigen applicable to developing helper/killer-hybrid epitope long peptide cancer vaccine.

    Science.gov (United States)

    Ohtake, Junya; Ohkuri, Takayuki; Togashi, Yuji; Kitamura, Hidemitsu; Okuno, Kiyotaka; Nishimura, Takashi

    2014-09-01

    We identified novel helper epitope peptides of Survivin cancer antigen, which are presented to both HLA-DRB1*01:01 and DQB1*06:01. The helper epitope also contained three distinct Survivin-killer epitopes presented to HLA-A*02:01 and A*24:02. This 19 amino-acids epitope peptide (SU18) induced weak responses of Survivin-specific CD4(+) and CD8(+) T cells though it contained both helper and killer epitopes. To enhance the vaccine efficacy, we synthesized a long peptide by conjugating SU18 peptide and another DR53-restricted helper epitope peptide (SU22; 12 amino-acids) using glycine-linker. We designated this artificial 40 amino-acids long peptide containing two helper and three killer epitopes as Survivin-helper/killer-hybrid epitope long peptide (Survivin-H/K-HELP). Survivin-H/K-HELP allowed superior activation of IFN-γ-producing CD4(+) Th1 cells and CD8(+) Tc1 cells compared with the mixture of its component peptides (SU18 and SU22) in the presence of OK-432-treated monocyte-derived DC (Mo-DC). Survivin-H/K-HELP-pulsed Mo-DC pretreated with OK-432 also exhibited sustained antigen-presentation capability of stimulating Survivin-specific Th1 cells compared with Mo-DC pulsed with a mixture of SU18 and SU22 short peptides. Moreover, we demonstrated that Survivin-H/K-HELP induced a complete response in a breast cancer patient with the induction of cellular and humoral immune responses. Thus, we believe that an artificially synthesized Survivin-H/K-HELP will become an innovative cancer vaccine.

  16. Antibody Recognition of a Highly Conserved Influenza Virus Epitope

    Energy Technology Data Exchange (ETDEWEB)

    Ekiert, Damian C.; Bhabha, Gira; Elsliger, Marc-André; Friesen, Robert H.E.; Jongeneelen, Mandy; Throsby, Mark; Goudsmit, Jaap; Wilson, Ian A.; Scripps; Crucell

    2009-05-21

    Influenza virus presents an important and persistent threat to public health worldwide, and current vaccines provide immunity to viral isolates similar to the vaccine strain. High-affinity antibodies against a conserved epitope could provide immunity to the diverse influenza subtypes and protection against future pandemic viruses. Cocrystal structures were determined at 2.2 and 2.7 angstrom resolutions for broadly neutralizing human antibody CR6261 Fab in complexes with the major surface antigen (hemagglutinin, HA) from viruses responsible for the 1918 H1N1 influenza pandemic and a recent lethal case of H5N1 avian influenza. In contrast to other structurally characterized influenza antibodies, CR6261 recognizes a highly conserved helical region in the membrane-proximal stem of HA1 and HA2. The antibody neutralizes the virus by blocking conformational rearrangements associated with membrane fusion. The CR6261 epitope identified here should accelerate the design and implementation of improved vaccines that can elicit CR6261-like antibodies, as well as antibody-based therapies for the treatment of influenza.

  17. Improving wheat to remove coeliac epitopes but retain functionality

    Science.gov (United States)

    Shewry, Peter R.; Tatham, Arthur S.

    2016-01-01

    Coeliac disease is an intolerance triggered by the ingestion of wheat gluten proteins. It is of increasing concern to consumers and health professionals as its incidence appears to be increasing. The amino acid sequences in gluten proteins that are responsible for triggering responses in sensitive individuals have been identified showing that they vary in distribution among and between different groups of gluten proteins. Conventional breeding may therefore be used to select for gluten protein fractions with lower contents of coeliac epitopes. Molecular breeding approaches can also be used to specifically down-regulate coeliac-toxic proteins or mutate coeliac epitopes within individual proteins. A combination of these approaches may therefore be used to develop a “coeliac-safe” wheat. However, this remains a formidable challenge due to the complex multigenic control of gluten protein composition. Furthermore, any modified wheats must retain acceptable properties for making bread and other processed foods. Not surprisingly, such coeliac-safe wheats have not yet been developed despite over a decade of research. PMID:26937068

  18. Improving wheat to remove coeliac epitopes but retain functionality.

    Science.gov (United States)

    Shewry, Peter R; Tatham, Arthur S

    2016-01-01

    Coeliac disease is an intolerance triggered by the ingestion of wheat gluten proteins. It is of increasing concern to consumers and health professionals as its incidence appears to be increasing. The amino acid sequences in gluten proteins that are responsible for triggering responses in sensitive individuals have been identified showing that they vary in distribution among and between different groups of gluten proteins. Conventional breeding may therefore be used to select for gluten protein fractions with lower contents of coeliac epitopes. Molecular breeding approaches can also be used to specifically down-regulate coeliac-toxic proteins or mutate coeliac epitopes within individual proteins. A combination of these approaches may therefore be used to develop a "coeliac-safe" wheat. However, this remains a formidable challenge due to the complex multigenic control of gluten protein composition. Furthermore, any modified wheats must retain acceptable properties for making bread and other processed foods. Not surprisingly, such coeliac-safe wheats have not yet been developed despite over a decade of research.

  19. Molecular Mapping of the Goodpasture's Epitope for Glomerulonephritis

    Science.gov (United States)

    Bolton, W. Kline; Chen, Lanlin; Hellmark, Thomas; Fox, Jay; Wieslander, Jorgen

    2005-01-01

    Goodpasture's syndrome is an autoimmune disease characterized by pulmonary hemorrhage, glomerulonephritis, and antiglomerular basement membrane (GBM) antibodies. We have studied a rat model with chimeric proteins (CPs) consisting of portions of the nephritogenic non-collagenous domain of α3 type IV collagen (α3(IV)NC1) and non-nephritogenic α1(IV)NC1. CPs with aminoterminal α3 that contains the major epitope for Goodpasture antibody binding induced EAG. We next immunized with D3, an α1(IV)NC1 CP with 69AA of α3(IV)NC1 (binds Goodpasture sera), D4, the D3 construct shortened by 4 AA (nonbinding), P9 and P10, single AA mutants (nonbinding) and S2, an α1(IV)NC1 with nine AA of α3(IV)NC1 (binding). GBM, S2 and D3 induced EAG. GBM immunized rats had intense IgG deposits but S2 and D3 rats had minimal deposits. A 13 mer rat peptide encompassing the aminoterminal site induced EAG sans antibody, while peptides not encompassing the region failed to induce GN. Asparagine at position 19 rather than isoleucine was essential for disease induction. These studies define critical limited AA sequences of α3(IV)NC1 associated with glomerulonephritis without antibody, and demonstrate that this region contains a T-cell epitope responsible for induction of glomerulonephritis. PMID:16555617

  20. Quasispecies dynamics in main core epitopes of hepatitis B virus by ultra-deep-pyrosequencing

    Institute of Scientific and Technical Information of China (English)

    Maria Homs; Maria Buti; David Tabernero; Josep Quer; Alex Sanchez; Noelia Corral; Rafael Esteban

    2012-01-01

    AIM:To investigate the variability of the main immunodominant motifs of hepatitis B virus (HBV) core gene by ultra-deep-pyrosequencing (UDPS).METHODS:Four samples (2 genotype A and 2 genotype D) from 4 treatment-naive patients were assessed for baseline variability.Two additional samples from one patient (patient 4,genotype D) were selected for analysis:one sample corresponded to a 36-mo treatment-free period from baseline and the other to the time of viral breakthrough after 18 mo of lamivudine treatment.The HBV region analyzed covered amino acids 40 to 95 of the core gene,and included the two main epitopic regions,Th50-69 and B74-84.UDPS was carried out in the Genome Sequencer FLX system (454 Life Sciences,Roche).After computer filtering of UDPS data based on a Poisson statistical model,122 813 sequences were analyzed.The most conserved position detected by UDPS was analyzed by site-directed mutagenesis and evaluated in cell culture.RESULTS:Positions with highest variability rates were mainly located in the main core epitopes,confirming their role as immune-stimulating regions.In addition,the distribution of variability showed a relationship with HBV genotype.Patient 1 (genotype A) presented the lowest variability rates and patient 2 (genotype A) had 3 codons with variability higher than 1%.Patient 3 and 4 (both genotype D) presented 5 and 8 codons with variability higher than 1%,respectively.The median baseline frequencies showed that genotype A samples had higher variability in epitopic positions than in the other positions analyzed,approaching significance (P =0.07,sample 1 and P =0.05,sample 2).In contrast,there were no significant differences in variability between the epitopic and other positions in genotype D cases.Interestingly,patient 1 presented a completely mutated motif from amino acid 64 to 67 (E64LMT67),which is commonly recognized by T helper cells.Additionally,the variability observed in all 4 patients was particularly associated with the E64

  1. High throughput functional epitope mapping: revisiting phage display platform to scan target antigen surface.

    Science.gov (United States)

    Rojas, Gertrudis; Tundidor, Yaima; Infante, Yanelys Cabrera

    2014-01-01

    Antibody engineering must be accompanied by mapping strategies focused on identifying the epitope recognized by each antibody to define its unique functional identity. High throughput fine specificity determination remains technically challenging. We review recent experiences aimed at revisiting the oldest and most extended display technology to develop a robust epitope mapping platform, based on the ability to manipulate target-derived molecules (ranging from the whole native antigen to antigen domains and smaller fragments) on filamentous phages. Single, multiple and combinatorial mutagenesis allowed comprehensive scanning of phage-displayed antigen surface that resulted in the identification of clusters of residues contributing to epitope formation. Functional pictures of the epitope(s) were thus delineated in the natural context. Successful mapping of antibodies against interleukin-2, epidermal growth factor and its receptor, and vascular endothelial growth factor showed the versatility of these procedures, which combine the accuracy of site-directed mutagenesis with the high throughput potential of phage display.

  2. 表位疫苗的研究进展%Advance in epitope vaccines

    Institute of Scientific and Technical Information of China (English)

    石晓妮; 窦永喜; 才学鹏

    2011-01-01

    综述了表位疫苗的免疫学理论基础、抗原表位的预测及构建表位疫苗的基本思路和方法,介绍了目前国内外已经研制成功的几种病原表位疫苗,为深入研制其他病原微生物的表位疫苗提供借鉴.%This article reviews the basic immune mechanisms of epitope vaccines and the methods on how to predict antigenic epitopes and design epitope vaccines.Some examples of successful epitope vaccines were included.From them,researchers may be able to get some useful information and help to develop new epitope vaccine.

  3. Further progress on defining highly conserved immunogenic epitopes for a global HIV vaccine

    DEFF Research Database (Denmark)

    De Groot, Anne S; Levitz, Lauren; Ardito, Matthew T;

    2012-01-01

    and that are conserved in sequence and across time may represent the "Achilles' heel" of HIV and would be excellent candidates for vaccine development. In this study, T-cell epitopes were selected using immunoinformatics tools, combining HLA-A3 binding predictions with relative sequence conservation in the context...... of global HIV evolution. Twenty-seven HLA-A3 epitopes were chosen from an analysis performed in 2003 on 10,803 HIV-1 sequences, and additional sequences were selected in 2009 based on an expanded set of 43,822 sequences. These epitopes were tested in vitro for HLA binding and for immunogenicity with PBMCs...... of HIV-infected donors from Providence, Rhode Island. Validation of these HLA-A3 epitopes conserved across time, clades, and geography supports the hypothesis that epitopes such as these would be candidates for inclusion in our globally relevant GAIA HIV vaccine constructs....

  4. High-throughput epitope binning of therapeutic monoclonal antibodies: why you need to bin the fridge.

    Science.gov (United States)

    Brooks, Benjamin D; Miles, Adam R; Abdiche, Yasmina N

    2014-08-01

    Analytical tools are evolving to meet the need for the higher-throughput characterization of therapeutic monoclonal antibodies. An antibody's epitope is arguably its most important property because it underpins its functional activity but, because epitope selection is innate, it remains an empirical process. Here, we focus on the emergence of label-free biosensors with throughput capabilities orders of magnitude higher than the previous state-of-the-art, which can facilitate large assays such as epitope binning so that they can be incorporated alongside functional activity screens, enabling the rapid identification of leads that exhibit unique and functional epitopes. In addition to streamlining the drug development process by saving time and cost, the information from epitope binning assays could provide the basis for intellectual property protection. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Notes on Discrete Subgroups of Möbius Transformations

    Indian Academy of Sciences (India)

    Hua Wang; Yueping Jiang; Wensheng Cao

    2013-05-01

    Jørgensen’s inequality gives a necessary condition for a nonelementary two generator subgroup of $SL(2,\\mathbb{C})$ to be discrete. By embedding $SL(2,\\mathbb{C})$ into $Û(1,1;\\mathbb{H})$, we obtain a new type of Jørgensen’s inequality, which is in terms of the coefficients of involved isometries. We provide an example to show that this result gives an improvement over the classical Jørgensen’s inequality.

  6. A representation theorem for linear discrete-space systems

    Directory of Open Access Journals (Sweden)

    Irwin W. Sandberg

    1998-01-01

    Full Text Available The cornerstone of the theory of discrete-time single-input single-output linear systems is the idea that every such system has an input–output map H that can be represented by a convolution or the familiar generalization of a convolution. This thinking involves an oversight which is corrected in this note by adding an additional term to the representation.

  7. Mapping of a conformational epitope on the cashew allergen Ana o 2: a discontinuous large subunit epitope dependent upon homologous or heterologous small subunit association.

    Science.gov (United States)

    Xia, Lixin; Willison, LeAnna N; Porter, Lauren; Robotham, Jason M; Teuber, Suzanne S; Sathe, Shridhar K; Roux, Kenneth H

    2010-05-01

    The 11S globulins are members of the cupin protein superfamily and represent an important class of tree nut allergens for which a number of linear epitopes have been mapped. However, specific conformational epitopes for these allergens have yet to be described. We have recently reported a cashew Ana o 2 conformational epitope defined by murine mAb 2B5 and competitively inhibited by a subset of patient IgE antibodies. The 2B5 epitope appears to reside on the large (acidic) subunit, is dependent upon small (basic) subunit association for expression, and is highly susceptible to denaturation. Here we fine map the epitope using a combination of recombinant chimeric cashew Ana o 2-soybean Gly m 6 chimeras, deletion and point mutations, molecular modeling, and electron microscopy of 2B5-Ana o 2 immune complexes. Key residues appear confined to a 24 amino acid segment near the N-terminus of the large subunit peptide, a portion of which makes direct contact with the small subunit. These data provide an explanation for both the small subunit dependence and the structurally labile nature of the epitope.

  8. ElliPro: a new structure-based tool for the prediction of antibody epitopes

    Directory of Open Access Journals (Sweden)

    Fusseder Nicholas

    2008-12-01

    Full Text Available Abstract Background Reliable prediction of antibody, or B-cell, epitopes remains challenging yet highly desirable for the design of vaccines and immunodiagnostics. A correlation between antigenicity, solvent accessibility, and flexibility in proteins was demonstrated. Subsequently, Thornton and colleagues proposed a method for identifying continuous epitopes in the protein regions protruding from the protein's globular surface. The aim of this work was to implement that method as a web-tool and evaluate its performance on discontinuous epitopes known from the structures of antibody-protein complexes. Results Here we present ElliPro, a web-tool that implements Thornton's method and, together with a residue clustering algorithm, the MODELLER program and the Jmol viewer, allows the prediction and visualization of antibody epitopes in a given protein sequence or structure. ElliPro has been tested on a benchmark dataset of discontinuous epitopes inferred from 3D structures of antibody-protein complexes. In comparison with six other structure-based methods that can be used for epitope prediction, ElliPro performed the best and gave an AUC value of 0.732, when the most significant prediction was considered for each protein. Since the rank of the best prediction was at most in the top three for more than 70% of proteins and never exceeded five, ElliPro is considered a useful research tool for identifying antibody epitopes in protein antigens. ElliPro is available at http://tools.immuneepitope.org/tools/ElliPro. Conclusion The results from ElliPro suggest that further research on antibody epitopes considering more features that discriminate epitopes from non-epitopes may further improve predictions. As ElliPro is based on the geometrical properties of protein structure and does not require training, it might be more generally applied for predicting different types of protein-protein interactions.

  9. Epitope-driven DNA vaccine design employing immunoinformatics against B-cell lymphoma: a biotech's challenge.

    Science.gov (United States)

    Iurescia, Sandra; Fioretti, Daniela; Fazio, Vito Michele; Rinaldi, Monica

    2012-01-01

    DNA vaccination has been widely explored to develop new, alternative and efficient vaccines for cancer immunotherapy. DNA vaccines offer several benefits such as specific targeting, use of multiple genes to enhance immunity and reduced risk compared to conventional vaccines. Rapid developments in molecular biology and immunoinformatics enable rational design approaches. These technologies allow construction of DNA vaccines encoding selected tumor antigens together with molecules to direct and amplify the desired effector pathways, as well as highly targeted vaccines aimed at specific epitopes. Reliable predictions of immunogenic T cell epitope peptides are crucial for rational vaccine design and represent a key problem in immunoinformatics. Computational approaches have been developed to facilitate the process of epitope detection and show potential applications to the immunotherapeutic treatment of cancer. In this review a number of different epitope prediction methods are briefly illustrated and effective use of these resources to support experimental studies is described. Epitope-driven vaccine design employs these bioinformatics algorithms to identify potential targets of vaccines against cancer. In this paper the selection of T cell epitopes to develop epitope-based vaccines, the need for CD4(+) T cell help for improved vaccines and the assessment of vaccine performance against tumor are reviewed. We focused on two applications, namely prediction of novel T cell epitopes and epitope enhancement by sequence modification, and combined rationale design with bioinformatics for creation of new synthetic mini-genes. This review describes the development of epitope-based DNA vaccines and their antitumor effects in preclinical research against B-cell lymphoma, corroborating the usefulness of this platform as a potential tool for cancer therapy. Achievements in the field of DNA vaccines allow to overcome hurdles to clinical translation. In a scenario where the vaccine

  10. Discrete quantum geometries and their effective dimension

    CERN Document Server

    Thürigen, Johannes

    2015-01-01

    In several approaches towards a quantum theory of gravity, such as group field theory and loop quantum gravity, quantum states and histories of the geometric degrees of freedom turn out to be based on discrete spacetime. The most pressing issue is then how the smooth geometries of general relativity, expressed in terms of suitable geometric observables, arise from such discrete quantum geometries in some semiclassical and continuum limit. In this thesis I tackle the question of suitable observables focusing on the effective dimension of discrete quantum geometries. For this purpose I give a purely combinatorial description of the discrete structures which these geometries have support on. As a side topic, this allows to present an extension of group field theory to cover the combinatorially larger kinematical state space of loop quantum gravity. Moreover, I introduce a discrete calculus for fields on such fundamentally discrete geometries with a particular focus on the Laplacian. This permits to define the ef...

  11. Evaluation of a chimeric multi-epitope-based DNA vaccine against subgroup J avian leukosis virus in chickens.

    Science.gov (United States)

    Xu, Qingqing; Cui, Ning; Ma, Xingjiang; Wang, Fangkun; Li, Hongmei; Shen, Zhiqiang; Zhao, Xiaomin

    2016-07-19

    The prokaryotic expressed recombinant chimeric multi-epitope protein X (rCMEPX) had been evaluated with good immunogenicity and protective efficacy against subgroup J avian leukosis virus (ALV-J) in our previous study. In the present research, we cloned the chimeric multi-epitope gene X into the eukaryotic expression vector pVAX1 to evaluate its potency as a DNA vaccine. The purified recombinant gp85 protein and rCMEPX were used as positive controls and a DNA prime-protein boost strategy was also studied. Six experimental groups of 7-day-old chickens (20 per group) were immunized intramuscularly three times at 2weeks interval with PBS, gp85, rCMEPX, pVAX1, pVAX-X and pVAX-X+rCMEPX respectively. The antibody titers and cellular immune responses were assayed after immunization. The efficacy of immunoprotection against the challenge of ALV-J NX0101 strain was also examined. The results showed that the DNA vaccine could elicit both neutralizing antibodies and cellular responses. Immune-challenge experiments showed good protection efficacy against ALV-J infection. Particularly, the regimen involving one priming pVAX-X and twice recombinant rCMEPX boosting, induced the highest antibody titers in all immunized groups. Our results suggest that the constructed chimeric multi-epitope DNA has potential for a candidate vaccine against ALV-J when used in proper prime-boost combinations. The data presented here may provide an alternative strategy for vaccine design in chicken ALV-J prevention.

  12. Discovery of low-affinity preproinsulin epitopes and detection of autoreactive CD8 T-cells using combinatorial MHC multimers.

    Science.gov (United States)

    Unger, Wendy W; Velthuis, Jurjen; Abreu, Joana R F; Laban, Sandra; Quinten, Edwin; Kester, Michel G D; Reker-Hadrup, Sine; Bakker, Arnold H; Duinkerken, Gaby; Mulder, Arend; Franken, Kees L M C; Hilbrands, Robert; Keymeulen, Bart; Peakman, Mark; Ossendorp, Ferry; Drijfhout, Jan Wouter; Schumacher, Ton N; Roep, Bart O

    2011-11-01

    Autoreactive cytotoxic CD8 T-cells (CTLs) play a key pathogenic role in the destruction of insulin-producing beta-cells resulting in type 1 diabetes. However, knowledge regarding their targets is limited, restricting the ability to monitor the course of the disease and immune interventions. In a multi-step discovery process to identify novel CTL epitopes in human preproinsulin (PPI), PPI was digested with purified human proteasomes, and resulting COOH-fragments aligned with algorithm-predicted HLA-binding peptides to yield nine potential HLA-A1, -A2, -A3 or -B7-restricted candidates. An UV-exchange method allowed the generation of a repertoire of multimers including low-affinity HLA-binding peptides. These were labeled with quantum dot-fluorochromes and encoded in a combinatorial fashion, allowing parallel and sensitive detection of specific, low-avidity T-cells. Significantly increased frequencies of T-cells against four novel PPI epitopes (PPI(4-13)/B7, PPI(29-38)/A2, PPI(76-84)/A3 and PPI(79-88)/A3) were detected in stored blood of patients with recent onset diabetes but not in controls. Changes in frequencies of circulating CD8 T-cells against these novel epitopes were detected in blood of islet graft recipients at different time points after transplantation, which correlated with clinical outcome. In conclusion, our novel strategy involving a sensitive multiplex detection technology and requiring minimal volumes of stored blood represents a major improvement in the direct ex-vivo characterization and enumeration of immune cells in the pathogenesis of type 1 diabetes. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Antibody responses to mycobacterial and self heat shock protein 65 in autoimmune arthritis: epitope specificity and implication in pathogenesis.

    Science.gov (United States)

    Kim, Hong Ro; Kim, Eugene Y; Cerny, Jan; Moudgil, Kamal D

    2006-11-15

    Many autoimmune diseases are believed to involve primarily T cell-mediated effector mechanisms. There is increasing realization, however, that Abs may also play a vital role in the propagation of T cell-driven disorders. In this study, on the rat adjuvant-induced arthritis (AA) model of human rheumatoid arthritis, we examined the characteristics of serum Ab response to mycobacterial heat shock protein (hsp) 65 (Bhsp65), self (rat) hsp65 (Rhsp65), and linear peptides spanning these two molecules. The AA-resistant WKY (RT.1(l)) rat responded to the heat-killed Mycobacterium tuberculosis immunization with a rapid burst of Abs to both Bhsp65 and Rhsp65. These Abs reacted with numerous peptide epitopes; however, this response was reduced to a few epitopes with time. On the contrary, the susceptible Lewis (RT.1(l)) rat developed a relatively lower Ab response to Bhsp65, and Abs to Rhsp65 did not appear until the recovery from the disease. The Ab response in Lewis rats diversified with progression of AA, and there was an intriguing overlap between the repertoire of Bhsp65-reactive B and T cells during the recovery phase of AA. Nonetheless, subsets of the repertoire of the late Abs in both rat strains became focused on the same epitope regions of Bhsp65 and Rhsp65. The functional relevance of these Abs was evident from the results showing that sera from recovery phase Lewis or WKY rats, but not that of naive rats, afforded protection against subsequent AA. These results are of significance in further understanding of the role of humoral immunity in the pathogenesis of autoimmune arthritis.

  14. Epitope mapping and identification on a 3D model built for the tartary buckwheat allergic protein TBb

    Institute of Scientific and Technical Information of China (English)

    Ping Li; Xiaodong Cui; Yuying Li; Zhuanhua Wang

    2011-01-01

    Allergic protein TBb, a major allergen in tartary buckwheat, was divided into four epitope-containing fragments and was named Fl, F2, F3, and F4, respectively.Results of immunological assays revealed that F2 had the strongest IgE-binding activity to patient's sera, which indicated that it might contain the linear IgE-binding epitope of TBb.According to the results of sequence analysis and molecular modeling of tartary buckwheat allergen, three mutants of F2 gene (R139A, R141A, and D144A) were reconstructed using site-directed mutagenesis, and each mutant was expressed in Escherichia coli BL21 (DE3).Following purification by Ni2+ affinity chromatography, enzyme-linked immunosorbent assay and dot blot were performed for wild-type F2 and its mutants using sera from buckwheat-allergic patients and a negative control (non-allergic patient).Results showed that mutants R139A and D144A had weaker IgE-binding activity to patient's sera than wild-type F2, implying that Arg139 and Asp144 might be involved in the allergic activity of TBb.However, R141A had the weakest IgE-binding activity,suggesting that Arg141 may be the critical amino acid of TBb.This is the first report on the epitope mapping and identification of TBb.Our findings will contribute to the production of TBb hypoallergens and to allergen-specific immunotherapy for tartary buckwheat allergy.

  15. A Note on Discrete Einstein Metric

    CERN Document Server

    Ge, Huabin

    2015-01-01

    In this short note, we prove that the space of all admissible piecewise linear metrics parameterized by length square on a triangulated manifolds is a convex cone. We further study Regge's Einstein-Hilbert action and give a much more reasonable definition of discrete Einstein metric than our former version in \\cite{G}. Finally, we introduce a discrete Ricci flow for three dimensional triangulated manifolds, which is closely related to the existence of discrete Einstein metrics.

  16. Discrete complex analysis on isoradial graphs

    OpenAIRE

    Chelkak, Dmitry; Smirnov, Stanislav

    2008-01-01

    We study discrete complex analysis and potential theory on a large family of planar graphs, the so-called isoradial ones. Along with discrete analogues of several classical results, we prove uniform convergence of discrete harmonic measures, Green's functions and Poisson kernels to their continuous counterparts. Among other applications, the results can be used to establish universality of the critical Ising and other lattice models.

  17. Discrete calculus methods for counting

    CERN Document Server

    Mariconda, Carlo

    2016-01-01

    This book provides an introduction to combinatorics, finite calculus, formal series, recurrences, and approximations of sums. Readers will find not only coverage of the basic elements of the subjects but also deep insights into a range of less common topics rarely considered within a single book, such as counting with occupancy constraints, a clear distinction between algebraic and analytical properties of formal power series, an introduction to discrete dynamical systems with a thorough description of Sarkovskii’s theorem, symbolic calculus, and a complete description of the Euler-Maclaurin formulas and their applications. Although several books touch on one or more of these aspects, precious few cover all of them. The authors, both pure mathematicians, have attempted to develop methods that will allow the student to formulate a given problem in a precise mathematical framework. The aim is to equip readers with a sound strategy for classifying and solving problems by pursuing a mathematically rigorous yet ...

  18. Modeling discrete competitive facility location

    CERN Document Server

    Karakitsiou, Athanasia

    2015-01-01

    This book presents an up-to-date review of modeling and optimization approaches for location problems along with a new bi-level programming methodology which captures the effect of competition of both producers and customers on facility location decisions. While many optimization approaches simplify location problems by assuming decision making in isolation, this monograph focuses on models which take into account the competitive environment in which such decisions are made. New insights in modeling, algorithmic and theoretical possibilities are opened by this approach and new applications are possible. Competition on equal term plus competition between market leader and followers are considered in this study, consequently bi-level optimization methodology is emphasized and further developed. This book provides insights regarding modeling complexity and algorithmic approaches to discrete competitive location problems. In traditional location modeling, assignment of customer demands to supply sources are made ...

  19. Efficient Discretization of Stochastic Integrals

    CERN Document Server

    Fukasawa, Masaaki

    2012-01-01

    Sharp asymptotic lower bounds of the expected quadratic variation of discretization error in stochastic integration are given. The theory relies on inequalities for the kurtosis and skewness of a general random variable which are themselves seemingly new. Asymptotically efficient schemes which attain the lower bounds are constructed explicitly. The result is directly applicable to practical hedging problem in mathematical finance; it gives an asymptotically optimal way to choose rebalancing dates and portofolios with respect to transaction costs. The asymptotically efficient strategies in fact reflect the structure of transaction costs. In particular a specific biased rebalancing scheme is shown to be superior to unbiased schemes if transaction costs follow a convex model. The problem is discussed also in terms of the exponential utility maximization.

  20. Discretized Volumes in Numerical Methods

    CERN Document Server

    Antal, Miklós

    2007-01-01

    We present two techniques novel in numerical methods. The first technique compiles the domain of the numerical methods as a discretized volume. Congruent elements are glued together to compile the domain over which the solution of a boundary value problem is sought. We associate a group and a graph to that volume. When the group is symmetry of the boundary value problem under investigation, one can specify the structure of the solution, and find out if there are equispectral volumes of a given type. The second technique uses a complex mapping to transplant the solution from volume to volume and a correction function. Equation for the correction function is given. A simple example demonstrates the feasibility of the suggested method.