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Sample records for structural core antigen

  1. Antigenic potential of a highly conserved Neisseria meningitidis lipopolysaccharide inner core structure defined by chemical synthesis.

    PubMed

    Reinhardt, Anika; Yang, You; Claus, Heike; Pereira, Claney L; Cox, Andrew D; Vogel, Ulrich; Anish, Chakkumkal; Seeberger, Peter H

    2015-01-22

    Neisseria meningitidis is a leading cause of bacterial meningitis worldwide. We studied the potential of synthetic lipopolysaccharide (LPS) inner core structures as broadly protective antigens against N. meningitidis. Based on the specific reactivity of human serum antibodies to synthetic LPS cores, we selected a highly conserved LPS core tetrasaccharide as a promising antigen. This LPS inner core tetrasaccharide induced a robust IgG response in mice when formulated as an immunogenic glycoconjugate. Binding of raised mouse serum to a broad collection of N. meningitidis strains demonstrated the accessibility of the LPS core on viable bacteria. The distal trisaccharide was identified as the crucial epitope, whereas the proximal Kdo moiety was immunodominant and induced mainly nonprotective antibodies that are responsible for lack of functional protection in polyclonal serum. Our results identified key antigenic determinants of LPS core glycan and, hence, may aid the design of a broadly protective immunization against N. meningitidis. PMID:25601073

  2. Structural Analysis of the Core Region of O-Lipopolysaccharide of Porphyromonas gingivalis from Mutants Defective in O-Antigen Ligase and O-Antigen Polymerase▿ †

    PubMed Central

    Paramonov, Nikolay A.; Aduse-Opoku, Joseph; Hashim, Ahmed; Rangarajan, Minnie; Curtis, Michael A.

    2009-01-01

    Porphyromonas gingivalis synthesizes two lipopolysaccharides (LPSs), O-LPS and A-LPS. Here, we elucidate the structure of the core oligosaccharide (OS) of O-LPS from two mutants of P. gingivalis W50, ΔPG1051 (WaaL, O-antigen ligase) and ΔPG1142 (O-antigen polymerase), which synthesize R-type LPS (core devoid of O antigen) and SR-type LPS (core plus one repeating unit of O antigen), respectively. Structural analyses were performed using one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy in combination with composition and methylation analysis. The outer core OS of O-LPS occurs in two glycoforms: an “uncapped core,” which is devoid of O polysaccharide (O-PS), and a “capped core,” which contains the site of O-PS attachment. The inner core region lacks l(d)-glycero-d(l)-manno-heptosyl residues and is linked to the outer core via 3-deoxy-d-manno-octulosonic acid, which is attached to a glycerol residue in the outer core via a monophosphodiester bridge. The outer region of the “uncapped core” is attached to the glycerol and is composed of a linear α-(1→3)-linked d-Man OS containing four or five mannopyranosyl residues, one-half of which are modified by phosphoethanolamine at position 6. An amino sugar, α-d-allosamine, is attached to the glycerol at position 3. In the “capped core,” there is a three- to five-residue extension of α-(1→3)-linked Man residues glycosylating the outer core at the nonreducing terminal residue. β-d-GalNAc from the O-PS repeating unit is attached to the nonreducing terminal Man at position 3. The core OS of P. gingivalis O-LPS is therefore a highly unusual structure, and it is the basis for further investigation of the mechanism of assembly of the outer membrane of this important periodontal bacterium. PMID:19525343

  3. Antigenic determinants and functional domains in core antigen and e antigen from hepatitis B virus

    SciTech Connect

    Salfeld, J.; Pfaff, E.; Noah, M.; Schaller, H.

    1989-02-01

    The precore/core gene of hepatitis B virus directs the synthesis of two polypeptides, the 21-kilodalton subunit (p21c) forming the viral nucleocapsid (serologically defined as core antigen (HBcAg)) and a secreted processed protein (p17e, serologically defined as HBe antigen (HBeAg)). Although most of their primary amino acid sequences are identical, HBcAg and HBeAg display different antigenic properties that are widely used in hepatitis B virus diagnosis. To locate and to characterize the corresponding determinants, segments of the core gene were expressed in Escherichia coli and probed with a panel of polyclonal or monoclonal antibodies in radioimmunoassays or enzyme-linked immunosorbent assays, Western blots, and competition assays. Three distinct major determinants were characterized. It is postulated that HBcAg and HBeAg share common basic three-dimensional structure exposing the common linear determinant HBe1 but that they differ in the presentation of two conformational determinants that are either introduced (HBc) or masked (HBe2) in the assembled core. The simultaneous presentation of HBe1 and HBc, two distinctly different antigenic determinants with overlapping amino acid sequences, is interpreted to indicate the presence of slightly differently folded, stable conformational states of p21c in the hepatitis virus nucleocapsid.

  4. Reaching for far-flung antigen: How solid-core podosomes of dendritic cells transform into protrusive structures

    PubMed Central

    Baranov, Maksim V; ter Beest, Martin; van den Bogaart, Geert

    2014-01-01

    We recently identified a novel role for podosomes in antigen sampling. Podosomes are dynamic cellular structures that consist of point-like concentrations of actin surrounded by integrins and adaptor proteins such as vinculin and talin. Podosomes establish cellular contact with the extracellular matrix (ECM) and facilitate cell migration via ECM degradation. In our recent paper, we studied podosomes of human dendritic cells (DCs), major antigen presenting cells (APC) that take-up, process, and present foreign antigen to naive T-cells. We employed gelatin-impregnated porous polycarbonate filters to demonstrate that the mechanosensitive podosomes of DCs selectively localize to regions of low-physical resistance such as the filter pores. After degradation of the gelatin, podosomes increasingly protrude into the lumen of these pores. These protrusive podosome-derived structures contain several endocytic and early endosomal markers such as clathrin, Rab5, and VAMP3, and, surprisingly, also contain C-type lectins, a type of pathogen recognition receptors (PRRs). Finally, we performed functional uptake experiments to demonstrate that these PRRs facilitate uptake of antigen from the opposite side of the filter. Our data provide mechanistic insight in how dendritic cells sample for antigen across epithelial barriers for instance from the lumen of the lung and gut. PMID:26843902

  5. Sd(a)-antigen-like structures carried on core 3 are prominent features of glycans from the mucin of normal human descending colon.

    PubMed Central

    Capon, C; Maes, E; Michalski, J C; Leffler, H; Kim, Y S

    2001-01-01

    This paper describes structural characterization by NMR, MS and degradative studies of mucin glycans from normal human descending colon obtained freshly at autopsy. The saccharides were mainly based on core 3 (GlcNAcbeta1-3GalNAc). Among the terminal saccharide determinants Sd(a)/Cad-antigen-like structures were prominent, and Lewis x, sialyl Lewis x and sulphated Lewis x were found as minor components, whereas blood group H and A antigenic determinants were absent. The saccharides were markedly different from those of mucins from colon cancers or colon cancer cell lines analysed so far, in which cores 1 and 2 are prominent features, and in which various other terminal determinants have been found, but not Sd(a)/Cad. PMID:11577689

  6. Radioimmunoassay for hepatitis B core antigen

    SciTech Connect

    Sagnelli, E.; Pereira, C.; Triolo, G.; Vernace, S.; Paronetto, F.

    1982-02-01

    Serum hepatitis B core antigen (HBcAg) is an important marker of hepatitis B virus replication. We describe an easy, sensitive radioimmunoassay for determination of HBcAg in detergent-treated serum pellets containing Dane particles. Components of a commercial kit for anticore determination are used, and HBcAG is measured by competitive inhibition of binding of /sub 125/I-labeled antibodies to HBcAg with HBcAg-coated beads. We assayed for HBcAG in the sera of 49 patients with hepatitis B surface antigen (HBsAg)-positive chronic hepatitis, 50 patients with HBsAg-negative chronic hepatitis, and 30 healthy volunteers. HBcAg was detected in 41% of patients with HBsAg-positive chronic hepatitis but not in patients with HBsAg-negative chronic hepatitis. Hepatitis Be antigen (an antigen closely associated with the core of Dane particles) determined in the same sera by radioimmunoassay, was not detected in 50% of HBcAg-positive sera.

  7. Immunological Properties of Hepatitis B Core Antigen Fusion Proteins

    NASA Astrophysics Data System (ADS)

    Francis, Michael J.; Hastings, Gillian Z.; Brown, Alan L.; Grace, Ken G.; Rowlands, David J.; Brown, Fred; Clarke, Berwyn E.

    1990-04-01

    The immunogenicity of a 19 amino acid peptide from foot-and-mouth disease virus has previously been shown to approach that of the inactivated virus from which it was derived after multimeric particulate presentation as an N-terminal fusion with hepatitis B core antigen. In this report we demonstrate that rhinovirus peptide-hepatitis B core antigen fusion proteins are 10-fold more immunogenic than peptide coupled to keyhole limpet hemocyanin and 100-fold more immunogenic than uncoupled peptide with an added helper T-cell epitope. The fusion proteins can be readily administered without adjuvant or with adjuvants acceptable for human and veterinary application and can elicit a response after nasal or oral dosing. The fusion proteins can also act as T-cell-independent antigens. These properties provide further support for their suitability as presentation systems for "foreign" epitopes in the development of vaccines.

  8. Core assembly storage structure

    DOEpatents

    Jones, Jr., Charles E.; Brunings, Jay E.

    1988-01-01

    A structure for the storage of core assemblies from a liquid metal-cooled nuclear reactor. The structure comprises an enclosed housing having a substantially flat horizontal top plate, a bottom plate and substantially vertical wall members extending therebetween. A plurality of thimble members extend downwardly through the top plate. Each thimble member is closed at its bottom end and has an open end adjacent said top plate. Each thimble member has a length and diameter greater than that of the core assembly to be stored therein. The housing is provided with an inlet duct for the admission of cooling air and an exhaust duct for the discharge of air therefrom, such that when hot core assemblies are placed in the thimbles, the heat generated will by convection cause air to flow from the inlet duct around the thimbles and out the exhaust duct maintaining the core assemblies at a safe temperature without the necessity of auxiliary powered cooling equipment.

  9. Hepatitis B Virus DNA in Blood Samples Positive for Antibodies to Core Antigen and Negative for Surface Antigen

    PubMed Central

    Gutiérrez, C.; León, G.; Loureiro, C. L.; Uzcátegui, N.; Liprandi, F.; Pujol, F. H.

    1999-01-01

    Anti-hepatitis B core antigen (HBcAg)-positive hepatitis B surface antigen (HBsAg)-negative plasma samples from blood donors were tested by nested PCR. DNA positivity was more significantly associated with high levels of anti-HBcAg than with low levels of anti-HBsAg antibodies. Analysis of a dilution of anti-HBcAg antibodies might result in a more rational exclusion of anti-HBcAg-positive HBsAg-negative samples, reducing the number of donations discarded and enabling more countries to incorporate anti-HBcAg testing. PMID:10473534

  10. Mutations of pre-core and basal core promoter before and after hepatitis B e antigen seroconversion

    PubMed Central

    Kamijo, Nozomi; Matsumoto, Akihiro; Umemura, Takeji; Shibata, Soichiro; Ichikawa, Yuki; Kimura, Takefumi; Komatsu, Michiharu; Tanaka, Eiji

    2015-01-01

    AIM: To investigate the role of pre-core and basal core promoter (BCP) mutations before and after hepatitis B e antigen (HBeAg) seroconversion. METHODS: The proportion of pre-core (G1896A) and basal core promoter (A1762T and G1764A) mutant viruses and serum levels of hepatitis B virus (HBV) DNA, hepatitis B surface antigen (HBsAg), and HB core-related antigen were analyzed in chronic hepatitis B patients before and after HBeAg seroconversion (n = 25), in those who were persistently HBeAg positive (n = 18), and in those who were persistently anti-HBe positive (n = 43). All patients were infected with HBV genotype C and were followed for a median of 9 years. RESULTS: Although the pre-core mutant became predominant (24% to 65%, P = 0.022) in the HBeAg seroconversion group during follow-up, the proportion of the basal core promoter mutation did not change. Median HBV viral markers were significantly higher in patients without the mutations in an HBeAg positive status (HBV DNA: P = 0.003; HBsAg: P < 0.001; HB core-related antigen: P = 0.001). In contrast, HBV DNA (P = 0.012) and HBsAg (P = 0.041) levels were significantly higher in patients with the pre-core mutation in an anti-HBe positive status. CONCLUSION: There is an opposite association of the pre-core mutation with viral load before and after HBeAg seroconversion in patients with HBV infection. PMID:25593470

  11. Structural, Mechanistic, and Antigenic Characterization of the Human Astrovirus Capsid

    PubMed Central

    York, Royce L.; Yousefi, Payam A.; Bogdanoff, Walter; Haile, Sara; Tripathi, Sarvind

    2015-01-01

    ABSTRACT Human astroviruses (HAstVs) are nonenveloped, positive-sense, single-stranded RNA viruses that are a leading cause of viral gastroenteritis. HAstV particles display T=3 icosahedral symmetry formed by 180 copies of the capsid protein (CP), which undergoes proteolytic maturation to generate infectious HAstV particles. Little is known about the molecular features that govern HAstV particle assembly, maturation, infectivity, and immunogenicity. Here we report the crystal structures of the two main structural domains of the HAstV CP: the core domain at 2.60-Å resolution and the spike domain at 0.95-Å resolution. Fitting of these structures into the previously determined 25-Å-resolution electron cryomicroscopy density maps of HAstV allowed us to characterize the molecular features on the surfaces of immature and mature T=3 HAstV particles. The highly electropositive inner surface of HAstV supports a model in which interaction of the HAstV CP core with viral RNA is a driving force in T=3 HAstV particle formation. Additionally, mapping of conserved residues onto the HAstV CP core and spike domains in the context of the immature and mature HAstV particles revealed dramatic changes to the exposure of conserved residues during virus maturation. Indeed, we show that antibodies raised against mature HAstV have reactivity to both the HAstV CP core and spike domains, revealing for the first time that the CP core domain is antigenic. Together, these data provide new molecular insights into HAstV that have practical applications for the development of vaccines and antiviral therapies. IMPORTANCE Astroviruses are a leading cause of viral diarrhea in young children, immunocompromised individuals, and the elderly. Despite the prevalence of astroviruses, little is known at the molecular level about how the astrovirus particle assembles and is converted into an infectious, mature virus. In this paper, we describe the high-resolution structures of the two main astrovirus

  12. Sinorhizobium fredii and Sinorhizobium meliloti produce structurally conserved lipopolysaccharides and strain-specific K antigens

    SciTech Connect

    Reuhs, B.L.; Geller, D.P.; Kim, J.S.; Fox, J.E.; Kolli, V.S.K.; Pueppke, S.G.

    1998-12-01

    Lipopolysaccharides (LPS) and capsular polysaccharides (K antigens) may influence the interaction of rhizobia with their specific hosts; therefore, the authors conducted a comparative analysis of Sinorhizobium fredii and Sinorhizobium meliloti, which are genetically related, yet symbiotically distinct, nitrogen-fixing microsymbionts of legumes. They found that both species typically produce strain-specific K antigens that consist of 3-deoxy-D-manno-2-octulosonic acid (Kdo), or other 1-carboxy-2-keto-3-deoxy sugars (such as sialic acid), and hexoses. The K antigens of each strain are distinguished by glycosyl composition, anomeric configuration, acetylation, and molecular weight distribution. One consistent difference between the K antigens of S. fredii and those of S. meliloti is the presence of N-acetyl groups in the polysaccharides of the latter. In contrast to the K antigens, the LPS of Sinorhizobium spp. are major common antigens. Rough (R) LPS is the predominant form of LPS produced by cultured cells, and some strains release almost no detectable smooth (S) LPS upon extraction. Sinorhizobium spp. are delineated into two major RLPS core serogroups, which do not correspond to species. The O antigens of the SLPS, when present, have similar degrees of polymerization and appear to be structurally conserved throughout the genus. Interestingly, one strain was found to be distinct from all others: S. fredii HH303 produces a unique K antigen, which contains galacturonic acid and rhamnose, and the RLPS did not fall into either of the RLPS core serogroups. The results of this study indicate that the conserved S- and RLPS of Sinorhizobium spp. lack the structural information necessary to influence host specificity, whereas the variable K antigens may affect strain-cultivar interactions.

  13. MHC structure and function – antigen presentation. Part 1

    PubMed Central

    Goldberg, Anna Carla; Rizzo, Luiz Vicente

    2015-01-01

    The setting for the occurrence of an immune response is that of the need to cope with a vast array of different antigens from both pathogenic and non-pathogenic sources. When the first barriers against infection and innate defense fail, adaptive immune response enters the stage for recognition of the antigens by means of extremely variable molecules, namely immunoglobulins and T-cell receptors. The latter recognize the antigen exposed on cell surfaces, in the form of peptides presented by the HLA molecule. The first part of this review details the central role played by these molecules, establishing the close connection existing between their structure and their antigen presenting function. PMID:25807245

  14. Quantitative determination of hepatitis C core antigen in therapy monitoring for chronic hepatitis C.

    PubMed

    Moscato, Giovanna A; Giannelli, Gianluigi; Grandi, Barbara; Pieri, Daniela; Marsi, Ombretta; Guarducci, Isabella; Batini, Irene; Altomare, Emanuele; Antonaci, Salvatore; Capria, Alfonso; Pellegrini, Giovanni; Sacco, Rodolfo

    2011-02-01

    The correlation and kinetics of hepatitis C virus (HCV) RNA and HCV core antigen levels in chronic hepatitis C patients treated with pegylated interferon + ribavirin were evaluated in order to envision a combined use of the two assays in therapy monitoring. HCV core antigen levels by a chemiluminescent immunoassay (Abbott ARCHITECT) and HCV-RNA levels by branched DNA (bDNA) or real-time PCR have been evaluated on plasma specimens from 32 patients treated for chronic hepatitis C. An early virological response (undetectable levels of HCV-RNA 4 weeks after start of treatment) was found in 10/23 subjects (43.5%) followed up for 5 months or more. The response was linked to the HCV genotype (20% in genotype 1B vs. 61.5% in other genotypes; p < 0.05). HCV RNA and HCV antigen showed a good correlation (r = 0.814); HCV antigen was still detectable in 3 samples with undetectable (<615 IU/ml) RNA by bDNA, while no differences in clinical sensitivity were recorded in comparison with real-time PCR. These findings suggest that HCV-RNA and HCV antigen may be used at different time points in order to tailor therapy monitoring to individual needs. PMID:20829601

  15. [The structure and significance of enterobacterial common antigen (ECA)].

    PubMed

    Goździewicz, Tomasz Kasper; Łukasiewicz, Jolanta; Ługowski, Czesław

    2015-01-01

    The enterobacterial common antigen (ECA) is a carbohydrate-derived cell surface antigen present in all Gram-negative bacteria belonging to Enterobacteriaceae family. Biosynthetic pathways shared by ECA and LPS (endotoxin) suggest close connections between these antigens. ECA occurs in three different forms: a phosphatidyl-linked linear polysaccharide anchored on the cell surface (ECAPG), a cyclic form built of 4-6 repeating units localized in the periplasm (ECACYC) and as a linear polysaccharide covalently linked to LPS core oligosaccharide (ECALPS). Regardless of ECA form, poly- and oligosaccharides of ECA consist of the biological trisaccharide repeating units: →3)-α-d-Fucp4NAc-(1→4)-β-d-ManpNAcA-(1→4)-α-d-GlcpNAc-(1→, where Fucp4NAc refers to 4-acetamido-2,4-dideoxygalactose, ManpNAcA to N-acetyl-mannosaminuronic acid and GlcpNAc to N-acetylglucosamine. ECAPG and ECALPS consisting of one unit with Fucp4NAc as a terminal sugar were also identified. The number of the studies shows its occurrence in all members of enteric bacteria with a few exceptions such as Erwinia chrysanthemi. The presence of ECA was also shown for such genera as Plesiomonas [4] and Yersinia [36], previously belonging to the Vibrionaceae and Pasteurellaceae families, respectively. It was one of the reasons to include these two taxa in the Enterobacteriaceae family. The function of ECA is not fully understood, but it was reported that its occurrence is important in resistance of bacterial cells to environmental conditions, such as bile salts in the human digestive tract. The immunogenicity of ECA seems very interesting in the fact that only sparse rough Gram-negative strains, such as Shigella sonnei phase II, Escherichia coli R1, R2, R4, K-12, and Yersinia enterocolitica O:3 are able to induce the production of specific anti-ECA antibodies. It is the effect of the ECALPS, and the evidence for the existence of such covalent linkage was provided by structural analysis of S. sonnei

  16. Antigen

    MedlinePlus

    An antigen is any substance that causes your immune system to produce antibodies against it. This means your immune ... and is trying to fight it off. An antigen may be a substance from the environment, such ...

  17. Atomic structure of anthrax protective antigen pore elucidates toxin translocation.

    PubMed

    Jiang, Jiansen; Pentelute, Bradley L; Collier, R John; Zhou, Z Hong

    2015-05-28

    Anthrax toxin, comprising protective antigen, lethal factor, and oedema factor, is the major virulence factor of Bacillus anthracis, an agent that causes high mortality in humans and animals. Protective antigen forms oligomeric prepores that undergo conversion to membrane-spanning pores by endosomal acidification, and these pores translocate the enzymes lethal factor and oedema factor into the cytosol of target cells. Protective antigen is not only a vaccine component and therapeutic target for anthrax infections but also an excellent model system for understanding the mechanism of protein translocation. On the basis of biochemical and electrophysiological results, researchers have proposed that a phi (Φ)-clamp composed of phenylalanine (Phe)427 residues of protective antigen catalyses protein translocation via a charge-state-dependent Brownian ratchet. Although atomic structures of protective antigen prepores are available, how protective antigen senses low pH, converts to active pore, and translocates lethal factor and oedema factor are not well defined without an atomic model of its pore. Here, by cryo-electron microscopy with direct electron counting, we determine the protective antigen pore structure at 2.9-Å resolution. The structure reveals the long-sought-after catalytic Φ-clamp and the membrane-spanning translocation channel, and supports the Brownian ratchet model for protein translocation. Comparisons of four structures reveal conformational changes in prepore to pore conversion that support a multi-step mechanism by which low pH is sensed and the membrane-spanning channel is formed. PMID:25778700

  18. Early predictive efficacy of core antigen on antiviral outcomes in genotype 1 hepatitis C virus infected patients.

    PubMed

    Feng, Bo; Yang, Rui-Feng; Zhang, Hai-Ying; Luo, Bi-Fen; Kong, Fan-Yun; Rao, Hui-Ying; Jin, Qian; Cong, Xu; Wei, Lai

    2015-01-01

    Response-guided therapy is of limited use in developing countries because hepatitis C virus RNA detection by sensitive molecular methods is time- and labor-consuming and expensive. We evaluated early predictive efficacy of serum hepatitis C virus core antigen kinetics on sustained virologic response in patients with genotype 1 hepatitis C virus during pegylated interferon plus ribavirin treatment. For 478 patients recruited, hepatitis C virus RNAs were detected at baseline, and at weeks 4, 12, 24, 48, and 72 using Cobas TaqMan. Architect hepatitis C virus core antigen was performed at baseline, and weeks 4 and 12. Predictive values of hepatitis C virus core antigen on sustained virologic response were compared to hepatitis C virus RNA. In the first 12 weeks after treatment initiation the dynamic patterns of serum hepatitis C virus core antigen and hepatitis C virus RNA levels were similar in sustained virologic response, relapse, and null response patients groups. Although areas under the receiver operating characteristics curves of hepatitis C virus core antigen were lower than those of hepatitis C virus RNA at the same time points, modeling analysis showed that undetectable hepatitis C virus core antigen (rapid virological response based on hepatitis C virus core antigen) had similar positive predictive value on sustained virologic response to hepatitis C virus RNA at week 4 (90.4% vs 93.3%), and hepatitis C virus core antigen decrease greater than 1log10IU/mL (early virological response based on hepatitis C virus core antigen) had similar negative predictive value to hepatitis C virus RNA at week 12 (94.1% vs 95.2%). Analysis on the validation group demonstrated a positive predictive value of 97.5% in rapid virological response based on hepatitis C virus core antigen and a negative predictive value of 100% in early virological response based on hepatitis C virus core antigen. In conclusion, hepatitis C virus core antigen is comparable to hepatitis C virus RNA in

  19. Inner Core Structure Behind the PKP Core Phase Triplication

    NASA Astrophysics Data System (ADS)

    Blom, N.; Paulssen, H.; Deuss, A. F.; Waszek, L.

    2015-12-01

    Despite its small size, the Earth's inner core plays an important role in the Earth's dynamics. Because it is slowly growing, its structure - and the variation thereof with depth - may reveal important clues about the history of the core, its convection and the resulting geodynamo. Learning more about this structure has been a prime effort in the past decades, leading to discoveries about anisotropy, hemispheres and heterogeneity in the inner core in general. In terms of detailed structure, mainly seismic body waves have contributed to these advances. However, at depths between ~100-200 km, the seismic structure is relatively poorly known. This is a result of the PKP core phase triplication and the existence of strong precursors to PKP phases, whose simultaneous arrival hinders the measurement of inner core waves PKIKP at epicentral distances between roughly 143-148°. As a consequence, the interpretation of deeper structure also remains difficult. To overcome these issues, we stack seismograms in slowness and time, separating PKP and PKIKP phases which arrive simultaneously, but with different slowness. We apply this method to study the inner core's Western hemisphere between South and Central America using paths travelling in the quasi-polar direction between epicentral distances of 140-150°. This enables us to measure PKiKP-PKIKP differential travel times up to greater epicentral distance than has previously been done. The resulting differential travel time residuals increase with epicentral distance, indicating a marked increase in seismic velocity with depth compared to reference model AK135 for the studied polar paths. Assuming a homogeneous outer core, these findings can be explained by either (i) inner core heterogeneity due to an increase in isotropic velocity, or (ii) increase in anisotropy over the studied depth range. Our current data set cannot distinguish between the two hypotheses, but in light of previous work we prefer the latter interpretation.

  20. Engineered Magnetic Core-Shell Structures.

    PubMed

    Alavi Nikje, Mir Mohammad; Vakili, Maryam

    2015-01-01

    In recent years, engineered magnetic core-shell structures are playing an important role in the wide range of various applications. These magnetic core-shell structures have attracted considerable attention because of their unique properties and various applications. Also, the synthesis of engineered magnetic core-shell structures has attracted practical interest because of potential applications in areas such as ferrofluids, medical imaging, drug targeting and delivery, cancer therapy, separations, and catalysis. So far a large number of engineered magnetic core-shell structures have been successfully synthesized. This review article focuses on the recent progress in synthesis and characterization of engineered magnetic core-shell structures. Also, this review gives a brief description of the various application of these structures. It is hoped that this review will play some small part in helping future developments in important field. PMID:26377655

  1. Characterizing Facesheet/Core Disbonding in Honeycomb Core Sandwich Structure

    NASA Technical Reports Server (NTRS)

    Rinker, Martin; Ratcliffe, James G.; Adams, Daniel O.; Krueger, Ronald

    2013-01-01

    Results are presented from an experimental investigation into facesheet core disbonding in carbon fiber reinforced plastic/Nomex honeycomb sandwich structures using a Single Cantilever Beam test. Specimens with three, six and twelve-ply facesheets were tested. Specimens with different honeycomb cores consisting of four different cell sizes were also tested, in addition to specimens with three different widths. Three different data reduction methods were employed for computing apparent fracture toughness values from the test data, namely an area method, a compliance calibration technique and a modified beam theory method. The compliance calibration and modified beam theory approaches yielded comparable apparent fracture toughness values, which were generally lower than those computed using the area method. Disbonding in the three-ply facesheet specimens took place at the facesheet/core interface and yielded the lowest apparent fracture toughness values. Disbonding in the six and twelve-ply facesheet specimens took place within the core, near to the facesheet/core interface. Specimen width was not found to have a significant effect on apparent fracture toughness. The amount of scatter in the apparent fracture toughness data was found to increase with honeycomb core cell size.

  2. Structural and antigenic analysis of meningococcal piliation.

    PubMed Central

    Olafson, R W; McCarthy, P J; Bhatti, A R; Dooley, J S; Heckels, J E; Trust, T J

    1985-01-01

    Pilin with an Mr of 16,500 was purified to homogeneity from Neisseria meningitidis SP3428. Procedures which provided useful separation during purification included high-pressure liquid chromatography with a TSK size exclusion column, Sephacryl S-200 column chromatography, ion-exchange chromatography with SP-Sephadex, and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The amino acid composition of this pilin was similar to that previously reported for this species. The sequence of N-terminal 51 amino acids was also determined. The protein lacked a modified phenylalanine at the amino terminus and displayed six residues which were different from Neisseria gonorrhoeae in that region of the molecule determined to be the lectin-binding domain. Monoclonal antibody raised to this pilin was employed, along with a monoclonal antibody to an epitope common to all gonococcal pilins, to analyze the intra- and interstrain heterogeneity of meningococcal piliation. The results indicate that N. meningitidis displays considerable intra- and interstrain heterogeneity with respect to both pilus subunit size and antigenicity. The Mr of subunits ranged from 13,000 to 20,000. Images PMID:2580788

  3. Mitotic Evolution of Plasmodium falciparum Shows a Stable Core Genome but Recombination in Antigen Families

    PubMed Central

    Bopp, Selina E. R.; Manary, Micah J.; Bright, A. Taylor; Johnston, Geoffrey L.; Dharia, Neekesh V.; Luna, Fabio L.; McCormack, Susan; Plouffe, David; McNamara, Case W.; Walker, John R.; Fidock, David A.; Denchi, Eros Lazzerini; Winzeler, Elizabeth A.

    2013-01-01

    Malaria parasites elude eradication attempts both within the human host and across nations. At the individual level, parasites evade the host immune responses through antigenic variation. At the global level, parasites escape drug pressure through single nucleotide variants and gene copy amplification events conferring drug resistance. Despite their importance to global health, the rates at which these genomic alterations emerge have not been determined. We studied the complete genomes of different Plasmodium falciparum clones that had been propagated asexually over one year in the presence and absence of drug pressure. A combination of whole-genome microarray analysis and next-generation deep resequencing (totaling 14 terabases) revealed a stable core genome with only 38 novel single nucleotide variants appearing in seventeen evolved clones (avg. 5.4 per clone). In clones exposed to atovaquone, we found cytochrome b mutations as well as an amplification event encompassing the P. falciparum multidrug resistance associated protein (mrp1) on chromosome 1. We observed 18 large-scale (>1 kb on average) deletions of telomere-proximal regions encoding multigene families, involved in immune evasion (9.5×10−6 structural variants per base pair per generation). Six of these deletions were associated with chromosomal crossovers generated during mitosis. We found only minor differences in rates between genetically distinct strains and between parasites cultured in the presence or absence of drug. Using these derived mutation rates for P. falciparum (1.0–9.7×10−9 mutations per base pair per generation), we can now model the frequency at which drug or immune resistance alleles will emerge under a well-defined set of assumptions. Further, the detection of mitotic recombination events in var gene families illustrates how multigene families can arise and change over time in P. falciparum. These results will help improve our understanding of how P. falciparum evolves to

  4. Synthetic DNA immunogen encoding hepatitis B core antigen drives immune response in liver.

    PubMed

    Obeng-Adjei, N; Choo, D K; Saini, J; Yan, J; Pankhong, P; Parikh, A; Chu, J S; Weiner, D B

    2012-11-01

    The prevalence of hepatitis B virus (HBV) infection in Asia and sub-Sahara Africa is alarming. With quarter of a billion people chronically infected worldwide and at risk of developing liver cancer, the need for a prophylactic or therapeutic vaccination approach that can effectively induce protective responses against the different genotypes of HBV is more important than ever. Such a strategy will require both the induction of a strong antigen-specific immune response and the subsequent deployment of immune response towards the liver. Here, we assessed the ability of a synthetic DNA vaccine encoding a recombinant consensus plasmid from genotype A through E of the HBV core antigen (HBcAg), to drive immunity in the liver. Intramuscular vaccination induced both strong antigen-specific T cell and high titer antibody responses systematically and in the liver. Furthermore, immunized mice showed strong cytotoxic responses that eliminate adoptively transferred HBV-coated target cells. Importantly, vaccine-induced immune responses provided protection from HBcAg plasmid-based liver transfection in a hydrodynamic liver transfection model. These data provide important insight into the generation of peripheral immune responses that are recruited to the liver-an approach that can be beneficial in the search for vaccines or immune-therapies to liver disease. PMID:23037809

  5. The predictive value of core antigen testing for the management of hepatitis C patients receiving pegylated interferon/ribavirin treatment.

    PubMed

    Pradat, Pierre; Maynard, Marianne; Buti, Maria; Berthillon, Pascale; Picchio, Gaston; Tillmann, Hans L; Wiegand, Johannes; Voirin, Nicolas; Manns, Michael P; Esteban, Juan-Ignacio; Martinot, Michèle; Marcellin, Patrick; Trepo, Christian

    2004-07-01

    A new quantitative marker of HCV viremia based on the detection of the core antigen of the virus has recently become commercially available in Europe. The usefulness of this test was examined for the management of patients treated with pegylated interferon/ribavirin. One hundred twenty-eight pegylated interferon/ribavirin treated patients were studied. Serum samples were available at baseline, week 4 and week 12 time-points, respectively. Core antigen was quantified using the trak-C assay (Ortho Clinical Diagnostics, Raritan, NJ). For all genotypes at week 4, the positive and negative predictive values of HCV core antigen were 81.4 and 92.9%, respectively, while at week 12 they were 67.9 and 100%, respectively. These predictive values varied substantially according to viral genotype. Among patients with a negative core antigen level (<1.5 pg/ml) at week 12, only 33% of those who were positive at week 4 achieved a sustained virological response whereas 85% of those who were already negative did (P < 0.001). The core antigen assay may be used at week 4 and week 12 to distinguish patients who will achieve a sustained virological response from those who will relapse/breakthrough. This assay is a new reliable alternative for early prediction of virological non-response in patients treated with pegylated interferon/ribavirin. PMID:15170634

  6. Core-Shell Structured Magnetic Ternary Nanocubes

    SciTech Connect

    Wang, Lingyan; Wang, Xin; Luo, Jin; Wanjala, Bridgid N.; Wang, Chong M.; Chernova, Natalya; Engelhard, Mark H.; Liu, Yao; Bae, In-Tae; Zhong, Chuan-Jian

    2010-12-01

    While transition metal-doped ferrite nanoparticles constitute an important class of soft magnetic nanomaterials with spinel structures, the ability to control the shape and composition would enable a wide range of applications in homogeneous or heterogeneous reactions such as catalysis and magnetic separation of biomolecules. This report describes novel findings of an investigation of core-shell structured MnZn ferrite nanocubes synthesized in organic solvents by manipulating the reaction temperature and capping agent composition in the absence of the conventionally-used reducing agents. The core-shell structure of the highly-monodispersed nanocubes (~20 nm) are shown to consist of an Fe3O4 core and an (Mn0.5Zn0.5)(Fe0.9, Mn1.1)O4 shell. In comparison with Fe3O4 and other binary ferrite nanoparticles, the core-shell structured nanocubes were shown to display magnetic properties regulated by a combination of the core-shell composition, leading to a higher coercivity (~350 Oe) and field-cool/zero-field-cool characteristics drastically different from many regular MnZn ferrite nanoparticles. The findings are discussed in terms of the unique core-shell composition, the understanding of which has important implication to the exploration of this class of soft magnetic nanomaterials in many potential applications such as magnetic resonance imaging, fuel cells, and batteries.

  7. Fingered core structure of nematic boojums

    NASA Astrophysics Data System (ADS)

    Kralj, Samo; Rosso, Riccardo; Virga, Epifanio G.

    2008-09-01

    Using the Landau-de Gennes phenomenological approach, we study the fine biaxial core structure of a boojum residing on the surface of a nematic liquid crystal phase. The core is formed by a negatively uniaxial finger, surrounded by a shell with maximal biaxiality. The characteristic finger’s length and the shell’s width are comparable to the biaxial correlation length. The finger tip is melted for topological reasons. Upon decreasing the surface anchoring strength below a critical value, the finger gradually leaves the bulk and it is expelled through the surface.

  8. Structure of the Chlamydia trachomatis immunodominant antigen Pgp3.

    PubMed

    Galaleldeen, Ahmad; Taylor, Alexander B; Chen, Ding; Schuermann, Jonathan P; Holloway, Stephen P; Hou, Shuping; Gong, Siqi; Zhong, Guangming; Hart, P John

    2013-07-26

    Chlamydia trachomatis infection is the most common sexually transmitted bacterial disease. Left untreated, it can lead to ectopic pregnancy, pelvic inflammatory disease, and infertility. Here we present the structure of the secreted C. trachomatis protein Pgp3, an immunodominant antigen and putative virulence factor. The ∼84-kDa Pgp3 homotrimer, encoded on a cryptic plasmid, consists of globular N- and C-terminal assemblies connected by a triple-helical coiled-coil. The C-terminal domains possess folds similar to members of the TNF family of cytokines. The closest Pgp3 C-terminal domain structural homologs include a lectin from Burkholderia cenocepacia, the C1q component of complement, and a portion of the Bacillus anthracis spore surface protein BclA, all of which play roles in bioadhesion. The N-terminal domain consists of a concatenation of structural motifs typically found in trimeric viral proteins. The central parallel triple-helical coiled-coil contains an unusual alternating pattern of apolar and polar residue pairs that generate a rare right-handed superhelical twist. The unique architecture of Pgp3 provides the basis for understanding its role in chlamydial pathogenesis and serves as the platform for its optimization as a potential vaccine antigen candidate. PMID:23703617

  9. Thermal processing effects on peanut allergen Ara h 2 allergenicity in mice and its antigenic epitope structure.

    PubMed

    Zhang, Wenju; Zhu, Qingqing; Zhang, Tong; Cai, Qin; Chen, Qin

    2016-12-01

    Ara h 2 was purified from peanuts that were thermally treated by various processes, including boiling, glycation, frying and roasting. The allergenicity of Ara h 2 in Balb/c mice and the influence of thermal processing on the structural characteristics, and binding capacity of three core antigenic epitopes were studied. The results demonstrated that boiling, glycation and frying induced the down-regulation of the allergenicity of Ara h 2 in Balb/c mice, the collapse of its tertiary/secondary structure, and a reduction in the core epitope binding capacity; roasting showed a comparable allergenicity and the weakest inhibitory effect on core epitope binding capacity. These results indicate that thermal processing causes alteration of the protein structure and core epitopes of Ara h 2, and may affect its allergenicity. PMID:27374581

  10. Sequences flanking the pentanucleotide T-antigen binding sites in the polyomavirus core origin help determine selectivity of DNA replication.

    PubMed Central

    Li, L; Li, B L; Hock, M; Wang, E; Folk, W R

    1995-01-01

    Replication of the genomes of the polyomaviruses requires two virus-specified elements, the cis-acting origin of DNA replication, with its auxiliary DNA elements, and the trans-acting viral large tumor antigen (T antigen). Appropriate interactions between them initiate the assembly of a replication complex which, together with cellular proteins, is responsible for primer synthesis and DNA chain elongation. The organization of cis-acting elements within the origins of the polyomaviruses which replicate in mammalian cells is conserved; however, these origins are sufficiently distinct that the T antigen of one virus may function inefficiently or not at all to initiate replication at the origin of another virus. We have studied the basis for such replication selectivity between the murine polyomavirus T antigen and the primate lymphotropic polyomavirus origin. The murine polyomavirus T antigen is capable of carrying out the early steps of the assembly of an initiation complex at the lymphotropic papovavirus origin, including binding to and deformation of origin sequences in vitro. However, the T antigen inefficiently unwinds the origin, and unwinding is influenced by sequences flanking the T antigen pentanucleotide binding sites on the late side of the viral core origin. These same sequences contribute to the replication selectivity observed in vivo and in vitro, suggesting that the inefficient unwinding is the cause of the replication defect. These observations suggest a mechanism by which origins of DNA replication can evolve replication selectivity and by which the function of diverse cellular origins might be temporally activated during the S phase of the eukaryotic cell cycle. PMID:7494263

  11. MultisHRP-DNA-coated CMWNTs as signal labels for an ultrasensitive hepatitis C virus core antigen electrochemical immunosensor.

    PubMed

    Ma, Cuixia; Liang, Mo; Wang, Li; Xiang, Hua; Jiang, Yingtao; Li, Yiyan; Xie, Guoming

    2013-09-15

    An ultrasensitive and selective electrochemical immunosensor was developed for the detection of hepatitis C virus (HCV) core antigen. The immunosensor consists of graphitized mesoporous carbon-methylene blue (GMCs-MB) nanocomposite as an electrode modified material and a horseradish peroxidase-DNA-coated carboxyl multi-wall carbon nanotubes (CMWNTs) as a secondary antibody layer. After modification of the electrode with GMCs-MB nanocomposite, Au nanoparticles were electrodeposited on to the electrode to immobilize the captured antibodies. The bridging probe and secondary antibodies linked to the CMWNTs, and DNA concatamers were obtained by hybridization of the biotin-tagged signal and auxiliary probes. Finally, streptavidin-horseradish peroxidases (HRP) were labeled on the secondary antibody layer via biotin-streptavidin system. The reduction current of MB were generated in the presence of hydrogen peroxide and monitored by square wave voltammetry. Under optimum conditions, the amperometric signal increased linearly with the core antigen concentration (0.25pgmL(-1) to 300pgmL(-1)). The immunosensor exhibites the detection limit as low as 0.01pgmL(-1) and it has a high selectivity. The new protocol showed acceptable stability and reproducibility, as well as favorable recovery for HCV core antigen in human serum. The proposed immunosensor has great potential for clinical applications. PMID:23624015

  12. Association of HCV Core Antigen Seropositivity with Long-Term Mortality in Patients on Regular Hemodialysis

    PubMed Central

    Kato, Akihiko; Takita, Takako; Furuhashi, Mitsuyoshi; Fujimoto, Taiki; Suzuki, Hiroo; Maruyama, Yukitaka; Sakao, Yukitoshi; Miyajima, Hiroaki

    2012-01-01

    Anti-hepatitis C virus (HCV) antibody seropositivity is independently associated with poor prognosis in hemodialysis (HD) patients. However, anti-HCV antibody cannot distinguish between patients with active infection and those who have recovered from infection. We therefore aimed in this study to examine the association of HCV core antigen (HCVcAg) seropositivity with mortality in HD patients. We first measured serum HCVcAg using an immunoradiometric assay and anti-HCV antibody in 405 patients on regular HD, and followed them for 104 months. There were 82 patients (20.2%) who had been positive for anti-HCV antibodies; 57 (69.5%) of these were positive for HCVcAg. During the follow-up, 29 patients were excluded, so we tested the association of HCVcAg seropositivity with all-cause, cardiovascular (CV) and non-CV mortalities in 376 patients. A total of 209 patients (55.6%) had expired during the observational period, 92 out of them due to CV causes. After adjusting for comorbid parameters, HCVcAg was independently associated with overall mortality (HR 1.61, 95% CI 1.05–2.47, p < 0.05). HCV infection was significantly related to liver disease-related mortality. Past HCV infection also contributed to CV mortality (HR 2.63, 95% CI 1.27–5.45, p < 0.01). In contrast, anti-HCV antibody and HCVcAg seropositivities did not associate with infectious disease-related and cancer-related (expect for hepatocellular carcinoma) mortality. It follows from these findings that HCVcAg serology is associated with all-cause and CV mortality in HD patients. PMID:22619670

  13. Sequence Requirements for the Assembly of Simian Virus 40 T Antigen and the T-Antigen Origin Binding Domain on the Viral Core Origin of Replication

    PubMed Central

    Kim, Henry Y.; Barbaro, Brett A.; Joo, Woo S.; Prack, Andrea E.; Sreekumar, K. R.; Bullock, Peter A.

    1999-01-01

    The regions of the simian virus 40 (SV40) core origin that are required for stable assembly of virally encoded T antigen (T-ag) and the T-ag origin binding domain (T-ag-obd131–260) have been determined. Binding of the purified T-ag-obd131–260 is mediated by interactions with the central region of the core origin, site II. In contrast, T-ag binding and hexamer assembly requires a larger region of the core origin that includes both site II and an additional fragment of DNA that may be positioned on either side of site II. These studies indicate that in the context of T-ag, the origin binding domain can engage the pentanucleotides in site II only if a second region of T-ag interacts with one of the flanking sequences. The requirements for T-ag double-hexamer assembly are complex; the nucleotide cofactor present in the reaction modulates the sequence requirements for oligomerization. Nevertheless, these experiments provide additional evidence that only a subset of the SV40 core origin is required for assembly of T-ag double hexamers. PMID:10438844

  14. Foam core materials for structural sandwich panels

    SciTech Connect

    Huang Jongshin.

    1991-01-01

    The author first investigates the creep of polymer foam cores. Models for the creep of linear and nonlinear viscoelastic polymer foams are proposed. Experimental results for the creep of a rigid polyurethane foam are compared to the mode; agreement is good. The results indicate that creep can limit the design of building panels with polymer foam cores. Next, he studies the potential of using ceramic foams as a core material in building panels. Ceramic foams have a high stiffness, high creep resistance, low cost, and are incombustible. Ceramic foams, however, have a low fracture toughness and tensile strength. Assuming that the variability of cell wall modulus of rupture follows a Weibull distribution, there is a cell size effect on both the fracture toughness and tensile strength. Both the tensile strength and fracture toughness of ceramic foams can be improved by controlling the cell size. Since cell wall deformation of cellular materials is primarily by bending, the mechanical properties of cellular materials may be improved by making cell walls into sandwich structures. Hollow-sphere composites are made by introducing thin-walled hollow spheres into a matrix.

  15. Low Cost Large Core Vehicle Structures Assessment

    NASA Technical Reports Server (NTRS)

    Hahn, Steven E.

    1998-01-01

    Boeing Information, Space, and Defense Systems executed a Low Cost Large Core Vehicle Structures Assessment (LCLCVSA) under contract to NASA Marshall Space Flight Center (MSFC) between November 1997 and March 1998. NASA is interested in a low-cost launch vehicle, code named Magnum, to place heavy payloads into low earth orbit for missions such as a manned mission to Mars, a Next Generation Space Telescope, a lunar-based telescope, the Air Force's proposed space based laser, and large commercial satellites. In this study, structural concepts with the potential to reduce fabrication costs were evaluated in application to the Magnum Launch Vehicle (MLV) and the Liquid Fly Back Booster (LFBB) shuttle upgrade program. Seventeen concepts were qualitatively evaluated to select four concepts for more in-depth study. The four structural concepts selected were: an aluminum-lithium monocoque structure, an aluminum-lithium machined isogrid structure, a unitized composite sandwich structure, and a unitized composite grid structure. These were compared against a baseline concept based on the Space Shuttle External Tank (ET) construction. It was found that unitized composite structures offer significant cost and weight benefits to MLV structures. The limited study of application to LFBB structures indicated lower, but still significant benefits. Technology and facilities development roadmaps to prepare the approaches studied for application to MLV and LFBB were constructed. It was found that the cost and schedule to develop these approaches were in line with both MLV and LFBB development schedules. Current Government and Boeing programs which address elements of the development of the technologies identified are underway. It is recommended that NASA devote resources in a timely fashion to address the specific elements related to MLV and LFBB structures.

  16. Tandem Fusion of Hepatitis B Core Antigen Allows Assembly of Virus-Like Particles in Bacteria and Plants with Enhanced Capacity to Accommodate Foreign Proteins

    PubMed Central

    Peyret, Hadrien; Gehin, Annick; Thuenemann, Eva C.; Blond, Donatienne; El Turabi, Aadil; Beales, Lucy; Clarke, Dean; Gilbert, Robert J. C.; Fry, Elizabeth E.; Stuart, David I.; Holmes, Kris; Stonehouse, Nicola J.; Whelan, Mike; Rosenberg, William; Lomonossoff, George P.; Rowlands, David J.

    2015-01-01

    The core protein of the hepatitis B virus, HBcAg, assembles into highly immunogenic virus-like particles (HBc VLPs) when expressed in a variety of heterologous systems. Specifically, the major insertion region (MIR) on the HBcAg protein allows the insertion of foreign sequences, which are then exposed on the tips of surface spike structures on the outside of the assembled particle. Here, we present a novel strategy which aids the display of whole proteins on the surface of HBc particles. This strategy, named tandem core, is based on the production of the HBcAg dimer as a single polypeptide chain by tandem fusion of two HBcAg open reading frames. This allows the insertion of large heterologous sequences in only one of the two MIRs in each spike, without compromising VLP formation. We present the use of tandem core technology in both plant and bacterial expression systems. The results show that tandem core particles can be produced with unmodified MIRs, or with one MIR in each tandem dimer modified to contain the entire sequence of GFP or of a camelid nanobody. Both inserted proteins are correctly folded and the nanobody fused to the surface of the tandem core particle (which we name tandibody) retains the ability to bind to its cognate antigen. This technology paves the way for the display of natively folded proteins on the surface of HBc particles either through direct fusion or through non-covalent attachment via a nanobody. PMID:25830365

  17. Combination delivery of antigens and CpG by lanthanides-based core-shell nanoparticles for enhanced immune response and dual-mode imaging.

    PubMed

    Li, Zhenhua; Liu, Zhen; Yin, Meili; Yang, Xinjian; Ren, Jinsong; Qu, Xiaogang

    2013-10-01

    Europium-doped GdPO4 hollow spheres/polymer core-shell nanoparticles are functionalized with ovalbumin (OVA) as a model antigen and an oligonucleotide (CpG) that stimulates the immune response. These functionalized core-shell nanoparticles are used as vaccines, where they enable efficient delivery of an antigen to target sites, tracking of the vaccines using non-invasive clinical imaging technology. PMID:23526798

  18. Electrochemical immunosensor based on hyperbranched structure for carcinoembryonic antigen detection.

    PubMed

    Miao, Jingjing; Wang, Xiaobo; Lu, Liandi; Zhu, Peiyuan; Mao, Chun; Zhao, Haolin; Song, Youchao; Shen, Jian

    2014-08-15

    Sensitive determination of carcinoembryonic antigen (CEA) is very important in clinical research and diagnosis. Herein we report the design and synthesis of a new kind of immunosensor based on the benefits of hyperbranched structure. The hyperbranched polyester was grafted to the surface of indium tin oxides glass (ITO) electrode, and the grafting processes were characterized by attentuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). After CEA and horse radish peroxidase (HRP)-labeled antibody-conjugated AuNPs (HRP-Ab2-AuNPs) bioconjugates were immobilized on the surface of the hyperbranched structure-modified electrode, the optimized conditions of the above electrode were investigated. Moreover, the analytical performance of the proposed immunosensor showed a high sensitivity, a linear range from 0.01 to 80ng/mL with a low detection limit of 2.36pg/mL, and good selectivity for CEA. The designed immunoassay system holds great potential for ultrasensitive electrochemical biosensing of other analytes. PMID:24607616

  19. Structural and Functional Insight into Proliferating Cell Nuclear Antigen.

    PubMed

    Park, So Young; Jeong, Mi Suk; Han, Chang Woo; Yu, Hak Sun; Jang, Se Bok

    2016-04-28

    Proliferating cell nuclear antigen (PCNA) is a critical eukaryotic replication accessory factor that supports DNA binding in DNA processing, such as DNA replication, repair, and recombination. PCNA consists of three toroidal-shaped monomers that encircle doublestranded DNA. The diverse functions of PCNA may be regulated by its interactions with partner proteins. Many of the PCNA partner proteins generally have a conserved PCNAinteracting peptide (PIP) motif, located at the N- or C- terminal region. The PIP motif forms a 310 helix that enters into the hydrophobic groove produced by an interdomain-connecting loop, a central loop, and a C-terminal tail in the PCNA. Post-translational modification of PCNA also plays a critical role in regulation of its function and binding partner proteins. Structural and biochemical studies of PCNA-protein will be useful in designing therapeutic agents, as well as estimating the outcome of anticancer drug development. This review summarizes the characterization of eukaryotic PCNA in relation to the protein structures, functions, and modifications, and interaction with proteins. PMID:26699741

  20. Benefit of hepatitis C virus core antigen assay in prediction of therapeutic response to interferon and ribavirin combination therapy.

    PubMed

    Takahashi, Masahiko; Saito, Hidetsugu; Higashimoto, Makiko; Atsukawa, Kazuhiro; Ishii, Hiromasa

    2005-01-01

    A highly sensitive second-generation hepatitis C virus (HCV) core antigen assay has recently been developed. We compared viral disappearance and first-phase kinetics between commercially available core antigen (Ag) assays, Lumipulse Ortho HCV Ag (Lumipulse-Ag), and a quantitative HCV RNA PCR assay, Cobas Amplicor HCV Monitor test, version 2 (Amplicor M), to estimate the predictive benefit of a sustained viral response (SVR) and non-SVR in 44 genotype 1b patients treated with interferon (IFN) and ribavirin. HCV core Ag negativity could predict SVR on day 1 (sensitivity = 100%, specificity = 85.0%, accuracy = 86.4%), whereas RNA negativity could predict SVR on day 7 (sensitivity = 100%, specificity = 87.2%, accuracy = 88.6%). None of the patients who had detectable serum core Ag or RNA on day 14 achieved SVR (specificity = 100%). The predictive accuracy on day 14 was higher by RNA negativity (93.2%) than that by core Ag negativity (75.0%). The combined predictive criterion of both viral load decline during the first 24 h and basal viral load was also predictive for SVR; the sensitivities of Lumipulse-Ag and Amplicor-M were 45.5 and 47.6%, respectively, and the specificity was 100%. Amplicor-M had better predictive accuracy than Lumipulse-Ag in 2-week disappearance tests because it had better sensitivity. On the other hand, estimates of kinetic parameters were similar regardless of the detection method. Although the correlations between Lumipulse-Ag and Amplicor-M were good both before and 24 h after IFN administration, HCV core Ag seemed to be relatively lower 24 h after IFN administration than before administration. Lumipulse-Ag seems to be useful for detecting the HCV concentration during IFN therapy; however, we still need to understand the characteristics of the assay. PMID:15634970

  1. The Structural Basis of Antibody-Antigen Recognition

    PubMed Central

    Sela-Culang, Inbal; Kunik, Vered; Ofran, Yanay

    2013-01-01

    The function of antibodies (Abs) involves specific binding to antigens (Ags) and activation of other components of the immune system to fight pathogens. The six hypervariable loops within the variable domains of Abs, commonly termed complementarity determining regions (CDRs), are widely assumed to be responsible for Ag recognition, while the constant domains are believed to mediate effector activation. Recent studies and analyses of the growing number of available Ab structures, indicate that this clear functional separation between the two regions may be an oversimplification. Some positions within the CDRs have been shown to never participate in Ag binding and some off-CDRs residues often contribute critically to the interaction with the Ag. Moreover, there is now growing evidence for non-local and even allosteric effects in Ab-Ag interaction in which Ag binding affects the constant region and vice versa. This review summarizes and discusses the structural basis of Ag recognition, elaborating on the contribution of different structural determinants of the Ab to Ag binding and recognition. We discuss the CDRs, the different approaches for their identification and their relationship to the Ag interface. We also review what is currently known about the contribution of non-CDRs regions to Ag recognition, namely the framework regions (FRs) and the constant domains. The suggested mechanisms by which these regions contribute to Ag binding are discussed. On the Ag side of the interaction, we discuss attempts to predict B-cell epitopes and the suggested idea to incorporate Ab information into B-cell epitope prediction schemes. Beyond improving the understanding of immunity, characterization of the functional role of different parts of the Ab molecule may help in Ab engineering, design of CDR-derived peptides, and epitope prediction. PMID:24115948

  2. Structural insights into the antigenicity of myelin oligodendrocyte glycoprotein

    PubMed Central

    Breithaupt, Constanze; Schubart, Anna; Zander, Hilke; Skerra, Arne; Huber, Robert; Linington, Christopher; Jacob, Uwe

    2003-01-01

    Multiple sclerosis is a chronic disease of the central nervous system (CNS) characterized by inflammation, demyelination, and axonal loss. The immunopathogenesis of demyelination in multiple sclerosis involves an autoantibody response to myelin oligodendrocyte glycoprotein (MOG), a type I transmembrane protein located at the surface of CNS myelin. Here we present the crystal structures of the extracellular domain of MOG (MOGIgd) at 1.45-Å resolution and the complex of MOGIgd with the antigen-binding fragment (Fab) of the MOG-specific demyelinating monoclonal antibody 8-18C5 at 3.0-Å resolution. MOGIgd adopts an IgV like fold with the A′GFCC′C″ sheet harboring a cavity similar to the one used by the costimulatory molecule B7-2 to bind its ligand CTLA4. The antibody 8-18C5 binds to three loops located at the membrane-distal side of MOG with a surprisingly dominant contribution made by MOG residues 101–108 containing a strained loop that forms the upper edge of the putative ligand binding site. The sequence R101DHSYQEE108 is unique for MOG, whereas large parts of the remaining sequence are conserved in potentially tolerogenic MOG homologues expressed outside the immuno-privileged environment of the CNS. Strikingly, the only sequence identical to DHSYQEE was found in a Chlamydia trachomatis protein of unknown function, raising the possibility that Chlamydia infections may play a role in the MOG-specific autoimmune response in man. Our data provide the structural basis for the development of diagnostic and therapeutic strategies targeting the pathogenic autoantibody response to MOG. PMID:12874380

  3. Structural Flexibility of a Conserved Antigenic Region in Hepatitis C Virus Glycoprotein E2 Recognized by Broadly Neutralizing Antibodies

    PubMed Central

    Meola, Annalisa; Tarr, Alexander W.; England, Patrick; Meredith, Luke W.; McClure, C. Patrick; Foung, Steven K. H.; McKeating, Jane A.; Ball, Jonathan K.; Rey, Felix A.

    2014-01-01

    ABSTRACT Neutralizing antibodies (NAbs) targeting glycoprotein E2 are important for the control of hepatitis C virus (HCV) infection. One conserved antigenic site (amino acids 412 to 423) is disordered in the reported E2 structure, but a synthetic peptide mimicking this site forms a β-hairpin in complex with three independent NAbs. Our structure of the same peptide in complex with NAb 3/11 demonstrates a strikingly different extended conformation. We also show that residues 412 to 423 are essential for virus entry but not for E2 folding. Together with the neutralizing capacity of the 3/11 Fab fragment, this indicates an unexpected structural flexibility within this epitope. NAbs 3/11 and AP33 (recognizing the extended and β-hairpin conformations, respectively) display similar neutralizing activities despite converse binding kinetics. Our results suggest that HCV utilizes conformational flexibility as an immune evasion strategy, contributing to the limited immunogenicity of this epitope in patients, similar to the conformational flexibility described for other enveloped and nonenveloped viruses. IMPORTANCE Approximately 180 million people worldwide are infected with hepatitis C virus (HCV), and neutralizing antibodies play an important role in controlling the replication of this major human pathogen. We show here that one of the most conserved antigenic sites within the major glycoprotein E2 (amino acids 412 to 423), which is disordered in the recently reported crystal structure of an E2 core fragment, can adopt different conformations in the context of the infectious virus particle. Recombinant Fab fragments recognizing different conformations of this antigenic site have similar neutralization activities in spite of converse kinetic binding parameters. Of note, an antibody response targeting this antigenic region is less frequent than those targeting other more immunogenic regions in E2. Our results suggest that the observed conformational flexibility in this

  4. Material with core-shell structure

    DOEpatents

    Luhrs, Claudia; Richard, Monique N.; Dehne, Aaron; Phillips, Jonathan; Stamm, Kimber L.; Fanson, Paul T.

    2011-11-15

    Disclosed is a material having a composite particle, the composite particle including an outer shell and a core. The core is made from a lithium alloying material and the outer shell has an inner volume that is greater in size than the core of the lithium alloying material. In some instances, the outer mean diameter of the outer shell is less than 500 nanometers and the core occupies between 5 and 99% of the inner volume. In addition, the outer shell can have an average wall thickness of less than 100 nanometers.

  5. The Structural Diversity of Carbohydrate Antigens of Selected Gram-Negative Marine Bacteria

    PubMed Central

    Nazarenko, Evgeny L.; Crawford, Russell J.; Ivanova, Elena P.

    2011-01-01

    Marine microorganisms have evolved for millions of years to survive in the environments characterized by one or more extreme physical or chemical parameters, e.g., high pressure, low temperature or high salinity. Marine bacteria have the ability to produce a range of biologically active molecules, such as antibiotics, toxins and antitoxins, antitumor and antimicrobial agents, and as a result, they have been a topic of research interest for many years. Among these biologically active molecules, the carbohydrate antigens, lipopolysaccharides (LPSs, O-antigens) found in cell walls of Gram-negative marine bacteria, show great potential as candidates in the development of drugs to prevent septic shock due to their low virulence. The structural diversity of LPSs is thought to be a reflection of the ability for these bacteria to adapt to an array of habitats, protecting the cell from being compromised by exposure to harsh environmental stress factors. Over the last few years, the variety of structures of core oligosaccharides and O-specific polysaccharides from LPSs of marine microrganisms has been discovered. In this review, we discuss the most recently encountered structures that have been identified from bacteria belonging to the genera Aeromonas, Alteromonas, Idiomarina, Microbulbifer, Pseudoalteromonas, Plesiomonas and Shewanella of the Gammaproteobacteria phylum; Sulfitobacter and Loktanella of the Alphaproteobactera phylum and to the genera Arenibacter, Cellulophaga, Chryseobacterium, Flavobacterium, Flexibacter of the Cytophaga-Flavobacterium-Bacteroides phylum. Particular attention is paid to the particular chemical features of the LPSs, such as the monosaccharide type, non-sugar substituents and phosphate groups, together with some of the typifying traits of LPSs obtained from marine bacteria. A possible correlation is then made between such features and the environmental adaptations undertaken by marine bacteria. PMID:22073003

  6. The structural diversity of carbohydrate antigens of selected gram-negative marine bacteria.

    PubMed

    Nazarenko, Evgeny L; Crawford, Russell J; Ivanova, Elena P

    2011-01-01

    Marine microorganisms have evolved for millions of years to survive in the environments characterized by one or more extreme physical or chemical parameters, e.g., high pressure, low temperature or high salinity. Marine bacteria have the ability to produce a range of biologically active molecules, such as antibiotics, toxins and antitoxins, antitumor and antimicrobial agents, and as a result, they have been a topic of research interest for many years. Among these biologically active molecules, the carbohydrate antigens, lipopolysaccharides (LPSs, O-antigens) found in cell walls of gram-negative marine bacteria, show great potential as candidates in the development of drugs to prevent septic shock due to their low virulence. The structural diversity of LPSs is thought to be a reflection of the ability for these bacteria to adapt to an array of habitats, protecting the cell from being compromised by exposure to harsh environmental stress factors. Over the last few years, the variety of structures of core oligosaccharides and O-specific polysaccharides from LPSs of marine microrganisms has been discovered. In this review, we discuss the most recently encountered structures that have been identified from bacteria belonging to the genera Aeromonas, Alteromonas, Idiomarina, Microbulbifer, Pseudoalteromonas, Plesiomonas and Shewanella of the Gammaproteobacteria phylum; Sulfitobacter and Loktanella of the Alphaproteobactera phylum and to the genera Arenibacter, Cellulophaga, Chryseobacterium, Flavobacterium, Flexibacter of the Cytophaga-Flavobacterium-Bacteroides phylum. Particular attention is paid to the particular chemical features of the LPSs, such as the monosaccharide type, non-sugar substituents and phosphate groups, together with some of the typifying traits of LPSs obtained from marine bacteria. A possible correlation is then made between such features and the environmental adaptations undertaken by marine bacteria. PMID:22073003

  7. Gold Sulfide Nanoclusters: A Unique Core-in-cage Structure

    SciTech Connect

    Jiang, Deen; Walter, Michael; Dai, Sheng

    2010-01-01

    By using a DFT-based basin-hopping method, we found putative global minima for three gold sulfide nanoclusters, observed in mass spectrometry, that all show a symmetric core-in-cage structure: a metallic Au core inside a cage with S as vertices and Au at the edges. This core-in-cage structure is distinct from bulk gold sulfide. This work fills the knowledge gap regarding the structure of gold sulfide nanoclusters of {approx}1 nm.

  8. Structure and antigenicity of the phosphorylated lipopolysaccharide antigens from the leprosy and tubercle bacilli.

    PubMed

    Hunter, S W; Gaylord, H; Brennan, P J

    1986-09-15

    A family of major arabinose- and mannose-containing phosphorylated lipopolysaccharides was isolated from Mycobacterium leprae and Mycobacterium tuberculosis. The only antigenic member of the family, lipoarabinomannan (LAM)-B, was purified by anion exchange and gel filtration chromatography in detergent and recovered in large quantities (15 mg/g of bacteria). It yielded a broad diffuse band on polyacrylamide gel electrophoresis but appeared homogeneous by this criterion and gel filtration. Besides arabinose and mannose, it contained glycerol and a polyol phosphate and was acylated by lactate, succinate, palmitate, and 10-methyloctadecanoate. The phosphate was released by alkalinolysis and identified by thin layer chromatography and gas chromatography-mass spectrometry as myoinositol 1-phosphate. Thus, the group-specific "arabinomannan" of the genus Mycobacterium in the native state is acylated, contains the substituents of phosphatidylinositol, and is apparently membrane associated. LAM-B is one of the dominant immunogens of the leprosy bacillus reacting readily with antibodies from lepromatous leprosy patients and monoclonal antibodies in plate and nitrocellulose enzyme-linked immunosorbent assay and on electrophoretic immunoblots. It is immunologically cross-reactive with a like product from M. tuberculosis. LAM-B is clearly the pervasive "glycoprotein" antigen of the leprosy bacillus and may be the long sought lipoteichoic acid-like polymer of Mycobacterium with a role in cell wall physiology, macrophage recognition, and perhaps an involvement in cross-protective immunity. PMID:3091602

  9. Network nestedness as generalized core-periphery structures

    NASA Astrophysics Data System (ADS)

    Lee, Sang Hoon

    2016-02-01

    The concept of nestedness, in particular for ecological and economical networks, has been introduced as a structural characteristic of real interacting systems. We suggest that the nestedness is in fact another way to express a mesoscale network property called the core-periphery structure. With real ecological mutualistic networks and synthetic model networks, we reveal the strong correlation between the nestedness and core-periphery-ness (likeness to the core-periphery structure), by defining the network-level measures for nestedness and core-periphery-ness in the case of weighted and bipartite networks. However, at the same time, via more sophisticated null-model analysis, we also discover that the degree (the number of connected neighbors of a node) distribution poses quite severe restrictions on the possible nestedness and core-periphery parameter space. Therefore, there must exist structurally interwoven properties in more fundamental levels of network formation, behind this seemingly obvious relation between nestedness and core-periphery structures.

  10. MHC structure and function − antigen presentation. Part 2

    PubMed Central

    Goldberg, Anna Carla; Rizzo, Luiz Vicente

    2015-01-01

    The second part of this review deals with the molecules and processes involved in the processing and presentation of the antigenic fragments to the T-cell receptor. Though the nature of the antigens presented varies, the most significant class of antigens is proteins, processed within the cell to be then recognized in the form of peptides, a mechanism that confers an extraordinary degree of precision to this mode of immune response. The efficiency and accuracy of this system is also the result of the myriad of mechanisms involved in the processing of proteins and production of peptides, in addition to the capture and recycling of alternative sources aiming to generate further diversity in the presentation to T-cells. PMID:25807243

  11. The structure of iron in Earth's inner core.

    PubMed

    Tateno, Shigehiko; Hirose, Kei; Ohishi, Yasuo; Tatsumi, Yoshiyuki

    2010-10-15

    Earth's solid inner core is mainly composed of iron (Fe). Because the relevant ultrahigh pressure and temperature conditions are difficult to produce experimentally, the preferred crystal structure of Fe at the inner core remains uncertain. Static compression experiments showed that the hexagonal close-packed (hcp) structure of Fe is stable up to 377 gigapascals and 5700 kelvin, corresponding to inner core conditions. The observed weak temperature dependence of the c/a axial ratio suggests that hcp Fe is elastically anisotropic at core temperatures. Preferred orientation of the hcp phase may explain previously observed inner core seismic anisotropy. PMID:20947762

  12. Mapping the Structural Core of Human Cerebral Cortex

    PubMed Central

    Hagmann, Patric; Cammoun, Leila; Gigandet, Xavier; Meuli, Reto; Honey, Christopher J; Wedeen, Van J; Sporns, Olaf

    2008-01-01

    Structurally segregated and functionally specialized regions of the human cerebral cortex are interconnected by a dense network of cortico-cortical axonal pathways. By using diffusion spectrum imaging, we noninvasively mapped these pathways within and across cortical hemispheres in individual human participants. An analysis of the resulting large-scale structural brain networks reveals a structural core within posterior medial and parietal cerebral cortex, as well as several distinct temporal and frontal modules. Brain regions within the structural core share high degree, strength, and betweenness centrality, and they constitute connector hubs that link all major structural modules. The structural core contains brain regions that form the posterior components of the human default network. Looking both within and outside of core regions, we observed a substantial correspondence between structural connectivity and resting-state functional connectivity measured in the same participants. The spatial and topological centrality of the core within cortex suggests an important role in functional integration. PMID:18597554

  13. Sandwiched structural panel having a bi-directional core structure

    NASA Technical Reports Server (NTRS)

    Weddendorf, Bruce (Inventor)

    1995-01-01

    A structural panel assembly has a bi-directional core structure sandwiched between and secured to a pair of outer side wall members. The core structure is formed from first and second perpendicular series of elongated strip members having crenelated configurations. The strip members in the first series thereof are transversely interwoven with the strip members in the second series thereof in a manner such that crest portions of the strip members in the first series overlie and oppose trough portions of the strip members in the second series, and trough portions of the strip members in the first series underlie and oppose crest portions of the strip members in the second series. The crest portions of all of the strip members lie generally in a first plane and are secured to the inner side of one of the panel assembly outer side walls, and the trough portions of all of the strip members lie generally in a second plane and are secured to the inner side of the other panel assembly outer side wall.

  14. The antigenic structure of the influenza B virus hemagglutinin: operational and topological mapping with monoclonal antibodies.

    PubMed

    Berton, M T; Webster, R G

    1985-06-01

    We have probed the antigenic structure of the influenza B virus hemagglutinin (HA) with monoclonal antibodies specific for the HA of influenza B virus, B/Oregon/5/80. Seventeen laboratory-selected antigenic variants of this virus were analyzed by hemagglutination-inhibition (HI) assays or ELISA and an operational antigenic map was constructed. In addition, the monoclonal antibodies were tested in a competitive binding assay to construct a topological map of the antigenic sites. In contrast to the influenza A virus HA, only a single immunodominant antigenic site composed of several overlapping clusters of epitopes was defined by the HI-positive antibodies. Three variants could be distinguished from the parental virus with polyclonal antisera by HI and infectivity reduction assays suggesting that changes in this antigenic site may be sufficient to provide an epidemiological advantage to influenza B viruses in nature. In addition, two nonoverlapping epitopes of unknown biological significance were identified in the competitive binding analysis by two monoclonal antibodies with no HI activity and little or no neutralizing activity. We previously identified single amino acid substitutions in the HAs of the antigenic variants used in this study (M. T. Berton, C. W. Naeve, and R. G. Webster (1984), J. Virol. 52, 919-927). These changes occurred in regions of the molecule which, by amino acid sequence alignment, appeared to correspond to proposed antigenic sites A and B on the H3 HA of influenza A virus. Correlation with the antigenic map established in this report, however, demonstrates that the amino acid residues actually contribute to a single antigenic site on the influenza B virus HA and suggests significant differences in the antigenic structures of the influenza A and B virus HAs. PMID:2414911

  15. Antigenic and structural features of goblet-cell mucin of human small intestine.

    PubMed Central

    Mantle, M; Forstner, G G; Forstner, J F

    1984-01-01

    With the use of a newly developed solid-phase radioimmunoassay method, the major antigenic determinants of human small-intestinal goblet-cell mucin were investigated and related to the overall tertiary structure of the mucin. Preliminary hapten inhibition studies with various oligosaccharides of known sequence and structure suggested that the determinants did not reside in carbohydrate. Exhaustive thiol reduction, however, almost abolished antigenicity, caused breakdown of the mucin into small heterogeneous glycopeptides, and liberated a 'link' peptide of Mr 118000. Western 'blots' of reduced mucin from polyacrylamide gels on to nitrocellulose sheets showed that a small amount of residual antigenicity remained in large-Mr glycopeptides (Mr greater than 200000). The 'link' peptide was not antigenic. Timed Pronase digestion of native mucin resulted in a progressive loss of antigenic determinants. Gel electrophoresis revealed that after 8h of digestion the 118000-Mr peptide had disappeared, whereas antigenicity, which was confined to large-Mr glycopeptides, was destroyed much more slowly with time (70% by 24h, 100% by 72h). Despite the loss of antigenicity, 72h-Pronase-digested glycopeptides retained all of the carbohydrate of the native mucin. Therefore the antibody to human small-intestinal mucin appears to recognize a 'naked' (non-glycosylated and Pronase-susceptible) peptide region(s) of mucin glycopeptides. For full antigenicity, however, disulphide bonds are required to stabilize a specific three-dimensional configuration of the 'naked' region. Images Fig. 4. Fig. 6. PMID:6199017

  16. Inhibition of the HCV core protein on the immune response to HBV surface antigen and on HBV gene expression and replication in vivo.

    PubMed

    Zhu, Wenbo; Wu, Chunchen; Deng, Wanyu; Pei, Rongjun; Wang, Yun; Cao, Liang; Qin, Bo; Lu, Mengji; Chen, Xinwen

    2012-01-01

    The hepatitis C virus (HCV) core protein is a multifunctional protein that can interfere with the induction of an immune response. It has been reported that the HCV core protein inhibits HBV replication in vitro. In this study, we test the effect of the HCV core gene on the priming of the immune response to hepatitis B surface antigen (HBsAg) and on the replication of HBV in vivo. Our results showed that the full-length HCV core gene inhibits the induction of an immune response to the heterogeneous antigen, HBsAg, at the site of inoculation when HCV core (pC191) and HBsAg (pHBsAg) expression plasmids are co-administered as DNA vaccines into BALB/c mice. The observed interference effect of the HCV core occurs in the priming stage and is limited to the DNA form of the HBsAg antigen, but not to the protein form. The HCV core reduces the protective effect of the HBsAg when the HBsAg and the HCV core are co-administered as vaccines in an HBV hydrodynamic mouse model because the HCV core induces immune tolerance to the heterogeneous HBsAg DNA antigen. These results suggest that HCV core may play an important role in viral persistence by the attenuation of host immune responses to different antigens. We further tested whether the HCV core interfered with the priming of the immune response in hepatocytes via the hydrodynamic co-injection of an HBV replication-competent plasmid and an HCV core plasmid. The HCV core inhibited HBV replication and antigen expression in both BALB/c (H-2d) and C57BL/6 (H-2b) mice, the mouse models of acute and chronic hepatitis B virus infections. Thus, the HCV core inhibits the induction of a specific immune response to an HBsAg DNA vaccine. However, HCV C also interferes with HBV gene expression and replication in vivo, as observed in patients with coinfection. PMID:23024803

  17. Submit and disulfide structure of monomeric and dimeric forms of detergent-soluble HLA antigens.

    PubMed

    Springer, T A; Robb, R J; Terhorst, C; Strominger, J L

    1977-07-10

    The structure of monomeric and disulfide-bonded dimeric forms of HLA antigens has been studied. Detergent-soluble HLA antigen heavy chains contain one or two easily reduced sulfhydryl groups not found in papain-solubilized HLA antigens, as demonstrated by amino acid analysis (Springer, T. A., and Strominger, J.L. (1976) Proc. Natl. Acad. Sci. U.S.A. 73, 2481-2485, and Terhorst, C., Parham, P., Mann, D.L., and Strominger, J.L. (1976) Proc. Natl. Acad. Sci. U.S.A. 73, 910-914) and by labeling with iodo[3H]acetate. Dimer formation occurred during purification, since it was prevented by pretreatment of membranes containing HLA antigen with iodoacetamide. Cross-linking studies showed that the non-disulfide-bonded form of HLA antigens contains one subunit each of the Mr = 44,000 heavy chain and the Mr = 12,000 light chain (beta2-microglobulin). PMID:873911

  18. Antigenic structures stably expressed by recombinant TGEV-derived vectors.

    PubMed

    Becares, Martina; Sanchez, Carlos M; Sola, Isabel; Enjuanes, Luis; Zuñiga, Sonia

    2014-09-01

    Coronaviruses (CoVs) are positive-stranded RNA viruses with potential as immunization vectors, expressing high levels of heterologous genes and eliciting both secretory and systemic immune responses. Nevertheless, its high recombination rate may result in the loss of the full-length foreign gene, limiting their use as vectors. Transmissible gastroenteritis virus (TGEV) was engineered to express porcine reproductive and respiratory syndrome virus (PRRSV) small protein domains, as a strategy to improve heterologous gene stability. After serial passage in tissue cultures, stable expression of small PRRSV protein antigenic domains was achieved. Therefore, size reduction of the heterologous genes inserted in CoV-derived vectors led to the stable expression of antigenic domains. Immunization of piglets with these TGEV vectors led to partial protection against a challenge with a virulent PRRSV strain, as immunized animals showed reduced clinical signs and lung damage. Further improvement of TGEV-derived vectors will require the engineering of vectors with decreased recombination rate. PMID:25108114

  19. Structural Basis For Antigenic Peptide Precursor Processing by the Endoplasmic Reticulum Aminopeptidase ERAP1

    SciTech Connect

    T Nguyen; S Chang; I Evnouchidou; I York; C Zikos; K Rock; A Goldberg; E Stratikos; L Stern

    2011-12-31

    ERAP1 trims antigen precursors to fit into MHC class I proteins. To fulfill this function, ERAP1 has unique substrate preferences, trimming long peptides but sparing shorter ones. To identify the structural basis for ERAP1's unusual properties, we determined the X-ray crystal structure of human ERAP1 bound to bestatin. The structure reveals an open conformation with a large interior compartment. An extended groove originating from the enzyme's catalytic center can accommodate long peptides and has features that explain ERAP1's broad specificity for antigenic peptide precursors. Structural and biochemical analyses suggest a mechanism for ERAP1's length-dependent trimming activity, whereby binding of long rather than short substrates induces a conformational change with reorientation of a key catalytic residue toward the active site. ERAP1's unique structural elements suggest how a generic aminopeptidase structure has been adapted for the specialized function of trimming antigenic precursors.

  20. Correlation of the content of hepatitis B core antigen in peripheral blood mononuclear cells with HBV virus load.

    PubMed

    Peng, Yanzhong; Xiong, Xiaojia; Tong, Xindeng; Li, Min; Yang, Xifei; Hu, Guoxin; Geng, Yijie; Li, Jianxin

    2016-06-01

    The dysfunction of peripheral blood mononuclear cell (PBMC) plays an important role in hepatitis B virus (HBV) chronic infection and tolerance. This study is aimed to explore the changes of expression and distribution of Hepatitis B virus core antigen (HBcAg) in the PBMCs of patients infected with chronic hepatitis B virus by using confocal laser scanning microscopy (CLSM). The levels of HBcAg in PBMCs were correlated with the HBV load in serum, and the change of HBcAg distribution in different PBMC organelles may represent various HBV infection states. HBcAg was mainly distributed in the nuclei of PBMC in the cases of immune tolerance and no inflammatory activity. Taken together, our data suggest that the measurement of HBcAg and its distribution in PBMCs using CLSM may serve as an alternative approach to monitor HBV load and the immune states of HBV infection with ease of using and improved sensitivity. PMID:26680298

  1. Profiling core-periphery network structure by random walkers

    PubMed Central

    Rossa, Fabio Della; Dercole, Fabio; Piccardi, Carlo

    2013-01-01

    Disclosing the main features of the structure of a network is crucial to understand a number of static and dynamic properties, such as robustness to failures, spreading dynamics, or collective behaviours. Among the possible characterizations, the core-periphery paradigm models the network as the union of a dense core with a sparsely connected periphery, highlighting the role of each node on the basis of its topological position. Here we show that the core-periphery structure can effectively be profiled by elaborating the behaviour of a random walker. A curve—the core-periphery profile—and a numerical indicator are derived, providing a global topological portrait. Simultaneously, a coreness value is attributed to each node, qualifying its position and role. The application to social, technological, economical, and biological networks reveals the power of this technique in disclosing the overall network structure and the peculiar role of some specific nodes. PMID:23507984

  2. Star cell type core configuration for structural sandwich materials

    DOEpatents

    Christensen, Richard M.

    1995-01-01

    A new pattern for cellular core material used in sandwich type structural materials. The new pattern involves star shaped cells intermixed with hexagonal shaped cells. The new patterned cellular core material includes star shaped cells interconnected at points thereof and having hexagonal shape cells positioned adjacent the star points. The new pattern allows more flexibility and can conform more easily to curved shapes.

  3. Immunochemistry of sea anemone toxins: structure-antigenicity relationships and toxin-receptor interactions probed by antibodies specific for one antigenic

    SciTech Connect

    Ayeb, M.E.; Bahraoui, E.M.; Granier, C.; Beress, L.; Rochat, H.

    1986-11-04

    Two antibody subpopulations directed against Anemonia sulcata toxin I or II have been purified by immunoaffinity chromatography. These antibodies are specific for a single antigenic region and were used in a structure-antigenicity relationship study using homologous toxins and chemically modified derivatives of A. sulcata toxin II. Asp-7 and/or Asp=9 and Gln-47 of toxin II were found to be implicated in the antigenic region recognized by the two antibody subpopulations. On the contrary, Arg-14, Lys-35, -36, and -46, and ..cap alpha..-NH/sub 2/ of the glycine residue of A. sulcata toxin II are not involved in the corresponding antigenic region. When assayed for interaction with the sodium channel, the antigenic region of toxin II, including Asp-9 and Gln-47, appeared fully accessible to its specific antibodies, suggesting that it is not involved in the binding of the toxin to its receptor.

  4. Immunoglobulin VH clan and family identity predicts variable domain structure and may influence antigen binding.

    PubMed Central

    Kirkham, P M; Mortari, F; Newton, J A; Schroeder, H W

    1992-01-01

    Mammalian immunoglobulin VH families can be grouped into three distinct clans based upon sequence conservation in two of the three framework (FR) intervals. Through replacement/silent site substitution analysis, molecular modeling and mathematical evaluation of known immunoglobulin crystal structures, we demonstrate that this conservation reflects preservation of protein sequence and structure. Each clan contains a characteristic FR 1 interval that is solvent-exposed and structurally separated from the antigen binding site. Families within a clan contain their own unique FR 3 interval that is capable of either influencing the conformation of the antigen binding site or interacting directly with antigen. Our results provide a structural context for theories that address differential use of VH families in the immune response. Images PMID:1537339

  5. [Structure and function of the T-lymphocyte antigen receptor and its role in infectious diseases].

    PubMed

    Peralta Zaragoza, O; Sánchez Magaña, T; Barrera Rodriguez, R; Madrid Marina, V

    1996-01-01

    The T lymphocytes recognize antigens through antigen receptors (TcRs) and the major histocompatibility complex (MHC) molecules: they lysate the cells that bear the antigen, or release cytokines that are mediators of the immune response. The TcRs recognize antigens in the form of short peptides bound to MHC molecules. So far, there are two isotypes of TcR: gamma/delta and alpha/beta, which appear in the sequence during T-cell ontogeny. The process of selection of TcRs during thymic ontogeny obeys to molecular mechanisms which generate intracellular events that will participate in the gene expression of the TcR. The aim of the present paper is to review the molecular, structural, and functional aspects of the TcRs, and their role in human autoimmune infectious disease. PMID:8815490

  6. A structural basis for antigen recognition by the T cell-like lymphocytes of sea lamprey

    SciTech Connect

    Deng, Lu; Velikovsky, C. Alejandro; Xu, Gang; Iyer, Lakshminarayan M.; Tasumi, Satoshi; Kerzic, Melissa C.; Flajnik, Martin F.; Aravind, L.; Pancer, Zeev; Mariuzza, Roy A.

    2010-10-28

    Adaptive immunity in jawless vertebrates is mediated by leucine-rich repeat proteins called 'variable lymphocyte receptors' (VLRs). Two types of VLR (A and B) are expressed by mutually exclusive lymphocyte populations in lamprey. VLRB lymphocytes resemble the B cells of jawed vertebrates; VLRA lymphocytes are similar to T cells. We determined the structure of a high-affinity VLRA isolated from lamprey immunized with hen egg white lysozyme (HEL) in unbound and antigen-bound forms. The VLRA-HEL complex demonstrates that certain VLRAs, like {gamma}{delta} T-cell receptors (TCRs) but unlike {alpha}{beta} TCRs, can recognize antigens directly, without a requirement for processing or antigen-presenting molecules. Thus, these VLRAs feature the nanomolar affinities of antibodies, the direct recognition of unprocessed antigens of both antibodies and {gamma}{delta} TCRs, and the exclusive expression on the lymphocyte surface that is unique to {alpha}{beta} and {gamma}{delta} TCRs.

  7. Aluminum core structures brazed without use of flux

    NASA Technical Reports Server (NTRS)

    1966-01-01

    Aluminum alloy face sheets are brazed to aluminum alloy honeycomb cores without using corrosive flux by means of one or three methods. The completed brazed structure has the high-strength characteristics of heat treated aluminum alloys.

  8. Structure, properties, and dynamic behavior of Earth's inner core

    NASA Astrophysics Data System (ADS)

    Reaman, Daniel Marcus

    Long-standing debate has persisted regarding the nature of the Earth's inner core, from its age and composition to its structure and dynamic high-pressure, high-temperature behavior. The equation of state of the alloy which comprises the inner core, the material transport properties of inner-core materials and the mechanism responsible for its structure are all required to gain further insight into the current and past state of the Earth's deep interior. Experimental work in the diamond-anvil cell (DAC) coupled with theoretical calculations are reported here to constrain these aspects of the Earth's inner core. Use of the DAC has allowed us to determine an equation of state of a planetary-core representative Fe64Ni36 alloy to 95 GP and ˜ 3000 K. Increasing the Ni content in these experiments relative to the estimated abundance in the inner core (˜5--10%) provides a critical investigation on the effects of increasing Ni content on the equation of state of FeNi alloys, thereby providing insight in to the behavior of these alloys at high pressures and temperatures with applications to other planetary cores. The use of micro-fabricated samples in the DAC is a novel new way of measuring material transport properties under high-pressure and temperature conditions. Using micro-fabricated samples in these experiments, with a controlled geometry of Fe and Ni, has allowed the measurement of interdiffusion coefficients in FeNi alloys and extended the previous pressure range of these experiments by a factor of three. The resulting data has been extrapolated to inner-core conditions to place constraints on material transport properties at those conditions while providing insight into some of the other physical properties of inner-core material, such as the solid-state viscosity. The seismically-anisotropic structure of the inner core remains a point of contention amongst geophysicists. Though many viable hypotheses have been put forth regarding the nature of this structure

  9. Process to make core-shell structured nanoparticles

    DOEpatents

    Luhrs, Claudia; Phillips, Jonathan; Richard, Monique N

    2014-01-07

    Disclosed is a process for making a composite material that contains core-shell structured nanoparticles. The process includes providing a precursor in the form of a powder a liquid and/or a vapor of a liquid that contains a core material and a shell material, and suspending the precursor in an aerosol gas to produce an aerosol containing the precursor. In addition, the process includes providing a plasma that has a hot zone and passing the aerosol through the hot zone of the plasma. As the aerosol passes through the hot zone of the plasma, at least part of the core material and at least part of the shell material in the aerosol is vaporized. Vapor that contains the core material and the shell material that has been vaporized is removed from the hot zone of the plasma and allowed to condense into core-shell structured nanoparticles.

  10. Evaluation of red blood cell and platelet antigen genotyping platforms (ID CORE XT/ID HPA XT) in routine clinical practice

    PubMed Central

    Finning, Kirstin; Bhandari, Radhika; Sellers, Fiona; Revelli, Nicoletta; Villa, Maria Antonietta; Muñiz-Díaz, Eduardo; Nogués, Núria

    2016-01-01

    Background High-throughput genotyping platforms enable simultaneous analysis of multiple polymorphisms for blood group typing. BLOODchip® ID is a genotyping platform based on Luminex® xMAP technology for simultaneous determination of 37 red blood cell (RBC) antigens (ID CORE XT) and 18 human platelet antigens (HPA) (ID HPA XT) using the BIDS XT software. Materials and methods In this international multicentre study, the performance of ID CORE XT and ID HPA XT, using the centres’ current genotyping methods as the reference for comparison, and the usability and practicality of these systems, were evaluated under working laboratory conditions. DNA was extracted from whole blood in EDTA with Qiagen methodologies. Ninety-six previously phenotyped/genotyped samples were processed per assay: 87 testing samples plus five positive controls and four negative controls. Results Results were available for 519 samples: 258 with ID CORE XT and 261 with ID HPA XT. There were three “no calls” that were either caused by human error or resolved after repeating the test. Agreement between the tests and reference methods was 99.94% for ID CORE XT (9,540/9,546 antigens determined) and 100% for ID HPA XT (all 4,698 alleles determined). There were six discrepancies in antigen results in five RBC samples, four of which (in VS, N, S and Doa) could not be investigated due to lack of sufficient sample to perform additional tests and two of which (in S and C) were resolved in favour of ID CORE XT (100% accuracy). The total hands-on time was 28–41 minutes for a batch of 16 samples. Compared with the reference platforms, ID CORE XT and ID HPA XT were considered simpler to use and had shorter processing times. Discussion ID CORE XT and ID HPA XT genotyping platforms for RBC and platelet systems were accurate and user-friendly in working laboratory settings. PMID:26674823

  11. Differential induction of structural changes in the simian virus 40 origin of replication by T antigen.

    PubMed Central

    Borowiec, J A; Dean, F B; Hurwitz, J

    1991-01-01

    The ATP-dependent binding of the simian virus 40 (SV40) large tumor antigen (T antigen) to the SV40 origin of replication (ori) results in the structural distortion of two critical elements within flanking regions of ori and the untwisting of the DNA helix. We examined the effect of changes in temperature, ATP concentration, and other reaction parameters on the generation of these DNA structural changes. We found that induction of the two localized structural transitions were highly and differentially sensitive to reaction conditions. Significant distortion of the early palindrome element, shown previously to result from DNA melting, required low levels of ATP (10 to 30 microM) but temperatures above 25 degrees C. Distortion of the AT tract occurred at low temperatures (5 degrees C) but required relatively high concentrations of ATP (greater than 300 microM). Thus, T antigen can induce structural changes within one critical element of ori without generating significant structural distortion within the second element. The response of ori untwisting to reaction conditions generally increased in parallel with or fell intermediate between the inductions of localized structural transitions. We suggest that ori untwisting and localized structural distortions are interdependent consequences of T-antigen binding to ori. These results suggest a model for the structural events occurring during the initial steps of SV40 DNA replication. Images PMID:1847451

  12. Dislocation core structures in Si-doped GaN

    SciTech Connect

    Rhode, S. L. Fu, W. Y.; Sahonta, S.-L.; Kappers, M. J.; Humphreys, C. J.; Horton, M. K.; Pennycook, T. J.; Dusane, R. O.; Moram, M. A.

    2015-12-14

    Aberration-corrected scanning transmission electron microscopy was used to investigate the core structures of threading dislocations in plan-view geometry of GaN films with a range of Si-doping levels and dislocation densities ranging between (5 ± 1) × 10{sup 8} and (10 ± 1) × 10{sup 9} cm{sup −2}. All a-type (edge) dislocation core structures in all samples formed 5/7-atom ring core structures, whereas all (a + c)-type (mixed) dislocations formed either double 5/6-atom, dissociated 7/4/8/4/9-atom, or dissociated 7/4/8/4/8/4/9-atom core structures. This shows that Si-doping does not affect threading dislocation core structures in GaN. However, electron beam damage at 300 keV produces 4-atom ring structures for (a + c)-type cores in Si-doped GaN.

  13. Therapy-induced clearance of HCV core antigen from plasma predicts an end of treatment viral response.

    PubMed

    Tedder, R S; Tuke, P; Wallis, N; Wright, M; Nicholson, L; Grant, P R

    2013-01-01

    During viral assembly, viral proteins are released into plasma and can be used to infer viral load. The Architect hepatitis C virus (HCV) core antigen (Ag) assay is a potential alternative to HCV RNA quantification for measuring response to therapy and predicting an end of treatment viral response (EOTR). The HCVp22Ag assay was used to infer viral load in 68 window RNA-containing samples and in 284 samples from baseline to week 14 of ribavirin/interferon treatment in 23 patients with EOTR including three who relapsed, 20 not achieving EOTR and 11 controls. HCV Ag and RNA correlated well (r = 0.86) with linear dose responses on dilution. In patients on therapy and control patients, plasma HCV antigen was detected in 51 of 54 with an interpolated LOD cut off between 10(3) and 10(4) RNA IU/mL. Plasma HCV antigenaemia and plasma RNA levels were significantly different in EOTR from non-EOTR patients at 3 days after treatment start and all times thereafter. Positive and negative EOTR predictive values for HCV RNA >2 log drop and HCV Ag loss at 12 weeks were 70% and 74%, 85% and 93% respectively. HCV Ag reactivity has a linear dose response independent of genotype and correlates well with HCV RNA. The failure to clear HCV Ag is as accurate as the failure to clear HCV RNA at twelve weeks into therapy in predicting the likelihood of failure to achieve EOTR. HCV Ag potentially offers a convenient alternative to RNA measurement for defining a futility flag in HCV therapy. PMID:23231086

  14. Lentiviral vector encoding ubiquitinated hepatitis B core antigen induces potent cellular immune responses and therapeutic immunity in HBV transgenic mice.

    PubMed

    Dai, Shenglan; Zhuo, Meng; Song, Linlin; Chen, Xiaohua; Yu, Yongsheng; Zang, Guoqing; Tang, Zhenghao

    2016-07-01

    Predominant T helper cell type 1 (Th1) immune responses accompanied by boosted HBV-specific cytotoxic T lymphocyte (CTL) activity are essential for the clearance of hepatitis B virus (HBV) in chronic hepatitis B (CHB) patients. Ubiquitin (Ub) serves as a signal for the target protein to be recognized and degraded through the ubiquitin-proteasome system (UPS). Ubiquitinated hepatitis B core antigen (Ub-HBcAg) has been proved to be efficiently degraded into the peptides, which can be presented by major histocompatibility complex (MHC) class I resulting in stimulating cell-mediated responses. In the present study, lentiviral vectors encoding Ub-HBcAg (LV-Ub-HBcAg) were designed and constructed as a therapeutic vaccine for immunotherapy. HBcAg-specific cellular immune responses and anti-viral effects induced by LV-Ub-HBcAg were evaluated in HBV transgenic mice. We demonstrated that immunization with LV-Ub-HBcAg promoted the secretion of cytokines interleukin-2 (IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), generated remarkably high percentages of IFN-γ-secreting CD8(+) T cells and CD4(+) T cells, and enhanced HBcAg-specific CTL activity in HBV transgenic mice. More importantly, vaccination with LV-Ub-HBcAg could efficiently decreased the levels of serum hepatitis B surface antigen (HBsAg), HBV DNA and the expression of HBsAg and HBcAg in liver tissues of HBV transgenic mice. In addition, LV-Ub-HBcAg could upregulate the expression of T cell-specific T-box transcription factor (T-bet) and downregulate the expression of GATA-binding protein 3 (GATA-3) in spleen T lymphocytes. The therapeutic vaccine LV-Ub-HBcAg could break immune tolerance, and induce potent HBcAg specific cellular immune responses and therapeutic effects in HBV transgenic mice. PMID:26874581

  15. Dislocation core structures in (0001) InGaN

    NASA Astrophysics Data System (ADS)

    Rhode, S. L.; Horton, M. K.; Sahonta, S.-L.; Kappers, M. J.; Haigh, S. J.; Pennycook, T. J.; McAleese, C.; Humphreys, C. J.; Dusane, R. O.; Moram, M. A.

    2016-03-01

    Threading dislocation core structures in c-plane GaN and InxGa1-xN (0.057 ≤ x ≤ 0.20) films were investigated by aberration-corrected scanning transmission electron microscopy. a-type dislocations are unaffected by alloying with indium and have a 5/7-atom ring core structure in both GaN and InxGa1-xN. In contrast, the dissociation lengths of (a + c)-type dislocations are reduced, and new 7/4/9-atom ring and 7/4/8/5-atom ring core structures were observed for the dissociated (a + c)-type dislocations in InxGa1-xN, which is associated with the segregation of indium near (a + c)-type and c-type dislocation cores in InxGa1-xN, consistent with predictions from atomistic Monte Carlo simulations.

  16. Structural and Biochemical Insights into the Regulation of Protein Phosphatase 2A by Small t Antigen of SV40

    SciTech Connect

    Chen,Y.; Xu, Y.; Bao, Q.; Xing, Y.; Li, Z.; Lin, Z.; Stock, J.; Jeffrey, P.; Shi, Y.

    2007-01-01

    The small t antigen (ST) of DNA tumor virus SV40 facilitates cellular transformation by disrupting the functions of protein phosphatase 2A (PP2A) through a poorly defined mechanism. The crystal structure of the core domain of SV40 ST bound to the scaffolding subunit of human PP2A reveals that the ST core domain has a novel zinc-binding fold and interacts with the conserved ridge of HEAT repeats 3-6, which overlaps with the binding site for the B' (also called PR61 or B56) regulatory subunit. ST has a lower binding affinity than B' for the PP2A core enzyme. Consequently, ST does not efficiently displace B' from PP2A holoenzymes in vitro. Notably, ST inhibits PP2A phosphatase activity through its N-terminal J domain. These findings suggest that ST may function mainly by inhibiting the phosphatase activity of the PP2A core enzyme, and to a lesser extent by modulating assembly of the PP2A holoenzymes.

  17. EK3D: an E. coli K antigen 3-dimensional structure database

    PubMed Central

    Kunduru, Bharathi Reddy; Nair, Sanjana Anilkumar; Rathinavelan, Thenmalarchelvi

    2016-01-01

    A very high rate of multidrug resistance (MDR) seen among Gram-negative bacteria such as Escherichia, Klebsiella, Salmonella, Shigella, etc. is a major threat to public health and safety. One of the major virulent determinants of Gram-negative bacteria is capsular polysaccharide or K antigen located on the bacterial outer membrane surface, which is a potential drug & vaccine target. It plays a key role in host–pathogen interactions as well as host immune evasion and thus, mandates detailed structural information. Nonetheless, acquiring structural information of K antigens is not straightforward due to their innate enormous conformational flexibility. Here, we have developed a manually curated database of K antigens corresponding to various E. coli serotypes, which differ from each other in their monosaccharide composition, linkage between the monosaccharides and their stereoisomeric forms. Subsequently, we have modeled their 3D structures and developed an organized repository, namely EK3D that can be accessed through www.iith.ac.in/EK3D/. Such a database would facilitate the development of antibacterial drugs to combat E. coli infections as it has evolved resistance against 2 major drugs namely, third-generation cephalosporins and fluoroquinolones. EK3D also enables the generation of polymeric K antigens of varying lengths and thus, provides comprehensive information about E. coli K antigens. PMID:26615200

  18. Exploiting the Burkholderia pseudomallei acute phase antigen BPSL2765 for structure-based epitope discovery/design in structural vaccinology.

    PubMed

    Gourlay, Louise J; Peri, Claudio; Ferrer-Navarro, Mario; Conchillo-Solé, Oscar; Gori, Alessandro; Rinchai, Darawan; Thomas, Rachael J; Champion, Olivia L; Michell, Stephen L; Kewcharoenwong, Chidchamai; Nithichanon, Arnone; Lassaux, Patricia; Perletti, Lucia; Longhi, Renato; Lertmemongkolchai, Ganjana; Titball, Richard W; Daura, Xavier; Colombo, Giorgio; Bolognesi, Martino

    2013-09-19

    We solved the crystal structure of Burkholderia pseudomallei acute phase antigen BPSL2765 in the context of a structural vaccinology study, in the area of melioidosis vaccine development. Based on the structure, we applied a recently developed method for epitope design that combines computational epitope predictions with in vitro mapping experiments and successfully identified a consensus sequence within the antigen that, when engineered as a synthetic peptide, was selectively immunorecognized to the same extent as the recombinant protein in sera from melioidosis-affected subjects. Antibodies raised against the consensus peptide were successfully tested in opsonization bacterial killing experiments and antibody-dependent agglutination tests of B. pseudomallei. Our strategy represents a step in the development of immunodiagnostics, in the production of specific antibodies and in the optimization of antigens for vaccine development, starting from structural and physicochemical principles. PMID:23993463

  19. Population structuring of multi-copy, antigen-encoding genes in Plasmodium falciparum

    PubMed Central

    Artzy-Randrup, Yael; Rorick, Mary M; Day, Karen; Chen, Donald; Dobson, Andrew P; Pascual, Mercedes

    2012-01-01

    The coexistence of multiple independently circulating strains in pathogen populations that undergo sexual recombination is a central question of epidemiology with profound implications for control. An agent-based model is developed that extends earlier ‘strain theory’ by addressing the var gene family of Plasmodium falciparum. The model explicitly considers the extensive diversity of multi-copy genes that undergo antigenic variation via sequential, mutually exclusive expression. It tracks the dynamics of all unique var repertoires in a population of hosts, and shows that even under high levels of sexual recombination, strain competition mediated through cross-immunity structures the parasite population into a subset of coexisting dominant repertoires of var genes whose degree of antigenic overlap depends on transmission intensity. Empirical comparison of patterns of genetic variation at antigenic and neutral sites supports this role for immune selection in structuring parasite diversity. DOI: http://dx.doi.org/10.7554/eLife.00093.001 PMID:23251784

  20. DNA vaccine cocktail expressing genotype A and C HBV surface and consensus core antigens generates robust cytotoxic and antibody responses in mice and Rhesus macaques.

    PubMed

    Obeng-Adjei, N; Hutnick, N A; Yan, J; Chu, J S; Myles, D J F; Morrow, M P; Sardesai, N Y; Weiner, D B

    2013-12-01

    There are well over a quarter of a billion chronic hepatitis B virus (HBV) carriers across the globe. Most carriers are at high risk for development of liver cirrhosis and subsequent progression to hepatocellular carcinoma. It is therefore imperative to develop new approaches for immunotherapy against this infection. Antibodies and cytotoxic T cells to different HBV antigens are believed to be important for reducing viral load and clearing HBV-infected cells from the liver. Some of the major challenges facing current vaccine candidates have been their inability to induce both humoral and cellular immunity to multiple antigenic targets and the induction of potent immune responses against the major genotypes of HBV. In this study, highly optimized synthetic DNA plasmids against the HBV consensus core (HBc) and surface (HBs) antigens genotypes A and C were developed and evaluated for their immune potential. These plasmids, which encode the most prevalent genotypes of the virus, were observed to individually induce binding antibodies to HBs antigens and drove robust cell-mediated immunity in animal models. Similar responses to both HBc and HBs antigens were observed when mice and non-human primates were inoculated with the HBc-HBs cocktails. In addition to the cytotoxic T lymphocyte activities exhibited by the immunized mice, the vaccine-induced responses were broadly distributed across multiple antigenic epitopes. These elements are believed to be important to develop an effective therapeutic vaccine. These data support further evaluation of multivalent synthetic plasmids as therapeutic HBV vaccines. PMID:24310062

  1. Functional and Structural Characterization of Francisella tularensis O-Antigen Antibodies at the Low End of Antigen Reactivity

    PubMed Central

    Lu, Zhaohua; Rynkiewicz, Michael J.; Yang, Chiou-Ying; Madico, Guillermo; Perkins, Hillary M.; Roche, Marly I.; Seaton, Barbara A.

    2014-01-01

    The O-antigen (OAg) of the Gram-negative bacterium Francisella tularensis (Ft), which is both a capsular polysaccharide and a component of lipopolysaccharide, is comprised of tetrasaccharide repeats and induces antibodies mainly against repeating internal epitopes. We previously reported on several BALB/c mouse monoclonal antibodies (MAbs) that bind to internal Ft OAg epitopes and are protective in mouse models of respiratory tularemia. We now characterize three new internal Ft OAg IgG2a MAbs, N203, N77, and N24, with 10- to 100-fold lower binding potency than previously characterized internal-OAg IgG2a MAbs, despite sharing one or more variable region germline genes with some of them. In a mouse model of respiratory tularemia with the highly virulent Ft type A strain SchuS4, the three new MAbs reduced blood bacterial burden with potencies that mirror their antigen-binding strength; the best binder of the new MAbs, N203, prolonged survival in a dose-dependent manner, but was at least 10-fold less potent than the best previously characterized IgG2a MAb, Ab52. X-ray crystallographic studies of N203 Fab showed a flexible binding site in the form of a partitioned groove, which cannot provide as many contacts to OAg as does the Ab52 binding site. These results reveal structural features of antibodies at the low end of reactivity with multi-repeat microbial carbohydrates and demonstrate that such antibodies still have substantial protective effects against infection. PMID:25171003

  2. Investigation of intravalence, core-valence and core-core electron correlation effects in polonium atomic structure calculations

    NASA Astrophysics Data System (ADS)

    Quinet, Pascal

    2014-09-01

    A detailed investigation of the atomic structure and radiative parameters involving the lowest states within the 6p4, 6p36d, 6p37s, 6p37p and 6p37d configurations of neutral polonium is reported in the present paper. Using different physical models based on the pseudo-relativistic Hartree-Fock approach, the influence of intravalence, core-valence and core-core electron correlation on the atomic parameters is discussed in detail. This work allowed us to fix the spectroscopic designation of some experimental level energy values and to provide for the first time a set of reliable oscillator strengths corresponding to 31 Po I spectral lines in the wavelength region from 175 to 987 nm.

  3. Composite Cocured Modular Eggcrate-Core Sandwich Structure

    NASA Technical Reports Server (NTRS)

    Magurany, Charles J.

    1995-01-01

    Lightweight composite-material (e.g., graphite fiber/epoxy matrix) cocured sandwich panels with eggcratelike cores developed for use as principal components of optical benches and other structures that support precise optical instruments. Structures offer greater thermal and mechanical stability. Advantages include easier fabrication and better mechanical properties.

  4. Detection of hepatitis B virus core antigen by phage display mediated TaqMan real-time immuno-PCR.

    PubMed

    Monjezi, Razieh; Tan, Sheau Wei; Tey, Beng Ti; Sieo, Chin Chin; Tan, Wen Siang

    2013-01-01

    The core antigen (HBcAg) of hepatitis B virus (HBV) is one of the markers for the identification of the viral infection. The main purpose of this study was to develop a TaqMan real-time detection assay based on the concept of phage display mediated immuno-PCR (PD-IPCR) for the detection of HBcAg. PD-IPCR combines the advantages of immuno-PCR (IPCR) and phage display technology. IPCR integrates the versatility of enzyme-linked immunosorbent assay (ELISA) with the sensitivity and signal generation power of PCR. Whereas, phage display technology exploits the physical association between the displayed peptide and the encoding DNA within the same phage particle. In this study, a constrained peptide displayed on the surface of an M13 recombinant bacteriophage that interacts tightly with HBcAg was applied as a diagnostic reagent in IPCR. The phage displayed peptide and its encoding DNA can be used to replace monoclonal antibody (mAb) and chemically bound DNA, respectively. This method is able to detect as low as 10ng of HBcAg with 10(8)pfu/ml of the recombinant phage which is about 10,000 times more sensitive than the phage-ELISA. The PD-IPCR provides an alternative means for the detection of HBcAg in human serum samples. PMID:23022731

  5. Response of health care workers with isolated antibody to hepatitis B core antigen to hepatitis B vaccine.

    PubMed

    Chiarakul, Supawadee; Eunumjitkul, Krissana; Vorapimol, Ar-Reerat; Kaewkungwal, Jaranit; Chimparlee, Nitinan; Poovorawan, Yong

    2011-07-01

    Isolated hepatitis B core antibody (antiHBc) without hepatitis B surface antigen (HBsAg) or hepatitis B surface antibody (antiHBs) is found during routine screening for hepatitis B virus (HBV) markers. Isolated antiHBc may indicate immunity against HBV or occult infection. To determine the immune response of health care workers (HCWs) with isolated antiHBc, HCWs were divided into two groups. A single dose of recombinant hepatitis B (HB) vaccine was administered to HCWs with isolated antiHBc (n = 36) and healthy HCWs (n = 20) seronegative for HBsAg, antiHBc and antiHBs. One month later, the subjects were tested for antiHBs. Twenty-one of 36 HCW (58.3%) in the antiHBc group had antiHBs, while only 1 of 20 HCW (5.0%) in the seronegative control group had a detectable antiHBs titer exceeding 10 mIU/ml. The antiHBs response in HCWs with antiHBc was significantly higher than in the seronegative group. The subjects' sera were tested for HBV DNA by nested PCR. Of those with antiHBc, 4 had detectable HBV DNA (occult HBV infection). None of these 4 responded to the vaccine. Therefore, the response elicited by a single dose of HB vaccine administered to patients with antiHBc may serve as an indicator of occult HBV infection. PMID:22299465

  6. Star cell type core configuration for structural sandwich materials

    DOEpatents

    Christensen, R.M.

    1995-08-01

    A new pattern for cellular core material used in sandwich type structural materials is disclosed. The new pattern involves star shaped cells intermixed with hexagonal shaped cells. The new patterned cellular core material includes star shaped cells interconnected at points thereof and having hexagonal shape cells positioned adjacent the star points. The new pattern allows more flexibility and can conform more easily to curved shapes. 3 figs.

  7. Differences in serological responses to specific glycopeptidolipid-core and common lipid antigens in patients with pulmonary disease due to Mycobacterium tuberculosis and Mycobacterium avium complex.

    PubMed

    Fujita, Yukiko; Doi, Takeshi; Maekura, Ryoji; Ito, Masami; Yano, Ikuya

    2006-02-01

    Disease due to the Mycobacterium avium complex (MAC) is one of the most important opportunistic pulmonary infections. Since the clinical features of MAC pulmonary disease and tuberculosis (TB) resemble each other, and the former is often difficult to treat with chemotherapy, early differential diagnosis is desirable. The humoral immune responses to both diseases were compared by a unique multiple-antigen ELISA using mycobacterial species-common and species-specific lipid antigens, including glycopeptidolipid (GPL)-core. The results were assessed for two patient groups hospitalized and diagnosed clinically as having TB or MAC pulmonary disease. Diverse IgG antibody responsiveness was demonstrated against five lipid antigens: (1) monoacyl phosphatidylinositol dimannoside (Ac-PIM2), (2) cord factor (trehalose 6,6'-dimycolate) (TDM-T) and (3) trehalose monomycolate from Mycobacterium bovis Bacillus Calmette-Guérin (BCG) (TMM-T), and (4) trehalose monomycolate (TMM-M) and (5) GPL-core from MAC. Anti-GPL-core IgG antibody was critical, and detected only in the primary and the secondary MAC diseases with high positivity, up to 88.4 %. However, IgG antibodies against Ac-PIM2, TDM-T and TMM-T were elevated in both TB and MAC patients. Anti-TMM-M IgG antibody was also elevated in MAC disease preferentially, with a positive rate of 89.9 %, and therefore, it was also useful for the diagnosis of the disease. IgG antibody levels were increased at the early stages of the disease and declined in parallel to the decrease of bacterial burden to near the normal healthy control level, when the anti-mycobacterial chemotherapy was completed successfully. Unexpectedly, about 25 % of hospitalized TB patient sera were anti-GPL-core IgG antibody positive, although the specificity of GPL-core was sufficiently high (95.8 % negative in healthy controls), suggesting that a considerable number of cases of latent co-infection with MAC may exist in TB patients. Taken together, the combination of

  8. Structural and Computational Biology in the Design of Immunogenic Vaccine Antigens

    PubMed Central

    Liljeroos, Lassi; Malito, Enrico; Ferlenghi, Ilaria; Bottomley, Matthew James

    2015-01-01

    Vaccination is historically one of the most important medical interventions for the prevention of infectious disease. Previously, vaccines were typically made of rather crude mixtures of inactivated or attenuated causative agents. However, over the last 10–20 years, several important technological and computational advances have enabled major progress in the discovery and design of potently immunogenic recombinant protein vaccine antigens. Here we discuss three key breakthrough approaches that have potentiated structural and computational vaccine design. Firstly, genomic sciences gave birth to the field of reverse vaccinology, which has enabled the rapid computational identification of potential vaccine antigens. Secondly, major advances in structural biology, experimental epitope mapping, and computational epitope prediction have yielded molecular insights into the immunogenic determinants defining protective antigens, enabling their rational optimization. Thirdly, and most recently, computational approaches have been used to convert this wealth of structural and immunological information into the design of improved vaccine antigens. This review aims to illustrate the growing power of combining sequencing, structural and computational approaches, and we discuss how this may drive the design of novel immunogens suitable for future vaccines urgently needed to increase the global prevention of infectious disease. PMID:26526043

  9. Shigella flexneri O-antigens revisited: final elucidation of the O-acetylation profiles and a survey of the O-antigen structure diversity.

    PubMed

    Perepelov, Andrei V; Shekht, Maria E; Liu, Bin; Shevelev, Sergei D; Ledov, Vladimir A; Senchenkova, Sof'ya N; L'vov, Vyacheslav L; Shashkov, Alexander S; Feng, Lu; Aparin, Petr G; Wang, Lei; Knirel, Yuriy A

    2012-11-01

    Shigella flexneri is an important human pathogen causing shigellosis. Strains of S. flexneri are serologically heterogeneous and, based on O-antigens, are currently classified into 14 types. Structures of the O-antigens (O-polysaccharides) of S. flexneri have been under study since 1960s but some gaps still remained. In this work, using one- and two-dimensional (1) H- and (13) C-NMR spectroscopy, the O-polysaccharides of several S. flexneri types were reinvestigated, and their structures were either confirmed (types 2b, 3b, 3c, 5b, X) or amended in respect to the O-acetylation pattern (types 3a, Y, 6, 6a). As a result, the O-acetylation sites were defined in all O-polysaccharides that had not been studied in detail earlier, and the long story of S. flexneri type strain O-antigen structure elucidation is thus completed. New and published data on the S. flexneri O-antigen structures are summarized and discussed in view of serological and genetic relationships of the O-antigens within the Shigella group and between S. flexneri and Escherichia coli. PMID:22724405

  10. Structure and gene cluster of the O-antigen of Escherichia coli O133.

    PubMed

    Shashkov, Alexander S; Zhang, Yuanyuan; Sun, Qiangzheng; Guo, Xi; Senchenkova, Sof'ya N; Perepelov, Andrei V; Knirel, Yuriy A

    2016-07-22

    The O-specific polysaccharide (O-antigen) of Escherichia coli O133 was obtained by mild acid hydrolysis of the lipopolysaccharide of E. coli O133. The structure of the hexasaccharide repeating unit of the polysaccharide was elucidated by (1)H and (13)C NMR spectroscopy, including a two-dimensional (1)H-(1)H ROESY experiment: Functions of genes in the O-antigen gene cluster were putatively identified by comparison with sequences in the available databases and, particularly, an encoded predicted multifunctional glycosyltransferase was assigned to three α-l-rhamnosidic linkages. PMID:27203746

  11. Antigenic peptide trimming by ER aminopeptidases--insights from structural studies.

    PubMed

    Stratikos, Efstratios; Stern, Lawrence J

    2013-10-01

    Generation and destruction of antigenic peptides by ER resident aminopeptidases ERAP1 and ERAP2 have been shown in the last few years to be important for the correct functioning and regulation of the adaptive immune response. These two highly homologous aminopeptidases appear to have evolved complex mechanisms well suited for their biological role in antigen presentation. Furthermore, polymorphic variability in these enzymes appears to affect their function and predispose individuals to disease. This review discusses our current understanding of the molecular mechanisms behind ERAP1/2 function as suggested by several recently determined crystallographic structures of these enzymes. PMID:23545452

  12. The thermal structure of low-mass cloud cores

    NASA Astrophysics Data System (ADS)

    Launhardt, Ralf; Stutz, Amelia; Schmiedecke, Anika; Henning, Thomas; Krause, Oliver; Balog, Zoltan; Beuther, Henrik; Kainulainen, Jouni; Linz, Hendrik; Lippok, Nils; Nielbock, Markus; Ragan, Sarah; Schmalzl, Markus; Shirley, Yancy; Steinacker, Juergen

    2013-07-01

    The evolution of the temperature and density structure of star-forming cloud cores is one of the key aspects in protostellar collapse models. Yet this structure, in particular the temperature, is not well-constrained observationally. In the framework of the EPoS Herschel key project, we observed the NIR extinction and FIR through mm dust emission from selected isolated nearby starless and protostellar cloud cores. Based on these data, we reconstruct the full dust temperature and density structure of the cores. We find that the thermal structure of all globules is completely dominated by external heating through the ISRF and moderate shielding by thin extended halos. All globules have warm outer envelopes (14-20 K) and colder dense interiors (7-11 K) with column densities of up to 10^23 cm^-2 and central volume densities of a few 10^5 cm^-3 (starless cores). The protostars embedded in some of the globules raise the local temperature of the dense cores only within radii out to about 5000 AU, but do not significantly affect the overall thermal balance of the globules.

  13. Temperature-sensitive mutants identify crucial structural regions of simian virus 40 large T antigen.

    PubMed Central

    Loeber, G; Tevethia, M J; Schwedes, J F; Tegtmeyer, P

    1989-01-01

    We have completed the cloning and sequencing of all known temperature-sensitive, amino acid substitution mutants of simian virus 40 large T antigen (tsA mutants). Surprisingly, many of the mutants isolated from distinct viral strains by different laboratories are identical. Thus, 17 independently isolated mutants represent only eight distinct genotypes. This remarkable clustering of tsA mutations in a few "hot spots" in the amino acid sequence of T antigen and the temperature-sensitive phenotypes of the mutations strongly suggest that these amino acids play crucial roles in organizing the structure of one or more functional domains. Most of the mutations are located in highly conserved regions of T antigen that correlate with DNA binding, protein-protein interactions, or ATP binding. With the exception of one mutant with a lesion in the putative ATP-binding region, all the mutants are temperature sensitive for DNA replication. PMID:2778883

  14. Magnetization processes in core/shell exchange-spring structures

    NASA Astrophysics Data System (ADS)

    Jiang, J. S.

    2015-05-01

    The magnetization reversal processes in cylindrical and spherical soft core/hard shell exchange-spring structures are investigated via the analytical nucleation theory and are verified with numerical micromagnetic simulations. At small core sizes, the nucleation of magnetic reversal proceeds via the modified bulging mode, where the transverse component of the magnetization is only semi-coherent in direction and the nucleation field contains a contribution from self-demagnetization. For large core sizes, the modified curling mode, where the magnetization configuration is vortex-like, is favored at nucleation. The preference for the modified curling mode is beneficial in that the flux-closure allows cylindrical and spherical core/shell exchange-spring elements to be densely packed into bulk permanent magnets without affecting the nucleation field, thereby offering the potential for high energy product.

  15. Structural organization of uniform momentum core in turbulent channel flow

    NASA Astrophysics Data System (ADS)

    Yang, Jongmin; Hwang, Jinyul; Sung, Hyung Jin

    2015-11-01

    The coherent structures across the boundary of the quiescent core region are explored using the direct numerical simulation data of a turbulent channel flow at Reτ = 930. The quiescent core is the region where the streamwise momentum is relatively uniform with low-level turbulence in channel flow. Across the boundary of this region, the turbulence intensity and the Reynolds shear stress decrease suddenly. The mean velocity profile shows a significant jump which indicates a strong mean shear layer at the boundary of the uniform core region. Due to the strong mean shear, the prograde vortices are dominantly distributed along the boundary with the retrograde vortices below them. The prograde and retrograde vortices are distributed in a pair with a uniform wall-normal distance. Large-scale low- and high-speed structures are characterized by the positions of the core boundary, revealing that the core boundary is modulated by the large-scale structures. This work was supported by the Creative Research Initiatives (No. 2015-001828) program of the National Research Foundation of Korea (MSIP) and supported by the Supercomputing Center (KISTI).

  16. Sensitivity of tropical cyclone intensification to inner-core structure

    NASA Astrophysics Data System (ADS)

    Ge, Xuyang; Xu, Wei; Zhou, Shunwu

    2015-10-01

    In this study, the dependence of tropical cyclone (TC) development on the inner-core structure of the parent vortex is examined using a pair of idealized numerical simulations. It is found that the radial profile of inner-core relative vorticity may have a great impact on its subsequent development. For a system with a larger inner-core relative vorticity/inertial stability, the conversion ratio of the diabatic heating to kinetic energy is greater. Furthermore, the behavior of the convective vorticity eddies is likely modulated by the system-scale circulation. For a parent vortex with a relatively higher inner-core vorticity and larger negative radial vorticity gradient, convective eddy formation and radially inward propagation is promoted through vorticity segregation. This provides a greater potential for these small-scale convective cells to self-organize into a mesoscale inner-core structure in the TC. In turn, convectively induced diabatic heating that is close to the center, along with higher inertial stability, efficiently enhances system-scale secondary circulation. This study provides a solid basis for further research into how the initial structure of a TC influences storm dynamics and thermodynamics.

  17. Structural Studies of Lipopolysaccharide-defective Mutants from Brucella melitensis Identify a Core Oligosaccharide Critical in Virulence.

    PubMed

    Fontana, Carolina; Conde-Álvarez, Raquel; Ståhle, Jonas; Holst, Otto; Iriarte, Maite; Zhao, Yun; Arce-Gorvel, Vilma; Hanniffy, Seán; Gorvel, Jean-Pierre; Moriyón, Ignacio; Widmalm, Göran

    2016-04-01

    The structures of the lipooligosaccharides fromBrucella melitensismutants affected in the WbkD and ManBcoreproteins have been fully characterized using NMR spectroscopy. The results revealed that disruption ofwbkDgives rise to a rough lipopolysaccharide (R-LPS) with a complete core structure (β-d-Glcp-(1→4)-α-Kdop-(2→4)[β-d-GlcpN-(1→6)-β-d-GlcpN-(1→4)[β-d-GlcpN-(1→6)]-β-d-GlcpN-(1→3)-α-d-Manp-(1→5)]-α-Kdop-(2→6)-β-d-GlcpN3N4P-(1→6)-α-d-GlcpN3N1P), in addition to components lacking one of the terminal β-d-GlcpN and/or the β-d-Glcpresidues (48 and 17%, respectively). These structures were identical to those of the R-LPS fromB. melitensisEP, a strain simultaneously expressing both smooth and R-LPS, also studied herein. In contrast, disruption ofmanBcoregives rise to a deep-rough pentasaccharide core (β-d-Glcp-(1→4)-α-Kdop-(2→4)-α-Kdop-(2→6)-β-d-GlcpN3N4P-(1→6)-α-d-GlcpN3N1P) as the major component (63%), as well as a minor tetrasaccharide component lacking the terminal β-d-Glcpresidue (37%). These results are in agreement with the predicted functions of the WbkD (glycosyltransferase involved in the biosynthesis of the O-antigen) and ManBcoreproteins (phosphomannomutase involved in the biosynthesis of a mannosyl precursor needed for the biosynthesis of the core and O-antigen). We also report that deletion ofB. melitensis wadCremoves the core oligosaccharide branch not linked to the O-antigen causing an increase in overall negative charge of the remaining LPS inner section. This is in agreement with the mannosyltransferase role predicted for WadC and the lack of GlcpN residues in the defective core oligosaccharide. Despite carrying the O-antigen essential inB. melitensisvirulence, the core deficiency in thewadCmutant structure resulted in a more efficient detection by innate immunity and attenuation, proving the role of the β-d-GlcpN-(1→6)-β-d-GlcpN-(1→4)[β-d-GlcpN-(1→6)]-β-d-GlcpN-(1→3)-α-d-Manp-(1→5) structure

  18. Structural Studies of Lipopolysaccharide-defective Mutants from Brucella melitensis Identify a Core Oligosaccharide Critical in Virulence*

    PubMed Central

    Fontana, Carolina; Conde-Álvarez, Raquel; Ståhle, Jonas; Holst, Otto; Iriarte, Maite; Zhao, Yun; Arce-Gorvel, Vilma; Hanniffy, Seán; Gorvel, Jean-Pierre; Moriyón, Ignacio; Widmalm, Göran

    2016-01-01

    The structures of the lipooligosaccharides from Brucella melitensis mutants affected in the WbkD and ManBcore proteins have been fully characterized using NMR spectroscopy. The results revealed that disruption of wbkD gives rise to a rough lipopolysaccharide (R-LPS) with a complete core structure (β-d-Glcp-(1→4)-α-Kdop-(2→4)[β-d-GlcpN-(1→6)-β-d-GlcpN-(1→4)[β-d-GlcpN-(1→6)]-β-d-GlcpN-(1→3)-α-d-Manp-(1→5)]-α-Kdop-(2→6)-β-d-GlcpN3N4P-(1→6)-α-d-GlcpN3N1P), in addition to components lacking one of the terminal β-d-GlcpN and/or the β-d-Glcp residues (48 and 17%, respectively). These structures were identical to those of the R-LPS from B. melitensis EP, a strain simultaneously expressing both smooth and R-LPS, also studied herein. In contrast, disruption of manBcore gives rise to a deep-rough pentasaccharide core (β-d-Glcp-(1→4)-α-Kdop-(2→4)-α-Kdop-(2→6)-β-d-GlcpN3N4P-(1→6)-α-d-GlcpN3N1P) as the major component (63%), as well as a minor tetrasaccharide component lacking the terminal β-d-Glcp residue (37%). These results are in agreement with the predicted functions of the WbkD (glycosyltransferase involved in the biosynthesis of the O-antigen) and ManBcore proteins (phosphomannomutase involved in the biosynthesis of a mannosyl precursor needed for the biosynthesis of the core and O-antigen). We also report that deletion of B. melitensis wadC removes the core oligosaccharide branch not linked to the O-antigen causing an increase in overall negative charge of the remaining LPS inner section. This is in agreement with the mannosyltransferase role predicted for WadC and the lack of GlcpN residues in the defective core oligosaccharide. Despite carrying the O-antigen essential in B. melitensis virulence, the core deficiency in the wadC mutant structure resulted in a more efficient detection by innate immunity and attenuation, proving the role of the β-d-GlcpN-(1→6)-β-d-GlcpN-(1→4)[β-d-GlcpN-(1→6)]-β-d-GlcpN-(1→3)-

  19. Identification of core-periphery structure in networks

    NASA Astrophysics Data System (ADS)

    Zhang, Xiao; Martin, Travis; Newman, M. E. J.

    2015-03-01

    Many networks can be usefully decomposed into a dense core plus an outlying, loosely connected periphery. Here we propose an algorithm for performing such a decomposition on empirical network data using methods of statistical inference. Our method fits a generative model of core-periphery structure to observed data using a combination of an expectation-maximization algorithm for calculating the parameters of the model and a belief propagation algorithm for calculating the decomposition itself. We find the method to be efficient, scaling easily to networks with a million or more nodes, and we test it on a range of networks, including real-world examples as well as computer-generated benchmarks, for which it successfully identifies known core-periphery structure with low error rate. We also demonstrate that the method is immune to the detectability transition observed in the related community detection problem, which prevents the detection of community structure when that structure is too weak. There is no such transition for core-periphery structure, which is detectable, albeit with some statistical error, no matter how weak it is.

  20. The elucidation of the structure of the core part of the LPS from Plesiomonas shigelloides serotype O17 expressing O-polysaccharide chain identical to the Shigella sonnei O-chain

    PubMed Central

    Kubler-Kielb, Joanna; Schneerson, Rachel; Mocca, Chris; Vinogradov, Evgeny

    2008-01-01

    Plesiomonas shigelloides O17 LPS contains the same O-antigenic polysaccharide chain as a causative agent of dysenteria Shigella sonnei. This polysaccharide can be used as a component of a vaccine against dysenteria. Core part of the P. shigelloides O17 LPS was studied using NMR and mass spectrometry and the following structure was proposed: Significant similarity of the P. shigelloides O17 LPS core with the structure of the P. shigelloides O54 core was observed. PMID:18954864

  1. Anomalous structure and dynamics of the Gaussian-core fluid.

    PubMed

    Krekelberg, William P; Kumar, Tanuj; Mittal, Jeetain; Errington, Jeffrey R; Truskett, Thomas M

    2009-03-01

    It is known that there are thermodynamic states for which the Gaussian-core fluid displays anomalous properties such as expansion upon isobaric cooling (density anomaly) and increased single-particle mobility upon isothermal compression (self-diffusivity anomaly). Here, we investigate how temperature and density affect its short-range translational structural order, as characterized by the two-body excess entropy. We find that there is a wide range of conditions for which the short-range translational order of the Gaussian-core fluid decreases upon isothermal compression (structural order anomaly). As we show, the origin of the structural anomaly is qualitatively similar to that of other anomalous fluids (e.g., water or colloids with short-range attractions) and is connected to how compression affects static correlations at different length scales. Interestingly, we find that the self-diffusivity of the Gaussian-core fluid obeys a scaling relationship with the two-body excess entropy that is very similar to the one observed for a variety of simple liquids. One consequence of this relationship is that the state points for which structural, self-diffusivity, and density anomalies of the Gaussian-core fluid occur appear as cascading regions on the temperature-density plane; a phenomenon observed earlier for models of waterlike fluids. There are, however, key differences between the anomalies of Gaussian-core and waterlike fluids, and we discuss how those can be qualitatively understood by considering the respective interparticle potentials of these models. Finally, we note that the self-diffusivity of the Gaussian-core fluid obeys different scaling laws depending on whether the two-body or total excess entropy is considered. This finding, which deserves more comprehensive future study, appears to underscore the significance of higher-body correlations for the behavior of fluids with bounded interactions. PMID:19391927

  2. The expanded FindCore method for identification of a core atom set for assessment of protein structure prediction.

    PubMed

    Snyder, David A; Grullon, Jennifer; Huang, Yuanpeng J; Tejero, Roberto; Montelione, Gaetano T

    2014-02-01

    Maximizing the scientific impact of NMR-based structure determination requires robust and statistically sound methods for assessing the precision of NMR-derived structures. In particular, a method to define a core atom set for calculating superimpositions and validating structure predictions is critical to the use of NMR-derived structures as targets in the CASP competition. FindCore (Snyder and Montelione, Proteins 2005;59:673-686) is a superimposition independent method for identifying a core atom set and partitioning that set into domains. However, as FindCore optimizes superimposition by sensitively excluding not-well-defined atoms, the FindCore core may not comprise all atoms suitable for use in certain applications of NMR structures, including the CASP assessment process. Adapting the FindCore approach to assess predicted models against experimental NMR structures in CASP10 required modification of the FindCore method. This paper describes conventions and a standard protocol to calculate an "Expanded FindCore" atom set suitable for validation and application in biological and biophysical contexts. A key application of the Expanded FindCore method is to identify a core set of atoms in the experimental NMR structure for which it makes sense to validate predicted protein structure models. We demonstrate the application of this Expanded FindCore method in characterizing well-defined regions of 18 NMR-derived CASP10 target structures. The Expanded FindCore protocol defines "expanded core atom sets" that match an expert's intuition of which parts of the structure are sufficiently well defined to use in assessing CASP model predictions. We also illustrate the impact of this analysis on the CASP GDT assessment scores. PMID:24327305

  3. Production of monoclonal antibodies to hepatitis B surface and core antigens, and use in the detection of viral antigens in liver biopsies.

    PubMed Central

    Tedder, R. S.; Guarascio, P.; Yao, J. L.; Lord, R. B.; Eddleston, A. L.

    1983-01-01

    Hybridomas secreting monoclonal antibodies to HBsAg and HBcAg were prepared from immunized mice. An antibody capture radioimmunoassay was used to detect and select appropriate hybrids for propagation and cloning. The advantages of this assay were discussed. The resulting monoclonal antibodies were compared with conventional polyclonal antisera for the detection of virus antigens in liver tissue and found to give excellent results. Images Plate 2 Plate 1 PMID:6337208

  4. Antigenic Variation in Plasmodium falciparum Malaria Involves a Highly Structured Switching Pattern

    PubMed Central

    Recker, Mario; Buckee, Caroline O.; Serazin, Andrew; Kyes, Sue; Pinches, Robert; Christodoulou, Zóe; Springer, Amy L.; Gupta, Sunetra; Newbold, Chris I.

    2011-01-01

    Many pathogenic bacteria, fungi, and protozoa achieve chronic infection through an immune evasion strategy known as antigenic variation. In the human malaria parasite Plasmodium falciparum, this involves transcriptional switching among members of the var gene family, causing parasites with different antigenic and phenotypic characteristics to appear at different times within a population. Here we use a genome-wide approach to explore this process in vitro within a set of cloned parasite populations. Our analyses reveal a non-random, highly structured switch pathway where an initially dominant transcript switches via a set of switch-intermediates either to a new dominant transcript, or back to the original. We show that this specific pathway can arise through an evolutionary conflict in which the pathogen has to optimise between safeguarding its limited antigenic repertoire and remaining capable of establishing infections in non-naïve individuals. Our results thus demonstrate a crucial role for structured switching during the early phases of infections and provide a unifying theory of antigenic variation in P. falciparum malaria as a balanced process of parasite-intrinsic switching and immune-mediated selection. PMID:21408201

  5. Genetic diversity and population structure of genes encoding vaccine candidate antigens of Plasmodium vivax

    PubMed Central

    2012-01-01

    Background A major concern in malaria vaccine development is genetic polymorphisms typically observed among Plasmodium isolates in different geographical areas across the world. Highly polymorphic regions have been observed in Plasmodium falciparum and Plasmodium vivax antigenic surface proteins such as Circumsporozoite protein (CSP), Duffy-binding protein (DBP), Merozoite surface protein-1 (MSP-1), Apical membrane antigen-1 (AMA-1) and Thrombospondin related anonymous protein (TRAP). Methods Genetic variability was assessed in important polymorphic regions of various vaccine candidate antigens in P. vivax among 106 isolates from the Amazon Region of Loreto, Peru. In addition, genetic diversity determined in Peruvian isolates was compared to population studies from various geographical locations worldwide. Results The structured diversity found in P. vivax populations did not show a geographic pattern and haplotypes from all gene candidates were distributed worldwide. In addition, evidence of balancing selection was found in polymorphic regions of the trap, dbp and ama-1 genes. Conclusions It is important to have a good representation of the haplotypes circulating worldwide when implementing a vaccine, regardless of the geographic region of deployment since selective pressure plays an important role in structuring antigen diversity. PMID:22417572

  6. Large-scale sequence and structural comparisons of human naive and antigen-experienced antibody repertoires.

    PubMed

    DeKosky, Brandon J; Lungu, Oana I; Park, Daechan; Johnson, Erik L; Charab, Wissam; Chrysostomou, Constantine; Kuroda, Daisuke; Ellington, Andrew D; Ippolito, Gregory C; Gray, Jeffrey J; Georgiou, George

    2016-05-10

    Elucidating how antigen exposure and selection shape the human antibody repertoire is fundamental to our understanding of B-cell immunity. We sequenced the paired heavy- and light-chain variable regions (VH and VL, respectively) from large populations of single B cells combined with computational modeling of antibody structures to evaluate sequence and structural features of human antibody repertoires at unprecedented depth. Analysis of a dataset comprising 55,000 antibody clusters from CD19(+)CD20(+)CD27(-) IgM-naive B cells, >120,000 antibody clusters from CD19(+)CD20(+)CD27(+) antigen-experienced B cells, and >2,000 RosettaAntibody-predicted structural models across three healthy donors led to a number of key findings: (i) VH and VL gene sequences pair in a combinatorial fashion without detectable pairing restrictions at the population level; (ii) certain VH:VL gene pairs were significantly enriched or depleted in the antigen-experienced repertoire relative to the naive repertoire; (iii) antigen selection increased antibody paratope net charge and solvent-accessible surface area; and (iv) public heavy-chain third complementarity-determining region (CDR-H3) antibodies in the antigen-experienced repertoire showed signs of convergent paired light-chain genetic signatures, including shared light-chain third complementarity-determining region (CDR-L3) amino acid sequences and/or Vκ,λ-Jκ,λ genes. The data reported here address several longstanding questions regarding antibody repertoire selection and development and provide a benchmark for future repertoire-scale analyses of antibody responses to vaccination and disease. PMID:27114511

  7. Hypervelocity Impact Evaluation of Metal Foam Core Sandwich Structures

    NASA Technical Reports Server (NTRS)

    Yasensky, John; Christiansen, Eric L.

    2007-01-01

    A series of hypervelocity impact (HVI) tests were conducted by the NASA Johnson Space Center (JSC) Hypervelocity Impact Technology Facility (HITF) [1], building 267 (Houston, Texas) between January 2003 and December 2005 to test the HVI performance of metal foams, as compared to the metal honeycomb panels currently in service. The HITF testing was conducted at the NASA JSC White Sands Testing Facility (WSTF) at Las Cruces, New Mexico. Eric L. Christiansen, Ph.D., and NASA Lead for Micro-Meteoroid Orbital Debris (MMOD) Protection requested these hypervelocity impact tests as part of shielding research conducted for the JSC Center Director Discretionary Fund (CDDF) project. The structure tested is a metal foam sandwich structure; a metal foam core between two metal facesheets. Aluminum and Titanium metals were tested for foam sandwich and honeycomb sandwich structures. Aluminum honeycomb core material is currently used in Orbiter Vehicle (OV) radiator panels and in other places in space structures. It has many desirable characteristics and performs well by many measures, especially when normalized by density. Aluminum honeycomb does not perform well in Hypervelocity Impact (HVI) Testing. This is a concern, as honeycomb panels are often exposed to space environments, and take on the role of Micrometeoroid / Orbital Debris (MMOD) shielding. Therefore, information on possible replacement core materials which perform adequately in all necessary functions of the material would be useful. In this report, HVI data is gathered for these two core materials in certain configurations and compared to gain understanding of the metal foam HVI performance.

  8. Antigenic and immunogenic properties of defined physical forms of tick-borne encephalitis virus structural proteins.

    PubMed Central

    Heinz, F X; Tuma, W; Kunz, C

    1981-01-01

    Polymeric, delipidated glycoprotein complexes of defined size and composition were prepared from tick-borne encephalitis virus by solubilization with Triton X-100 or cetyltrimethylammonium bromide, followed by centrifugation into detergent-free sucrose density gradients. The antigenic reactivities and immunogenicities of these complexes were compared with those of complete inactivated virus. These glycoprotein preparations induced hemagglutination-inhibiting and neutralizing antibodies which proved to be protective in passive mouse protection tests and monospecifically reacted only with the viral envelope and not with the internal core. In a competitive radioimmunoassay the glycoprotein complexes revealed about 10-fold higher antigenicity than whole virus when tested at equal protein concentrations. The important implications of these results with respect to antigen quantification in vaccines are discussed. As shown in the mouse challenge potency test, glycoprotein complexes prepared after Triton X-100 solubilization actively protected mice almost as well as did complete inactivated virus at the same protein concentration, whereas those prepared after cetyltrimethylammonium bromide solubilization had a somewhat lower protective activity per microgram of protein. Images PMID:7263062

  9. Research core drilling in the Manson impact structure, Iowa

    NASA Astrophysics Data System (ADS)

    Anderson, R. R.; Hartung, J. B.; Roddy, D. J.; Shoemaker, E. M.

    1992-12-01

    The Manson impact structure (MIS) has a diameter of 35 km and is the largest confirmed impact structure in the United States. The MIS has yielded a Ar-40/Ar-39 age of 65.7 Ma on microcline from its central peak, an age that is indistinguishable from the age of the Cretaceous-Tertiary boundary. In the summer of 1991 the Iowa Geological Survey Bureau and U.S. Geological Survey initiated a research core drilling project on the MIS. The first core was beneath 55 m of glacial drift. The core penetrated a 6-m layered sequence of shale and siltstone and 42 m of Cretaceous shale-dominated sedimentary clast breccia. Below this breccia, the core encountered two crystalline rock clast breccia units. The upper unit is 53 m thick, with a glassy matrix displaying various degrees of devitrification. The upper half of this unit is dominated by the glassy matrix, with shock-deformed mineral grains (especially quartz) the most common clast. The glassy-matrix unit grades downward into the basal unit in the core, a crystalline rock breccia with a sandy matrix, the matrix dominated by igneous and metamorphic rock fragments or disaggregated grains from those rocks. The unit is about 45 m thick, and grains display abundant shock deformation features. Preliminary interpretations suggest that the crystalline rock breccias are the transient crater floor, lifted up with the central peak. The sedimentary clast breccia probably represents a postimpact debris flow from the crater rim, and the uppermost layered unit probably represents a large block associated with the flow. The second core (M-2) was drilled near the center of the crater moat in an area where an early crater model suggested the presence of postimpact lake sediments. The core encountered 39 m of sedimentary clast breccia, similar to that in the M-1 core. Beneath the breccia, 120 m of poorly consolidated, mildly deformed, and sheared siltstone, shale, and sandstone was encountered. The basal unit in the core was another sequence

  10. Research core drilling in the Manson impact structure, Iowa

    NASA Technical Reports Server (NTRS)

    Anderson, R. R.; Hartung, J. B.; Roddy, D. J.; Shoemaker, E. M.

    1992-01-01

    The Manson impact structure (MIS) has a diameter of 35 km and is the largest confirmed impact structure in the United States. The MIS has yielded a Ar-40/Ar-39 age of 65.7 Ma on microcline from its central peak, an age that is indistinguishable from the age of the Cretaceous-Tertiary boundary. In the summer of 1991 the Iowa Geological Survey Bureau and U.S. Geological Survey initiated a research core drilling project on the MIS. The first core was beneath 55 m of glacial drift. The core penetrated a 6-m layered sequence of shale and siltstone and 42 m of Cretaceous shale-dominated sedimentary clast breccia. Below this breccia, the core encountered two crystalline rock clast breccia units. The upper unit is 53 m thick, with a glassy matrix displaying various degrees of devitrification. The upper half of this unit is dominated by the glassy matrix, with shock-deformed mineral grains (especially quartz) the most common clast. The glassy-matrix unit grades downward into the basal unit in the core, a crystalline rock breccia with a sandy matrix, the matrix dominated by igneous and metamorphic rock fragments or disaggregated grains from those rocks. The unit is about 45 m thick, and grains display abundant shock deformation features. Preliminary interpretations suggest that the crystalline rock breccias are the transient crater floor, lifted up with the central peak. The sedimentary clast breccia probably represents a postimpact debris flow from the crater rim, and the uppermost layered unit probably represents a large block associated with the flow. The second core (M-2) was drilled near the center of the crater moat in an area where an early crater model suggested the presence of postimpact lake sediments. The core encountered 39 m of sedimentary clast breccia, similar to that in the M-1 core. Beneath the breccia, 120 m of poorly consolidated, mildly deformed, and sheared siltstone, shale, and sandstone was encountered. The basal unit in the core was another sequence

  11. Disentangling bipartite and core-periphery structure in financial networks

    NASA Astrophysics Data System (ADS)

    Barucca, Paolo; Lillo, Fabrizio

    2016-07-01

    A growing number of systems are represented as networks whose architecture conveys significant information and determines many of their properties. Examples of network architecture include modular, bipartite, and core-periphery structures. However inferring the network structure is a non trivial task and can depend sometimes on the chosen null model. Here we propose a method for classifying network structures and ranking its nodes in a statistically well-grounded fashion. The method is based on the use of Belief Propagation for learning through Entropy Maximization on both the Stochastic Block Model (SBM) and the degree-corrected Stochastic Block Model (dcSBM). As a specific application we show how the combined use of the two ensembles -SBM and dcSBM- allows to disentangle the bipartite and the core-periphery structure in the case of the e-MID interbank network. Specifically we find that, taking into account the degree, this interbank network is better described by a bipartite structure, while using the SBM the core-periphery structure emerges only when data are aggregated for more than a week.

  12. The Expanded FindCore Method for Identification of a Core Atom Set for Assessment of Protein Structure Prediction

    PubMed Central

    Snyder, David A.; Grullon, Jennifer; Huang, Yuanpeng J.; Tejero, Roberto; Montelione, Gaetano T.

    2014-01-01

    Maximizing the scientific impact of NMR-based structure determination requires robust and statistically sound methods for assessing the precision of NMR-derived structures. In particular, a method to define a core atom set for calculating superimpositions and validating structure predictions is critical to the use of NMR-derived structures as targets in the CASP competition. FindCore (D.A. Snyder and G.T. Montelione PROTEINS 2005;59:673–686) is a superimposition independent method for identifying a core atom set, and partitioning that set into domains. However, as FindCore optimizes superimposition by sensitively excluding not-well-defined atoms, the FindCore core may not comprise all atoms suitable for use in certain applications of NMR structures, including the CASP assessment process. Adapting the FindCore approach to assess predicted models against experimental NMR structures in CASP10 required modification of the FindCore method. This paper describes conventions and a standard protocol to calculate an “Expanded FindCore” atom set suitable for validation and application in biological and biophysical contexts. A key application of the Expanded FindCore method is to identify a core set of atoms in the experimental NMR structure for which it makes sense to validate predicted protein structure models. We demonstrate the application of this Expanded FindCore method in characterizing well-defined regions of 18 NMR-derived CASP10 target structures. The Expanded FindCore protocol defines “expanded core atom sets” that match an expert’s intuition of which parts of the structure are sufficiently well-defined to use in assessing CASP model predictions. We also illustrate the impact of this analysis on the CASP GDT assessment scores. PMID:24327305

  13. Is iron at the Earth's core conditions hcp-structured?

    SciTech Connect

    Dubrovinsky, L; Dubrovinskaia, N; Prakapenka, V

    2012-02-07

    Iron is the main component of the Earth's core and its structure and properties are important for interpretation of geophysical observations and modeling dynamics of the core. We argue that the diffraction lines in the high temperature high pressure X-ray diffraction pattern, presented by Tateno et al., 2010 and interpreted as those of solely hot hcp-Fe, correspond indeed to the insufficiently heated part of the sample. We show that observed diffraction spots are either due to bcc-Fe or carbides.

  14. Atypical antigen recognition mode of a shark immunoglobulin new antigen receptor (IgNAR) variable domain characterized by humanization and structural analysis.

    PubMed

    Kovalenko, Oleg V; Olland, Andrea; Piché-Nicholas, Nicole; Godbole, Adarsh; King, Daniel; Svenson, Kristine; Calabro, Valerie; Müller, Mischa R; Barelle, Caroline J; Somers, William; Gill, Davinder S; Mosyak, Lidia; Tchistiakova, Lioudmila

    2013-06-14

    The immunoglobulin new antigen receptors (IgNARs) are a class of Ig-like molecules of the shark immune system that exist as heavy chain-only homodimers and bind antigens by their single domain variable regions (V-NARs). Following shark immunization and/or in vitro selection, V-NARs can be generated as soluble, stable, and specific high affinity monomeric binding proteins of ∼12 kDa. We have previously isolated a V-NAR from an immunized spiny dogfish shark, named E06, that binds specifically and with high affinity to human, mouse, and rat serum albumins. Humanization of E06 was carried out by converting over 60% of non-complementarity-determining region residues to those of a human germ line Vκ1 sequence, DPK9. The resulting huE06 molecules have largely retained the specificity and affinity of antigen binding of the parental V-NAR. Crystal structures of the shark E06 and its humanized variant (huE06 v1.1) in complex with human serum albumin (HSA) were determined at 3- and 2.3-Å resolution, respectively. The huE06 v1.1 molecule retained all but one amino acid residues involved in the binding site for HSA. Structural analysis of these V-NARs has revealed an unusual variable domain-antigen interaction. E06 interacts with HSA in an atypical mode that utilizes extensive framework contacts in addition to complementarity-determining regions that has not been seen previously in V-NARs. On the basis of the structure, the roles of various elements of the molecule are described with respect to antigen binding and V-NAR stability. This information broadens the general understanding of antigen recognition and provides a framework for further design and humanization of shark IgNARs. PMID:23632026

  15. X-ray absorption fine structure of artificial antigens for cadmium

    NASA Astrophysics Data System (ADS)

    Lu, Liang; Liu, Aiping; Chen, Fusheng; Wang, Xiaohong

    2011-11-01

    Immunoassay technology as a quick and large-scale screening method to detect metal ions in foods and environmental samples has rapidly been developed due to several advantages over conventional instrument-intensive methods. Unlike biomacromolecule, metal ions are haptens without immunogenicity, so successful preparation of artificial antigens is the first critical step for establishing immunoassay methods for them. In the current paper, cadmium ions were conjugated to BSA and OVA, respectively, using bifunctional chelator, p-SCN-Bn-DTPA. The ultraviolet analysis indicated that the maximum absorption peak of Cd-p-SCN-DTPA-BSA and Cd-p-SCN-DTPA-OVA had a small peak shift and an apparent absorbance increase compared to that of BSA and OVA, and the extents of substitution of ɛ-amino in both conjugates were 51.2% and 58.6%, respectively. In addition, the EXAFS of conjugates implied that Cd 2+ coordinated with N and O atoms of DTPA in artificial antigens, the coordination type and number of Cd-DTPA, Cd-p-SCN-Bn-DTPA-BSA, Cd-p-SCN-Bn-DTPA-OVA were the same. XANES region and geometries of the three compounds were also same. These results implied that the three antigens had the similar local structure and atomic geometry. This was the first time that the XAFS was attempted for the identification of artificial heavy metal ion antigens.

  16. Antigens with glycoprotein structure in the gastric juice. I. Immunological and chemical determinations.

    PubMed

    Vântu, A; Voiculet, N; Ivănescu, M; Balaban, C

    1978-01-01

    To demonstrate the presence of specific antigens in the normal and malignant gastric juice the immunological and chemical features of certain antigens with glycoprotein structure from malignant gastric jucice and gastric tumors were studied comparatively with those of antigens obtained from normal gastric juice and gastric tissue. The investigation was carried out in tumor tissue extracts from 7 patients with malignant gastric tumors and in gastric juice from 45 patients with other non-cancerous diseases. From the five fractions obtained, which gave immunoelectrophoretic precipitin lines in the beta and alpha-globulin regions with the antiserum against total normal gastric juice, a single specific was separated by means of successive chromatographies on sephadex G--100 and DEAE-Sephadex -a--50 (eluted in NaCl concentration gradient). This fraction represented 11.1 per cent of the total proteins. None of the five fractions could be identified with carcinoembryonic antigen (value in gastric juice and gastric malignant tumors = 2 to 10 ng per mg lyophilized products). PMID:635406

  17. Structure of the Malaria Antigen AMA1 in Complex with a Growth-Inhibitory Antibody

    PubMed Central

    Bai, Tao; Kim, Hanna; Anders, Robin F; Foley, Michael; Batchelor, Adrian H

    2007-01-01

    Identifying functionally critical regions of the malaria antigen AMA1 (apical membrane antigen 1) is necessary to understand the significance of the polymorphisms within this antigen for vaccine development. The crystal structure of AMA1 in complex with the Fab fragment of inhibitory monoclonal antibody 1F9 reveals that 1F9 binds to the AMA1 solvent-exposed hydrophobic trough, confirming its importance. 1F9 uses the heavy and light chain complementarity-determining regions (CDRs) to wrap around the polymorphic loops adjacent to the trough, but uses a ridge of framework residues to bind to the hydrophobic trough. The resulting 1F9-AMA1–combined buried surface of 2,470 Å2 is considerably larger than previously reported Fab–antigen interfaces. Mutations of polymorphic AMA1 residues within the 1F9 epitope disrupt 1F9 binding and dramatically reduce the binding of affinity-purified human antibodies. Moreover, 1F9 binding to AMA1 is competed by naturally acquired human antibodies, confirming that the 1F9 epitope is a frequent target of immunological attack. PMID:17907804

  18. Structural characterization of Mumps virus fusion protein core

    SciTech Connect

    Liu Yueyong; Xu Yanhui; Lou Zhiyong; Zhu Jieqing; Hu Xuebo; Gao, George F.; Qiu Bingsheng . E-mail: Qiubs@sun.im.ac.cn; Rao Zihe . E-mail: raozh@xtal.tsinghua.edu.cn; Tien, Po . E-mail: tienpo@sun.im.ac.cn

    2006-09-29

    The fusion proteins of enveloped viruses mediating the fusion between the viral and cellular membranes comprise two discontinuous heptad repeat (HR) domains located at the ectodomain of the enveloped glycoproteins. The crystal structure of the fusion protein core of Mumps virus (MuV) was determined at 2.2 A resolution. The complex is a six-helix bundle in which three HR1 peptides form a central highly hydrophobic coiled-coil and three HR2 peptides pack against the hydrophobic grooves on the surface of central coiled-coil in an oblique antiparallel manner. Fusion core of MuV, like those of simian virus 5 and human respiratory syncytium virus, forms typical 3-4-4-4-3 spacing. The similar charecterization in HR1 regions, as well as the existence of O-X-O motif in extended regions of HR2 helix, suggests a basic rule for the formation of the fusion core of viral fusion proteins.

  19. Structure and gene cluster of the O-antigen of Escherichia coli O137.

    PubMed

    Perepelov, Andrei V; Guo, Xi; Senchenkova, Sof'ya N; Li, Yayue; Shashkov, Alexander S; Liu, Bin; Knirel, Yuriy A

    2016-03-01

    The O-polysaccharide (O-antigen) was isolated from the lipopolysaccharide of Escherichia coli O137 and studied by sugar analysis and NMR spectroscopy. The following structure of the branched tetrasaccharide repeating unit was established: Formula: see text] Both structure and gene cluster of the E. coli O137 polysaccharide are related to those of the E. coli K40 polysaccharide (Amor et al., 1999), which lacks the side-chain glucosylation but contains serine that is amide-linked to GlcA. Functions of genes in the O137-antigen gene cluster were assigned by a comparison with those in K40 and sequences in the available databases. Particularly, predicted glycosyltransferases encoded in the gene cluster were assigned to the formation of three glycosidic linkages in the O-polysaccharide repeating unit. PMID:26845703

  20. The role of antigenically different virus neuraminidases as structures implicated in receptor-binding processes.

    PubMed

    Coimbra, M V; Luiz, M O; Cabral, M C; Couceiro, J N

    1995-06-01

    Influenza A viruses exhibit segmented nucleic acid coding for eight different proteins, two of them as glycoproteins exposed on their lipoprotein envelopes, hemagglutinin (HA) and neuraminidase (NA). Hemagglutinin exhibits receptor-binding activity while neuraminidase develops sialidase cleavage activity which acts on cell receptors. Influenza A strains responsible for human, avian, equine and porcine respiratory infections all over the world present antigenically different hemagglutinin (H1 to H14) and neuraminidase (N1 to N9) structures on their surface. The objective of the present investigation was to study the role of N2, N8, and N9, antigenically diverse neuraminidase structures of human (N2) and animal (N8 and N9) influenza viruses, in the receptor-binding process. Receptor-binding activity of N2 and N8 was analyzed by crossed tests using H3N2 and H3N8 antisera and the hemagglutination inhibition test as a model. Hemagglutinating activity of antigenically different N2 and N8 structures was demonstrable and was inhibited by homologous antisera (N2-H3N2, N8-H3N8) but not by heterologous antisera (N2-H3N8,N8-H3N2). This previously demonstrated N9 hemagglutinating activity was analyzed for receptor-binding specificity using hemagglutination tests and NeuAc alpha2,3Gal and NeuAc alpha2,6Gal derivatized erythrocytes. This highly purified N9 strain was obtained from a virus strain isolated from terns by Dr. Peter Colman (CSIRO Division of Biomolecular Engineering, Parkville, Victoria, Australia). It exhibited receptor-binding specificity for NeuAc alpha2,3Gal sequences, a property similar to that observed in hemagglutinins from avian strains. These results indicate the importance of antigenically different neuraminidase structures as alternative agents for developing receptor-binding activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8547843

  1. An Efficient Analysis Methodology for Fluted-Core Composite Structures

    NASA Technical Reports Server (NTRS)

    Oremont, Leonard; Schultz, Marc R.

    2012-01-01

    The primary loading condition in launch-vehicle barrel sections is axial compression, and it is therefore important to understand the compression behavior of any structures, structural concepts, and materials considered in launch-vehicle designs. This understanding will necessarily come from a combination of test and analysis. However, certain potentially beneficial structures and structural concepts do not lend themselves to commonly used simplified analysis methods, and therefore innovative analysis methodologies must be developed if these structures and structural concepts are to be considered. This paper discusses such an analysis technique for the fluted-core sandwich composite structural concept. The presented technique is based on commercially available finite-element codes, and uses shell elements to capture behavior that would normally require solid elements to capture the detailed mechanical response of the structure. The shell thicknesses and offsets using this analysis technique are parameterized, and the parameters are adjusted through a heuristic procedure until this model matches the mechanical behavior of a more detailed shell-and-solid model. Additionally, the detailed shell-and-solid model can be strategically placed in a larger, global shell-only model to capture important local behavior. Comparisons between shell-only models, experiments, and more detailed shell-and-solid models show excellent agreement. The discussed analysis methodology, though only discussed in the context of fluted-core composites, is widely applicable to other concepts.

  2. Seismic structures in the Earth's inner core below Southeastern Asia

    NASA Astrophysics Data System (ADS)

    Krasnoshchekov, Dmitry; Kaazik, Petr; Ovtchinnikov, Vladimir

    2015-04-01

    Studying seismic heterogeneities in the Earth's inner core is important in terms of understanding its history and dynamics. Measurements of body waves refracted in the vicinity of the inner core boundary yield a powerful tool for studying properties and spatial structure of such heterogeneities. We present investigation of the eastern hemisphere of the solid core by means of PKP(BC)-PKP(DF) differential travel times that sample depths from 140 to 360 km below its boundary. The study includes 292 polar and 133 equatorial residuals measured over the traces that probe roughly the same volume of the inner core in both planes. Equatorial residuals show slight spatial variations in the sampled inner core volume mostly below the level of 0.5%, whereas polar residuals are up to 1.3% and exhibit higher local variations and direction dependency. On the base of these measurements we report fast changes in seismic velocity within a restricted volume of the inner core. The observations are interpreted in terms of anisotropy and checked against several anisotropy models. Few models are capable of fitting the residuals scatter, and one of such models features a dipping discontinuity that separates fully isotropic roof of the inner core from its anisotropic body. The depth of the isotropy-anisotropy transition in the model increases in southeast direction from 190 km below Southeastern Asia (off the coast of China) to 350 km beneath Australia. Another acceptable model invokes localized anisotropic heterogeneities. It is valid if 33 largest polar measurements over the rays sampling a small volume below Southeastern Asia and the rest of polar data are treated separately. This model envisages almost isotropic eastern hemisphere of the inner core at least down to the depth of 360 km below the inner core boundary and constrains the anisotropic volume only to the ranges of North latitudes from 18 to 23 degrees, East longitudes from 125 to 135 degrees and depths exceeding 170 km. The

  3. Dynamics of beta and proliferating cell nuclear antigen sliding clamps in traversing DNA secondary structure.

    PubMed

    Yao, N; Hurwitz, J; O'Donnell, M

    2000-01-14

    Chromosomal replicases of cellular organisms utilize a ring shaped protein that encircles DNA as a mobile tether for high processivity in DNA synthesis. These "sliding clamps" have sufficiently large linear diameters to encircle duplex DNA and are perhaps even large enough to slide over certain DNA secondary structural elements. This report examines the Escherichia coli beta and human proliferating cell nuclear antigen clamps for their ability to slide over various DNA secondary structures. The results show that these clamps are capable of traversing a 13-nucleotide ssDNA loop, a 4-base pair stem-loop, a 4-nucleotide 5' tail, and a 15-mer bubble within the duplex. However, upon increasing the size of these structures (20-nucleotide loop, 12-base pair stem-loop, 28-nucleotide 5' tail, and 20-nucleotide bubble) the sliding motion of the beta and proliferating cell nuclear antigen over these elements is halted. Studies of the E. coli replicase, DNA polymerase III holoenzyme, in chain elongation with the beta clamp demonstrate that upon encounter with an oligonucleotide annealed in its path, it traverses the duplex and resumes synthesis on the 3' terminus of the oligonucleotide. This sliding and resumption of synthesis occurs even when the oligonucleotide contains a secondary structure element, provided the beta clamp can traverse the structure. However, upon encounter with a downstream oligonucleotide containing a large internal secondary structure, the holoenzyme clears the obstacle by strand displacing the oligonucleotide from the template. Implications of these protein dynamics to DNA transactions are discussed. PMID:10625694

  4. The Crystal Structure of the SV40 T-Antigen Origin Binding Domain in Complex with DNA

    PubMed Central

    Meinke, Gretchen; Phelan, Paul; Moine, Stephanie; Bochkareva, Elena; Bochkarev, Alexey; Bullock, Peter A; Bohm, Andrew

    2007-01-01

    DNA replication is initiated upon binding of “initiators” to origins of replication. In simian virus 40 (SV40), the core origin contains four pentanucleotide binding sites organized as pairs of inverted repeats. Here we describe the crystal structures of the origin binding domain (obd) of the SV40 large T-antigen (T-ag) both with and without a subfragment of origin-containing DNA. In the co-structure, two T-ag obds are oriented in a head-to-head fashion on the same face of the DNA, and each T-ag obd engages the major groove. Although the obds are very close to each other when bound to this DNA target, they do not contact one another. These data provide a high-resolution structural model that explains site-specific binding to the origin and suggests how these interactions help direct the oligomerization events that culminate in assembly of the helicase-active dodecameric complex of T-ag. PMID:17253903

  5. Structural Insights into the Inhibition of Wnt Signaling by Cancer Antigen 5T4/Wnt-Activated Inhibitory Factor 1

    PubMed Central

    Zhao, Yuguang; Malinauskas, Tomas; Harlos, Karl; Jones, E. Yvonne

    2014-01-01

    Summary The tumor antigen 5T4/WAIF1 (Wnt-activated inhibitory factor 1; also known as Trophoblast glycoprotein TPBG) is a cell surface protein targeted in multiple cancer immunotherapy clinical trials. Recently, it has been shown that 5T4/WAIF1 inhibits Wnt/β-catenin signaling, a signaling system central to many developmental and pathological processes. Wnt/β-catenin signaling is controlled by multiple inhibitors and activators. Here, we report crystal structures for the extracellular domain of 5T4/WAIF1 at 1.8 Å resolution. They reveal a highly glycosylated, rigid core, comprising eight leucine-rich repeats (LRRs), which serves as a platform to present evolutionarily conserved surface residues in the N-terminal LRR1. Structural and cell-based analyses, coupled with previously reported in vivo data, suggest that Tyr325 plus the LRR1 surface centered on a second exposed aromatic residue, Phe97, are essential for inhibition of Wnt/β-catenin signaling. These results provide a structural basis for the development of 5T4/WAIF1-targeted therapies that preserve or block 5T4/WAIF1-mediated inhibition of Wnt/β-catenin signaling. PMID:24582434

  6. Uncommon structural motifs dominate the antigen binding site in human autoantibodies reactive with basement membrane collagen.

    PubMed

    Foster, Mary H; Buckley, Elizabeth S; Chen, Benny J; Hwang, Kwan-Ki; Clark, Amy G

    2016-08-01

    Autoantibodies mediate organ destruction in multiple autoimmune diseases, yet their origins in patients remain poorly understood. To probe the genetic origins and structure of disease-associated autoantibodies, we engrafted immunodeficient mice with human CD34+ hematopoietic stem cells and immunized with the non-collagenous-1 (NC1) domain of the alpha3 chain of type IV collagen. This antigen is expressed in lungs and kidneys and is targeted by autoantibodies in anti-glomerular basement membrane (GBM) nephritis and Goodpasture syndrome (GPS), prototypic human organ-specific autoimmune diseases. Using Epstein Barr virus transformation and cell fusion, six human anti-alpha3(IV)NC1 collagen monoclonal autoantibodies (mAb) were recovered, including subsets reactive with human kidney and with epitopes recognized by patients' IgG. Sequence analysis reveals a long to exceptionally long heavy chain complementarity determining region3 (HCDR3), the major site of antigen binding, in all six mAb. Mean HCDR3 length is 25.5 amino acids (range 20-36), generated from inherently long DH and JH genes and extended regions of non-templated N-nucleotides. Long HCDR3 are suited to forming noncontiguous antigen contacts and to binding recessed, immunologically silent epitopes hidden from conventional antibodies, as seen with self-antigen crossreactive broadly neutralizing anti-HIV Ig (bnAb). The anti-alpha3(IV)NC1 collagen mAb also show preferential use of unmutated variable region genes that are enriched among human chronic lymphocytic leukemia antibodies that share features with natural polyreactive Ig. Our findings suggest unexpected relationships between pathogenic anti-collagen Ig, bnAb, and autoreactive Ig associated with malignancy, all of which arise from B cells expressing unconventional structural elements that may require transient escape from tolerance for successful expansion. PMID:27450516

  7. Crystal structure of an antigenic outer-membrane protein from Salmonella Typhi suggests a potential antigenic loop and an efflux mechanism.

    PubMed

    Guan, Hong-Hsiang; Yoshimura, Masato; Chuankhayan, Phimonphan; Lin, Chien-Chih; Chen, Nai-Chi; Yang, Ming-Chi; Ismail, Asma; Fun, Hoong-Kun; Chen, Chun-Jung

    2015-01-01

    ST50, an outer-membrane component of the multi-drug efflux system from Salmonella enterica serovar Typhi, is an obligatory diagnostic antigen for typhoid fever. ST50 is an excellent and unique diagnostic antigen with 95% specificity and 90% sensitivity and is used in the commercial diagnosis test kit (TYPHIDOT(TM)). The crystal structure of ST50 at a resolution of 2.98 Å reveals a trimer that forms an α-helical tunnel and a β-barrel transmembrane channel traversing the periplasmic space and outer membrane. Structural investigations suggest significant conformational variations in the extracellular loop regions, especially extracellular loop 2. This is the location of the most plausible antibody-binding domain that could be used to target the design of new antigenic epitopes for the development of better diagnostics or drugs for the treatment of typhoid fever. A molecule of the detergent n-octyl-β-D-glucoside is observed in the D-cage, which comprises three sets of Asp361 and Asp371 residues at the periplasmic entrance. These structural insights suggest a possible substrate transport mechanism in which the substrate first binds at the periplasmic entrance of ST50 and subsequently, via iris-like structural movements to open the periplasmic end, penetrates the periplasmic domain for efflux pumping of molecules, including poisonous metabolites or xenobiotics, for excretion outside the pathogen. PMID:26563565

  8. Crystal structure of an antigenic outer-membrane protein from Salmonella Typhi suggests a potential antigenic loop and an efflux mechanism

    PubMed Central

    Guan, Hong-Hsiang; Yoshimura, Masato; Chuankhayan, Phimonphan; Lin, Chien-Chih; Chen, Nai-Chi; Yang, Ming-Chi; Ismail, Asma; Fun, Hoong-Kun; Chen, Chun-Jung

    2015-01-01

    ST50, an outer-membrane component of the multi-drug efflux system from Salmonella enterica serovar Typhi, is an obligatory diagnostic antigen for typhoid fever. ST50 is an excellent and unique diagnostic antigen with 95% specificity and 90% sensitivity and is used in the commercial diagnosis test kit (TYPHIDOTTM). The crystal structure of ST50 at a resolution of 2.98 Å reveals a trimer that forms an α-helical tunnel and a β-barrel transmembrane channel traversing the periplasmic space and outer membrane. Structural investigations suggest significant conformational variations in the extracellular loop regions, especially extracellular loop 2. This is the location of the most plausible antibody-binding domain that could be used to target the design of new antigenic epitopes for the development of better diagnostics or drugs for the treatment of typhoid fever. A molecule of the detergent n-octyl-β-D-glucoside is observed in the D-cage, which comprises three sets of Asp361 and Asp371 residues at the periplasmic entrance. These structural insights suggest a possible substrate transport mechanism in which the substrate first binds at the periplasmic entrance of ST50 and subsequently, via iris-like structural movements to open the periplasmic end, penetrates the periplasmic domain for efflux pumping of molecules, including poisonous metabolites or xenobiotics, for excretion outside the pathogen. PMID:26563565

  9. FRESH INSIGHTS ON THE STRUCTURE OF THE SOLAR CORE

    SciTech Connect

    Basu, Sarbani; Chaplin, William J.; Elsworth, Yvonne; New, Roger; Serenelli, Aldo M. E-mail: w.j.chaplin@bham.ac.uk E-mail: r.new@shu.ac.uk

    2009-07-10

    We present new results on the structure of the solar core, obtained with new sets of frequencies of solar low-degree p modes obtained from the BiSON network. We find that different methods used in extracting the different sets of frequencies cause shifts in frequencies, but the shifts are not large enough to affect solar structure results. We find that the BiSON frequencies show that the solar sound speed in the core is slightly larger than that inferred from data from Michelson Doppler Imager low-degree modes, and the uncertainties on the inversion results are smaller. Density results also change by a larger amount, and we find that solar models now tend to show smaller differences in density compared to the Sun. The result is seen at all radii, a result of the fact that conservation of mass implies that density differences in one region have to cancel out density differences in others, since our models are constructed to have the same mass as the Sun. The uncertainties on the density results are much smaller too. We attribute the change in results to having more, and lower frequency, low-degree mode frequencies available. These modes provide greater sensitivity to conditions in the core.

  10. Galaxy Structure: Core Radii, and Central Mass Deficits

    NASA Astrophysics Data System (ADS)

    Graham, A. W.; Trujillo, I.; Erwin, P.

    2004-05-01

    We investigate the nuclear and global structure of elliptical galaxies, and the apparent disparity between the Nuker and Sérsic light-profile models. We show that the so-called ``power-law" galaxies in fact have Sérsic r1/n profiles over their entire observed radial range. Consequently, only three (Sérsic-profile) parameters are required to simultaneously describe both the inner (HST-resolved) and outer profiles of low-luminosity (M > -20.5 B-mag) elliptical galaxies. We also find that ``core galaxies" have Sérsic profiles with a (partially evacuated) single power-law core. We have developed a modified (5-parameter) Sérsic profile with a power-law core to model the complete radial extent of luminous galaxies with cores. In addition to quantifying the global stellar distribution in these systems, we have derived new estimates of their core radii and other central properties. Comparison of the central stellar deficits with the galaxies' black hole masses suggests that the number of (dissipationless) major mergers that have produced luminous elliptical galaxies is around 1-2, rather than 8-10, which agrees with theory and implies that the galactic merger history of the Universe is roughly an order of magnitude less violent than previous observational analyses had suggested. Support for proposal number HST-AR-09927.01-A was provided by NASA through a grant from the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS5-26555.

  11. Incorporating structure context of HA protein to improve antigenicity calculation for influenza virus A/H3N2.

    PubMed

    Qiu, Jingxuan; Qiu, Tianyi; Yang, Yiyan; Wu, Dingfeng; Cao, Zhiwei

    2016-01-01

    The rapid and consistent mutation of influenza requires frequent evaluation of antigenicity variation among newly emerged strains, during which several in-silico methods have been reported to facilitate the assays. In this paper, we designed a structure-based antigenicity scoring model instead of those sequence-based previously published. Protein structural context was adopted to derive the antigenicity-dominant positions, as well as the physic-chemical change of local micro-environment in correlation with antigenicity change. Then a position specific scoring matrix (PSSM) profile and local environmental change over above positions were integrated to predict the antigenicity variance. Independent testing showed a high accuracy of 0.875, and sensitivity of 0.986, with a significant ability to discover antigenic-escaping strains. When applying this model to the historical data, global and regional antigenic drift events can be successfully detected. Furthermore, two well-known vaccine failure events were clearly suggested. Therefore, this structure-context model may be particularly useful to identify those to-be-failed vaccine strains, in addition to suggest potential new vaccine strains. PMID:27498613

  12. Incorporating structure context of HA protein to improve antigenicity calculation for influenza virus A/H3N2

    PubMed Central

    Qiu, Jingxuan; Qiu, Tianyi; Yang, Yiyan; Wu, Dingfeng; Cao, Zhiwei

    2016-01-01

    The rapid and consistent mutation of influenza requires frequent evaluation of antigenicity variation among newly emerged strains, during which several in-silico methods have been reported to facilitate the assays. In this paper, we designed a structure-based antigenicity scoring model instead of those sequence-based previously published. Protein structural context was adopted to derive the antigenicity-dominant positions, as well as the physic-chemical change of local micro-environment in correlation with antigenicity change. Then a position specific scoring matrix (PSSM) profile and local environmental change over above positions were integrated to predict the antigenicity variance. Independent testing showed a high accuracy of 0.875, and sensitivity of 0.986, with a significant ability to discover antigenic-escaping strains. When applying this model to the historical data, global and regional antigenic drift events can be successfully detected. Furthermore, two well-known vaccine failure events were clearly suggested. Therefore, this structure-context model may be particularly useful to identify those to-be-failed vaccine strains, in addition to suggest potential new vaccine strains. PMID:27498613

  13. Structure of air shower disc near the core

    NASA Technical Reports Server (NTRS)

    Inoue, N.; Kawamoto, M.; Misaki, Y.; Maeda, T.; Takeuchi, T.; Toyoda, Y.

    1985-01-01

    The longitudinal structure of the air shower disk is studied by measuring the arrival time distributions of air shower particles for showers with electron size in the range 3.2 x 10 to the 5.5. power to 3.2 x 10 to the 7.5 power in the Akeno air-shower array (930 gcm squared atmospheric depth). The average FWHM as a parameter of thickness of air shower disk increases with core distances at less than 50m. AT the present stage, dependence on electron size, zenith angle and air shower age is not apparent. The average thickness of the air shower disk within a core distance of 50m could be determined by an electromagnetic cascade starting from the lower altitude.

  14. Geochemical Comparison of Four Cores from the Manson Impact Structure

    NASA Technical Reports Server (NTRS)

    Korotev, Randy L.; Rockow, Kaylynn M.; Jolliff, Bradley L.; Haskin, Larry A.; McCarville, Peter; Crossey, Laura J.

    1996-01-01

    Concentrations of 33 elements were determined in relatively unaltered, matrix-rich samples of impact breccia at approximately 3-m-depth intervals in the M-1 core from the Manson impact structure, Iowa. In addition, 46 matrix-rich samples from visibly altered regions of the M-7, M-8, and M-10 cores were studied, along with 42 small clasts from all four cores. Major element compositions were determined for a subset of impact breccias from the M-1 core, including matrix-rich impact-melt breccia. Major- and trace-element compositions were also determined for a suite of likely target rocks. In the M-1 core, different breccia units identified from lithologic examination of cores are compositionally distinct. There is a sharp compositional discontinuity at the boundary between the Keweenawan-shale-clast breccia and the underlying unit of impact-melt breccia (IMB) for most elements, suggesting minimal physical mixing between the two units during emplacement. Samples from the 40-m-thick IMB (M-1) are all similar to each other in composition, although there are slight increases in concentration with depth for those elements that have high concentrations in the underlying fragmental-matrix suevite breccia (SB) (e.g., Na, Ca, Fe, Sc), presumably as a result of greater clast proportions at the bottom margin of the unit of impact-melt breccia. The high degree of compositional similarity we observe in the impact-melt breccias supports the interpretation that the matrix of this unit represents impact melt. That our analyses show such compositional similarity results in part from our technique for sampling these breccias: for each sample we analyzed a few small fragments (total mass: approximately 200 mg) selected to be relatively free of large clasts and visible signs of alteration instead of subsamples of powders prepared from a large mass of breccia. The mean composition of the matrix-rich part of impact-melt breccia from the M-1 core can be modeled as a mixture of approximately

  15. Tyrosine 114 is essential for the trimeric structure and the functional activities of human proliferating cell nuclear antigen.

    PubMed Central

    Jónsson, Z O; Podust, V N; Podust, L M; Hübscher, U

    1995-01-01

    In order to study the effect of trimerization of proliferating cell nuclear antigen (PCNA) on its interaction with DNA polymerase (pol) delta and its loading onto DNA by replication factor C (RF-C) we have mutated a single tyrosine residue located at the subunit interface (Tyr114) to alanine. This mutation (Y114A) had a profound effect on PCNA, since it completely abolished trimer formation as seen by glycerol gradient sedimentation and native gel electrophoresis. Furthermore, the mutant protein was unable to stimulate DNA synthesis by pol delta and did not compete effectively with wild-type PCNA for pol delta, although it was able to oligomerize and could to some extent interact with subunits of functionally active PCNA. We thus conclude that PCNA molecules that are not part of a circular trimeric complex cannot interact with the pol delta core. furthermore, the mutant protein could not be loaded onto DNA by RF-C and did not compete with wild-type PCNA for loading onto DNA, indicating that PCNA trimerization may also be a prerequisite for its recognition by RF-C. The adverse effects caused by this single mutation suggest that trimerization of PCNA is essential for the monomers to keep their overall structure and that the structural changes imposed by trimerization are important for interaction with other proteins. Images PMID:8521831

  16. New approach to the design of core support structures for large LMFBR plants

    SciTech Connect

    Burelbach, J.P.; Kann, W.J.; Pan, Y.C.; Saiveau, J.G.; Seidensticker, R.W.

    1984-01-01

    The paper describes an innovative design concept for a LMFBR Core Support Structure. A hanging Core Support Structure is described and analyzed. The design offers inherent safety features, constructibility advantages, and potential cost reductions.

  17. High Velocity Impact Response of Composite Lattice Core Sandwich Structures

    NASA Astrophysics Data System (ADS)

    Wang, Bing; Zhang, Guoqi; Wang, Shixun; Ma, Li; Wu, Linzhi

    2014-04-01

    In this research, carbon fiber reinforced polymer (CFRP) composite sandwich structures with pyramidal lattice core subjected to high velocity impact ranging from 180 to 2,000 m/s have been investigated by experimental and numerical methods. Experiments using a two-stage light gas gun are conducted to investigate the impact process and to validate the finite element (FE) model. The energy absorption efficiency (EAE) in carbon fiber composite sandwich panels is compared with that of 304 stainless-steel and aluminum alloy lattice core sandwich structures. In a specific impact energy range, energy absorption efficiency in carbon fiber composite sandwich panels is higher than that of 304 stainless-steel sandwich panels and aluminum alloy sandwich panels owing to the big density of metal materials. Therefore, in addition to the multi-functional applications, carbon fiber composite sandwich panels have a potential advantage to substitute the metal sandwich panels as high velocity impact resistance structures under a specific impact energy range.

  18. Band structure of core-shell semiconductor nanowires

    NASA Astrophysics Data System (ADS)

    Pistol, Mats-Erik; Pryor, Craig

    2009-03-01

    We present band structures of strained core-shell nanowires composed of zincblende III-V (binary) semiconductors. We consider all combinations of AlN, GaN, InN, and all combinations of AlP, GaP, AlAs, GaAs, InP, InAs, AlSb, GaSb, and InSb. We compute the γ- and X-conduction band minima as well as the valence band maximum, all as functions of the core and shell radii. The calculations were performed using continuum elasticity theory for the strain, eight-band strain-dependent k.p theory for the γ-point energies, and single band approximation for the X-point conduction minima. We identify structures with type-I, type-II and type-III band alignment, as well as systems in which one material becomes metallic due to a negative band-gap. We identify structures that may support exciton crystals with and without photoexcitation. We have also computed the effective masses, from which the confinement energy may be estimated. All the results [Pistol and Pryor, Phys. Rev. B 78, 115319] are available in graphical and tabular form at www.semiconductor.physics.uiowa.edu

  19. Structural and functional studies of a 50 kDa antigenic protein from Salmonella enterica serovar Typhi.

    PubMed

    Choong, Yee Siew; Lim, Theam Soon; Chew, Ai Lan; Aziah, Ismail; Ismail, Asma

    2011-04-01

    The high typhoid incidence rate in developing and under-developed countries emphasizes the need for a rapid, affordable and accessible diagnostic test for effective therapy and disease management. TYPHIDOT®, a rapid dot enzyme immunoassay test for typhoid, was developed from the discovery of a ∼50 kDa protein specific for Salmonella enterica serovar Typhi. However, the structure of this antigen remains unknown till today. Studies on the structure of this antigen are important to elucidate its function, which will in turn increase the efficiency of the development and improvement of the typhoid detection test. This paper described the predictive structure and function of the antigenically specific protein. The homology modeling approach was employed to construct the three-dimensional structure of the antigen. The built structure possesses the features of TolC-like outer membrane protein. Molecular docking simulation was also performed to further probe the functionality of the antigen. Docking results showed that hexamminecobalt, Co(NH(3))(6)(3+), as an inhibitor of TolC protein, formed favorable hydrogen bonds with D368 and D371 of the antigen. The single point (D368A, D371A) and double point (D368A and D371A) mutations of the antigen showed a decrease (single point mutation) and loss (double point mutations) of binding affinity towards hexamminecobalt. The architecture features of the built model and the docking simulation reinforced and supported that this antigen is indeed the variant of outer membrane protein, TolC. As channel proteins are important for the virulence and survival of bacteria, therefore this ∼50 kDa channel protein is a good specific target for typhoid detection test. PMID:21371926

  20. New principle for the simultaneous detection of total and immunoglobulin M antibodies applied to the measurement of antibody to hepatitis B core antigen.

    PubMed Central

    Angarano, G; Monno, L; Santantonio, T A; Pastore, G

    1984-01-01

    A new test principle for the simultaneous detection of total approximate titers and immunoglobulin M antibodies has been developed and applied to the detection of antibody to hepatitis B core antigen. The method is based on the combination of a competition radioimmunoassay, for the determination of total antibody titer, with an indirect enzyme-linked immunosorbent assay for the determination of single class antibodies. The interference of the rheumatoid factor was avoided by including heat-aggregated immunoglobulin G in the dilution buffer. The specificity, sensitivity, and clinical application of the test are discussed. The results presented suggest that the simultaneous detection of total and immunoglobulin M antibody to hepatitis B core antigen might be helpful in the differentiation between previous and recent or ongoing hepatitis B infection, as well as in the differential diagnosis of acute hepatitis, in monitoring viral activity in chronic infections, and in helping to differentiate acute from chronic infections. The test principle appears applicable in the accurate diagnosis of other infectious diseases by a single test on only one serum sample. PMID:6381530

  1. Structural Basis for Antigenic Peptide Recognition and Processing by Endoplasmic Reticulum (ER) Aminopeptidase 2.

    PubMed

    Mpakali, Anastasia; Giastas, Petros; Mathioudakis, Nikolas; Mavridis, Irene M; Saridakis, Emmanuel; Stratikos, Efstratios

    2015-10-23

    Endoplasmic reticulum (ER) aminopeptidases process antigenic peptide precursors to generate epitopes for presentation by MHC class I molecules and help shape the antigenic peptide repertoire and cytotoxic T-cell responses. To perform this function, ER aminopeptidases have to recognize and process a vast variety of peptide sequences. To understand how these enzymes recognize substrates, we determined crystal structures of ER aminopeptidase 2 (ERAP2) in complex with a substrate analogue and a peptidic product to 2.5 and 2.7 Å, respectively, and compared them to the apo-form structure determined to 3.0 Å. The peptides were found within the internal cavity of the enzyme with no direct access to the outside solvent. The substrate analogue extends away from the catalytic center toward the distal end of the internal cavity, making interactions with several shallow pockets along the path. A similar configuration was evident for the peptidic product, although decreasing electron density toward its C terminus indicated progressive disorder. Enzymatic analysis confirmed that visualized interactions can either positively or negatively impact in vitro trimming rates. Opportunistic side-chain interactions and lack of deep specificity pockets support a limited-selectivity model for antigenic peptide processing by ERAP2. In contrast to proposed models for the homologous ERAP1, no specific recognition of the peptide C terminus by ERAP2 was evident, consistent with functional differences in length selection and self-activation between these two enzymes. Our results suggest that ERAP2 selects substrates by sequestering them in its internal cavity and allowing opportunistic interactions to determine trimming rates, thus combining substrate permissiveness with sequence bias. PMID:26381406

  2. Fabrication method for cores of structural sandwich materials including star shaped core cells

    DOEpatents

    Christensen, Richard M.

    1997-01-01

    A method for fabricating structural sandwich materials having a core pattern which utilizes star and non-star shaped cells. The sheets of material are bonded together or a single folded sheet is used, and bonded or welded at specific locations, into a flat configuration, and are then mechanically pulled or expanded normal to the plane of the sheets which expand to form the cells. This method can be utilized to fabricate other geometric cell arrangements than the star/non-star shaped cells. Four sheets of material (either a pair of bonded sheets or a single folded sheet) are bonded so as to define an area therebetween, which forms the star shaped cell when expanded.

  3. Fabrication method for cores of structural sandwich materials including star shaped core cells

    DOEpatents

    Christensen, R.M.

    1997-07-15

    A method for fabricating structural sandwich materials having a core pattern which utilizes star and non-star shaped cells is disclosed. The sheets of material are bonded together or a single folded sheet is used, and bonded or welded at specific locations, into a flat configuration, and are then mechanically pulled or expanded normal to the plane of the sheets which expand to form the cells. This method can be utilized to fabricate other geometric cell arrangements than the star/non-star shaped cells. Four sheets of material (either a pair of bonded sheets or a single folded sheet) are bonded so as to define an area therebetween, which forms the star shaped cell when expanded. 3 figs.

  4. Hepatitis C Virus E2 Envelope Glycoprotein Core Structure

    SciTech Connect

    Kong, Leopold; Giang, Erick; Nieusma, Travis; Kadam, Rameshwar U.; Cogburn, Kristin E.; Hua, Yuanzi; Dai, Xiaoping; Stanfield, Robyn L.; Burton, Dennis R.; Ward, Andrew B.; Wilson, Ian A.; Law, Mansun

    2014-08-26

    Hepatitis C virus (HCV), a Hepacivirus, is a major cause of viral hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV envelope glycoproteins E1 and E2 mediate fusion and entry into host cells and are the primary targets of the humoral immune response. The crystal structure of the E2 core bound to broadly neutralizing antibody AR3C at 2.65 angstroms reveals a compact architecture composed of a central immunoglobulin-fold β sandwich flanked by two additional protein layers. The CD81 receptor binding site was identified by electron microscopy and site-directed mutagenesis and overlaps with the AR3C epitope. The x-ray and electron microscopy E2 structures differ markedly from predictions of an extended, three-domain, class II fusion protein fold and therefore provide valuable information for HCV drug and vaccine design.

  5. Structural and Biochemical Analysis of a Single Amino-Acid Mutant of WzzBSF That Alters Lipopolysaccharide O-Antigen Chain Length in Shigella flexneri.

    PubMed

    Chang, Chiung-Wen; Tran, Elizabeth N H; Ericsson, Daniel J; Casey, Lachlan W; Lonhienne, Thierry; Benning, Friederike; Morona, Renato; Kobe, Bostjan

    2015-01-01

    Lipopolysaccharide (LPS), a surface polymer of Gram-negative bacteria, helps bacteria survive in different environments and acts as a virulence determinant of host infection. The O-antigen (Oag) component of LPS exhibits a modal chain-length distribution that is controlled by polysaccharide co-polymerases (PCPs). The molecular basis of the regulation of Oag chain-lengths remains unclear, despite extensive mutagenesis and structural studies of PCPs from Escherichia coli and Shigella. Here, we identified a single mutation (A107P) of the Shigella flexneri WzzBSF, by a random mutagenesis approach, that causes a shortened Oag chain-length distribution in bacteria. We determined the crystal structures of the periplasmic domains of wild-type WzzBSF and the A107P mutant. Both structures form a highly similar open trimeric assembly in the crystals, and show a similar tendency to self-associate in solution. Binding studies by bio-layer interferometry reveal cooperative binding of very short (VS)-core-plus-O-antigen polysaccharide (COPS) to the periplasmic domains of both proteins, but with decreased affinity for the A107P mutant. Our studies reveal that subtle and localized structural differences in PCPs can have dramatic effects on LPS chain-length distribution in bacteria, for example by altering the affinity for the substrate, which supports the role of the structure of the growing Oag polymer in this process. PMID:26378781

  6. Structural and Biochemical Analysis of a Single Amino-Acid Mutant of WzzBSF That Alters Lipopolysaccharide O-Antigen Chain Length in Shigella flexneri

    PubMed Central

    Casey, Lachlan W.; Lonhienne, Thierry; Benning, Friederike; Morona, Renato; Kobe, Bostjan

    2015-01-01

    Lipopolysaccharide (LPS), a surface polymer of Gram-negative bacteria, helps bacteria survive in different environments and acts as a virulence determinant of host infection. The O-antigen (Oag) component of LPS exhibits a modal chain-length distribution that is controlled by polysaccharide co-polymerases (PCPs). The molecular basis of the regulation of Oag chain-lengths remains unclear, despite extensive mutagenesis and structural studies of PCPs from Escherichia coli and Shigella. Here, we identified a single mutation (A107P) of the Shigella flexneri WzzBSF, by a random mutagenesis approach, that causes a shortened Oag chain-length distribution in bacteria. We determined the crystal structures of the periplasmic domains of wild-type WzzBSF and the A107P mutant. Both structures form a highly similar open trimeric assembly in the crystals, and show a similar tendency to self-associate in solution. Binding studies by bio-layer interferometry reveal cooperative binding of very short (VS)-core-plus-O-antigen polysaccharide (COPS) to the periplasmic domains of both proteins, but with decreased affinity for the A107P mutant. Our studies reveal that subtle and localized structural differences in PCPs can have dramatic effects on LPS chain-length distribution in bacteria, for example by altering the affinity for the substrate, which supports the role of the structure of the growing Oag polymer in this process. PMID:26378781

  7. Hepatitis C virus (HCV) Infection Rate among Seronegative Hemodialysis Patients Screened by Two Methods; HCV Core Antigen and Polymerase Chain Reaction

    PubMed Central

    Moini, Maryam; Ziyaeyan, Mazyar; Aghaei, Shapoor; Sagheb, Mohammad Mahdi; Taghavi, Seyed Alireza; Moeini, Mahsa; Jamalidoust, Marzieh; Hamidpour, Laleh

    2013-01-01

    Background End-stage renal disease patients on chronic hemodialysis are among high risk groups for hepatitis C virus (HCV) infection for whom routine HCV screening is recommended. Anti-HCV antibody (ab) testing may not be reliable to detect all infected cases because of the blunted ab response due to depressed immune state in these patients. Using a more reliable, cost-effective and non-complex HCV screening test may be necessary in this group of patients for case finding and management, and also for prevention of infection spread. Objectives The aim of this study was to find the prevalence of HCV infection in HCV ab negative hemodialysis patients by Real time PCR and total HCV core antigen (ag) test and comparing the results of the two tests. Patients and Methods From a single hemodialysis center, 181 anti- HCV ab negative patients were screened by total HCV core ag using an ELISA kit. Real time PCR was used for determination of the virus and viral load quantity. Results Among the 181 anti-HCV ab negative patients, 13 (7.2%) were positive for HCV core ag and 11 (6%) had detectable HCV RNA with a range of 40-336543 IU/ml by PCR. The two tests had a high measurement agreement (Kappa=0.82, P<0.001). Of the 13 patients with positive HCV core ag test results, 3 were negative for HCV RNA. Considering real time PCR for HCV RNA as the gold standard for HCV infection determination in this patient population, HCV core ag assay yielded a sensitivity of 90.9%, specificity of 98.2%, positive predictive value of 76.9% and negative predictive value of 99.4%. Discussion The rate of HCV infection among HCV ab negative hemodialysis patients was high. HCV core ag testing could be used as a sensitive method for HCV infection screening in this group of patients. PMID:24032048

  8. DNA secondary structures are associated with recombination in major Plasmodium falciparum variable surface antigen gene families

    PubMed Central

    Sander, Adam F.; Lavstsen, Thomas; Rask, Thomas S.; Lisby, Michael; Salanti, Ali; Fordyce, Sarah L.; Jespersen, Jakob S.; Carter, Richard; Deitsch, Kirk W.; Theander, Thor G.; Pedersen, Anders Gorm; Arnot, David E.

    2014-01-01

    Many bacterial, viral and parasitic pathogens undergo antigenic variation to counter host immune defense mechanisms. In Plasmodium falciparum, the most lethal of human malaria parasites, switching of var gene expression results in alternating expression of the adhesion proteins of the Plasmodium falciparum-erythrocyte membrane protein 1 class on the infected erythrocyte surface. Recombination clearly generates var diversity, but the nature and control of the genetic exchanges involved remain unclear. By experimental and bioinformatic identification of recombination events and genome-wide recombination hotspots in var genes, we show that during the parasite’s sexual stages, ectopic recombination between isogenous var paralogs occurs near low folding free energy DNA 50-mers and that these sequences are heavily concentrated at the boundaries of regions encoding individual Plasmodium falciparum-erythrocyte membrane protein 1 structural domains. The recombinogenic potential of these 50-mers is not parasite-specific because these sequences also induce recombination when transferred to the yeast Saccharomyces cerevisiae. Genetic cross data suggest that DNA secondary structures (DSS) act as inducers of recombination during DNA replication in P. falciparum sexual stages, and that these DSS-regulated genetic exchanges generate functional and diverse P. falciparum adhesion antigens. DSS-induced recombination may represent a common mechanism for optimizing the evolvability of virulence gene families in pathogens. PMID:24253306

  9. Structural, Antigenic, and Evolutionary Characterizations of the Envelope Protein of Newly Emerging Duck Tembusu Virus

    PubMed Central

    Huang, Bing; Ma, Xiuli; Li, Yufeng; Yuan, Xiaoyuan; Qin, Zhuoming; Wang, Dan; Chakravarty, Suvobrata; Li, Feng; Song, Minxun; Sun, Huaichang

    2013-01-01

    Since the first reported cases of ducks infected with a previously unknown flavivirus in eastern China in April 2010, the virus, provisionally designated Duck Tembusu Virus (DTMUV), has spread widely in domestic ducks in China and caused significant economic losses to poultry industry. In this study, we examined in detail structural, antigenic, and evolutionary properties of envelope (E) proteins of six DTMUV isolates spanning 2010–2012, each being isolated from individual farms with different geographical locations where disease outbreaks were documented. Structural analysis showed that E proteins of DTMUV and its closely related flavivirus (Japanese Encephalitis Virus) shared a conserved array of predicted functional domains and motifs. Among the six DTMUV strains, mutations were observed only at thirteen amino acid positions across three separate domains of the E protein. Interestingly, these genetic polymorphisms resulted in no detectable change in viral neutralization properties as demonstrated in a serum neutralization assay. Furthermore, phylogenetic analysis of the nucleotide sequences of the E proteins showed that viruses evolved into two distinct genotypes, termed as DTMUV.I and DTMUV.II, with II emerging as the dominant genotype. New findings described here shall give insights into the antigenicity and evolution of this new pathogen and provide guidance for further functional studies of the E protein for which no effective vaccine has yet been developed. PMID:23990944

  10. Scattering loss analysis and structure optimization of hollow-core photonic bandgap fiber

    NASA Astrophysics Data System (ADS)

    Song, Jingming; Wu, Rong; Sun, Kang; Xu, Xiaoliang

    2016-06-01

    Effects of core structure in 7 cell hollow-core photonic bandgap fibers (HC-PBGFs) on scattering loss are analyzed by means of investigating normalized interface field intensity. Fibers with different core wall thickness, core radius and rounding corner of air hole are simulated. Results show that with thick core wall and expanded core radius, scattering loss could be greatly reduced. The scattering loss of the HC-PBGFs in the wavelength range of 1.5-1.56 μm could be decreased by about 50 % of the present level with optimized core structure design.

  11. Identification of CD4+ and CD8+ T cell epitopes of woodchuck hepatitis virus core and surface antigens in BALB/c mice.

    PubMed

    Ochoa-Callejero, L; Otano, I; Vales, A; Olagüe, C; Sarobe, P; Lasarte, J J; Prieto, J; Menne, S; González-Aseguinolaza, G

    2010-07-19

    A therapeutic vaccine against chronic hepatitis B virus (HBV) infection requires the development of a strong and multispecific Th1 cell immune response. Woodchucks chronically infected with the woodchuck hepatitis virus (WHV) closely resemble HBV infection and represent the best animal model for this hepadnavirus-induced disease. Using the BIMAS "HLA Peptide Binding Predictions" program, we have identified and further characterized novel H-2 d-restricted CD8+ epitopes within the WHV core (peptides C#12-21, C#18-32, C#19-27, C#61-69) and surface antigens (peptides preS2#10-18, preS2#27-35, S#76-84, S#133-140 and S#257-265), respectively. These peptides bind to H-2 d with high efficiency and upon immunization of mice with peptide and Freund's adjuvant they induce the development of IFN-gamma producing T cells. More importantly, WHV core peptides C#19-27 and C#61-69 and WHV surface peptides S#133-140 and S#257-265 were also recognized by CD8+ T cells after immunization of mice with DNA/PEI nanoparticles. Direct stimulation of splenocytes obtained from such DNA-immunized mice with peptides C#18-32, S#76-84, and S#257-265 resulted in significant production of IFN-gamma. Thus, we have identified T cell determinants in mice from WHV core and surface antigens that have important value for designing and evaluating an effective vaccine against hepadnavirus infection. PMID:20665977

  12. Molecular and Structural Bases for the Antigenicity of VP2 of Infectious Bursal Disease Virus▿

    PubMed Central

    Letzel, Tobias; Coulibaly, Fasseli; Rey, Felix A.; Delmas, Bernard; Jagt, Erik; van Loon, Adriaan A. M. W.; Mundt, Egbert

    2007-01-01

    Infectious bursal disease virus (IBDV), a member of the family Birnaviridae, is responsible for a highly contagious and economically important disease causing immunosuppression in chickens. IBDV variants isolated in the United States exhibit antigenic drift affecting neutralizing epitopes in the capsid protein VP2. To understand antigenic determinants of the virus, we have used a reverse-genetics approach to introduce selected amino acid changes—individually or in combination—into the VP2 gene of the classical IBDV strain D78. We thus generated a total of 42 mutants with changes in 8 amino acids selected by sequence comparison and their locations on loops PBC and PHI at the tip of the VP2 spikes, as shown by the crystal structure of the virion. The antibody reactivities of the mutants generated were assessed using a panel of five monoclonal antibodies (MAbs). Our results show that a few amino acids of the projecting domain of VP2 control the reactivity pattern. Indeed, the binding of four out of the five MAbs analyzed here is affected by mutations in these loops. Furthermore, their importance is highlighted by the fact that some of the engineered mutants display identical reactivity patterns but have different growth phenotypes. Finally, this analysis shows that a new field strain isolated from a chicken flock in Belgium (Bel-IBDV) represents an IBDV variant with a hitherto unobserved antigenic profile, involving one change (P222S) in the PBC loop. Overall, our data provide important new insights for devising efficient vaccines that protect against circulating IBDV strains. PMID:17881448

  13. Engineering N-linked protein glycosylation with diverse O antigen lipopolysaccharide structures in Escherichia coli.

    PubMed

    Feldman, Mario F; Wacker, Michael; Hernandez, Marcela; Hitchen, Paul G; Marolda, Cristina L; Kowarik, Michael; Morris, Howard R; Dell, Anne; Valvano, Miguel A; Aebi, Markus

    2005-02-22

    Campylobacter jejuni has a general N-linked protein glycosylation system that can be functionally transferred to Escherichia coli. In this study, we engineered E. coli cells in a way that two different pathways, protein N-glycosylation and lipopolysaccharide (LPS) biosynthesis, converge at the step in which PglB, the key enzyme of the C. jejuni N-glycosylation system, transfers O polysaccharide from a lipid carrier (undecaprenyl pyrophosphate) to an acceptor protein. PglB was the only protein of the bacterial N-glycosylation machinery both necessary and sufficient for the transfer. The relaxed specificity of the PglB oligosaccharyltransferase toward the glycan structure was exploited to create novel N-glycan structures containing two distinct E. coli or Pseudomonas aeruginosa O antigens. PglB-mediated transfer of polysaccharides might be valuable for in vivo production of O polysaccharides-protein conjugates for use as antibacterial vaccines. PMID:15703289

  14. Structure elucidation and gene cluster characterization of the O-antigen of Escherichia coli O80.

    PubMed

    Senchenkova, Sof'ya N; Guo, Xi; Filatov, Andrei V; Perepelov, Andrei V; Liu, Bin; Shashkov, Alexander S; Knirel, Yuriy A

    2016-09-01

    Mild alkaline degradation of the lipopolysaccharide of Escherichia coli O80 afforded a polysaccharide, which was studied by sugar analysis, selective cleavage of glycosidic linkages, and (1)H and (13)C NMR spectroscopy. Solvolysis of the polysaccharide with CF3CO2H cleaved the linkages of α-Fuc and β-linked GlcNAc and GalNAc residues to give two disaccharides. The following structure of the hexasaccharide repeating unit of the O-polysaccharide was established: The polysaccharide repeat also contains a minor O-acetyl group but its position was not determined. The O-antigen gene cluster of E. coli O80 between the conserved galF and gnd genes was analyzed and found to be consistent with the O-polysaccharide structure established. PMID:27454490

  15. Structure and gene cluster of the O-antigen of Enterobacter cloacae G3421.

    PubMed

    Perepelov, Andrei V; Filatov, Andrei V; Wang, Min; Shashkov, Alexander S; Wang, Lei; Knirel, Yuriy A

    2016-06-01

    The O-polysaccharide was isolated by mild acid degradation of the lipopolysaccharide of Enterobacter cloacae G3421 and studied by sugar analysis along with 1D and 2D (1)H and (13)C NMR spectroscopy. In addition, partial solvolysis with anhydrous trifluoroacetic acid was applied, which cleaved selectively the α-l-rhamnopyranosidic linkages. The following structure of the branched hexasaccharide repeating unit was established. The O-polysaccharide studied shares the β-l-Rhap-(1→4)-α-l-Rhap-(1→2)-α-l-Rhap trisaccharide fragment with the O-polysaccharide of Shigella boydii type 18. The O-antigen gene cluster of E. cloacae G3421 was sequenced. Functions of genes in the cluster, including those for glycosyltransferases, were tentatively assigned by a comparison with sequences in the available databases and found to be consistent with the O-polysaccharide structure. PMID:27131290

  16. Structure and biochemical characterization of proliferating cellular nuclear antigen from a parasitic protozoon

    SciTech Connect

    Cardona-Felix, Cesar S.; Lara-Gonzalez, Samuel; Brieba, Luis G.

    2012-02-08

    Proliferating cellular nuclear antigen (PCNA) is a toroidal-shaped protein that is involved in cell-cycle control, DNA replication and DNA repair. Parasitic protozoa are early-diverged eukaryotes that are responsible for neglected diseases. In this work, a PCNA from a parasitic protozoon was identified, cloned and biochemically characterized and its crystal structure was determined. Structural and biochemical studies demonstrate that PCNA from Entamoeba histolytica assembles as a homotrimer that is able to interact with and stimulate the activity of a PCNA-interacting peptide-motif protein from E. histolytica, EhDNAligI. The data indicate a conservation of the biochemical mechanisms of PCNA-mediated interactions between metazoa, yeast and parasitic protozoa.

  17. Structure of a lamprey variable lymphocyte receptor in complex with a protein antigen

    PubMed Central

    Velikovsky, C Alejandro; Deng, Lu; Tasumi, Satoshi; Iyer, Lakshminarayan M; Kerzic, Melissa C; Aravind, L; Pancer, Zeev; Mariuzza, Roy A

    2009-01-01

    Variable lymphocyte receptors (VLRs) are leucine-rich repeat (LRR) proteins that mediate adaptive immunity in jawless vertebrates. VLRs are fundamentally different from the antibodies of jawed vertebrates, which consist of immunoglobulin (Ig) domains. We determined the structure of an anti-hen egg white lysozyme (HEL) VLRB, isolated by yeast display, bound to HEL. The VLR, whose affinity resembles that of IgM antibodies, uses nearly all its concave surface to bind the protein, in addition to a loop that penetrates into the enzyme active site. The VLR-HEL structure, combined with sequence analysis, revealed an almost perfect match between ligand-contacting positions and positions with highest sequence diversity. Thus, we have defined the generalized antigen-binding site of VLRs. We further demonstrated that VLRs can be affinity-matured to affinities as high as those of IgG antibodies, making VLRs potential alternatives to antibodies for biotechnology applications. PMID:19543291

  18. Crystal Structure of Insulin-Regulated Aminopeptidase with Bound Substrate Analogue Provides Insight on Antigenic Epitope Precursor Recognition and Processing.

    PubMed

    Mpakali, Anastasia; Saridakis, Emmanuel; Harlos, Karl; Zhao, Yuguang; Papakyriakou, Athanasios; Kokkala, Paraskevi; Georgiadis, Dimitris; Stratikos, Efstratios

    2015-09-15

    Aminopeptidases that generate antigenic peptides influence immunodominance and adaptive cytotoxic immune responses. The mechanisms that allow these enzymes to efficiently process a vast number of different long peptide substrates are poorly understood. In this work, we report the structure of insulin-regulated aminopeptidase, an enzyme that prepares antigenic epitopes for cross-presentation in dendritic cells, in complex with an antigenic peptide precursor analog. Insulin-regulated aminopeptidase is found in a semiclosed conformation with an extended internal cavity with limited access to the solvent. The N-terminal moiety of the peptide is located at the active site, positioned optimally for catalysis, whereas the C-terminal moiety of the peptide is stabilized along the extended internal cavity lodged between domains II and IV. Hydrophobic interactions and shape complementarity enhance peptide affinity beyond the catalytic site and support a limited selectivity model for antigenic peptide selection that may underlie the generation of complex immunopeptidomes. PMID:26259583

  19. Sandwich Composite, Syntactic Foam Core Based, Application for Space Structures

    NASA Technical Reports Server (NTRS)

    Hodge, Andrew J.; Kaul, Raj K.; McMahon, William M.; Reinarts, Thomas

    2000-01-01

    The current Solid Rocket Booster (SRB) launch vehicle has several metal based components that require a Thermal Protective System (TPS) be applied to the exterior surface to ensure its structural integrity and to protect the interior hardware from aerodynamic heating. TPS materials have distinct disadvantages associated with their use. One disadvantage to the application of TPS is that it can act as a debris source to the Space Shuttle Orbiter during flight and it also adds weight to the system without directly contributing any structural strength. One of the specific areas examined under this program was to replace a metal/TPS system with polymer based composites. A polymer matrix based sandwich composite was developed which had both structural and insulative properties to meet the high aerodynamic structural and heating load survival requirements. The SRB Nose Cap was selected as a candidate for this application. The sandwich system being qualified for this application is a carbon/epoxy outer and inner skin with a high strength-low thermal conductivity syntactic foam core.

  20. Structural basis of Lewisb antigen binding by the Helicobacter pylori adhesin BabA

    PubMed Central

    Hage, Naim; Howard, Tina; Phillips, Chris; Brassington, Claire; Overman, Ross; Debreczeni, Judit; Gellert, Paul; Stolnik, Snow; Winkler, G. Sebastiaan; Falcone, Franco H.

    2015-01-01

    Helicobacter pylori is a leading cause of peptic ulceration and gastric cancer worldwide. To achieve colonization of the stomach, this Gram-negative bacterium adheres to Lewisb (Leb) antigens in the gastric mucosa using its outer membrane protein BabA. Structural information for BabA has been elusive, and thus, its molecular mechanism for recognizing Leb antigens remains unknown. We present the crystal structure of the extracellular domain of BabA, from H. pylori strain J99, in the absence and presence of Leb at 2.0- and 2.1-Å resolutions, respectively. BabA is a predominantly α-helical molecule with a markedly kinked tertiary structure containing a single, shallow Leb binding site at its tip within a β-strand motif. No conformational change occurs in BabA upon binding of Leb, which is characterized by low affinity under acidic [KD (dissociation constant) of ~227 μM] and neutral (KD of ~252 μM) conditions. Binding is mediated by a network of hydrogen bonds between Leb Fuc1, GlcNAc3, Fuc4, and Gal5 residues and a total of eight BabA amino acids (C189, G191, N194, N206, D233, S234, S244, and T246) through both carbonyl backbone and side-chain interactions. The structural model was validated through the generation of two BabA variants containing N206A and combined D233A/S244A substitutions, which result in a reduction and complete loss of binding affinity to Leb, respectively. Knowledge of the molecular basis of Leb recognition by BabA provides a platform for the development of therapeutics targeted at inhibiting H. pylori adherence to the gastric mucosa. PMID:26601230

  1. Structural basis of Lewis(b) antigen binding by the Helicobacter pylori adhesin BabA.

    PubMed

    Hage, Naim; Howard, Tina; Phillips, Chris; Brassington, Claire; Overman, Ross; Debreczeni, Judit; Gellert, Paul; Stolnik, Snow; Winkler, G Sebastiaan; Falcone, Franco H

    2015-08-01

    Helicobacter pylori is a leading cause of peptic ulceration and gastric cancer worldwide. To achieve colonization of the stomach, this Gram-negative bacterium adheres to Lewis(b) (Le(b)) antigens in the gastric mucosa using its outer membrane protein BabA. Structural information for BabA has been elusive, and thus, its molecular mechanism for recognizing Le(b) antigens remains unknown. We present the crystal structure of the extracellular domain of BabA, from H. pylori strain J99, in the absence and presence of Le(b) at 2.0- and 2.1-Å resolutions, respectively. BabA is a predominantly α-helical molecule with a markedly kinked tertiary structure containing a single, shallow Le(b) binding site at its tip within a β-strand motif. No conformational change occurs in BabA upon binding of Le(b), which is characterized by low affinity under acidic [K D (dissociation constant) of ~227 μM] and neutral (K D of ~252 μM) conditions. Binding is mediated by a network of hydrogen bonds between Le(b) Fuc1, GlcNAc3, Fuc4, and Gal5 residues and a total of eight BabA amino acids (C189, G191, N194, N206, D233, S234, S244, and T246) through both carbonyl backbone and side-chain interactions. The structural model was validated through the generation of two BabA variants containing N206A and combined D233A/S244A substitutions, which result in a reduction and complete loss of binding affinity to Le(b), respectively. Knowledge of the molecular basis of Le(b) recognition by BabA provides a platform for the development of therapeutics targeted at inhibiting H. pylori adherence to the gastric mucosa. PMID:26601230

  2. Research Update: Enabling ultra-thin lightweight structures: Microsandwich structures with microlattice cores

    NASA Astrophysics Data System (ADS)

    Kolodziejska, J. A.; Roper, C. S.; Yang, S. S.; Carter, W. B.; Jacobsen, A. J.

    2015-05-01

    We achieve the benefits of large-scale structural hierarchy at the micro-scale by utilizing a self-propagating photopolymer waveguide process to form ultra-thin sandwich structures. A single step forms the microlattice sandwich core and bonds the core to both facesheets, minimizing adhesive mass and manufacturing time, with core thicknesses <2 mm, facesheet thicknesses ranging from 12.7 to 300 μm, areal densities 0.030-0.041 g cm-2, and flexural rigidity per unit width up to 0.62 Nm. This work extends the lightweighting benefit of sandwich structures to lower thicknesses and areal densities that were previously the exclusive domain of monolithic materials.

  3. Identification of antigenic domains in the non-structural protein of Muscovy duck parvovirus.

    PubMed

    Yu, Tian-Fei; Li, Ming; Yan, Bing; Shao, Shu-Li; Fan, Xing-Dong; Wang, Jia; Wang, Dan-Na

    2016-08-01

    Muscovy duck parvovirus (MDPV) infection is widespread in many Muscovy-duck-farming countries, leading to a huge economic loss. By means of overlapping peptides expressed in Escherichia coli in combination with Western blot, antigenic domains on the non-structural protein (NSP) of MDPV were identified for the first time. On the Western blot, the fragments NS(481-510), NS (501-530), NS (521-550), NS (541-570), NS (561-590), NS (581-610) and NS (601-627) were positive (the numbers in parentheses indicate the location of amino acids), and other fragments were negative. These seven fragments were also reactive in an indirect enzyme-linked immunosorbent assay (i-ELISA). We therefore conclude that a linear antigenic domain of the NSP is located at its C-terminal end (amino acid residues 481-627). These results may facilitate future investigations into the function of NSP of MDPV and the development of immunoassays for the diagnosis of MDPV infection. PMID:27154558

  4. The structural basis for T-antigen hydrolysis by Streptococcus pneumoniae: a target for structure-based vaccine design.

    PubMed

    Caines, Matthew E C; Zhu, Haizhong; Vuckovic, Marija; Willis, Lisa M; Withers, Stephen G; Wakarchuk, Warren W; Strynadka, Natalie C J

    2008-11-14

    Streptococcus pneumoniae endo-alpha-N-acetylgalactosaminidase is a cell surface-anchored glycoside hydrolase from family GH101 involved in the breakdown of mucin type O-linked glycans. The 189-kDa mature enzyme specifically hydrolyzes the T-antigen disaccharide from extracellular host glycoproteins and is representative of a broadly important class of virulence factors that have remained structurally uncharacterized due to their large size and highly modular nature. Here we report a 2.9 angstroms resolution crystal structure that remarkably captures the multidomain architecture and characterizes a catalytic center unexpectedly resembling that of alpha-amylases. Our analysis presents a complete model of glycoprotein recognition and provides a basis for the structure-based design of novel Streptococcus vaccines and therapeutics. PMID:18784084

  5. Descriptions and preliminary interpretations of cores recovered from the Manson Impact Structure (Iowa)

    NASA Astrophysics Data System (ADS)

    Anderson, R. R.; Witzke, B. J.; Hartung, J. B.; Shoemaker, E. M.; Roddy, D. J.

    1993-03-01

    A core drilling program initiated by the Iowa Geological Survey Bureau and U.S. Geological Survey in 1991 and 1992 collected 12 cores totalling over 1200 m from the Manson Impact Structure, a probable K-T boundary structure located in north-central Iowa. Cores were recovered from each of the major structural terranes, with 2 cores (M-3 and M-4) from the Terrace Terrane, 4 cores (M-2, M-2A, M-6, and M-9) from the Crater Moat, and 6 cores (M-1, M-5, M-7, M-8, M-10, and M-11) from the Central Peak. These supplemented 2 central peak cores (1-A and 2-A) drilled in 1953. The cores penetrated five major impact lithologies: (1) sedimentary clast breccia; (2) impact ejecta; (3) central peak crystallite rocks; (4) crystalline clast breccia with sandy matrix; and (5) crystallite clast breccia with a melt matrix. Descriptions and preliminary interpretations of these cores are presented.

  6. Descriptions and preliminary interpretations of cores recovered from the Manson Impact Structure (Iowa)

    NASA Technical Reports Server (NTRS)

    Anderson, R. R.; Witzke, B. J.; Hartung, J. B.; Shoemaker, E. M.; Roddy, D. J.

    1993-01-01

    A core drilling program initiated by the Iowa Geological Survey Bureau and U.S. Geological Survey in 1991 and 1992 collected 12 cores totalling over 1200 m from the Manson Impact Structure, a probable K-T boundary structure located in north-central Iowa. Cores were recovered from each of the major structural terranes, with 2 cores (M-3 and M-4) from the Terrace Terrane, 4 cores (M-2, M-2A, M-6, and M-9) from the Crater Moat, and 6 cores (M-1, M-5, M-7, M-8, M-10, and M-11) from the Central Peak. These supplemented 2 central peak cores (1-A and 2-A) drilled in 1953. The cores penetrated five major impact lithologies: (1) sedimentary clast breccia; (2) impact ejecta; (3) central peak crystallite rocks; (4) crystalline clast breccia with sandy matrix; and (5) crystallite clast breccia with a melt matrix. Descriptions and preliminary interpretations of these cores are presented.

  7. Hierarchical Velocity Structure in the Core of Abell 2597

    NASA Technical Reports Server (NTRS)

    Still, Martin; Mushotzky, Richard

    2004-01-01

    We present XMM-Newton RGS and EPIC data of the putative cooling flow cluster Abell 2597. Velocities of the low-ionization emission lines in the spectrum are blue shifted with respect to the high-ionization lines by 1320 (sup +660) (sub -210) kilometers per second, which is consistent with the difference in the two peaks of the galaxy velocity distribution and may be the signature of bulk turbulence, infall, rotation or damped oscillation in the cluster. A hierarchical velocity structure such as this could be the direct result of galaxy mergers in the cluster core, or the injection of power into the cluster gas from a central engine. The uniform X-ray morphology of the cluster, the absence of fine scale temperature structure and the random distribution of the the galaxy positions, independent of velocity, suggests that our line of sight is close to the direction of motion. These results have strong implications for cooling flow models of the cluster Abell 2597. They give impetus to those models which account for the observed temperature structure of some clusters using mergers instead of cooling flows.

  8. Population structure and minimum core genome typing of Legionella pneumophila

    PubMed Central

    Qin, Tian; Zhang, Wen; Liu, Wenbin; Zhou, Haijian; Ren, Hongyu; Shao, Zhujun; Lan, Ruiting; Xu, Jianguo

    2016-01-01

    Legionella pneumophila is an important human pathogen causing Legionnaires’ disease. In this study, whole genome sequencing (WGS) was used to study the characteristics and population structure of L. pneumophila strains. We sequenced and compared 53 isolates of L. pneumophila covering different serogroups and sequence-based typing (SBT) types (STs). We found that 1,896 single-copy orthologous genes were shared by all isolates and were defined as the minimum core genome (MCG) of L. pneumophila. A total of 323,224 single-nucleotide polymorphisms (SNPs) were identified among the 53 strains. After excluding 314,059 SNPs which were likely to be results of recombination, the remaining 9,165 SNPs were referred to as MCG SNPs. Population Structure analysis based on MCG divided the 53 L. pneumophila into nine MCG groups. The within-group distances were much smaller than the between-group distances, indicating considerable divergence between MCG groups. MCG groups were also supplied by phylogenetic analysis and may be considered as robust taxonomic units within L. pneumophila. Among the nine MCG groups, eight showed high intracellular growth ability while one showed low intracellular growth ability. Furthermore, MCG typing also showed high resolution in subtyping ST1 strains. The results obtained in this study provided significant insights into the evolution, population structure and pathogenicity of L. pneumophila. PMID:26888563

  9. Population structure and minimum core genome typing of Legionella pneumophila.

    PubMed

    Qin, Tian; Zhang, Wen; Liu, Wenbin; Zhou, Haijian; Ren, Hongyu; Shao, Zhujun; Lan, Ruiting; Xu, Jianguo

    2016-01-01

    Legionella pneumophila is an important human pathogen causing Legionnaires' disease. In this study, whole genome sequencing (WGS) was used to study the characteristics and population structure of L. pneumophila strains. We sequenced and compared 53 isolates of L. pneumophila covering different serogroups and sequence-based typing (SBT) types (STs). We found that 1,896 single-copy orthologous genes were shared by all isolates and were defined as the minimum core genome (MCG) of L. pneumophila. A total of 323,224 single-nucleotide polymorphisms (SNPs) were identified among the 53 strains. After excluding 314,059 SNPs which were likely to be results of recombination, the remaining 9,165 SNPs were referred to as MCG SNPs. Population Structure analysis based on MCG divided the 53 L. pneumophila into nine MCG groups. The within-group distances were much smaller than the between-group distances, indicating considerable divergence between MCG groups. MCG groups were also supplied by phylogenetic analysis and may be considered as robust taxonomic units within L. pneumophila. Among the nine MCG groups, eight showed high intracellular growth ability while one showed low intracellular growth ability. Furthermore, MCG typing also showed high resolution in subtyping ST1 strains. The results obtained in this study provided significant insights into the evolution, population structure and pathogenicity of L. pneumophila. PMID:26888563

  10. Dendritic cell-based vaccination with lentiviral vectors encoding ubiquitinated hepatitis B core antigen enhances hepatitis B virus-specific immune responses in vivo.

    PubMed

    Dai, Shenglan; Zhuo, Meng; Song, Linlin; Chen, Xiaohua; Yu, Yongsheng; Tang, Zhenghao; Zang, Guoqing

    2015-11-01

    The activity of hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) plays a predominant role in the clearance of HBV. Dendritic cells (DCs) are key antigen-presenting cells and play an important role in the initiation of immune responses. We previously verified that lentiviral vector encoding ubiquitinated hepatitis B core antigen (LV-Ub-HBcAg) effectively transduced DCs to induce maturation, and the mature DCs efficiently induced T cell polarization to Th1 and generated HBcAg-specific CTLs ex vivo. In this study, HBV-specific immune responses of LV-Ub-HBcAg in BALB/c mice (H-2Kd) were evaluated. It was shown that direct injection of LV-Ub-HBcAg increased the production of cytokines IL-2 and IFN-γ, elicited strong antibody responses, and remarkably generated a high percentage of IFN-γ+CD8+ T cells with HBV-specific CTL responses in BALB/c mice. In addition, direct injection of LV-Ub-HBcAg induced potent anti-HBV immune responses, similar to those elicited by in vitro-transduced DCs. In conclusion, the DC-based therapeutic vaccine LV-Ub-HBcAg elicited specific antibody immune responses and induced robust specific CTL activity in vivo. PMID:26373843

  11. Hepatitis B virus core antigen as a carrier for Chlamydia trachomatis MOMP multi-epitope peptide enhances protection against genital chlamydial infection

    PubMed Central

    Xiong, Yirong; Lv, Yan; Feng, Juan; Zhu, Shanli; Xue, Xiangyang; Chen, Shao; Zhang, Lifang

    2015-01-01

    Chlamydia trachomatis (Ct) is the leading cause of sexually transmitted diseases worldwide. There is no safe and effective vaccine to control the spread of Ct. In development of Ct vaccine, selection of appropriate candidate antigens and an effective delivery system may be the main challenges. Multi-epitope of major outer membrane protein (MOMPm) is the most suitable candidate for a Ct vaccine, while hepatitis B virus core antigen (HBcAg) has unique advantages as vaccine delivery system. Therefore, in this study, we evaluated the immunogenicity and protective immune response of a novel candidate vaccine in a murine model of chlamydial genital infection. This candidate vaccine comprises MOMPm peptide delivered with HBcAg. Our results of Ct-specific serum IgG and secretory IgA assay, cytokine assay, and cytotoxic T-lymphocyte assay revealed that immunogenicity of the candidate vaccine was much better than that of the corresponding synthetic MOMPm peptide. Furthermore, the protective effect of the candidate vaccine was also shown much better than that of the synthetic peptide by calculating the isolation of Chlamydia from vaginal swabs and histopathological analysis. Taken together, our results indicate that HBcAg carrying Ct MOMPm could be an effective immune prophylactic for chlamydial infection. PMID:26657117

  12. [The development and certification of the Hepabest anti-HBc IgG test system for detecting antibodies to the core antigen of the hepatitis B virus].

    PubMed

    Iaroslavtseva, O A; Netesova, I G; Karpenko, L I; Mel'nikova, O V; Zaĭtsev, S A; Il'ichev, A A

    1998-01-01

    The comparison of the newly developed "HepaBest anti-HBc IgG" assay system for the detection of hepatitis B virus (HBV) core antigen with the reference system "ImmunoComb HBc IgG" (Orgenics, France-Israel) and its approbation on 91 serum samples from patients in the Infectious Clinical Hospital were carried out. The coincidence rate of the results obtained with the use of the two assay systems was 87.9%. The system "HepaBest anti-HBc IgG" permitted the detection of patients whose sera contained no other HBV markers, except anti-HBc IgG. This assay system may be recommended for use in clinical and epidemiological investigations for ascertaining the diagnosis. PMID:9783401

  13. A general approach to the localization of antigenic determinants of a linear type in proteins of unknown primary structure.

    PubMed

    Beresten, S F; Rubikaite, B I; Kisselev, L L

    1988-10-26

    A method is proposed which permits the localization of antigenic determinants of a linear type on the polypeptide chain of a protein molecule of unknown primary structure. An antigen modified with maleic anhydride at the amino-terminal groups and at the epsilon-NH2 groups of lysine residues was subjected to partial enzymic digestion, so that the antigenic protein had, on average, less than one cleavage site per polypeptide chain. The resultant ends were labeled with 125I-labeled Bolton and Hunter reagent and the maleic group removed. The detection of the two larger labeled fragments (a longer one which still could bind to a monoclonal antibody and a shorter one which was incapable of binding) made it possible to determine the distance from the antigenic determinant to the C-terminus of the polypeptide chain. The position of the antigenic determinant could be established in more detail using partial chemical degradation of the original antigen using information about the maximal length of a fragment which has lost its ability to interact with the monoclonal antibody. The method has been applied to bovine tryptophanyl-tRNA synthetase (EC 6.1.1.2). PMID:2459255

  14. Effects of messenger RNA structure and other translational control mechanisms on major histocompatibility complex-I mediated antigen presentation

    PubMed Central

    Murat, Pierre; Tellam, Judy

    2015-01-01

    Effective T-cell surveillance of antigen-presenting cells is dependent on the expression of an array of antigenic peptides bound to major histocompatibility complex (MHC) class I (MHC-I) or class II (MHC-II) molecules. Pathogens co-evolving with their hosts exploit crucial translational regulatory mechanisms in order to evade host immune recognition and thereby sustain their infection. Evasion strategies that downregulate viral protein synthesis and thereby restrict antigen presentation to cytotoxic T-cells through the endogenous MHC-I pathway have been implicated in the pathogenesis of viral-associated malignancies. An understanding of the mechanisms by which messenger RNA (mRNA) structure modulates both viral mRNA translation and the antigen processing machinery to escape immune surveillance, will stimulate the development of alternative therapeutic strategies focused on RNA-directed drugs designed to enhance immune responses against infected cells. In this review, we discuss regulatory aspects of the MHC-I pathway and summarize current knowledge of the role attributed by mRNA structure and other translational regulatory mechanisms in immune evasion. In particular we highlight the impact of recently identified G-quadruplex structures within virally encoded transcripts as unique regulatory signals for translational control and antigen presentation. WIREs RNA 2015, 6:157–171. doi: 10.1002/wrna.1262 PMID:25264139

  15. High copy numbers and N terminal insertion position of influenza A M2E fused with hepatitis B core antigen enhanced immunogenicity.

    PubMed

    Sun, Xincheng; Wang, Yunlong; Dong, Caiwen; Hu, Jinqiang; Yang, Liping

    2015-08-01

    The extra domain of influenza M2 protein (M2e) is almost completely conserved among all influenza A virus subtypes. M2e is a promising candidate target for the development of a broad-spectrum recombinant influenza A vaccine. However, the immunogenicity of M2e needs to be improved. Copy numbers of M2e and its fusion expression with different carrier proteins may affect its immunopotency. In this study, we designed and created different constructs through genetic fusion of M2e (MSLLTEVETPTRSEWECRCSDSSD) (A/California/05/2009 (H1N1)) with the N-terminus (HBcAg1-149aa + Cys) by insertion in the N-terminus Hepatitis B Core (HBc) antigen 1-149aa and Middle 78-81aa of HBcAg1-149aa to construct a recombinant M2e-based vaccine candidate. These chimeric sequences were expressed in Escherichia coli. We constructed fusion proteins containing influenza A H1N1 influenza virus (2009), as well as one, two, and three copies of M2e and hepatitis B core antigen1-149aa amino acid-optimized codon inserted N and its intermediate. The recombinant protein was expressed and purified. Western blot analysis was employed to evaluate the expression of the M2e recombinant protein containing different copy numbers of M2e. Mice were immunized for two times with the purified fusion protein HBc/M2e BALB/c. Serum levels of M2e antibody gradually increased along with increase in immunity. The levels of different fusion protein M2e antibodies increase with increasing M2e copy number. In addition, the protein antibody level in the N terminal fusion protein is higher than that in intermediate fusion. PMID:26355223

  16. Form follows function - the three-dimensional structure of antigen receptor gene loci.

    PubMed

    Fugmann, Sebastian D

    2014-04-01

    Antigen receptor genes are assembled during lymphocyte development from individual gene segments by a somatic gene rearrangement process named V(D)J recombination. This process is tightly regulated to ensure the generation of an unbiased broad primary repertoire of immunoglobulins and T cell receptors, and to prevent aberrant recombination products that could initiate lymphomagenesis. One important mode of regulation that has recently been discovered for the immunoglobulin heavy chain (IGH) gene locus is the adoption of distinct three-dimensional structures of the locus. Changes in the spatial conformation are thought to ensure the appropriate access of the V(D)J recombinase machinery at each developmental stage, and the formation of extensive chromosome loops has been implicated in allowing equal access to widely dispersed gene elements. PMID:24549092

  17. Solution structure of the origin DNA-binding domain of SV40 T-antigen.

    PubMed

    Luo, X; Sanford, D G; Bullock, P A; Bachovchin, W W

    1996-12-01

    The structure of the domain from simian virus 40 (SV40) large T-antigen that binds to the SV40 origin of DNA replication (T-ag-OBD131-260) has been determined by nuclear magnetic resonance spectroscopy. The overall fold, consisting of a central five-stranded antiparallel beta-sheet flanked by two alpha-helices on one side and one alpha-helix and one 3(10)-helix on the other, is a new one. Previous mutational analyses have identified two elements, termed A (approximately 152-155) and B2 (203-207), as essential for origin-specific recognition. These elements form two closely juxtaposed loops that define a continuous surface on the protein. The addition of a duplex oligonucleotide containing the origin recognition pentanucleotide GAGGC induces chemical shift changes and slows amide proton exchange in resonances from this region, indicating that this surface directly contacts the DNA. PMID:8946857

  18. Structural Constraints on Human Norovirus Binding to Histo-Blood Group Antigens

    PubMed Central

    Singh, Bishal K.; Leuthold, Mila M.

    2016-01-01

    ABSTRACT Human norovirus interacts with the polymorphic human histo-blood group antigens (HBGAs), and this interaction is thought to be important for infection. The genogroup II genotype 4 (GII.4) noroviruses are the dominant cluster, evolve every other year, and are thought to modify their binding interactions with different HBGA types. Most human noroviruses bind HBGAs, while some strains were found to have minimal or no HBGA interactions. Here, we explain some possible structural constraints for several noroviruses that were found to bind poorly to HBGAs by using X-ray crystallography. We showed that one aspartic acid was flexible or positioned away from the fucose moiety of the HBGAs and this likely hindered binding, although other fucose-interacting residues were perfectly oriented. Interestingly, a neighboring loop also appeared to influence the loop hosting the aspartic acid. These new findings might explain why some human noroviruses bound HBGAs poorly, although further studies are required. PMID:27303720

  19. Structural Constraints on Human Norovirus Binding to Histo-Blood Group Antigens.

    PubMed

    Singh, Bishal K; Leuthold, Mila M; Hansman, Grant S

    2016-01-01

    Human norovirus interacts with the polymorphic human histo-blood group antigens (HBGAs), and this interaction is thought to be important for infection. The genogroup II genotype 4 (GII.4) noroviruses are the dominant cluster, evolve every other year, and are thought to modify their binding interactions with different HBGA types. Most human noroviruses bind HBGAs, while some strains were found to have minimal or no HBGA interactions. Here, we explain some possible structural constraints for several noroviruses that were found to bind poorly to HBGAs by using X-ray crystallography. We showed that one aspartic acid was flexible or positioned away from the fucose moiety of the HBGAs and this likely hindered binding, although other fucose-interacting residues were perfectly oriented. Interestingly, a neighboring loop also appeared to influence the loop hosting the aspartic acid. These new findings might explain why some human noroviruses bound HBGAs poorly, although further studies are required. PMID:27303720

  20. Variation in the structural subunit and basal protein antigens of Bacteroides nodosus fimbriae.

    PubMed Central

    Anderson, B J; Kristo, C L; Egerton, J R; Mattick, J S

    1986-01-01

    The fimbriae of Bacteroides nodosus play a major role in protective immunity against ovine footrot and are an important determinant in the serological classification system that divides field isolates into at least eight serogroups and 16 serotypes. Purified fimbriae contain two polypeptide antigens, the structural subunit of the fimbrial strand (molecular weight about 17,000) and a basal protein (molecular weight about 80,000), both of which exhibit structural variation. Fimbriae were prepared from all prototype strains, as well as from a number of other isolates representative of each of the B. nodosus serotypes, and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Substantial variation was observed in the electrophoretic mobility of the fimbrial subunits from the prototypes of each of the eight serogroups. With the exception of serogroup H, which is an unusual case, the apparent molecular weights of the fimbrial subunits ranged from about 16,500 in serogroup D to 19,000 in serogroup F (serotype 1); in serogroup A, B, C and E, the apparent molecular weights were clustered in the range of 17,000 to 17,500, whereas serogroup G was about 18,500. Serogroup H fimbriae appeared to consist of two smaller polypeptides, which in the prototype (H1) had apparent molecular weights of about 6,000 and 10,000 and which seem to have arisen as a consequence of an internal proteolytic nick in the original subunit. Electrophoretic variation in the fimbrial subunit was also observed between different serotypes, although with the exceptions of serogroups F and H, this was not as pronounced as between the serogroups. Examination of a number of isolates classified within the same serotypes showed that some variation, although minor, also occurred at this level. The basal antigen exhibited significant variation at all levels of the serotypic hierarchy in a manner apparently unrelated to the classification system. Among the range of isolates examined, the apparent

  1. Seismic Structures in the Earth's Inner Core Below Southeastern Asia

    NASA Astrophysics Data System (ADS)

    Krasnoshchekov, Dmitry; Kaazik, Petr; Kozlovskaya, Elena; Ovtchinnikov, Vladimir

    2016-02-01

    Documenting seismic heterogeneities in the Earth's inner core (IC) is important in terms of getting an insight into its history and dynamics. A valuable means for studying properties and spatial structure of such heterogeneities is provided by measurements of body waves refracted in the vicinity of the inner core boundary (ICB). Here, we investigate eastern hemisphere of the solid core by means of PKPBC-PKPDF differential travel times that sample depths from 140 to 360 km below its boundary. We study 292 polar and 133 equatorial residuals measured over the traces that probe roughly the same volume of the IC in both planes. Equatorial residuals show slight spatial variations in the sampled IC volume mostly below the level of 0.5 %, whereas polar residuals are up to three times as big, direction dependent and can exhibit higher local variations. The measurements reveal fast changes in seismic velocity within a restricted volume of the IC. We interpret the observations in terms of anisotropy and check against several anisotropy models few of which have been found capable of fitting the residuals scatter. We particularly quantify the model where a dipping discontinuity separates fully isotropic roof of the IC from its anisotropic body, whereas the depth of isotropy-anisotropy transition increases in southeast direction from 190 km below Southeastern Asia (off the coast of China) to 350 km beneath Australia. Another acceptable model cast in terms of localized anisotropic heterogeneities is valid if 33 largest polar measurements over the rays sampling a small volume below Southeastern Asia and the rest of polar data are treated separately. This model envisages almost isotropic eastern hemisphere of the IC at least down to the depth of 360 km below the ICB and constrains the anisotropic volume only to the ranges of North latitudes from 18° to 23°, East longitudes from 125° to 135° and depths exceeding 170 km. The anisotropy strength in either model is about 2

  2. Seismic Structures in the Earth's Inner Core Below Southeastern Asia

    NASA Astrophysics Data System (ADS)

    Krasnoshchekov, Dmitry; Kaazik, Petr; Kozlovskaya, Elena; Ovtchinnikov, Vladimir

    2016-05-01

    Documenting seismic heterogeneities in the Earth's inner core (IC) is important in terms of getting an insight into its history and dynamics. A valuable means for studying properties and spatial structure of such heterogeneities is provided by measurements of body waves refracted in the vicinity of the inner core boundary (ICB). Here, we investigate eastern hemisphere of the solid core by means of PKPBC-PKPDF differential travel times that sample depths from 140 to 360 km below its boundary. We study 292 polar and 133 equatorial residuals measured over the traces that probe roughly the same volume of the IC in both planes. Equatorial residuals show slight spatial variations in the sampled IC volume mostly below the level of 0.5 %, whereas polar residuals are up to three times as big, direction dependent and can exhibit higher local variations. The measurements reveal fast changes in seismic velocity within a restricted volume of the IC. We interpret the observations in terms of anisotropy and check against several anisotropy models few of which have been found capable of fitting the residuals scatter. We particularly quantify the model where a dipping discontinuity separates fully isotropic roof of the IC from its anisotropic body, whereas the depth of isotropy-anisotropy transition increases in southeast direction from 190 km below Southeastern Asia (off the coast of China) to 350 km beneath Australia. Another acceptable model cast in terms of localized anisotropic heterogeneities is valid if 33 largest polar measurements over the rays sampling a small volume below Southeastern Asia and the rest of polar data are treated separately. This model envisages almost isotropic eastern hemisphere of the IC at least down to the depth of 360 km below the ICB and constrains the anisotropic volume only to the ranges of North latitudes from 18° to 23°, East longitudes from 125° to 135° and depths exceeding 170 km. The anisotropy strength in either model is about 2

  3. Structural and Biochemical Insights into MLL1 Core Complex Assembly

    SciTech Connect

    Avdic, Vanja; Zhang, Pamela; Lanouette, Sylvain; Groulx, Adam; Tremblay, Véronique; Brunzelle, Joseph; Couture, Jean-François

    2012-05-02

    Histone H3 Lys-4 methylation is predominantly catalyzed by a family of methyltransferases whose enzymatic activity depends on their interaction with a three-subunit complex composed of WDR5, RbBP5, and Ash2L. Here, we report that a segment of 50 residues of RbBP5 bridges the Ash2L C-terminal domain to WDR5. The crystal structure of WDR5 in ternary complex with RbBP5 and MLL1 reveals that both proteins binds peptide-binding clefts located on opposite sides of WDR5s {beta}-propeller domain. RbBP5 engages in several hydrogen bonds and van der Waals contacts within a V-shaped cleft formed by the junction of two blades on WDR5. Mutational analyses of both the WDR5 V-shaped cleft and RbBP5 residues reveal that the interactions between RbBP5 and WDR5 are important for the stimulation of MLL1 methyltransferase activity. Overall, this study provides the structural basis underlying the formation of the WDR5-RbBP5 subcomplex and further highlight the crucial role of WDR5 in scaffolding the MLL1 core complex.

  4. Massive quiescent cores in Orion. V. The internal structures and physical and chemical properties of two extremely dense cores

    SciTech Connect

    Ren, Zhiyuan; Li, Di; Chapman, N. E-mail: dili@nao.cas.cn

    2014-06-20

    We present a high-resolution (∼ 1.''5) observational study of two massive dust-gas cores, ORI8nw{sub 2} and ORI2{sub 6}, in the Orion molecular cloud using the Combined Array for Research in Millimeter-wave Astronomy. In each region the 3.2 mm continuum emission exhibits a dense and compact dust core at the center with 1-3 solar masses. The cores have number densities exceeding 10{sup 9} cm{sup –3}, which are among the highest volume densities observed in star-forming cores. In both regions the N{sub 2}H{sup +} shows clumpy structures that are spatially displaced from the densest gas. In OIR8nw{sub 2} in particular, the N{sub 2}H{sup +} shows a noticeable filament structure with a central cavity shell. The calculation for the dynamical state shows that this core can be potentially supported by the magnetic field against its gravitational instability, but the fragmentation might still occur and produce the observed N{sub 2}H{sup +} clumps if the gas density exceeds 5 × 10{sup 7} cm{sup –3} and this value is available within the observed density range. Also, the extremely high density at the core center suggests super-Jeans condition and the possibility for further fragmentation. For the chemical properties, the N{sub 2}H{sup +}-to-HCO{sup +} abundance ratios are shown to be different than those observed in infrared dark clouds. A combined analysis with the other Orion cores and the chemical model suggests that the different abundance ratios can be explained by the low CO abundances in our cores. To further reveal the evolution of such dense cores, higher resolution and sensitivity are required.

  5. Aspherical structural heterogeneity within the uppermost inner core: Insights into the hemispherical boundaries and core formation

    NASA Astrophysics Data System (ADS)

    Miller, Meghan S.; Niu, Fenglin; Vanacore, Elizabeth A.

    2013-10-01

    Lateral heterogeneities at the top of the inner core are investigated using earthquakes that occurred in Indonesia and southeast Asia and were recorded in the southeastern Caribbean. Using seismic observations of attenuation and seismic velocity, we were able to constrain the characteristics of the boundary between the inner and outer core to further investigate the dynamics and evolution of the Earth’s core. Our seismic observations from core phases confirm that the outermost inner core is asymmetrically heterogeneous and we are able to further constrain the morphology and physical properties of this layer. Comparison of data from earthquakes with ray paths traversing from east to the west versus those with ray paths from west to east allow us to map the aspherical heterogeneity of the boundary layer and specifically image the boundary between the proposed quasi-eastern and western hemispheres of the inner core. The variation of differential travel times between PKPdf and PKPbc, attenuation in terms of Q factor, and latitudinal changes for both of these observations, can be attributed to localized heterogeneity at the quasi-hemispherical boundaries of the inner core. We constrain the change in the thickness of outermost core boundary layer from 100 to 250 km within a distance of a few 10s of kilometers at 45°E ± 2°, for the western boundary, with an overall P-wave velocity decrease in the western hemisphere of 0.5% and increase of 0.5% in the eastern hemisphere. We constrain the eastern boundary at latitudes greater than 45°N to 173°E ± 4° with an overall P-wave velocity decrease in the western hemisphere of 1.0% in the uppermost 200 km of the inner core. The eastern boundary at equatorial latitudes is constrained to a region <170°E with a western hemisphere with a 0.5% drop in P-wave velocity in the uppermost 250 km.

  6. Antigenic structure of simian virus 40 large tumor antigen and association with cellular protein p53 on the surfaces of simian virus 40-infected and -transformed cells.

    PubMed Central

    Santos, M; Butel, J S

    1984-01-01

    The antigenic structure of simian virus 40 (SV40) large tumor antigen (T-ag) in the plasma membranes of SV40-transformed mouse cells and SV40-infected monkey cells was characterized as a step toward defining possible biological function(s). Wild-type SV40, as well as a deletion mutant of SV40 (dl1263) which codes for a truncated T-ag with an altered carboxy terminus, was used to infect permissive cells. Members of a series of monoclonal antibodies directed against antigenic determinants on either the amino or the carboxy terminus of the T-ag polypeptide were able to precipitate surface T-ag (as well as nuclear T-ag) from both SV40-transformed and SV40-infected cells. Cellular protein p53 was coprecipitated with T-ag by all T-ag-reactive reagents from the surface and nucleus of SV40-transformed cells. In contrast, T-ag, but not T-ag-p53 complex, was recovered from the surface of SV40-infected cells. These results confirm that nuclear T-ag and surface T-ag are highly related molecules and that a complex of SV40 T-ag and p53 is present at the surface of SV40-transformed cells. Detectable levels of such a complex do not appear to be present on SV40-infected cells. Both the carboxy and amino termini of T-ag are exposed on the surfaces of SV40-transformed and -infected cells. The possible relevance of the presence of a T-ag-p53 complex on the surface of SV40-transformed cells and its absence from SV40-infected cells is considered. Images PMID:6205166

  7. Understanding the structural specificity of Tn antigen for its receptor: an NMR solution study.

    PubMed

    D'Amelio, Nicola; Coslovi, Anna; Rossi, Marco; Uggeri, Fulvio; Paoletti, Sergio

    2012-04-01

    The present work aims at understanding the structural basis of the biological recognition of Tn antigen (GalNAc-α-O-L-Ser), a specific epitope expressed by tumor cells, and the role of its amino acidic moiety in the interaction with its receptor (the isolectin B4 extracted from Vicia villosa). An NMR structural characterization of the α and β anomers, based on J couplings and molecular modeling revealed a structure in very good agreement with data reported in literature for variants of the same molecules. In order to demonstrate the involvement of the amino acid in the ligand-receptor recognition, also GalNAc-α-O-D-Ser was studied; the change in the stereochemistry is in fact expected to impact on the interaction only in case the serine is part of the epitope. Relaxation properties in the presence of the receptor clearly indicated a selective recognition of the natural L form, probably due to the formation of a water-mediated hydrogen bond with Asn 129 of the protein. PMID:22341503

  8. Structure-based Epitope Mapping of Mycobacterium tuberculosis Secretary Antigen MTC28.

    PubMed

    Kundu, Prasun; Biswas, Rupam; Mukherjee, Somnath; Reinhard, Linda; Dutta, Anirudha; Mueller-Dieckmann, Jochen; Weiss, Manfred S; Pal, Nishit Kumar; Das, Amit Kumar

    2016-07-01

    Secretary proteins of Mycobacterium tuberculosis are key players of the mycobacterial infection pathway. MTC28 is a 28-kDa proline-rich secretary antigen of Mycobacterium tuberculosis and is only conserved in pathogenic strains of mycobacteria. Here we report the crystal structure of MTC28 at 2.8- and 2.15-Å resolutions for the structure-based epitope design. MTC28 shares a "mog1p"-fold consisting of seven antiparallel β strands stacked between α helices. Five probable epitopes have been located on a solvent-accessible flexible region by computational analysis of the structure of MTC28. Simultaneously, the protein is digested with trypsin and the resulting fragments are purified by HPLC. Such 10 purified peptide fragments are screened against sera from patients infected with pulmonary tuberculosis (PTB). Two of these 10 fragments, namely (127)ALDITLPMPPR(137) and (138)WTQVPDPNVPDAFVVIADR(156),are found to be major immunogenic epitopes that are localized on the outer surface of the protein molecule and are part of a single continuous epitope that have been predicted in silico Mutagenesis and antibody inhibition studies are in accordance with the results obtained from epitope mapping. PMID:27189947

  9. Core Oligosaccharide of Plesiomonas shigelloides PCM 2231 (Serotype O17) Lipopolysaccharide—Structural and Serological Analysis

    PubMed Central

    Maciejewska, Anna; Lukasiewicz, Jolanta; Kaszowska, Marta; Man-Kupisinska, Aleksandra; Jachymek, Wojciech; Lugowski, Czeslaw

    2013-01-01

    The herein presented complete structure of the core oligosaccharide of lipopolysaccharide (LPS) P. shigelloides Polish Collection of Microorganisms (PCM) 2231 (serotype O17) was investigated by 1H, 13C NMR spectroscopy, mass spectrometry, chemical analyses and serological methods. The core oligosaccharide is composed of an undecasaccharide, which represents the second core type identified for P. shigelloides serotype O17 LPS. This structure is similar to that of the core oligosaccharide of P. shigelloides strains 302-73 (serotype O1) and 7-63 (serotype O17) and differs from these only by one sugar residue. Serological screening of 55 strains of P. shigelloides with the use of serum against identified core oligosaccharide conjugated with bovine serum albumin (BSA) indicated the presence of similar structures in the LPS core region of 28 O-serotypes. This observation suggests that the core oligosaccharide structure present in strain PCM 2231 could be the most common type among P. shigelloides lipopolysaccharides. PMID:23389090

  10. Structures of Coxsackievirus A16 Capsids with Native Antigenicity: Implications for Particle Expansion, Receptor Binding, and Immunogenicity

    PubMed Central

    Ren, Jingshan; Wang, Xiangxi; Zhu, Ling; Hu, Zhongyu; Gao, Qiang; Yang, Pan; Li, Xuemei; Wang, Junzhi; Shen, Xinliang; Fry, Elizabeth E.

    2015-01-01

    ABSTRACT Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the primary causes of the epidemics of hand-foot-and-mouth disease (HFMD) that affect more than a million children in China each year and lead to hundreds of deaths. Although there has been progress with vaccines for EV71, the development of a CVA16 vaccine has proved more challenging, and the EV71 vaccine does not give useful cross-protection, despite the capsid proteins of the two viruses sharing about 80% sequence identity. The structural details of the expanded forms of the capsids, which possess nonnative antigenicity, are now well understood, but high resolution information for the native antigenic form of CVA16 has been missing. Here, we remedy this with high resolution X-ray structures of both mature and natural empty CVA16 particles and also of empty recombinant viruslike particles of CVA16 produced in insect cells, a potential vaccine antigen. All three structures are unexpanded native particles and antigenically identical. The recombinant particles have recruited a lipid moiety to stabilize the native antigenic state that is different from the one used in a natural virus infection. As expected, the mature CVA16 virus is similar to EV71; however, structural and immunogenic comparisons highlight differences that may have implications for vaccine production. IMPORTANCE Hand-foot-and-mouth disease is a serious public health threat to children in Asian-Pacific countries, resulting in millions of cases. EV71 and CVA16 are the two dominant causative agents of the disease that, while usually mild, can cause severe neurological complications, leading to hundreds of deaths. EV71 vaccines do not provide protection against CVA16. A CVA16 vaccine or bivalent EV71/CVA16 vaccine is therefore urgently needed. We report atomic structures for the mature CVA16 virus, a natural empty particle, and a recombinant CVA16 virus-like particle that does not contain the viral genome. All three particles have similar

  11. Phosphorylation of Simian Virus 40 T Antigen on Thr 124 Selectively Promotes Double-Hexamer Formation on Subfragments of the Viral Core Origin

    PubMed Central

    Barbaro, Brett A.; Sreekumar, K. R.; Winters, Danielle R.; Prack, Andrea E.; Bullock, Peter A.

    2000-01-01

    Cell cycle-dependent phosphorylation of simian virus 40 (SV40) large tumor antigen (T-ag) on threonine 124 is essential for the initiation of viral DNA replication. A T-ag molecule containing a Thr→Ala substitution at this position (T124A) was previously shown to bind to the SV40 core origin but to be defective in DNA unwinding and initiation of DNA replication. However, exactly what step in the initiation process is defective as a result of the T124A mutation has not been established. Therefore, to better understand the control of SV40 replication, we have reinvestigated the assembly of T124A molecules on the SV40 origin. Herein it is demonstrated that hexamer formation is unaffected by the phosphorylation state of Thr 124. In contrast, T124A molecules are defective in double-hexamer assembly on subfragments of the core origin containing single assembly units. We also report that T124A molecules are inhibitors of T-ag double hexamer formation. These and related studies indicate that phosphorylation of T-ag on Thr 124 is a necessary step for completing the assembly of functional double hexamers on the SV40 origin. The implications of these studies for the cell cycle control of SV40 DNA replication are discussed. PMID:10954562

  12. Core-hole effect on XANES and electronic structure of minor actinide dioxides with fluorite structure

    NASA Astrophysics Data System (ADS)

    Suzuki, Chikashi; Nishi, Tsuyoshi; Nakada, Masami; Akabori, Mitsuo; Hirata, Masaru; Kaji, Yoshiyuki

    2012-02-01

    The authors investigated theoretically core-hole effects on X-ray absorption near-edge structures (XANES) of Np and Am LIII in neptunium dioxide (NpO2) and americium dioxide (AmO2) with CaF2-type crystal lattices using the all-electron full-potential linearized augmented plane-wave (FP-LAPW) method. The peak creation mechanism of XANES was shown by examining the electronic structures of these oxides, which indicated that core-hole screening was more marked for AmO2 than for NpO2 because of the difference in the charge transfer between these oxides. Furthermore, the results of charge density analysis suggested that the white line was assigned to the quasi-bound state composed of the localized Np d or Am d components and O components, and that the tail structure was created as a result of delocalized standing waves between the Np or Am atoms.

  13. Doppler Scanning of Sediment Cores: A Useful Method for Studying Sedimentary Structures and Defining the Cutting Angle for Half Cores

    NASA Astrophysics Data System (ADS)

    Acar, Dursun; Cagatay, Namik; Biltekin, Demet; Eris, Kadir; Albut, Gulum; Ogretmen, Nazik; Arslan, Tugce; Sari, Erol

    2014-05-01

    We tested the doppler ultrasound scanning of sediment cores in PVC liners using 8 megahertz ultrasonic waves for detection of angular laminations. The method was tested with artificially prepared cores as well as marine and lake sediment cores, and proven to be a useful and fast technique for imaging and determining the vertical angularity of sedimentary structures, such as laminations and beddings. Random cutting axes provide two angularities on X and Y dimensions. In this study, the main scientific problem is 'sequential angular disconformity'. Importance of detection of these anomalies on whole cores before dividing into half cores based on determining the right cutting axes. Successful imaging was obtained from top three centimeter depth of the sediments below the PVC liner, using a linear Doppler probe. Other Doppler probes (e.g., convex probe) did not work for core scanning because of their wave-form and reflection characteristics. Longitudinal and rotational scanning with gap filler and ultrasonic wave conductive gel material for keeping energy range of wave is necessary for detecting the variation in the dip of the bedding and laminae in the cores before separation. Another angular reasoned problem is about horizontal surface and can be easily solved with adjustable position of sensor or ray source placement. Border of sampling points between two different lithology must be stay with regard to neighbour sediment angles. Vertical angularity correction is not easy and its effect on signal propagation, detection biases and effectible to mixed samples contamination during physical sampling (particle size analyzing). Determining the attitude of angled bedding before core splitting is important for further core analyses such as elemental analysis and digital X-ray radiography. After Doppler scanning, the splitting direction (i.e., vertical to bedding and lamination) can be determined. The method is cheap, quick and non- hazardous to health, unlike the x

  14. Structural investigation of the alpha-1-antichymotrypsin: prostate-specific antigen complex by comparative model building.

    PubMed Central

    Villoutreix, B. O.; Lilja, H.; Pettersson, K.; Lövgren, T.; Teleman, O.

    1996-01-01

    Prostate-specific antigen (PSA), produced by prostate cells, provides an excellent serum marker for prostate cancer. It belongs to the human kallikrein family of enzymes, a second prostate-derived member of which is human glandular kallikrein-1 (hK2). Active PSA and hK2 are both 237-residue kallikrein-like proteases, based on sequence homology. An hK2 model structure based on the serine protease fold is presented and compared to PSA and six other serine proteases in order to analyze in depth the role of the surface-accessible loops surrounding the active site. The results show that PSA and hK2 share extensive structural similarity and that most amino acid replacements are centered on the loops surrounding the active site. Furthermore, the electrostatic potential surfaces are very similar for PSA and hK2. PSA interacts with at least two serine protease inhibitors (serpins): alpha-1-antichymotrypsin (ACT) and protein C inhibitor (PCI). Three-dimensional model structures of the uncleaved ACT molecule were developed based upon the recent X-ray structure of uncleaved antithrombin. The serpin was docked both to PSA and hK2. Amino acid replacements and electrostatic complementarities indicate that the overall orientation of the proteins in these complexes is reasonable. In order to investigate PSA's heparin interaction sites, electrostatic computations were carried out on PSA, hK2, protein C, ACT, and PCI. Two heparin binding sites are suggested on the PSA surface and could explain the enhanced complex formation between PSA and PCI, while inhibiting the formation of the ACT-PSA complex, PSA, hK2, and their preliminary complexes with ACT should facilitate the understanding and prediction of structural and functional properties for these important proteins also with respect to prostate diseases. PMID:8732755

  15. Structure binding relationship of human surfactant protein D and various lipopolysaccharide inner core structures.

    PubMed

    Reinhardt, Anika; Wehle, Marko; Geissner, Andreas; Crouch, Erika C; Kang, Yu; Yang, You; Anish, Chakkumkal; Santer, Mark; Seeberger, Peter H

    2016-09-01

    As a major player of the innate immune system, surfactant protein D (SP-D) recognizes and promotes elimination of various pathogens such as Gram-negative bacteria. SP-D binds to l-glycero-d-manno-heptose (Hep), a constituent of the partially conserved lipopolysaccharide (LPS) inner core of many Gram-negative bacteria. Binding and affinity of trimeric human SP-D to Hep in distinct LPS inner core glycans differing in linkages and adjacent residues was elucidated using glycan array and surface plasmon resonance measurements that were compared to in silico interaction studies. The combination of in vitro assays using defined glycans and molecular docking and dynamic simulation approaches provides insights into the interaction of trimeric SP-D with those glycan ligands. Trimeric SP-D wildtype recognized larger LPS inner core oligosaccharides with slightly enhanced affinity than smaller compounds suggesting the involvement of stabilizing secondary interactions. A trimeric human SP-D mutant D324N+D325N+R343K resembling rat SP-D bound to various LPS inner core structures in a similar pattern as observed for the wildtype but with higher affinity. The selective mutation of SP-D promotes targeting of LPS inner core oligosaccharides on Gram-negative bacteria to develop novel therapeutic agents. PMID:27350640

  16. Solution structure and backbone dynamics of an antigen-free heavy chain variable domain (VHH) from Llama.

    PubMed

    Renisio, Jean-Guillaume; Pérez, Janice; Czisch, Michael; Guenneugues, Marc; Bornet, Olivier; Frenken, Leon; Cambillau, Christian; Darbon, Hervé

    2002-06-01

    Camelids, (dromedaries, camels, and llamas) produce heavy-chains antibodies, with their antigen recognition sites composed of a single VH-like domain, referred to as VHH. The solution structure of one of these VHHs domains (VHH-H14), raised against the alpha subunit of the human chorionic gonadotropin hormone (hCG), has been determined by (15)N heteronuclear three-dimensional NMR spectroscopy. The framework is well resolved within the set of 20 best-calculated NMR structures and is close to that of classical VH domains from vertebrate antibodies, consisting of two antiparallel beta-sheets organized in a beta-barrel. Loops display a lower precision, especially the Complementarity Determining Regions (CDRs), involved in antigen recognition. Comparison of the three-dimensional VHH-H14 solution structure with its previously solved crystal structure (Spinelli et al., Nature Struct. Biol. 1996;3:752-757) reveals a high similarity to the framework, whereas significant conformational differences occur on CDRs, leading to the assumption that the antigen recognition site is a more mobile part. In order to deepen our insights into the dynamics of VHH-H14 in solution, (15)N relaxation was measured with longitudinal R1 and transverse R2 self-relaxation rates, and (15)N steady-state heteronuclear nuclear Overhauser enhancements (NOE), making it possible to probe picosecond-to-millisecond internal motions. Determination of dynamic parameters (S(2), tau(e), and Rex) through the Lipari-Szabo Model-free approach enables the identification of several regions with enhanced dynamics. Especially, the mobility measurements from NMR confirm that the antigen recognition site is the most mobile part of the VHH-H14 domain on picosecond-to-nanosecond fast time scales. Several residues belonging to the three CDRs are submitted to chemical exchange processes occurring on slow microsecond-to-millisecond time scales, suggesting that the formation of the VHH/antigen complex should be accompanied

  17. Structures of Two Melanoma-Associated Antigens Suggest Allosteric Regulation of Effector Binding

    PubMed Central

    Roos, Anette K.; Aitkenhead, Hazel; Oppermann, Udo C. T.; Cho, Hearn J.; Osman, Roman; Gileadi, Opher

    2016-01-01

    The MAGE (melanoma associated antigen) protein family are tumour-associated proteins normally present only in reproductive tissues such as germ cells of the testis. The human genome encodes over 60 MAGE genes of which one class (containing MAGE-A3 and MAGE-A4) are exclusively expressed in tumours, making them an attractive target for the development of targeted and immunotherapeutic cancer treatments. Some MAGE proteins are thought to play an active role in driving cancer, modulating the activity of E3 ubiquitin ligases on targets related to apoptosis. Here we determined the crystal structures of MAGE-A3 and MAGE-A4. Both proteins crystallized with a terminal peptide bound in a deep cleft between two tandem-arranged winged helix domains. MAGE-A3 (but not MAGE-A4), is predominantly dimeric in solution. Comparison of MAGE-A3 and MAGE-A3 with a structure of an effector-bound MAGE-G1 suggests that a major conformational rearrangement is required for binding, and that this conformational plasticity may be targeted by allosteric binders. PMID:26910052

  18. Multi-scale silica structures for improved HIV-1 Capsid (p24) antigen detection.

    PubMed

    Lin, Sophia; Hedde, Per Niklas; Venugopalan, Vasan; Gratton, Enrico; Khine, Michelle

    2016-06-20

    Silica (SiO2) micro- and nanostructures fabricated with pre-stressed thermoplastic shrink wrap film have been shown to yield far-field fluorescence signal enhancements over their planar or wrinkled counterparts. The SiO2 structures have previously been used for improved detection of fluorescently labelled proteins and DNA. In this work, we probe the mechanism responsible for the dramatic increases in fluorescence signal intensity. Optical characterization studies attribute the fluorescence signal enhancements to increased surface density and light scattering from the rough SiO2 structures. Using this information, we come up with a theoretical approximation for the enhancement factor based off the scattering effects alone. We show that increased deposition thickness of SiO2 yields improved fluorescence signal enhancements, with an optimal SiO2 thin layer achieved at 20 nm. Finally, we show that the SiO2 substrates serve as a suitable platform for disease diagnostics, and show improved limits of detection (LOD) for the human immunodeficiency virus type 1 (HIV-1) p24 antigen. PMID:27163263

  19. Structural features of the O-antigen of Rickettsia typhi, the etiological agent of endemic typhus.

    PubMed

    Peturova, M; Vitiazeva, V; Toman, R

    2015-09-01

    Elucidation of the O-specific polysaccharide chain of lipopolysaccharide (LPS) from Rickettsia typhi, the etiological agent of endemic typhus, is described. Structural information was established by a combination of monosaccharide and methylation analyses of the O-chain, and by mass (MS) and nuclear magnetic resonance (NMR) spectrometries of oligosaccharides arised through its hydrofluoric (HF) acid degradation. Based on the combined data from these experiments, two major polymer populations of the O-specific chain have been determined with the following structural features: α-L-QuiNAc-(1→4)-[α-D-Glc-(1→3)-α-L-QuiNAc-(1→4)]n-α-D-Glc-(1→4)-α-D-Glc→, α-D-Glc-(1→3)-α-L-QuiNAc-(1→4)-[α-D-Glc-(1→3)-α-L-QuiNAc-(1→4)]n-α-D-Glc→. The linear backbone is most probably flanked with short side chains of D-GlcNAc-(1→3)-α-L-QuiNAc-(1→3)-D-GlcNAc→ that are attached to it via L-QuiNAc as a branching point. It is suggested that a dimer α-L-QuiNAc-(1→3)-α-D-GlcNAc may represent a common epitope in the O-antigens of Proteus vulgaris OX19 and R. typhi responsible for the observed serological cross-reactivity. PMID:26435145

  20. Structure of the meningococcal vaccine antigen NadA and epitope mapping of a bactericidal antibody

    PubMed Central

    Malito, Enrico; Biancucci, Marco; Faleri, Agnese; Ferlenghi, Ilaria; Scarselli, Maria; Maruggi, Giulietta; Lo Surdo, Paola; Veggi, Daniele; Liguori, Alessia; Santini, Laura; Bertoldi, Isabella; Petracca, Roberto; Marchi, Sara; Romagnoli, Giacomo; Cartocci, Elena; Vercellino, Irene; Savino, Silvana; Spraggon, Glen; Norais, Nathalie; Pizza, Mariagrazia; Rappuoli, Rino; Masignani, Vega; Bottomley, Matthew James

    2014-01-01

    Serogroup B Neisseria meningitidis (MenB) is a major cause of severe sepsis and invasive meningococcal disease, which is associated with 5–15% mortality and devastating long-term sequelae. Neisserial adhesin A (NadA), a trimeric autotransporter adhesin (TAA) that acts in adhesion to and invasion of host epithelial cells, is one of the three antigens discovered by genome mining that are part of the MenB vaccine that recently was approved by the European Medicines Agency. Here we present the crystal structure of NadA variant 5 at 2 Å resolution and transmission electron microscopy data for NadA variant 3 that is present in the vaccine. The two variants show similar overall topology with a novel TAA fold predominantly composed of trimeric coiled-coils with three protruding wing-like structures that create an unusual N-terminal head domain. Detailed mapping of the binding site of a bactericidal antibody by hydrogen/deuterium exchange MS shows that a protective conformational epitope is located in the head of NadA. These results provide information that is important for elucidating the biological function and vaccine efficacy of NadA. PMID:25404323

  1. Generation of Antigenic Diversity in Plasmodium falciparum by Structured Rearrangement of Var Genes During Mitosis

    PubMed Central

    Kekre, Mihir; Otto, Thomas D.; Faizullabhoy, Adnan; Rayner, Julian C.; Kwiatkowski, Dominic

    2014-01-01

    The most polymorphic gene family in P. falciparum is the ∼60 var genes distributed across parasite chromosomes, both in the subtelomeres and in internal regions. They encode hypervariable surface proteins known as P. falciparum erythrocyte membrane protein 1 (PfEMP1) that are critical for pathogenesis and immune evasion in Plasmodium falciparum. How var gene sequence diversity is generated is not currently completely understood. To address this, we constructed large clone trees and performed whole genome sequence analysis to study the generation of novel var gene sequences in asexually replicating parasites. While single nucleotide polymorphisms (SNPs) were scattered across the genome, structural variants (deletions, duplications, translocations) were focused in and around var genes, with considerable variation in frequency between strains. Analysis of more than 100 recombination events involving var exon 1 revealed that the average nucleotide sequence identity of two recombining exons was only 63% (range: 52.7–72.4%) yet the crossovers were error-free and occurred in such a way that the resulting sequence was in frame and domain architecture was preserved. Var exon 1, which encodes the immunologically exposed part of the protein, recombined in up to 0.2% of infected erythrocytes in vitro per life cycle. The high rate of var exon 1 recombination indicates that millions of new antigenic structures could potentially be generated each day in a single infected individual. We propose a model whereby var gene sequence polymorphism is mainly generated during the asexual part of the life cycle. PMID:25521112

  2. Accurate structure prediction of peptide–MHC complexes for identifying highly immunogenic antigens

    SciTech Connect

    Park, Min-Sun; Park, Sung Yong; Miller, Keith R.; Collins, Edward J.; Lee, Ha Youn

    2013-11-01

    Designing an optimal HIV-1 vaccine faces the challenge of identifying antigens that induce a broad immune capacity. One factor to control the breadth of T cell responses is the surface morphology of a peptide–MHC complex. Here, we present an in silico protocol for predicting peptide–MHC structure. A robust signature of a conformational transition was identified during all-atom molecular dynamics, which results in a model with high accuracy. A large test set was used in constructing our protocol and we went another step further using a blind test with a wild-type peptide and two highly immunogenic mutants, which predicted substantial conformational changes in both mutants. The center residues at position five of the analogs were configured to be accessible to solvent, forming a prominent surface, while the residue of the wild-type peptide was to point laterally toward the side of the binding cleft. We then experimentally determined the structures of the blind test set, using high resolution of X-ray crystallography, which verified predicted conformational changes. Our observation strongly supports a positive association of the surface morphology of a peptide–MHC complex to its immunogenicity. Our study offers the prospect of enhancing immunogenicity of vaccines by identifying MHC binding immunogens.

  3. CCD photometry of globular cluster core structure. 2: U-band profiles for 15 candidate collapsed-core clusters

    NASA Technical Reports Server (NTRS)

    Lugger, Phyllis M.; Cohn, Haldan N.; Grindlay, Jonathan E.

    1995-01-01

    We present U-band CCD surface brightness profiles for 15 of the 21 globular clusters that have been identified as having collapsed cores by Djorgovski & King (1986). Fourteen of the clusters were observed with the Cerro Tololo 4 m telescope; NGC 7078 was observed with the Canada-France-Hawaii 3.6 m telescope (CFHT). We have fitted the profiles with seeing-convolved power laws, both with and without cores, to assess the evidence for central power-law structure and to place upper limits on core radius r(sub c). We find nine of the clusters (NGC 5946, NGC 6284, NGC 6293, NGC 6325, NGC 6342, NGC 6558, NGC 6624, NGC 6681, and NGC 7078) to have unresolved cores, with upper limits r(sub c) less than or = 1.9 arcsecs. Three of the clusters (NGC 6453, NGC 6522, and NGC 7099) have marginally resolved cores, with upper limits in the range 2.7 arcsecs less than or = r(sub c) less than or = 3.4 arcsecs. The remaining three clusters (NGC 6355, NGC 6397, and NGC 6752) have resolved cores. Of the latter three clusters, NGC 6355 and NGC 6752 are consistent with single-mass King model structure. The median cluster distances are 9.2 kpc for those with unresolved cores, 7.2 kpc for those with marginally resolved cores, and 4.1 kpc for those with resolved cores. The 13 clusters that do not resemble single-mass King models have central power-law structure with surface brightness slopes in the range of d ln S/d ln r = -0.6 to -0.8. These slopes are consistent with the models of Grabhorn et al. (1992) for clusters evolving beyond core collapse. The models include a centrally concentrated population of nonluminous remnants with masses in the range 1.2-1.4 solar mass, thus providing evidence for significant neutron star populations in most of our cluster sample. This finding is consistent with the observation of centrally concentrated low-mass X-ray binary and millisecond pulsar populations in several clusters.

  4. Modelling the structure of full-length Epstein-Barr virus nuclear antigen 1.

    PubMed

    Hussain, Mushtaq; Gatherer, Derek; Wilson, Joanna B

    2014-12-01

    Epstein-Barr virus is a clinically important human virus associated with several cancers and is the etiologic agent of infectious mononucleosis. The viral nuclear antigen-1 (EBNA1) is central to the replication and propagation of the viral genome and likely contributes to tumourigenesis. We have compared EBNA1 homologues from other primate lymphocryptoviruses and found that the central glycine/alanine repeat (GAr) domain as well as predicted cellular protein (USP7 and CK2) binding sites are present in homologues in the Old World primates, but not the marmoset, suggesting that these motifs may have co-evolved. Using the resolved structure of the C-terminal one-third of EBNA1 (homodimerization and DNA binding domain), we have gone on to develop monomeric and dimeric models in silico of the full-length protein. The C-terminal domain is predicted to be structurally highly similar between homologues, indicating conserved function. Zinc could be stably incorporated into the model, bonding with two N-terminal cysteines predicted to facilitate multimerisation. The GAr contains secondary structural elements in the models, while the protein binding regions are unstructured, irrespective of the prediction approach used and sequence origin. These intrinsically disordered regions may facilitate the diversity observed in partner interactions. We hypothesize that the structured GAr could mask the disordered regions, thereby protecting the protein from default degradation. In the dimer conformation, the C-terminal tails of each monomer wrap around a proline-rich protruding loop of the partner monomer, providing dimer stability, a feature which could be exploited in therapeutic design. PMID:25011696

  5. Occurrence and structure of cyclic Enterobacterial Common Antigen in Escherichia coli O157:H⁻.

    PubMed

    Fregolino, Eleonora; Ivanova, Radka; Lanzetta, Rosa; Molinaro, Antonio; Parrilli, Michelangelo; Paunova-Krasteva, Tsvetelina; Stoitsova, Stoyanka R; De Castro, Cristina

    2012-12-01

    Two cyclic forms of the Enterobacterial Common Antigen were isolated from Escherichia coli O157:H(-). These antigenic determinants were purified from the biomass through extensive chemical, enzymatic and chromatographic procedures whereas MALDI MS spectrometry indicated their cyclic nature with a polymerization degree of 4 or 5. The two species, denoted as ECA(CYC-4) and ECA(CYC-5), were assigned by NMR and showed no further substitution with other appendages such as acetyl groups as usually described for similar cyclic antigens from other Enterobacteriaceae. PMID:23103511

  6. Atomic resolution structural characterization of recognition of histo-blood group antigens by Norwalk virus

    SciTech Connect

    Choi, Jae-Mun; Hutson, Anne M.; Estes, Mary K.; Prasad, B.V. Venkataram

    2008-07-28

    Members of Norovirus, a genus in the family Caliciviridae, are causative agents of epidemic diarrhea in humans. Susceptibility to several noroviruses is linked to human histo-blood type, and its determinant histo-blood group antigens (HBGAs) are regarded as receptors for these viruses. Specificity for these carbohydrates is strain-dependent. Norwalk virus (NV) is the prototype genogroup I norovirus that specifically recognizes A- and H-type HBGA, in contrast to genogroup II noroviruses that exhibit a more diverse HBGA binding pattern. To understand the structural basis for how HBGAs interact with the NV capsid protein, and how the specificity is achieved, we carried out x-ray crystallographic analysis of the capsid protein domain by itself and in complex with A- and H-type HBGA at a resolution of {approx}1.4 {angstrom}. Despite differences in their carbohydrate sequence and linkage, both HBGAs bind to the same surface-exposed site in the capsid protein and project outward from the capsid surface, substantiating their possible role in initiating cell attachment. Precisely juxtaposed polar side chains that engage the sugar hydroxyls in a cooperative hydrogen bonding and a His/Trp pair involved in a cation-p interaction contribute to selective and specific recognition of A- and H-type HBGAs. This unique binding epitope, confirmed by mutational analysis, is highly conserved, but only in the genogroup I noroviruses, suggesting that a mechanism by which noroviruses infect broader human populations is by evolving different sites with altered HBGA specificities.

  7. Analysis of the effect of core structure upon dineutron correlation using antisymmetrized molecular dynamics

    NASA Astrophysics Data System (ADS)

    Kobayashi, Fumiharu; Kanada-En'yo, Yoshiko

    2016-02-01

    We extend the method of antisymmetrized molecular dynamics (AMD) to investigate dineutron correlation. We regard the total system as the core plus two valence neutrons in the AMD framework and treat the valence neutron wave functions by multirange Gaussians with the d -constraint method, in which the distance between the core and the center of mass of the two neutrons is constrained, to describe the size changing effect and the motion of two neutrons. We apply this method to the ground state of 10Be as an example and investigate the motion of two neutrons around a largely deformed 8Be core by analyzing the two-neutron overlap function around the core. Comparing the results including the different 8Be core structures, we show that the core structure plays an important role in dineutron formation and expansion from the core. The radial fluctuation in the core leads to the expansion of the core potential to the farther region and, as a result, two valence neutrons can be expanded far from the core to form a dineutron. Differently, when the core is less deformed, the dineutron is dissociated by the spin-orbit potential at the surface of the core. We can investigate the dineutron correlation clearly by using the present framework and conclude that the framework is effective for the studies of dineutron correlation.

  8. Structure and dynamics of the Earth's inner core

    NASA Astrophysics Data System (ADS)

    Deuss, A. F.; Irving, J. C. E.; Waszek, L.; Lythgoe, K.

    2015-12-01

    Seismic observations, using both body wave and normal mode data, provide strong evidence that the Earth's inner core is anisotropic (e.g. Morelli at al, 1986, Woodhouse et al, 1986), finding cylindrical anisotropy with the fast axis aligned with the Earth's rotation axis. More recently, hemispherical anisotropy variations have been found in both body wave and normal mode data, with the west being more strongly anisotropic than the east (e.g. Tanaka & Hamaguchi, 1997, Deuss et al, 2010). However, it has proven difficult to reconcile both data types. Here, we try to reconcile body waves and modes, making a comprehensive model. We find that a top layer with isotropic velocity of about 70km thick fits both the body wave and normal mode data. Hemispherical variations in isotropic velocity, with the west being slow and the east being fast, exist in the top 275 km of the inner core. Strong anisotropy starts below 70km depth, and only exists in a wedge in the western hemisphere, increasing in strength with depth. The location of the anisotropic wedge seems unrelated to the isotropic hemispheres found at the top of the inner core. The isotropic hemispheres are most likely due to variations in solidification rate at the inner core boundary. The deeper anisotropic alignment of crystals is most likely due to a deformation process. Recent work fitting normal mode frequencies suggests that the top layer of the inner core may in fact be radially anisotropic with the fastest velocity perpendicular to the inner core boundary (Lythgoe & Deuss, 2015). Such radial anisotropy would be in line with the model proposed by Yoshida et al (1996) where the inner core grows preferentially near the equator, leading to a flow from the equator to the poles generating both the shallow radial anisotropy and deeper cylindrical anisotropy.

  9. Periodic variation in side-chain polarities of T-cell antigenic peptides correlates with their structure and activity.

    PubMed Central

    Cornette, J L; Margalit, H; Berzofsky, J A; DeLisi, C

    1995-01-01

    We present an analysis that synthesizes information on the sequence, structure, and motifs of antigenic peptides, which previously appeared to be in conflict. Fourier analysis of T-cell antigenic peptides indicates a periodic variation in amino acid polarities of 3-3.6 residues per period, suggesting an amphipathic alpha-helical structure. However, the diffraction patterns of major histocompatibility complex (MHC) molecules indicate that their ligands are in an extended non-alpha-helical conformation. We present two mutually consistent structural explanations for the source of the alpha-helical periodicity, based on an observation that the side chains of MHC-bound peptides generally partition with hydrophobic (hydrophilic) side chains pointing into (out of) the cleft. First, an analysis of haplotype-dependent peptide motifs indicates that the locations of their defining residues tend to force a period 3-4 variation in hydrophobicity along the peptide sequence, in a manner consistent with the spacing of pockets in the MHC. Second, recent crystallographic determination of the structure of a peptide bound to a class II MHC molecule reveals an extended but regularly twisted peptide with a rotation angle of about 130 degrees. We show that similar structures with rotation angles of 100-130 degrees are energetically acceptable and also span the length of the MHC cleft. These results provide a sound physical chemical and structural basis for the existence of a haplotype-independent antigenic motif which can be particularly important in limiting the search time for antigenic peptides. Images Fig. 3 PMID:7667297

  10. Podosomes of dendritic cells facilitate antigen sampling

    PubMed Central

    Reinieren-Beeren, Inge; Cambi, Alessandra; Figdor, Carl G.; van den Bogaart, Geert

    2014-01-01

    Summary Dendritic cells sample the environment for antigens and play an important role in establishing the link between innate and acquired immunity. Dendritic cells contain mechanosensitive adhesive structures called podosomes that consist of an actin-rich core surrounded by integrins, adaptor proteins and actin network filaments. They facilitate cell migration via localized degradation of extracellular matrix. Here we show that podosomes of human dendritic cells locate to spots of low physical resistance in the substrate (soft spots) where they can evolve into protrusive structures. Pathogen recognition receptors locate to these protrusive structures where they can trigger localized antigen uptake, processing and presentation to activate T-cells. Our data demonstrate a novel role in antigen sampling for podosomes of dendritic cells. PMID:24424029

  11. Ubiquitin-hepatitis B core antigen-cytoplasmic transduction peptide enhances HBV-specific humoral and CTL immune responses in vivo.

    PubMed

    Song, Linlin; Zhuo, Meng; Tang, Yuyan; Chen, Xiaohua; Tang, Zhenghao; Zang, Guoqing

    2014-11-01

    Therapeutic strategies based on an enhanced hepatitis B virus (HBV)-specific cytotoxic T lymphocyte (CTL) activity may eradicate HBV. We previously verified that a fusion protein ubiquitin (Ub)-hepatitis B core antigen (HBcAg)-cytoplasmic transduction peptide (CTP) can enter the cytoplasm of dendritic cells and enhance T cell response to generate HBV-specific CTLs efficiently in vitro. Ub, a marker of protein degradation, may promote the generation of peptides appropriate for major histocompatibility complex class I presentation. In the present study, the specific immune responses of the fusion protein Ub-HBcAg-CTP in BALB/c mice were evaluated and the underlying mechanisms were investigated. Results showed that Ub-HBcAg-CTP increased the anti-HBcAg titer and produced the cytokines IFN-γ and IL-2. This fusion protein also induced higher percentages of IFN-γ(+)CD8(+) cells and specific CTL responses. Ub-HBcAg-CTP could also upregulate the expressions of Jak2, Tyk2, STAT1, and STAT4 in T lymphocytes. In conclusion, Ub-HBcAg-CTP enhanced cellular and humoral immune responses and induced robust HBV-specific CTL activities in BALB/c mice. PMID:25135878

  12. Deletion of fusion peptide or destabilization of fusion core of HIV gp41 enhances antigenicity and immunogenicity of 4E10 epitope

    SciTech Connect

    Li Jing; Chen Xi; Jiang Shibo Chen Yinghua

    2008-11-07

    The human monoclonal antibody 4E10 against the membrane-proximal external region (MPER) of HIV-1 gp41 demonstrates broad neutralizing activity across various strains, and makes its epitope an attractive target for HIV-1 vaccine development. Although the contiguous epitope of 4E10 has been identified, attempts to re-elicit 4E10-like antibodies have failed, possibly due to the lack of proper conformation of the 4E10 epitope. Here we used pIg-tail expression system to construct a panel of eukaryotic cell-surface expression plasmids encoding the extracellular domain of gp41 with deletion of fusion peptide and/or introduction of L568P mutation that may disrupt the gp41 six-helix bundle core conformation as DNA vaccines for immunization of mice. We found that these changes resulted in significant increase of the antigenicity and immunogenicity of 4E10 epitope. This information is thus useful for rational design of vaccines targeting the HIV-1 gp41 MPER.

  13. Clinical Utility of a New Automated Hepatitis C Virus Core Antigen Assay for Prediction of Treatment Response in Patients with Chronic Hepatitis C.

    PubMed

    Kim, Mi Na; Kim, Hyon Suk; Kim, Ja Kyung; Kim, Beom Kyung; Kim, Seung Up; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Han, Kwang Hyub

    2016-09-01

    Hepatitis C virus core antigen (HCV Ag) is a recently developed marker of hepatitis C virus (HCV) infection. We investigated the clinical utility of the new HCV Ag assay for prediction of treatment response in HCV infection. We analyzed serum from 92 patients with HCV infection who had been treated with pegylated interferon and ribavirin. HCV Ag levels were determined at baseline in all enrolled patients and at week 4 in 15 patients. Baseline HCV Ag levels showed good correlations with HCV RNA (r = 0.79, P < 0.001). Mean HCV Ag levels at baseline were significantly lower in patients with a sustained virologic response (SVR) than in those with a non SVR (relapse plus non responder) based on HCV RNA analysis (2.8 log₁₀fmol/L vs. 3.27 log₁₀fmol/L, P = 0.023). Monitoring of the viral kinetics by determination of HCV RNA and HCV Ag levels resulted in similarly shaped curves. Patients with undetectable HCV Ag levels at week 4 had a 92.3% probability of achieving SVR based on HCV RNA assay results. The HCV Ag assay may be used as a supplement for predicting treatment response in HCV infection, but not as an alternative to the HCV RNA assay. PMID:27510387

  14. Clinical Utility of a New Automated Hepatitis C Virus Core Antigen Assay for Prediction of Treatment Response in Patients with Chronic Hepatitis C

    PubMed Central

    2016-01-01

    Hepatitis C virus core antigen (HCV Ag) is a recently developed marker of hepatitis C virus (HCV) infection. We investigated the clinical utility of the new HCV Ag assay for prediction of treatment response in HCV infection. We analyzed serum from 92 patients with HCV infection who had been treated with pegylated interferon and ribavirin. HCV Ag levels were determined at baseline in all enrolled patients and at week 4 in 15 patients. Baseline HCV Ag levels showed good correlations with HCV RNA (r = 0.79, P < 0.001). Mean HCV Ag levels at baseline were significantly lower in patients with a sustained virologic response (SVR) than in those with a non SVR (relapse plus non responder) based on HCV RNA analysis (2.8 log10fmol/L vs. 3.27 log10fmol/L, P = 0.023). Monitoring of the viral kinetics by determination of HCV RNA and HCV Ag levels resulted in similarly shaped curves. Patients with undetectable HCV Ag levels at week 4 had a 92.3% probability of achieving SVR based on HCV RNA assay results. The HCV Ag assay may be used as a supplement for predicting treatment response in HCV infection, but not as an alternative to the HCV RNA assay. PMID:27510387

  15. Graphene oxide quantum dots@silver core-shell nanocrystals as turn-on fluorescent nanoprobe for ultrasensitive detection of prostate specific antigen.

    PubMed

    Pei, Haimeng; Zhu, Shuyun; Yang, Minghui; Kong, Rongmei; Zheng, Yiqun; Qu, Fengli

    2015-12-15

    We report a fluorescent turn-on nanoprobe for ultrasensitive detection of prostate specific antigen (PSA) based on graphene oxide quantum dots@silver (GQDs@Ag) core-shell nanocrystals. The success of this work relies on the assembly of quantities of GQDs in one GQDs@Ag probe, which makes the ratio of probe to target significantly increased and thus enables the fluorescent signal enhancement. When the silver shell was removed via oxidative etching using hydrogen peroxide (H2O2), the incorporated GQDs could be readily released and the whole process caused little change to their fluorescence performance. We tested the probe for the ultrasensitive detection of PSA based on the sandwich protocol of immunosensors. In particular, magnetic beads (MBs) were employed to immobilize anti-PSA antibody (Ab1) and acted as a separable capture probe, while GQDs@Ag was used as detection probe by linking antibody (Ab2). The developed immunosensor showed a good linear relationship between the fluorescence intensity and the concentration of PSA in the range from 1 pg/mL to 20 ng/mL with a detection limit of 0.3 pg/mL. The immunosensor used for the analysis of clinical serum samples exhibited satisfactory results, which demonstrated its potential for practical diagnostic applications. This method provides a possible solution to the application of GQDs in immunosensing and could be potentially extended to other similar systems. PMID:26257182

  16. Core-linked LPS expression of Shigella dysenteriae serotype 1 O-antigen in live Salmonella Typhi vaccine vector Ty21a: preclinical evidence of immunogenicity and protection.

    PubMed

    Xu, De Qi; Cisar, John O; Osorio, Manuel; Wai, Tint T; Kopecko, Dennis J

    2007-08-14

    Shigella dysenteriae serotype 1 (S. dysenteriae 1) causes severe shigellosis that is typically associated with high mortality. Antibodies against Shigella serotype-specific O-polysaccharide (O-Ps) have been shown to be host protective. In this study, the rfb locus and the rfp gene with their cognate promoter regions were PCR-amplified from S. dysenteriae 1, cloned, and sequenced. Deletion analysis showed that eight rfb ORFs plus rfp are necessary for biosynthesis of this O-Ps. A tandemly-linked rfb-rfp gene cassette was cloned into low copy plasmid pGB2 to create pSd1. Avirulent Salmonella enterica serovar Typhi (S. Typhi) Ty21a harboring pSd1 synthesized S. Typhi 9, 12 LPS as well as typical core-linked S. dysenteriae 1 LPS. Animal immunization studies showed that Ty21a (pSd1) induces protective immunity against high stringency challenge with virulent S. dysenteriae 1 strain 1617. These data further demonstrate the utility of S. Typhi Ty21a as a live, bacterial vaccine delivery system for heterologous O-antigens, supporting the promise of a bifunctional oral vaccine for prevention of shigellosis and typhoid fever. PMID:17629369

  17. Dust Structure and Composition Within Molecular Clouds and Cores

    NASA Astrophysics Data System (ADS)

    Chapman, Nicholas L.; Mundy, L. G.

    2007-12-01

    We observed three molecular clouds and four isolated cores in both the JHK and Spitzer wavelengths. Our goal was to use these deep infrared data to map changes in the extinction law and the dust properties throughout our observed regions. The clouds we observed were Ophiuchus, Perseus, and Serpens and the cores were L204C-2, L1152, L1155C-2, and L1228. From 3.6-8 microns, we found that regions with column densities Ak < 0.5 in our clouds have an extinction law similar to the one observed in the diffuse ISM. At higher extinctions, there is evidence for grain growth because the extinction law flattens compared to that of the diffuse ISM and becomes more consistent with the extinction law predicted by the Weingartner & Draine (2001) Rv = 5.5 dust model. This model utilizes dust grains up to 10 times larger than those in the diffuse ISM. We observed this same extinction law in the cores, even for column densities Ak 1-2 in some of our clouds and cores, we see evidence at 5.8 microns for water ice forming on the dust grains. Two of our cores have molecular outflows which appear to be destroying large dust grains resulting in an extinction law similar to that found in the diffuse ISM. In both our clouds and cores, the extinction law at 24 microns is almost always 2-3 times higher than the value predicted by current dust models, consistent with the results found by Flaherty et al. (2007). Overall, there are relatively few stars with high S/N detections at 24 microns. More observations are needed to understand the nature of the extinction law at this wavelength. Support for this work was provided by NASA through JPL contracts 1224608, 1230782, 1230779, 1264793, and 1264492.

  18. Structure, Receptor Binding, and Antigenicity of Influenza Virus Hemagglutinins from the 1957 H2N2 Pandemic

    SciTech Connect

    Xu, Rui; McBride, Ryan; Paulson, James C.; Basler, Christopher F.; Wilson, Ian A.

    2010-03-04

    The hemagglutinin (HA) envelope protein of influenza viruses mediates essential viral functions, including receptor binding and membrane fusion, and is the major viral antigen for antibody neutralization. The 1957 H2N2 subtype (Asian flu) was one of the three great influenza pandemics of the last century and caused 1 million deaths globally from 1957 to 1968. Three crystal structures of 1957 H2 HAs have been determined at 1.60 to 1.75 {angstrom} resolutions to investigate the structural basis for their antigenicity and evolution from avian to human binding specificity that contributed to its introduction into the human population. These structures, which represent the highest resolutions yet recorded for a complete ectodomain of a glycosylated viral surface antigen, along with the results of glycan microarray binding analysis, suggest that a hydrophobicity switch at residue 226 and elongation of receptor-binding sites were both critical for avian H2 HA to acquire human receptor specificity. H2 influenza viruses continue to circulate in birds and pigs and, therefore, remain a substantial threat for transmission to humans. The H2 HA structure also reveals a highly conserved epitope that could be harnessed in the design of a broader and more universal influenza A virus vaccine.

  19. Rigid polyurethane foam – kenaf core composites for structural applications

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Kenaf (Hibiscus cannabinus L.) is a fast growing summer annual crop with numerous commercial applications (fibers, biofuels, bioremediation, paper pulp, building materials, cover crops, and livestock forages). The stalks of the kenaf plants contain two distinct fiber types, bast and core fibers. The...

  20. Direct core structuring of microstructured optical fibers using focused ion beam milling.

    PubMed

    Warren-Smith, Stephen C; André, Ricardo M; Perrella, Christopher; Dellith, Jan; Bartelt, Hartmut

    2016-01-11

    We demonstrate the use of focused ion beam milling to machine optical structures directly into the core of microstructured optical fibers. The particular fiber used was exposed-core microstructured optical fiber, which allowed direct access to the optically guiding core. Two different designs of Fabry-Perot cavity were fabricated and optically characterized. The first cavity was formed by completely removing a section of the fiber core, while the second cavity consisted of a shallow slot milled into the core, leaving the majority of the core intact. This work highlights the possibility of machining complex optical devices directly onto the core of microstructured optical fibers using focused ion beam milling for applications including environmental, chemical, and biological sensing. PMID:26832268

  1. Coordination polymer core/shell structures: Preparation and up/down-conversion luminescence.

    PubMed

    Li, Bingmei; Xu, Hualan; Xiao, Chen; Shuai, Min; Chen, Weimin; Zhong, Shengliang

    2016-10-01

    Coordination polymer (CP) core-shell nanoparticles with Gd-based CP (GdCP) as core and Eu-based CP (EuCP) as shell have been successfully prepared. Allantoin was employed as the organic building block without the assistance of any template. The composition, size and structure of the core-shell nanospheres were well characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray (EDX), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR), thermo-gravimetric analysis (TG). Results show that the resultant cores are uniform nanospheres with diameter of approximately 45nm, while the diameters of the core-shell nanospheres are increased to approximately 60nm. The core-shell products show enhanced luminescence efficiency than the core under 980nm laser excitation and decreased down-conversion luminescence when excited at 394nm. PMID:27344485

  2. Structure of a mushy layer at the inner core boundary

    NASA Astrophysics Data System (ADS)

    Deguen, R.; Huguet, L.; Bergman, M. I.; Labrosse, S.; Alboussiere, T.

    2015-12-01

    We present experimental results on the solidification of ammonium chloride from an aqueous solution, yielding a mushy zone, under hyper-gravity. A commercial centrifuge has been equipped with a slip-ring so that electric power, temperature and ultrasonic signals could be transmitted between the experimental setup and the laboratory. A Peltier element provides cooling at the bottom of the cell. Probes monitor the temperature along the height of the cell. Ultrasound measurements (2 to 6 MHz) is used to detect the position of the front of the mushy zone and to determine attenuation in the mush. A significant increase of solid fraction (or decrease of mushy layer thickness) and attenuation in the mush is observed as gravity is increased. Kinetic undercooling is significant in our experiments and has been included in a macroscopic mush model. The other ingredients of the model are conservation of energy and chemical species, along with heat/species transfer between the mush and the liquid phase: boundary-layer exchanges at the top of the mush and bulk convection within the mush (formation of chimneys). The outputs of the model compare well with our experiments. We have then run the model in a range of parameters suitable for the Earth's inner core, which has shown the role of bulk mush convection for the inner core and the reason why a solid fraction very close to unity should be expected. We have also run melting experiments: after crystallization of a mush, the liquid has been heated from above until the mush started to melt, while the bottom cold temperature was maintained. These melting experiments were motivated by the possible local melting at the inner core boundary that has been invoked to explain the formation of the anomalously slow F-layer at the bottom of the outer core or inner core hemispherical asymmetry. Oddly, the consequences of melting are an increase in solid fraction and a decrease in attenuation. It is hence possible that surface seismic velocity

  3. Multiple genome alignment for identifying the core structure among moderately related microbial genomes

    PubMed Central

    Uchiyama, Ikuo

    2008-01-01

    Background Identifying the set of intrinsically conserved genes, or the genomic core, among related genomes is crucial for understanding prokaryotic genomes where horizontal gene transfers are common. Although core genome identification appears to be obvious among very closely related genomes, it becomes more difficult when more distantly related genomes are compared. Here, we consider the core structure as a set of sufficiently long segments in which gene orders are conserved so that they are likely to have been inherited mainly through vertical transfer, and developed a method for identifying the core structure by finding the order of pre-identified orthologous groups (OGs) that maximally retains the conserved gene orders. Results The method was applied to genome comparisons of two well-characterized families, Bacillaceae and Enterobacteriaceae, and identified their core structures comprising 1438 and 2125 OGs, respectively. The core sets contained most of the essential genes and their related genes, which were primarily included in the intersection of the two core sets comprising around 700 OGs. The definition of the genomic core based on gene order conservation was demonstrated to be more robust than the simpler approach based only on gene conservation. We also investigated the core structures in terms of G+C content homogeneity and phylogenetic congruence, and found that the core genes primarily exhibited the expected characteristic, i.e., being indigenous and sharing the same history, more than the non-core genes. Conclusion The results demonstrate that our strategy of genome alignment based on gene order conservation can provide an effective approach to identify the genomic core among moderately related microbial genomes. PMID:18976470

  4. Hepatitis B virus core antigen epitopes presented by HLA-A2 single-chain trimers induce functional epitope-specific CD8+ T-cell responses in HLA-A2.1/Kb transgenic mice.

    PubMed

    Zhang, Yuxia; Li, Shu; Shan, Ming; Pan, Xuwen; Zhuang, Ke; He, Lihua; Gould, Keith; Tien, Po

    2007-05-01

    The potency of CD8+ cytotoxic T lymphocyte (CTL) responses toward core antigen has been shown to affect the outcomes of hepatitis B virus (HBV) infection. Since single-chain trimers (SCT) composed of peptide epitope beta2-microglobulin (beta2m) and major histocompatibility complex (MHC) class I heavy chain covalently linked together in a single molecule have been shown to stimulate efficient CTL responses, we investigated the properties of human leucocyte antigen (HLA)-A2 SCTs encoding the HBV core antigen (HBcAg) epitopes C(18-27) and C(107-115). Transfection of NIH-3T3 cells with pcDNA3.0-SCT-C(18-27) and SCT-C(107-115) leads to stable presentation of HBcAg epitopes at the cell surface. HLA-A2.1/Kb transgenic mice vaccinated with the SCT constructs, either as a DNA vaccine alone or followed by a boost with recombinant vaccinia virus, were shown to generate HBcAg-specific CTL responses by enzyme-linked immunospot assay (ELISPOT) and in vitro interferon-gamma release experiments. HBcAg-specific CTLs from vaccinated HLA-A2.1/Kb transgenic mice were able to inhibit HBV surface and e antigen expression as indicated by HepG2.2.15 cells. Our data indicate that a DNA vaccine encoding a human HLA-A2 SCT with HBV epitopes can lead to stable, enhanced HBV core antigen presentation, and may be useful for the control of HBV infection in HLA-A2-positive HBV carriers. PMID:17244158

  5. Structural and spectral studies of sunspots. [umbral core modelling

    NASA Technical Reports Server (NTRS)

    Wyller, A. A.

    1974-01-01

    Observations of umbral cores, both by multicolor photometry and by narrow band photometry in the vicinity of the sodium D lines, are described, and evidence is given which supports the validity of many umbral models, each of which describes different aspects of the observed umbral cores. Theoretical studies carried on at the observatory include the following: (1) Zeeman profiles of the sodium D sub 2 line and other lines; (2) turbulent heat conduction, sound waves, and the missing flux in sunspots; (3) chromospheric heating above spots by Alfven waves; (4) magnetic convection in the sun and solar neutrinos; (5) models of starspots on flare stars; (5) starspots on the primaries of contact binary systems; and (6) implications of starspots on red dwarfs.

  6. Assembly and solution structure of the core retromer protein complex.

    PubMed

    Norwood, Suzanne J; Shaw, Daniel J; Cowieson, Nathan P; Owen, David J; Teasdale, Rohan D; Collins, Brett M

    2011-01-01

    Retromer is a peripheral membrane protein complex that has pleiotropic roles in endosomal membrane trafficking. The core of retromer possesses three subunits, VPS35, VPS29 and VPS26, that play different roles in binding to cargo, regulatory proteins and complex stabilization. We have performed an investigation of the thermodynamics of core retromer assembly using isothermal titration calorimetry (ITC) demonstrating that VPS35 acts as the central subunit to which VPS29 and VPS26 bind independently. Furthermore, we confirm that the conserved PRLYL motif of the large VPS35 subunit is critical for direct VPS26 interaction. Heat capacity measurements of VPS29 and VPS26 binding to VPS35 indicate extensive binding interfaces and suggest conformational alterations in VPS29 or VPS35 upon complex formation. Solution studies of the retromer core using small-angle X-ray scattering allow us to propose a model whereby VPS35 forms an extended platform with VPS29 and VPS26 bound at distal ends, with the potential for forming dimeric assemblies. PMID:20875039

  7. Dark matter halos with cores from hierarchical structure formation

    NASA Astrophysics Data System (ADS)

    Strigari, Louis E.; Kaplinghat, Manoj; Bullock, James S.

    2007-03-01

    We show that dark matter emerging from late decays (z≲1000) produces a linear power spectrum identical to that of cold dark matter (CDM) on all observationally relevant scales (≳0.1Mpc), and simultaneously generates observable constant-density cores in small dark matter halos. We refer to this class of models as meta-cold dark matter (mCDM), because it is born with nonrelativistic velocities from the decays of cold thermal relics. The constant-density cores are a result of the low phase-space density of mCDM at birth. Warm dark matter cannot produce similar size phase-space limited cores without saturating the Lyα power spectrum bounds. Dark matter-dominated galaxy rotation curves and stellar velocity dispersion profiles may provide the best means to discriminate between mCDM and CDM. mCDM candidates are motivated by the particle spectrum of supersymmetric and extra dimensional extensions to the standard model of particle physics.

  8. Complex N-glycans or core 1-derived O-glycans are not required for the expression of stage-specific antigens SSEA-1, SSEA-3, SSEA-4, or LeY in the preimplantation mouse embryo

    PubMed Central

    Williams, Suzannah A; Stanley, Pamela

    2010-01-01

    The glycan epitopes termed stage-specific embryonic antigens (SSEA) occur on glycoproteins and glycolipids in mammals. However, it is not known whether these epitopes are attached to N- or O-glycans on glycoproteins and/or on glycolipids in the developing mouse embryo. In this paper the expression of the antigens SSEA-1, SSEA-3, SSEA-4 and LeY was examined on ovulated eggs, early embryos and blastocysts lacking either complex and hybrid N-glycans or core-1 derived O-glycans. In all cases, antigen expression determined by fluorescence microscopy of bound monoclonal antibodies to embryos at the stage of development of maximal expression, was similar in mutant and control embryos. Thus, none of these developmental antigens are expressed solely on either complex N- or core 1-derived O-glycans attached to glycoproteins in the preimplantation mouse embryo. Furthermore, neither of these classes of glycan is essential for the expression of SSEA-1, SSEA-3, SSEA-4 or LeY on mouse embryos. PMID:18773292

  9. Cladding-mode obtained by core-offset structure and applied in fiber Bragg grating sensor

    NASA Astrophysics Data System (ADS)

    Zhang, Xinpu; Peng, Wei; Liu, Yun; Li, Hong; Jing, Zhenguo; Yu, Qi; Zhou, Xinlei; Yao, Wenjuan; Wang, Yanjie; Liang, Yuzhang

    2011-12-01

    Comparing to core-modes of optical fibers, some cladding-modes are more sensitive to the surroundings which are very valuable to sensing application; recently, a novel type of FBG sensor with core-offset structure attracts more and more interests. Normally, the forward core-mode is not only reflected and coupled to the backward core mode by the Fiber Bragg Grating in the step-type photosensitive single mode fiber, but also coupled to the backward cladding-modes and the radiation modes, eventually they will leak or be absorbed by the high refraction index coating layer. These backward cladding-modes can also be used for sensing analysis. In this paper, we propose and develop a core-offset structure to obtain the backward core-mode and backward cladding-modes by using the wavelength shift of the backward core-mode and the power of the backward cladding-modes in Fiber Bragg Grating sensor, and the power of the backward cladding-modes are independent from temperature variation. We develop a mode coupling sensor model between the forward core-mode and the backward cladding-modes, and demonstrate two coupling methods in the core-offset structure experimentally. The sensor is fabricated and demonstrated for refractive index monitoring. Some specific works are under investigation now, more analysis and fabrication will be done to improve this cladding-mode based sensor design for applicable sensing technology.

  10. Sensitivity of immune response quality to influenza helix 190 antigen structure displayed on a modular virus-like particle.

    PubMed

    Anggraeni, Melisa R; Connors, Natalie K; Wu, Yang; Chuan, Yap P; Lua, Linda H L; Middelberg, Anton P J

    2013-09-13

    Biomolecular engineering enables synthesis of improved proteins through synergistic fusion of modules from unrelated biomolecules. Modularization of peptide antigen from an unrelated pathogen for presentation on a modular virus-like particle (VLP) represents a new and promising approach to synthesize safe and efficacious vaccines. Addressing a key knowledge gap in modular VLP engineering, this study investigates the underlying fundamentals affecting the ability of induced antibodies to recognize the native pathogen. Specifically, this quality of immune response is correlated to the peptide antigen module structure. We modularized a helical peptide antigen element, helix 190 (H190) from the influenza hemagglutinin (HA) receptor binding region, for presentation on murine polyomavirus VLP, using two strategies aimed to promote H190 helicity on the VLP. In the first strategy, H190 was flanked by GCN4 structure-promoting elements within the antigen module; in the second, dual H190 copies were arrayed as tandem repeats in the module. Molecular dynamics simulation predicted that tandem repeat arraying would minimize secondary structural deviation of modularized H190 from its native conformation. In vivo testing supported this finding, showing that although both modularization strategies conferred high H190-specific immunogenicity, tandem repeat arraying of H190 led to a strikingly higher immune response quality, as measured by ability to generate antibodies recognizing a recombinant HA domain and split influenza virion. These findings provide new insights into the rational engineering of VLP vaccines, and could ultimately enable safe and efficacious vaccine design as an alternative to conventional approaches necessitating pathogen cultivation. PMID:23845811

  11. A New Program for Detecting the Geometrical Core of a Set of Structures of Macromolecular Complexes.

    PubMed

    Vakulenko, Yu A; Nagaev, B E; Alexeevski, A V; Karyagina, A S; Spirin, S A

    2016-04-01

    Comparison of structures of homological proteins often helps to understand functionally significant features of these structures. This concerns not only structures of separate protein chains, but also structures of macromolecular complexes. In particular, a comparison of complexes of homologous proteins with DNA is significant for analysis of the recognition of DNA by proteins. We present program LCore for detecting geometrical cores of a family of structures; a geometrical core is a set of amino acid residues and nucleotides that disposed similarly in all structures of the family. We describe the algorithm of the program, its web interface, and an example of its application to analysis of complexes of homeodomains with DNA. PMID:27293101

  12. Formation of core-shell structure in high entropy alloy coating by laser cladding

    NASA Astrophysics Data System (ADS)

    Zhang, Hui; Wu, Wanfei; He, Yizhu; Li, Mingxi; Guo, Sheng

    2016-02-01

    The formation of core-shell structure is an interesting phenomenon occurring during the solidification process, due to the liquid phase separation. The formation of core-shell structure in high-entropy alloys, a new class of advanced metallic materials, has not been reported previously, and thus constitutes an intriguing scientific question. Here, we firstly report the formation of core-shell structure in one laser cladded high-entropy alloy, where we show the nanosized-Y2O3 powder addition, serves as the catalyst for the liquid phase separation.

  13. Replication of the Adjustment Scales for Children and Adolescents Core Syndrome Factor Structure

    ERIC Educational Resources Information Center

    Canivez, Gary L.

    2004-01-01

    Independent examination and replication of the core syndrome factor structure of the Adjustment Scales for Children and Adolescents (ASCA; McDermott, Marston, & Stott, 1993) is reported. A sample of 1,020 children were randomly selected from their classroom and rated on the ASCA by their teacher. The six ASCA core syndromes produced a two-factor…

  14. Naive CD8+ T-cell precursors display structured TCR repertoires and composite antigen-driven selection dynamics

    PubMed Central

    Neller, Michelle A; Ladell, Kristin; McLaren, James E; Matthews, Katherine K; Gostick, Emma; Pentier, Johanne M; Dolton, Garry; Schauenburg, Andrea JA; Koning, Dan; Fontaine Costa, Ana Isabel CA; Watkins, Thomas S; Venturi, Vanessa; Smith, Corey; Khanna, Rajiv; Miners, Kelly; Clement, Mathew; Wooldridge, Linda; Cole, David K; van Baarle, Debbie; Sewell, Andrew K; Burrows, Scott R; Price, David A; Miles, John J

    2015-01-01

    Basic parameters of the naive antigen (Ag)-specific T-cell repertoire in humans remain poorly defined. Systematic characterization of this ‘ground state' immunity in comparison with memory will allow a better understanding of clonal selection during immune challenge. Here, we used high-definition cell isolation from umbilical cord blood samples to establish the baseline frequency, phenotype and T-cell antigen receptor (TCR) repertoire of CD8+ T-cell precursor populations specific for a range of viral and self-derived Ags. Across the board, these precursor populations were phenotypically naive and occurred with hierarchical frequencies clustered by Ag specificity. The corresponding patterns of TCR architecture were highly ordered and displayed partial overlap with adult memory, indicating biased structuring of the T-cell repertoire during Ag-driven selection. Collectively, these results provide new insights into the complex nature and dynamics of the naive T-cell compartment. PMID:25801351

  15. Usefulness of a new immunoradiometric assay of HCV core antigen to predict virological response during PEG-IFN/RBV combination therapy for chronic hepatitis with high viral load of serum HCV RNA genotype 1b.

    PubMed

    Sasase, Noriko; Kim, Soo Ryang; Kim, Ke Ih; Taniguchi, Miyuki; Imoto, Susumu; Mita, Keiji; Hotta, Hak; Shouji, Ikuo; El-Shamy, Ahmed; Kawada, Norifumi; Kudo, Masatoshi; Hayashi, Yoshitake

    2008-01-01

    We investigated the clinical usefulness of a new immunoradiometric (IRM) assay of hepatitis C virus (HCV) core antigen in predicting virological response during pegylated interferon plus ribavirin (PEG-IFN/RBV) combination therapy for chronic hepatitis with high viral loads of serum HCV RNA genotype 1b. Thirty-nine patients received a regimen of PEG-IFNalpha-2b (1.5 microg/kg/week s.c.) in combination with RBV (600-1,000 mg/day). Of the 39 patients, 18 (46.2%) achieved sustained virological response (SVR), 11 (28.2%) attained partial response (PR) and 10 (25.6%) showed no response (NR). Four weeks after the start of therapy, 1- and 2-log reductions in the amount of HCV core antigen were observed in 20 (2/10) and 0% (0/10) showing NR, 91 (10/11) and 63.6% (7/11) with PRs, and 88.9 (16/18) and 55.6% (10/18) of patients with SVR, respectively. The 1- and 2-log reductions 4 weeks after the start of therapy were not a defining condition for PR and SVR. The amount of HCV core antigen was significantly different between SVR and PR patients on days 1 and 7, and between patients with NR and SVR at all points of time. In conclusion, this new IRM assay is useful in predicting virological response during PEG-IFN/RBV therapy. PMID:18544951

  16. A novel sandwich electrochemiluminescence immunosensor for ultrasensitive detection of carbohydrate antigen 19-9 based on immobilizing luminol on Ag@BSA core/shell microspheres.

    PubMed

    Zhang, Amin; Xiang, Hongkun; Zhang, Xin; Guo, Weiwei; Yuan, Enhui; Huang, Chusen; Jia, Nengqin

    2016-01-15

    A novel sandwich-type electrochemiluminescence immunosensor based on immobilizing luminol on Ag@BSA core/shell microspheres (Ag@BSA-luminol) for ultrasensitive detection of tumor marker carbohydrate antigen 19-9 (CA19-9) has been developed. Herein, magnetic carbon nanotubes (MAGCNTs) decorated with polyethylenimine (PEI) was used to construct the base of the immunosensor. MAGCNTs with prominent electrical conductivity and high surface area could be beneficial for promoting the electron transfer and loading plenty of primary antibodies (Ab1) via glutaraldehyde (GA). Meanwhile, the magnetic property of MAGCNTs makes it easy to be attached to the surface of magnetic glass carbon electrode (MGCE) through magnetism interaction, which provides an outstanding platform for this immunosensor. Moreover, Ag@BSA microspheres with large surface area, good stability, and excellent biocompatibility were desirable candidates for effective cross-link of CA19-9 detection antibodies (Ab2). A more interesting thing was that ELISA color reaction was used as an ultrasensitive strategy for identifying Ab2 was successfully coated on Ag@BSA with the naked eye. Additionally, we immobilized the luminol on the surface of Ag@BSA to prepare the target immunosensor. Immobilization of luminol on the surface of Ag@BSA could decrease the distance between luminophores and the electrode surface, leading to great enhancement of the ECL intensity of luminol in the present of hydrogen peroxide (H2O2). Under the optimal conditions, the intensity of the ECL immunosensor increased linearly with the logarithm of CA19-9 concentration in a wide linear range from 0.0005 to 150UmL(-1) with a detection limit of 0.0002UmL(-1) (S/N=3). All the results suggested the prepared CA19-9 immunosensor displayed high sensitivity, excellent stability and good specificity. The developed method opened a new avenue to clinical bioassay. PMID:26319163

  17. Near-Edge X-Ray Absorption Fine Structures Revealed in Core Ionization Photoelectron Spectroscopy

    NASA Astrophysics Data System (ADS)

    Nakano, M.; Selles, P.; Lablanquie, P.; Hikosaka, Y.; Penent, F.; Shigemasa, E.; Ito, K.; Carniato, S.

    2013-09-01

    Simultaneous core ionization and core excitation have been observed in the C2H2n (n=1, 2, 3) molecular series using synchrotron radiation and a magnetic bottle time-of-flight electron spectrometer. Rich satellite patterns corresponding to (K-2V) core excited states of the K-1 molecular ions have been identified by detecting in coincidence the photoelectron with the two Auger electrons resulting from the double core hole relaxation. A theoretical model is proposed providing absolute photoionization cross sections and revealing clear signatures of direct (monopolar) and conjugate (dipolar near-edge x-ray absorption fine structure) shakeup lines of comparable magnitude.

  18. Near-edge x-ray absorption fine structures revealed in core ionization photoelectron spectroscopy.

    PubMed

    Nakano, M; Selles, P; Lablanquie, P; Hikosaka, Y; Penent, F; Shigemasa, E; Ito, K; Carniato, S

    2013-09-20

    Simultaneous core ionization and core excitation have been observed in the C(2)H(2n) (n=1, 2, 3) molecular series using synchrotron radiation and a magnetic bottle time-of-flight electron spectrometer. Rich satellite patterns corresponding to (K(-2)V) core excited states of the K(-1) molecular ions have been identified by detecting in coincidence the photoelectron with the two Auger electrons resulting from the double core hole relaxation. A theoretical model is proposed providing absolute photoionization cross sections and revealing clear signatures of direct (monopolar) and conjugate (dipolar near-edge x-ray absorption fine structure) shakeup lines of comparable magnitude. PMID:24093255

  19. Measuring Core/Facesheet Bond Toughness in Honeycomb Sandwich Structures

    NASA Technical Reports Server (NTRS)

    Nettles, A. T.

    2006-01-01

    This study examines two test methods to evaluate the peel toughness of the skin to core debond of sandwich panels. The methods tested were the climbing drum (CD) peel test and the double cantilever beam (DCB) test. While the CD peel test is only intended for qualitative measurements, it is shown in this study that qualitative measurements can be performed and compare well with DCB test data. It is also shown that artificially stiffening the facesheets of a DCB specimen can cause the test to behave more like a flatwise tensile test than a peel test.

  20. Structure and gene cluster of the O-antigen of Escherichia coli O156 containing a pyruvic acid acetal.

    PubMed

    Duan, Zhifeng; Senchenkova, Sof'ya N; Guo, Xi; Perepelov, Andrei V; Shashkov, Alexander S; Liu, Bin; Knirel, Yuriy A

    2016-07-22

    The lipopolysaccharide of Escherichia coli O156 was degraded under mild acidic and alkaline conditions and the resulting polysaccharides were studied by sugar analysis and (1)H and (13)C NMR spectroscopy. The following structure of the pentasaccharide repeating unit of the O-polysaccharide was established: where Rpyr indicates R-configurated pyruvic acid acetal. Minor O-acetyl groups also were present and tentatively localized on the Gal residues. The gene cluster for biosynthesis of the O-antigen of E. coli O156 was analyzed and shown to be consistent with the O-polysaccharide structure. PMID:27177202

  1. Solution structure of p53 core domain: Structural basis for its instability

    PubMed Central

    Cañadillas, José Manuel Pérez; Tidow, Henning; Freund, Stefan M. V.; Rutherford, Trevor J.; Ang, Hwee Ching; Fersht, Alan R.

    2006-01-01

    The 25-kDa core domain of the tumor suppressor p53 is inherently unstable and melts at just above body temperature, which makes it susceptible to oncogenic mutations that inactivate it by lowering its stability. We determined its structure in solution using state-of-the-art isotopic labeling techniques and NMR spectroscopy to complement its crystal structure. The structure was very similar to that in the crystal but far more mobile than expected. Importantly, we were able to analyze by NMR the structural environment of several buried polar groups, which indicated structural reasons for the instability. NMR spectroscopy, with its ability to detect protons, located buried hydroxyl and sulfhydryl groups that form suboptimal hydrogen-bond networks. We mutated one such buried pair, Tyr-236 and Thr-253 to Phe-236 and Ile-253 (as found in the paralogs p63 and p73), and stabilized p53 by 1.6 kcal/mol. We also detected differences in the conformation of a mobile loop that might reflect the existence of physiologically relevant alternative conformations. The effects of temperature on the dynamics of aromatic residues indicated that the protein also experiences several dynamic processes that might be related to the presence of alternative hydrogen-bond patterns in the protein interior. p53 appears to have evolved to be dynamic and unstable. PMID:16461916

  2. Density-based and transport-based core-periphery structures in networks

    NASA Astrophysics Data System (ADS)

    Lee, Sang Hoon; Cucuringu, Mihai; Porter, Mason A.

    2014-03-01

    Networks often possess mesoscale structures, and studying them can yield insights into both structure and function. It is most common to study community structure, but numerous other types of mesoscale structures also exist. In this paper, we examine core-periphery structures based on both density and transport. In such structures, core network components are well-connected both among themselves and to peripheral components, which are not well-connected to anything. We examine core-periphery structures in a wide range of examples of transportation, social, and financial networks—including road networks in large urban areas, a rabbit warren, a dolphin social network, a European interbank network, and a migration network between counties in the United States. We illustrate that a recently developed transport-based notion of node coreness is very useful for characterizing transportation networks. We also generalize this notion to examine core versus peripheral edges, and we show that the resulting diagnostic is also useful for transportation networks. To examine the properties of transportation networks further, we develop a family of generative models of roadlike networks. We illustrate the effect of the dimensionality of the embedding space on transportation networks, and we demonstrate that the correlations between different measures of coreness can be very different for different types of networks.

  3. The Structure of Gas-accreting Protoplanets and the Condition of the Critical Core Mass

    NASA Astrophysics Data System (ADS)

    Kanagawa, Kazuhiro D.; Fujimoto, Masayuki Y.

    2013-03-01

    In the core accretion model for the formation of gas giant planets, runaway gas accretion onto a core is the primary requisite, triggered when the core mass reaches a critical value. The recently revealed wide diversity of the extrasolar giant planets suggests the necessity to further the understanding of the conditions resulting in the critical core mass that initiates runaway accretion. We study the internal structure of protoplanets under hydrostatic and thermal equilibria represented in terms of a polytropic equation of state to investigate what factors determine and affect the critical core mass. We find that the protoplanets, embedded in protoplanetary disks, have the same configuration as red giants, characterized by the envelope of the centrally condensed type solution. Applying the theory of stellar structure with homology invariants, we demonstrate that there are three types of criteria for the critical core mass depending on the stiffness of polytrope and the nature of outer boundary condition. For the stiff polytropes of index N <= 3 with the Bondi radius as the outer boundary, the criterion governing the critical core mass occurs at the surface. For stiff polytropes with the Hill outer boundary and for soft polytropes of N > 3, this criterion acts at the bottom of gaseous envelope. Further, we elucidate the roles and effects of coexistent radiative and convective zones in the envelope of critical core mass. Based on the results, we discuss the relevance of Bondi and Hill surface conditions and explore the parameter dependences of critical core mass.

  4. THE STRUCTURE OF GAS-ACCRETING PROTOPLANETS AND THE CONDITION OF THE CRITICAL CORE MASS

    SciTech Connect

    Kanagawa, Kazuhiro D.; Fujimoto, Masayuki Y.

    2013-03-01

    In the core accretion model for the formation of gas giant planets, runaway gas accretion onto a core is the primary requisite, triggered when the core mass reaches a critical value. The recently revealed wide diversity of the extrasolar giant planets suggests the necessity to further the understanding of the conditions resulting in the critical core mass that initiates runaway accretion. We study the internal structure of protoplanets under hydrostatic and thermal equilibria represented in terms of a polytropic equation of state to investigate what factors determine and affect the critical core mass. We find that the protoplanets, embedded in protoplanetary disks, have the same configuration as red giants, characterized by the envelope of the centrally condensed type solution. Applying the theory of stellar structure with homology invariants, we demonstrate that there are three types of criteria for the critical core mass depending on the stiffness of polytrope and the nature of outer boundary condition. For the stiff polytropes of index N {<=} 3 with the Bondi radius as the outer boundary, the criterion governing the critical core mass occurs at the surface. For stiff polytropes with the Hill outer boundary and for soft polytropes of N > 3, this criterion acts at the bottom of gaseous envelope. Further, we elucidate the roles and effects of coexistent radiative and convective zones in the envelope of critical core mass. Based on the results, we discuss the relevance of Bondi and Hill surface conditions and explore the parameter dependences of critical core mass.

  5. Magnetic field structure around cores with very low luminosity objects

    NASA Astrophysics Data System (ADS)

    Soam, A.; Maheswar, G.; Lee, Chang Won; Dib, Sami; Bhatt, H. C.; Tamura, Motohide; Kim, Gwanjeong

    2015-01-01

    Aims: We carried out optical polarimetry of five dense cores, (IRAM 04191, L1521F, L328, L673-7, and L1014) which are found to harbour very low luminosity objects (VeLLOs; Lint ≲ 0.1 L⊙). This study was conducted mainly to understand the role played by the magnetic field in the formation of very low and substellar mass range objects. Methods: Light from the stars, while passing through the dust grains that are aligned with their short axis parallel to an external magnetic field, becomes linearly polarised. The polarisation position angles measured for the stars can provide the plane-of-the sky magnetic field orientation. Because the light in the optical wavelength range is most efficiently polarised by the dust grains typically found at the outer layers of the molecular clouds, optical polarimetry mostly traces the magnetic field orientation of the core envelope. Results: The polarisation observations of stars projected on IRAM 04191, L328, L673-7, and L1014 were obtained in the R-band and those of L1521F were obtained in the V-band. The angular offsets between the envelope magnetic field direction (inferred from optical polarisation measurements) and the outflow position angles from the VeLLOs in IRAM 04191, L1521F, L328, L673-7, and L1014 are found to be 84°, 53°, 24°, 08°, and 15°, respectively. The mean value of the offsets for all the five clouds is ~ 37°. If we exclude IRAM 04191, the mean value reduces to become ~ 25°. In IRAM 04191, the offset between the projected envelope and the inner magnetic field (inferred from the submillimetre data obtained using SCUBA-POL) is found to be ~ 68°. The inner magnetic field, however, is found to be nearly aligned with the projected position angles of the minor axis, the rotation axis of the cloud, and the outflow from the IRAM 04191-IRS. We discuss a possible explanation for the nearly perpendicular orientation between the envelope and core scale magnetic fields in IRAM 04191. The angular offset between the

  6. Human prostate-specific antigen: structural and functional similarity with serine proteases.

    PubMed Central

    Watt, K W; Lee, P J; M'Timkulu, T; Chan, W P; Loor, R

    1986-01-01

    The complete amino acid sequence of the prostate-specific antigen (PA) from human seminal plasma has been determined from analyses of the peptides generated by cyanogen bromide, hydroxylamine, endoproteinases Arg-C and Lys-C. The single polypeptide chain of PA contains 240-amino acid residues and has a calculated Mr of 26,496. An N-linked carbohydrate side chain is predicted at asparagine-45, and O-linked carbohydrate side chains are possibly attached to serine-69, threonine-70, and serine-71. The primary structure of PA shows a high degree of sequence homology with other serine proteases of the kallikrein family. The active site residues of histidine, aspartic acid, and serine comprising the charge-relay system of typical serine proteases were found in similar positions in PA (histidine-41, aspartic acid-96, and serine-192). At pH 7.8, PA hydrolyzed insulin A and B chains, recombinant interleukin 2, and--to a lesser extent--gelatin, myoglobin, ovalbumin, and fibrinogen. The cleavage sites of these proteins by PA were chemically analyzed as the alpha-carboxyl side of some hydrophobic residues, tyrosine, leucine, valine, and phenylalanine, and of basic residues histidine, lysine, and arginine. The chymotrypsin-like activity of PA exhibited with the chromogenic substrate N-succinyl-L-alanyl-L-alanyl-L-prolyl-L-phenylalanine p-nitroanilide yielded a specific activity of 9.21 microM per min per mg of PA and Km and kcat values of 15.3 mM and 0.075s-1, respectively. "Trypsin-like" activity of PA was also detected with N alpha-benzoyl-DL-arginine p-nitroanilide and gave a specific activity of 1.98 microM per min per mg of PA. Protease inhibitors such as phenylmethylsulfonyl fluoride, diisopropyl fluorophosphate, L-1-tosylamido-2-phenylethyl chloromethyl ketone, aprotinin, leupeptin, soybean trypsin inhibitor as well as Zn2+ and spermidine were effective inhibitors of PA enzymatic activity. PMID:2422647

  7. Total Synthesis of (+)-Minfiensine: Construction of the Tetracyclic Core Structure by an Asymmetric Cascade Cyclization.

    PubMed

    Zhang, Ze-Xin; Chen, Si-Cong; Jiao, Lei

    2016-07-01

    A new method for one-step construction of the tetracyclic core structure of the indole alkaloid (+)-minfiensine was developed utilizing a palladium-catalyzed asymmetric indole dearomatization/iminium cyclization cascade. An efficient total synthesis of (+)-minfiensine was realized using this strategy. The present method enables access to the common core structure of a series of monoterpene indole alkaloids, such as vincorine, echitamine, and aspidosphylline A. PMID:27172972

  8. Structure and electronic properties of mixed (a + c) dislocation cores in GaN

    SciTech Connect

    Horton, M. K.; Rhode, S. L.; Moram, M. A.

    2014-08-14

    Classical atomistic models and atomic-resolution scanning transmission electron microscopy studies of GaN films reveal that mixed (a + c)-type dislocations have multiple different core structures, including a dissociated structure consisting of a planar fault on one of the (12{sup ¯}10) planes terminated by two different partial dislocations. Density functional theory calculations show that all cores introduce localized states into the band gap, which affects device performance.

  9. Core oligosaccharide of Escherichia coli B-the structure required for bacteriophage T4 recognition.

    PubMed

    Kaszowska, Marta; Niedziela, Tomasz; Maciejewska, Anna; Lukasiewicz, Jolanta; Jachymek, Wojciech; Lugowski, Czeslaw

    2015-09-01

    The structure of Escherichia coli B strain PCM 1935 core oligosaccharide has been investigated by (1)H and (13)C NMR spectroscopy, MALDI-TOF MS and ESI MS(n). It was concluded that the core oligosaccharide is a pentasaccharide with the following structure: ESI MS/MS analysis revealed that the glycine (a minor component) is linked to the →3,7)-l-α-d-Hepp-(1→ residue. PMID:26091777

  10. Effect of initial vortex core size on the coherent structures in the swirling jet near field

    NASA Astrophysics Data System (ADS)

    Rukes, Lothar; Sieber, Moritz; Paschereit, C. Oliver; Oberleithner, Kilian

    2015-10-01

    This study investigates the sensitivity to initial conditions of swirling jets undergoing vortex breakdown. Emphasis is placed on the recirculation bubble and on the helical coherent structures that evolve in its periphery. It is proposed that the vortex core size of the incoming swirling jet is the critical parameter that determines the dynamics of these coherent structures. This proposition is assessed with Stereo Particle-Image-Velocimetry (PIV) measurements of the breakdown region of two swirling jet configurations with different vortex core sizes at very similar overall swirl intensities. The swirling jets were generated by radial vanes entering a mixing tube, and the vortex core size was adjusted by using different center-body geometries. The time-averaged flow fields in the breakdown region reveal substantial differences in the jet spreading and the size of the recirculation bubble. Proper Ortogonal Decomposition (POD) was applied to the anti-axisymmetric and axisymmetric velocity fluctuations, to reconstruct the dynamics of the helical instability and the breakdown bubble, respectively. We find that the mode shape of the helical instability is not affected by the vortex core size. The frequency is found to coincide with the vortex core rotation rate, which relates inversely to the core size. The shape and dynamics of the non-periodic breakdown bubble are significantly affected by a change in vortex core size. The POD reveals that the energy content of the dominant non-periodic structure is changed markedly with the vortex core size. The bubble dynamics are further investigated by tracking the upstream stagnation point from the PIV snapshots. It is shown that a larger vortex core promotes smooth fluctuations of the recirculation bubble, while a small initial vortex core is linked to bimodal fluctuations of the recirculation bubble. The conclusions drawn from this study are relevant for fundamental swirling jet studies, as well as for the design of swirl

  11. The core structure of dislocations and their relationship to the material γ-surface

    SciTech Connect

    Hunter, A.; Zhang, R. F.; Beyerlein, I. J.

    2014-04-07

    Using a density functional theory-phase field dislocation dynamics model, we reveal a strong inverse relationship between the dislocation equilibrium core width and the normalized intrinsic stacking fault energy for nine face centered cubic (fcc) metals, in quantitative agreement with experiments but not with conventional continuum models. In addition, we show that due to an anomalous feature in its γ-surface, platinum has a fundamentally different core structure and a much wider equilibrium core width than expected. Based on ab initio electronic structure calculations, we attribute this anomaly to distinct differences in the directionality of charge transfer in platinum.

  12. Core ionization energies of amides as a probe of structure and bonding

    NASA Astrophysics Data System (ADS)

    Greenberg, Arthur; Moore, David T.

    1997-09-01

    Core orbital energies are computed for planar ground-state and rotational transition-state structures for formamide and N,N-dimethylacetamide using ab initio molecular orbital calculations at the 6-31G∗ level. Distortion of the amide linkage decreases the core ionization energy of nitrogen and increases the core ionization energies of oxygen and the carbonyl carbon. Similar trends are observed for bridgehead bicyclic lactams and are corroborated by the limited experimental data available. A simple interpretation can be made in the language of resonance theories through reference to contributions of three canonical structures ( 1A-1C) and in particular, the reduced contribution of 1B in distorted amides.

  13. Gregarious Data Re-structuring in a Many Core Architecture

    SciTech Connect

    Shrestha, Sunil; Manzano Franco, Joseph B.; Marquez, Andres; Zuckerman, Stephane; Song, Shuaiwen; Gao, Guang R.

    2015-08-24

    this paper, we have developed a new methodology that takes in consideration the access patterns from a single parallel actor (e.g. a thread), as well as, the access patterns of “grouped” parallel actors that share a resource (e.g. a distributed Level 3 cache). We start with a hierarchical tile code for our target machine and apply a series of transformations at the tile level to improve data residence in a given memory hierarchy level. The contribution of this paper includes (a) collaborative data restructuring for group reuse and (b) low overhead transformation technique to improve access pattern and bring closely connected data elements together. Preliminary results in a many core architecture, Tilera TileGX, shows promising improvements over optimized OpenMP code (up to 31% increase in GFLOPS) and over our own previous work on fine grained runtimes (up to 16%) for selected kernels

  14. Solution Structure and Characterisation of the Human Pyruvate Dehydrogenase Complex Core Assembly

    PubMed Central

    Vijayakrishnan, S.; Kelly, S.M.; Gilbert, R.J.C.; Callow, P.; Bhella, D.; Forsyth, T.; Lindsay, J.G.; Byron, O.

    2010-01-01

    Mammalian pyruvate dehydrogenase complex (PDC) is a key multi-enzyme assembly that is responsible for glucose homeostasis maintenance and conversion of pyruvate into acetyl-CoA. It comprises a central pentagonal dodecahedral core consisting of two subunit types (E2 and E3BP) to which peripheral enzymes (E1 and E3) bind tightly but non-covalently. Currently, there are two conflicting models of PDC (E2 + E3BP) core organisation: the ‘addition’ model (60 + 12) and the ‘substitution’ model (48 + 12). Here we present the first ever low-resolution structures of human recombinant full-length PDC core (rE2/E3BP), truncated PDC core (tE2/E3BP) and native bovine heart PDC core (bE2/E3BP) obtained by small-angle X-ray scattering and small-angle neutron scattering. These structures, corroborated by negative-stain and cryo electron microscopy data, clearly reveal open pentagonal core faces, favouring the ‘substitution’ model of core organisation. The native and recombinant core structures are all similar to the truncated bacterial E2 core crystal structure obtained previously. Cryo-electron microscopy reconstructions of rE2/E3BP and rE2/E3BP:E3 directly confirm that the core has open pentagonal faces, agree with scattering-derived models and show density extending outwards from their surfaces, which is much more structurally ordered in the presence of E3. Additionally, analytical ultracentrifugation characterisation of rE2/E3BP, rE2 (full-length recombinant E2-only) and tE2/E3BP supports the substitution model. Superimposition of the small-angle neutron scattering tE2/E3BP and truncated bacterial E2 crystal structures demonstrates conservation of the overall pentagonal dodecahedral morphology, despite evolutionary diversity. In addition, unfolding studies using circular dichroism and tryptophan fluorescence spectroscopy show that the rE2/E3BP is less stable than its rE2 counterpart, indicative of a role for E3BP in core destabilisation. The architectural

  15. Time-Dependent Inner Core Structures Examined by Repeating Earthquakes in the Southwest Pacific Subduction Zones

    NASA Astrophysics Data System (ADS)

    Yu, W. C.

    2014-12-01

    Time-dependent inner core structure is interpreted as differential rotation of the Earth's inner core. This inference is made on the basis of variations deviated from an isotropic and homogeneous inner core structure and the amount of velocity perturbations progressively evolving as a function of calendar time. Most compelling evidences for inner core rotation come from the inner core structures beneath Colombia and Venezuela, characterized by strong anisotropy and lateral variation, for the South Sandwich Islands earthquakes recorded by College (COL) and other seismic stations in Alaska. Repeating earthquakes with highly similar waveforms can minimize the potential artifacts due to inter-event separation and unknown short-scale mantle heterogeneities, and can acquire robust measurement of time shift due to temporal change of inner core structures. Moderate repeating earthquake sequences (RES) in the Tonga-Kermadec-Vanuatu in the southwest Pacific subduction zones are studied over a 20-year time window between 1990 and 2009. I select 13 RES consisting of two or three events with time separation of 2 - 14.4 years and analyze the PKiKP-PKPdf, PKPbc-PKPdf, and PKPab-PKPdf phase pairs recorded by the European, African, and central Asian stations sampling the eastern hemisphere of the inner core. I measure the double differential time of the phase pairs using waveform cross-correlation. Majority of the double differential time measurements within ±50 millisecond can largely be explained by the time shift due to inter-event distance on the order of hundreds of meters or less and null change of the PKPdf phase. These observations indicate inner core structures in the eastern hemisphere are uniform and probably insensitive to motion of the inner core.

  16. Structure of a Major Antigenic Site on the Respiratory Syncytial Virus Fusion Glycoprotein in Complex with Neutralizing Antibody 101F

    SciTech Connect

    McLellan, Jason S.; Chen, Man; Chang, Jung-San; Yang, Yongping; Kim, Albert; Graham, Barney S.; Kwong, Peter D.

    2010-11-19

    Respiratory syncytial virus (RSV) is a major cause of pneumonia and bronchiolitis in infants and elderly people. Currently there is no effective vaccine against RSV, but passive prophylaxis with neutralizing antibodies reduces hospitalizations. To investigate the mechanism of antibody-mediated RSV neutralization, we undertook structure-function studies of monoclonal antibody 101F, which binds a linear epitope in the RSV fusion glycoprotein. Crystal structures of the 101F antigen-binding fragment in complex with peptides from the fusion glycoprotein defined both the extent of the linear epitope and the interactions of residues that are mutated in antibody escape variants. The structure allowed for modeling of 101F in complex with trimers of the fusion glycoprotein, and the resulting models suggested that 101F may contact additional surfaces located outside the linear epitope. This hypothesis was supported by surface plasmon resonance experiments that demonstrated 101F bound the peptide epitope {approx}16,000-fold more weakly than the fusion glycoprotein. The modeling also showed no substantial clashes between 101F and the fusion glycoprotein in either the pre- or postfusion state, and cell-based assays indicated that 101F neutralization was not associated with blocking virus attachment. Collectively, these results provide a structural basis for RSV neutralization by antibodies that target a major antigenic site on the fusion glycoprotein.

  17. X-ray imaging of vortex cores in confined magnetic structures

    SciTech Connect

    Fischer, P; Im, M -Y; Kasai, S; Yamada, K; Ono, T; Thiaville, A

    2011-02-11

    Cores of magnetic vortices in micron-sized NiFe disk structures, with thicknesses between 150 and 50 nm, were imaged and analyzed by high-resolution magnetic soft x-ray microscopy. A decrease of the vortex-core radius was observed from approximately 38 to 18 nm with decreasing disk thickness. By comparing with full three-dimensional micromagnetic simulations showing the well-known barrel structure, we obtained excellent agreement, taking into account instrumental broadening and a small perpendicular anisotropy. The proven magnetic spatial resolution of better than 25 nm was sufficient to identify a negative dip close to the vortex core, originating from stray fields of the core. Magnetic vortex structures can serve as test objects for evaluating sensitivity and spatial resolution of advanced magnetic microscopy techniques.

  18. A study of the structural efficiency of fluted core graphite-epoxy panels

    NASA Technical Reports Server (NTRS)

    Jegley, Dawn C.

    1990-01-01

    The structural efficiency of compression-loaded graphite-epoxy sandwich panels with fluted cores is studied to determine their weight saving potential. Graphite-epoxy equilateral triangular elements are used to construct the fluted cores for the sandwich panels. Two panel configurations are considered. One configuration has two layers of triangular elements in the fluted core and the second configuration has only one layer of triangular elements in the core. An optimization code is used to find the minimum weight design for each panel configuration. Laminate ply orientations are limited to approx. 45, 0, and 90 deg. A constraint on the axial stiffness is included in the design process so the panel will conform to typical constraints for aircraft wing structures. Minimum thickness requirements for each laminate and maximum allowable strains are also included. A comparison is made of the calculated structural efficiency of the fluted core panels to the structural efficiency of aluminum transport aircraft structures and simple blade-stiffened graphite-epoxy panels. Limited experimental results are also included for comparison with the analytical predictions and to identify the critical failure mechanisms of graphite-epoxy fluted-core sandwich panels.

  19. Structure determination of lipopeptides from Mycobacterium avium subspecies paratuberculosis and identification of antigenic lipopeptide probes.

    PubMed

    Mitachi, Katsuhiko; Sharma Gautam, Lekh Nath; Rice, Jeffrey H; Eda, Keiko; Wadhwa, Ashutosh; Momotani, Eiichi; Hlopak, Joseph P; Eda, Shigetoshi; Kurosu, Michio

    2016-07-15

    Mycobacterium avium subspecies paratuberculosis (MAP) causes chronic illnesses mostly in ruminants. MAP infection of intestinal tissue triggers a fatal inflammatory disorder, Johne's disease (paratuberculosis). Development of fast and reliable diagnostic methods for Johne's disease in clinically suspected ruminants requires the discovery of MAP-specific antigens that induce immune responses. Despite a longtime interest in finding such antigens that can detect serum antibody responses with high sensitivity, the antigens currently used for a diagnosis of the MAP infections are the crude extracts from the whole cell. We performed the serum antibody response assay-guided purification of the ethanol extract from MAP isolated from an infected cow. With the results of extensive fractionations and in vitro assays, we identified that arachidyl-d-Phe-N-Me-l-Val-l-Ile-l-Phe-l-Ala-OH (named lipopeptide IIß, 3) exhibited the highest antibody binding activity in serum of a MAP-infected cattle compared with the other lipopeptides isolated from MAP. The absolute chemistry of 3 was determined unequivocally via our high-performance liquid chromatography (HPLC)-amino acid databases. α-Amino lipopeptide IIß and its fluorescent probes were synthesized and evaluated in serum antibody binding activity assays. Lipopeptide IIß-(2S)-NH2 (9) and its dansyl and fluorescein isothiocyanate (FITC) probes (10 and 11) exhibited antibody-mediated binding activity; thus, such MAP-specific lipopeptide probes can be potential biomarkers for the development of rapid and accurate diagnosis of Johne's disease. PMID:27114041

  20. Antigen structure and genetic basis of histo-blood groups A, B and O: their changes associated with human cancer.

    PubMed

    Hakomori, S

    1999-12-01

    Three areas of research involved in blood group (or histo-blood group) ABO antigens and their genes, developed by our research group, are reviewed: (1) Antigen structures. The structural basis of A and H, A(1) and A(2), i and I antigens expressed in erythrocyte membranes. Major carriers of A and H determinants in erythrocytes are type 2 chain poly-LacNAc, short vs. long and unbranched vs. branched structures termed A(a), A(b), A(c), A(d) and H(1), H(2), H(3), H(4). Regular A (A(1)) and weak A (A(2)) were identified respectively as repetitive A (type 3 chain A) and A-associated H. A(1)- and A(2)-specific type 3 chain A and H, type 1 chain (representing Lewis blood group antigens), and type 4 chain (globo-series antigen; an extremely minor component in erythrocytes) are all glycosphingolipids. A and H determinants in fetal and newborn erythrocytes are carried by unbranched poly-LacNAc, whereas these determinants in adult erythrocytes are carried by branched poly-LacNAc. (2) ABO genes. A few cDNAs encoding A enzyme (UDP-GalNAc: H-a-GalNAc transferase) were cloned based on the amino acid sequence of purified A enzyme and their structures were compared with those of homologous cDNA from blood cells of B and O individuals (genotype BB, OO). Four nucleotide substitutions and four corresponding amino acid sequences essential for expression of A(1) allele and B allele, and differences between A and B enzymes, were identified. Amino acids 266 and 268, i.e. Leu and Gly for A enzyme vs. Met and Ala for B enzyme, were dominant in determining A vs. B activity (presumably recognizing UDP-GalNAc vs. UDP-Gal). The A(2) allele was characterized by deletion of the termination codon, extending nucleotides up to 1128 and thus encoding 21 extra amino acids at the C terminus, which may affect (diminish) the dominant function of amino acids 266 and 268. Typical O allele (O(1)) is characterized by deletion of nucleotide 261 G, causing frame shift and encoding of an entirely different

  1. [Scattering properties of core-shell structure of mist wrapped dust particles].

    PubMed

    Feng, Shi-qi; Song, Wei; Wang, Yan; Miao, Xin-hui; Xu, Li-jun; Liu, Yu; Li, Cheng; Li Wen-long; Wang, Yi-ran; Cai, Hong-xing

    2014-12-01

    The authors have investigated the optical properties of core-shell structure of mist wrapped dust particles based on the method of discrete dipole approximation (DDA). The influence on the thickness of the elliptical core-shell structure were calculated which the ratio of long axis and short axis is 2:1, and the change of scattering angle for scattering characteristics. The results shows that the thickness of outer layer increase from 1.2 to 4.8 μm with the scattering and extinction coefficient of double core-shell layers particles decrease from 3.4 and 3.43 to 2.543 and 2.545, when the size of inner core isn't change. And scattering relative strength also increased obviously. The thickness of inner core increase from 0.6 to 2.4 μm with the of scattering and extinction coefficient change from 2.59 and 2.88 to 2.6 and 2.76 when thickness of outer remain constant. Effect of the thickness of visible outer layer on the scattering characteristics of double core-shell layers particles is greater, because of the interaction between scattering light and outer materials. The scattering relative intensity decrease with wavelength increased, while increased with the scale of core-shell structure increase. The results make a promotion on the study of the transportation characteristics of laser and scattering characteristics when the atmospheric aerosol and water mist interact together. PMID:25881412

  2. Tropical Cyclone Warm Core Structure Retrieved from ATMS

    NASA Astrophysics Data System (ADS)

    Zhu, B.; Zhu, T.; Weng, F.

    2012-12-01

    The Advanced Technology Microwave Sounder (ATMS) on board Suomi NPP was successfully launched on October 28, 2011. ATMS consists of a microwave radiometer that measures microwave radiances at 22 channels from 23.8 GHz to 183.3 GHz. Combining the capabilities of current Advanced Microwave Sounding Unit (AMSU-A) and Microwave Humidity Sounder (MHS), ATMS provides sounding observations with improved sampling and coverage for retrieving atmospheric vertical temperature and moisture profiles. A new algorithm is developed to retrieve atmospheric temperature profiles for tropical cyclone with ATMS data. The cross-track asymmetric pattern is investigated for ATMS three window channels. It is found that the asymmetric biases are close to the simulations when the polarization alignment angles are set between 91o and 92o. The algorithm is applied for Tropical Cyclone Giovanna case study and compared with the retrievals from NOAA-15 AMSU-A observation. ATMS retrievals clearly depict the cold temperature anomalies in TC spiral rain bands and the storm warm core. More case study results will be provided at the conference.

  3. Glycan analysis of Fonsecaea monophora from clinical and environmental origins reveals different structural profile and human antigenic response.

    PubMed

    Burjack, Juliana R; Santana-Filho, Arquimedes P; Ruthes, Andrea C; Riter, Daniel S; Vicente, Vania A; Alvarenga, Larissa M; Sassaki, Guilherme L

    2014-01-01

    Dematiaceous fungi constitute a large and heterogeneous group, characterized by having a dark pigment, the dihydroxynaftalen melanin-DHN, inside their cell walls. In nature they are found mainly as soil microbiota or decomposing organic matter, and are spread in tropical and subtropical regions. The fungus Fonsecaea monophora causes chromoblastomycosis in humans, and possesses essential mechanisms that may enhance pathogenicity, proliferation and dissemination inside the host. Glycoconjugates confer important properties to these pathogenic microorganisms. In this work, structural characterization of glycan structures present in two different strains of F. monophora MMHC82 and FE5p4, from clinical and environmental origins, respectively, was performed. Each one were grown on Minimal Medium (MM) and Czapeck-Dox (CD) medium, and the water soluble cell wall glycoconjugates and exopolysaccharides (EPS) were evaluated by NMR, methylation and principal component analysis (PCA). By combining the methylation and 2D NMR analyses, it was possible to visualize the glycosidic profiles of the complex carbohydrate mixtures. Significant differences were observed in β-D-Galf-(1→5) and (1→6) linkages, α- and β-D-Glcp-(1→3), (1→4), and (1→6) units, as well as in α-D-Manp. PCA from (1)H-NMR data showed that MMHC82 from CD medium showed a higher variation in the cell wall carbohydrates, mainly related to O-2 substituted β-D-Galf (δ 106.0/5.23 and δ 105.3/5.23) units. In order to investigate the antigenic response of the glycoconjugates, these were screened against serum from chromoblastomycosis patients. The antigen which contained the cell wall of MMHC82 grown in MM had β-D-Manp units that promoted higher antigenic response. The distribution of these fungal species in nature and the knowledge of how cell wall polysaccharides and glycoconjugates structure vary, may contribute to the better understanding and the elucidation of the pathology caused by this fungus. PMID

  4. Glycan analysis of Fonsecaea monophora from clinical and environmental origins reveals different structural profile and human antigenic response

    PubMed Central

    Burjack, Juliana R.; Santana-Filho, Arquimedes P.; Ruthes, Andrea C.; Riter, Daniel S.; Vicente, Vania A.; Alvarenga, Larissa M.; Sassaki, Guilherme L.

    2014-01-01

    Dematiaceous fungi constitute a large and heterogeneous group, characterized by having a dark pigment, the dihydroxynaftalen melanin—DHN, inside their cell walls. In nature they are found mainly as soil microbiota or decomposing organic matter, and are spread in tropical and subtropical regions. The fungus Fonsecaea monophora causes chromoblastomycosis in humans, and possesses essential mechanisms that may enhance pathogenicity, proliferation and dissemination inside the host. Glycoconjugates confer important properties to these pathogenic microorganisms. In this work, structural characterization of glycan structures present in two different strains of F. monophora MMHC82 and FE5p4, from clinical and environmental origins, respectively, was performed. Each one were grown on Minimal Medium (MM) and Czapeck-Dox (CD) medium, and the water soluble cell wall glycoconjugates and exopolysaccharides (EPS) were evaluated by NMR, methylation and principal component analysis (PCA). By combining the methylation and 2D NMR analyses, it was possible to visualize the glycosidic profiles of the complex carbohydrate mixtures. Significant differences were observed in β-D-Galf-(1→5) and (1→6) linkages, α- and β-D-Glcp-(1→3), (1→4), and (1→6) units, as well as in α-D-Manp. PCA from 1H-NMR data showed that MMHC82 from CD medium showed a higher variation in the cell wall carbohydrates, mainly related to O-2 substituted β-D-Galf (δ 106.0/5.23 and δ 105.3/5.23) units. In order to investigate the antigenic response of the glycoconjugates, these were screened against serum from chromoblastomycosis patients. The antigen which contained the cell wall of MMHC82 grown in MM had β-D-Manp units that promoted higher antigenic response. The distribution of these fungal species in nature and the knowledge of how cell wall polysaccharides and glycoconjugates structure vary, may contribute to the better understanding and the elucidation of the pathology caused by this fungus. PMID

  5. Structure is three to ten times more conserved than sequence--a study of structural response in protein cores.

    PubMed

    Illergård, Kristoffer; Ardell, David H; Elofsson, Arne

    2009-11-15

    Protein structures change during evolution in response to mutations. Here, we analyze the mapping between sequence and structure in a set of structurally aligned protein domains. To avoid artifacts, we restricted our attention only to the core components of these structures. We found that on average, using different measures of structural change, protein cores evolve linearly with evolutionary distance (amino acid substitutions per site). This is true irrespective of which measure of structural change we used, whether RMSD or discrete structural descriptors for secondary structure, accessibility, or contacts. This linear response allows us to quantify the claim that structure is more conserved than sequence. Using structural alphabets of similar cardinality to the sequence alphabet, structural cores evolve three to ten times slower than sequences. Although we observed an average linear response, we found a wide variance. Different domain families varied fivefold in structural response to evolution. An attempt to categorically analyze this variance among subgroups by structural and functional category revealed only one statistically significant trend. This trend can be explained by the fact that beta-sheets change faster than alpha-helices, most likely due to that they are shorter and that change occurs at the ends of the secondary structure elements. PMID:19507241

  6. Physical property data from the ICDP-USGS Eyreville cores A and B, Chesapeake Bay impact structure, Virginia, USA, acquired using a multisensor core logger

    USGS Publications Warehouse

    Pierce, H.A.; Murray, J.B.

    2009-01-01

    The International Continental Scientific Drilling Program (ICDP) and the U.S. Geological Survey (USGS) drilled three core holes to a composite depth of 1766 m within the moat of the Chesapeake Bay impact structure. Core recovery rates from the drilling were high (??90%), but problems with core hole collapse limited the geophysical downhole logging to natural-gamma and temperature logs. To supplement the downhole logs, ??5% of the Chesapeake Bay impact structure cores was processed through the USGS GeoTek multisensor core logger (MSCL) located in Menlo Park, California. The measured physical properties included core thickness (cm), density (g cm-3), P-wave velocity (m s-1), P-wave amplitude (%), magnetic susceptibility (cgs), and resistivity (ohm-m). Fractional porosity was a secondary calculated property. The MSCL data-sampling interval for all core sections was 1 cm longitudinally. Photos of each MSCL sampled core section were imbedded with the physical property data for direct comparison. These data have been used in seismic, geologic, thermal history, magnetic, and gravity models of the Chesapeake Bay impact structure. Each physical property curve has a unique signature when viewed over the full depth of the Chesapeake Bay impact structure core holes. Variations in the measured properties reflect differences in pre-impact target-rock lithologies and spatial variations in impact-related deformation during late-stage crater collapse and ocean resurge. ?? 2009 The Geological Society of America.

  7. Comparison of serum hepatitis C virus (HCV) RNA and core antigen levels in patients coinfected with human immunodeficiency virus and HCV and treated with interferon plus ribavirin.

    PubMed

    Pivert, A; Payan, C; Morand, P; Fafi-Kremer, S; Deshayes, J; Carrat, F; Pol, S; Cacoub, P; Perronne, C; Lunel, F

    2006-02-01

    Trak-C (Ortho-Clinical Diagnostics) is an enzyme-linked immunosorbent assay-based method capable of quantifying hepatitis C virus (HCV) core antigen (CA) in serum and could be an alternative to molecular detection and quantification of HCV RNA. We have evaluated the Trak-C assay in comparison with an HCV RNA quantitative assay (Versant HCV v3.0; Bayer Diagnostics) in the follow-up of 348 treated, human immunodeficiency virus (HIV)/HCV-coinfected patients included in the ANRS HC02 RIBAVIC trial. ANRS HC02 RIBAVIC is a therapeutic, multicenter, randomized protocol comparing the efficacy of alpha interferon 2b (IFN-alpha2b) (3 million units three times a week)-ribavirin (800 mg/day) to that of pegylated IFN-alpha2b (1.5 mug/kg of body weight/week)-ribavirin (800 mg/day) during 48 weeks of treatment of HIV/HCV-coinfected patients naïve to HCV treatment. Patients were assessed for virological analysis at day 0 and weeks 4, 12, 24, 48, and 72. Correlation of HCV RNA and HCV CA at the initiation of treatment was excellent (r = 0.92). HCV RNA and CA kinetics were similar during follow-up of HCV treatment from day 0 to week 72 whatever the group of response and genotype. The positive and negative predictive values of response to the treatment at week 4 were 59 and 94%, respectively, for HCV RNA load reduction of >2 log and 54 and 94%, respectively, for HCV CA below the threshold value (4.18 log(10) pg/ml . 10(4)). Trak-C, a new assay able to quantify CA in HIV/HCV-coinfected patients, correlates well with quantitative HCV RNA assays and is cheaper and easier to perform than molecular technology. HCV CA could be a valuable alternative test for therapeutic follow-up of coinfected patients treated with IFN plus ribavirin in developing countries. PMID:16455894

  8. Nanowire-in-microtube structured core/shell fibers via multifluidic coaxial electrospinning.

    PubMed

    Chen, Hongyan; Wang, Nü; Di, Jiancheng; Zhao, Yong; Song, Yanlin; Jiang, Lei

    2010-07-01

    A multifluidic coaxial electrospinning approach is reported here to fabricate core/shell ultrathin fibers with a novel nanowire-in-microtube structure from more optional fluid pairs than routine coaxial electrospinning. The advantage of this approach lies in the fact that it introduces an extra middle fluid between the core and shell fluids of traditional coaxial electrospinning, which can work as an effective spacer to decrease the interaction of the other two fluids. Under the protection of a proper middle fluid, more fluid pairs, even mutually miscible fluids, can be operated to generate "sandwich"-structured ultrathin fibers with a sharp boundary between the core and shell materials. It thereby largely extends the scope of optional materials. Selectively removing the middle layer of the as-prepared fibers results in an interesting nanowire-in-microtube structure. Either homogeneous or heterogeneous fibers with well-tailored sandwich structures have been successfully fabricated. This method is an important extension of traditional co-electrospinning that affords a more universal avenue to preparing core/shell fibers; moreover, the special hollow cavity structure may introduce some extra properties into the conventional core/shell structure, which may find potential applications such as optical applications, microelectronics, and others. PMID:20337483

  9. Small Angle Neutron-Scattering Studies of the Core Structure of Intact Neurosecretory Vesicles.

    NASA Astrophysics Data System (ADS)

    Krueger, Susan Takacs

    Small angle neutron scattering (SANS) was used to study the state of the dense cores within intact neurosecretory vesicles. These vesicles transport the neurophysin proteins, along with their associated hormones, oxytocin or vasopressin, from the posterior pituitary gland to the bloodstream, where the entire vesicle contents are released. Knowledge of the vesicle core structure is important in developing an understanding of this release mechanism. Since the core constituents exist in a dense state at concentrations which cannot be reproduced (in solution) in the laboratory, a new method was developed to determine the core structure from SANS experiments performed on intact neurosecretory vesicles. These studies were complemented by biochemical assays performed to determine the role, if any, played by phospholipids in the interactions between the core constituents. H_2O/D_2 O ratio in the solvent can be adjusted, using the method of contrast variation, such that the scattering due to the vesicle membranes is minimized, thus emphasizing the scattering originating from the cores. The applicability of this method for examining the interior of biological vesicles was tested by performing an initial study on human red blood cells, which are similar in structure to other biological vesicles. Changes in intermolecular hemoglobin interactions, occurring when the ionic strength of the solvent was varied or when the cells were deoxygenated, were examined. The results agreed with those expected for dense protein solutions, indicating that the method developed was suitable for the study of hemoglobin within the cells. Similar SANS studies were then performed on intact neurosecretory vesicles. The experimental results were inconsistent with model calculations which assumed that the cores consisted of small, densely-packed particles or large, globular aggregates. Although a unique model could not be determined, the data suggest that the core constituents form long aggregates of

  10. Structure and thermodynamics of core-softened models for alcohols

    SciTech Connect

    Munaò, Gianmarco; Urbic, Tomaz

    2015-06-07

    The phase behavior and the fluid structure of coarse-grain models for alcohols are studied by means of reference interaction site model (RISM) theory and Monte Carlo simulations. Specifically, we model ethanol and 1-propanol as linear rigid chains constituted by three (trimers) and four (tetramers) partially fused spheres, respectively. Thermodynamic properties of these models are examined in the RISM context, by employing closed formulæ for the calculation of free energy and pressure. Gas-liquid coexistence curves for trimers and tetramers are reported and compared with already existing data for a dimer model of methanol. Critical temperatures slightly increase with the number of CH{sub 2} groups in the chain, while critical pressures and densities decrease. Such a behavior qualitatively reproduces the trend observed in experiments on methanol, ethanol, and 1-propanol and suggests that our coarse-grain models, despite their simplicity, can reproduce the essential features of the phase behavior of such alcohols. The fluid structure of these models is investigated by computing radial distribution function g{sub ij}(r) and static structure factor S{sub ij}(k); the latter shows the presence of a low−k peak at intermediate-high packing fractions and low temperatures, suggesting the presence of aggregates for both trimers and tetramers.

  11. Crystal structure of a core spliceosomal protein interface.

    PubMed

    Schellenberg, Matthew J; Edwards, Ross A; Ritchie, Dustin B; Kent, Oliver A; Golas, Monika M; Stark, Holger; Lührmann, Reinhard; Glover, J N Mark; MacMillan, Andrew M

    2006-01-31

    The precise excision of introns from precursor mRNAs (pre-mRNAs) in eukaryotes is accomplished by the spliceosome, a complex assembly containing five small nuclear ribonucleoprotein (snRNP) particles. Human p14, a component of the spliceosomal U2 and U11/U12 snRNPs, has been shown to associate directly with the pre-mRNA branch adenosine early in spliceosome assembly and within the fully assembled spliceosome. Here we report the 2.5-A crystal structure of a complex containing p14 and a peptide derived from the p14-associated U2 snRNP component SF3b155. p14 contains an RNA recognition motif (RRM), the surface of which is largely occluded by a C-terminal alpha-helix and a portion of the SF3b155 peptide. An analysis of RNA.protein crosslinking to wild-type and mutant p14 shows that the branch adenosine directly interacts with a conserved aromatic within a pocket on the surface of the complex. This result, combined with a comparison of the structure with known RRMs and pseudoRRMs as well as model-building by using the electron cryomicroscopy structure of a spliceosomal U11/U12 di-snRNP, suggests that p14.SF3b155 presents a noncanonical surface for RNA recognition at the heart of the mammalian spliceosome. PMID:16432215

  12. Comparative analysis of core amino acid residues of H-2D(b)-restricted cytotoxic T-lymphocyte recognition epitopes in simian virus 40 T antigen.

    PubMed Central

    Deckhut, A M; Lippolis, J D; Tevethia, S S

    1992-01-01

    Simian virus 40 (SV40) tumor (T) antigen expressed in H-2b SV40-transformed cells induces the generation of Lyt-2+ (CD8+) cytotoxic T lymphocytes (CTL), which are involved in tumor rejection, in syngeneic mice. Five CTL recognition sites on T antigen have been described by using mutant T antigens. Four of the sites (I, II, III, and V) are H-2Db restricted and have been broadly mapped with synthetic peptides of 15 amino acids in length overlapping by 5 residues at the amino and carboxy termini. The goal of this study was to define the minimal and optimal amino acid sequences of T antigen which would serve as recognition elements for the H-2Db-restricted CTL clones Y-1, Y-2, Y-3, and Y-5, which recognizes sites I, II, III, and V, respectively. The minimal and optimal residues of T antigen recognized by the four CTL clones were determined by using synthetic peptides truncated at the amino or carboxy terminus and an H-2Db peptide-binding motif. The minimal site recognized by CTL clone Y-1 was defined as amino acids 207 to 215 of SV40 T antigen. However, the optimal sequence recognized by CTL clone Y-1 spanned T-antigen amino acids 205 to 215. The T-antigen peptide sequence LT223-231 was the optimal and minimal sequence recognized by both CTL clones Y-2 and Y-3. Site V was determined to be contained within amino acids 489 to 497 of T antigen. The lytic activities of CTL clones Y-2 and Y-3, which recognize a single nonamer peptide, LT223-231, were affected differently by anti-Lyt-2 antibody, suggesting that the T-cell receptors of these two CTL clones differ in their avidities. As the minimal and optimal H-2Db-restricted CTL recognition sites have been defined by nonamer synthetic peptides, it is now possible to search for naturally processed H-2Db-restricted epitopes of T antigen and identify critical residues involved in processing, presentation, and recognition by SV40-specific CTL. PMID:1370091

  13. Guided wave propagation in a honeycomb composite sandwich structure in presence of a high density core.

    PubMed

    Sikdar, Shirsendu; Banerjee, Sauvik

    2016-09-01

    A coordinated theoretical, numerical and experimental study is carried out in an effort to interpret the characteristics of propagating guided Lamb wave modes in presence of a high-density (HD) core region in a honeycomb composite sandwich structure (HCSS). Initially, a two-dimensional (2D) semi-analytical model based on the global matrix method is used to study the response and dispersion characteristics of the HCSS with a soft core. Due to the complex structural characteristics, the study of guided wave (GW) propagation in HCSS with HD-core region inherently poses many challenges. Therefore, a numerical simulation of GW propagation in the HCSS with and without the HD-core region is carried out, using surface-bonded piezoelectric wafer transducer (PWT) network. From the numerical results, it is observed that the presence of HD-core significantly decreases both the group velocity and the amplitude of the received GW signal. Laboratory experiments are then conducted in order to verify the theoretical and numerical results. A good agreement between the theoretical, numerical and experimental results is observed in all the cases studied. An extensive parametric study is also carried out for a range of HD-core sizes and densities in order to study the effect due to the change in size and density of the HD zone on the characteristics of propagating GW modes. It is found that the amplitudes and group velocities of the GW modes decrease with the increase in HD-core width and density. PMID:27290650

  14. Ising nanowires with simple core-shell structure; Their characteristic phenomena

    NASA Astrophysics Data System (ADS)

    Kaneyoshi, T.

    2016-09-01

    The phase diagrams and magnetizations of Ising nanowires with simple core-shell structure are investigated by the use of the effective field theory with correlations. A lot of characteristic behaviors observed in ferromagnetic and ferrimagnetic materials as well as novel phenomena have been obtained, although one section of the system is consisted of one spin-1/2 surface shell atom and one spin-1/2 core atom and they are coupled with a positive or a negative shell-core exchange interaction.

  15. How is kinematic structure connected to the core scale from filament scale?; Mopra mapping observations with multi-lines of dense cores in Lupus I

    NASA Astrophysics Data System (ADS)

    Kiyokane, Kazuhiro; Saito, Masao; Tachihara, Kengo; Saigo, Kazuya; van Kempen, Tim; Cortes, Paulo; Hill, Tracey; Knee, Lewis; Kurono, Yasutaka; Takahashi, Satoko; Aya, Higuchi; Nyman, Lars-Ake

    2014-06-01

    Recently, high sensitivity mappings of nearby molecular clouds in far-infrared and submillimeter wavelengths with Hershel and AzTEC/ASTE show ubiquitous existence of the filamentary structures with 0.1-pc uniform width. It is important to investigate dense core formation from large scale structure via fragmentation. We have conducted MOPRA multi-line mapping observations covered on 0.02 - 0.2 pc scales of 8 dense cores in a filamentary cloud of nearby Lupus I at 140 pc. A class 0/I protostellar core IRAS 15398-3359 is included as a sample, which has an adjacent prestellar core with the separation of 0.13pc in the west. The maps of N2H+, HNC, HC3N show well associated with each core. The velocity field of C18O shows 1.4 km/s/pc from north to south over the region containing two dense cores, which is consistent with past observation of NANTEN. In contrast to C18O results, the velocity field of HC3N shows different structures, which suggest counter rotation of two dense cores; 1.2 km/s/pc from north-west to south-east around a protostellar core and 0.8 km/s/pc from east to west around a presteller core. The filament will be fragmentized and collapsed to dense cores when the line density is over 2Cs/G (where Cs is sound speed and G is gravitational constant). If that velocity gradient was caused by such situation, it should be red-blue-red-blue across two dense cores but the observed kinematics is not consistent with this scenario, which requires that the filament structure would be extremely curved with a skew angle. Although we cannot reject the collapsing interruption, those results suggest the spin-up rotating picture separated from large-scale structure.

  16. Structure of a Folding Intermediate Reveals the Interplay Between Core and Peripheral Elements in RNA Folding

    SciTech Connect

    Baird, Nathan J.; Westhof, Eric; Qin, Hong; Pan, Tao; Sosnick, Tobin R.

    2010-07-13

    Though the molecular architecture of many native RNA structures has been characterized, the structures of folding intermediates are poorly defined. Here, we present a nucleotide-level model of a highly structured equilibrium folding intermediate of the specificity domain of the Bacillus subtilis RNase P RNA, obtained using chemical and nuclease mapping, circular dichroism spectroscopy, small-angle X-ray scattering and molecular modeling. The crystal structure indicates that the 154 nucleotide specificity domain is composed of several secondary and tertiary structural modules. The structure of the intermediate contains modules composed of secondary structures and short-range tertiary interactions, implying a sequential order of tertiary structure formation during folding. The intermediate lacks the native core and several long-range interactions among peripheral regions, such as a GAAA tetraloop and its receptor. Folding to the native structure requires the local rearrangement of a T-loop in the core in concert with the formation of the GAAA tetraloop-receptor interaction. The interplay of core and peripheral structure formation rationalizes the high degree of cooperativity observed in the folding transition leading to the native structure.

  17. Effect of trimerization motifs on quaternary structure, antigenicity, and immunogenicity of a noncleavable HIV-1 gp140 envelope glycoprotein

    SciTech Connect

    Du, Sean X.; Idiart, Rebecca J.; Mariano, Ellaine B.; Chen, Helen; Jiang Peifeng; Xu Li; Ostrow, Kristin M.; Wrin, Terri; Phung, Pham; Binley, James M.; Petropoulos, Christos J.; Ballantyne, John A.; Whalen, Robert G.

    2009-12-05

    The external domains of the HIV-1 envelope glycoprotein (gp120 and the gp41 ectodomain, collectively known as gp140) contain all known viral neutralization epitopes. Various strategies have been used to create soluble trimers of the envelope to mimic the structure of the native viral protein, including mutation of the gp120-gp41 cleavage site, introduction of disulfide bonds, and fusion to heterologous trimerization motifs. We compared the effects on quaternary structure, antigenicity, and immunogenicity of three such motifs: T4 fibritin, a GCN4 variant, and the Escherichia coli aspartate transcarbamoylase catalytic subunit. Fusion of each motif to the C-terminus of a noncleavable JRCSF gp140(-) envelope protein led to enhanced trimerization but had limited effects on the antigenic profile and CD4-binding ability of the trimers. Immunization of rabbits provided no evidence that the trimerized gp140(-) constructs induced significantly improved neutralizing antibodies to several HIV-1 pseudoviruses, compared to gp140 lacking a trimerization motif. However, modest differences in both binding specificity and neutralizing antibody responses were observed among the various immunogens.

  18. Primary structure of the human melanoma-associated antigen p97 (melanotransferrin) deduced from the mRNA sequence.

    PubMed Central

    Rose, T M; Plowman, G D; Teplow, D B; Dreyer, W J; Hellström, K E; Brown, J P

    1986-01-01

    p97 is a cell-surface glycoprotein that is present in most human melanomas but only in trace amounts in normal adult tissues. To determine the structure of this tumor-associated antigen and to identify its functional domains, we have purified and cloned p97 mRNA and determined its nucleotide sequence. The mRNA encodes a 738-residue precursor, which contains the previously determined N-terminal amino acid sequence of p97. After removal of a 19-residue signal peptide, the mature p97 molecule comprises extracellular domains of 342 and 352 residues and a C-terminal 25-residue stretch of predominantly uncharged and hydrophobic amino acids, which we believe acts as a membrane anchor. Each extracellular domain contains 14 cysteine residues, which form seven intradomain disulfide bridges, and one or two potential N-glycosylation sites. Protease digestion studies show that the three major antigenic determinants of p97 are present on the N-terminal domain. The domains are strikingly homologous to each other (46% amino acid sequence homology) and to the corresponding domains of human serum transferrin (39% homology). Conservation of disulfide bridges and of amino acids thought to compose the iron binding pockets suggests that p97 is also related to transferrin in tertiary structure and function. We propose that p97 be renamed melanotransferrin to denote its original identification in melanoma cells and its evolutionary relationship to serotransferrin and lactotransferrin, the other members of the transferrin superfamily. Images PMID:2419904

  19. Controllable synthesis of a novel hedgehog-like core/shell structure

    SciTech Connect

    Wang Shumin; Tian Hongwei; Pei Yanhui; Meng Qingnan; Chen Jianli; Wang Huan; Zeng Yi; Zheng Weitao; Liu Yichun

    2012-02-15

    A novel hedgehog-like core/shell structure, consisting of a high density of vertically aligned graphene sheets and a thin graphene shell/a copper core (VGs-GS/CC), has been synthesized via a simple one-step synthesis route using radio-frequency plasma-enhanced chemical vapor deposition (RF-PECVD). Scanning and transmission electron microscopy investigations show that the morphology of this core/shell material could be controlled by deposition time. For a short deposition time, only multilayer graphene shell tightly surrounds the copper particle, while as the deposition time is relative long, graphene sheets extend from the surface of GS/CC. The GS can protect CC particles from oxidation. The growth mechanism for the obtained GS/CC and VGs-GS/CC has been revealed. Compared to VGs, VGs-GS/CC material exhibits a better electron field emission property. This investigation opens a possibility for designing a core/shell structure of different carbon-metal hybrid materials for a wide variety of practical applications. - Graphical abstract: With increasing deposition time, graphene sheets extend from the surface of GS/CC, causing the multilayer graphene encapsulated copper to be converted into vertically aligned graphene sheets-graphene shell/copper core structure. Highlights: Black-Right-Pointing-Pointer A novel hedgehog-like core/shell structure has been synthesized. Black-Right-Pointing-Pointer The structure consists of vertical graphene sheets-graphene shell and copper core. Black-Right-Pointing-Pointer The morphology of VGs-GS/CC can be controlled by choosing a proper deposition time. Black-Right-Pointing-Pointer With increasing deposition time, graphene sheets extend from the surface of GS/CC. Black-Right-Pointing-Pointer VGs-GS/CC exhibits a better electron field emission property as compared with VGs.

  20. Mode I Toughness Measurements of Core/Facesheet Bonds in Honeycomb Sandwich Structures

    NASA Technical Reports Server (NTRS)

    Nettles, Alan T.; Ratcliffe, James G.

    2006-01-01

    Composite sandwich structures will be used in many future applications in aerospace, marine and offshore industries due to the fact that the strength and stiffness to mass ratios surpass any other structural type. Sandwich structure also offers advantages over traditional stiffened panels such as ease of manufacturing and repair. During the last three decades, sandwich structure has been used extensively for secondary structure in aircraft (fuselage floors, rudders and radome structure). Sandwich structure is also used as primary structure in rotorcraft, the most common example being the trailing edge of rotor blades. As with other types of composite construction, sandwich structure exhibits several types of failure mode such as facesheet wrinkling, core crushing and sandwich buckling. Facesheet/core debonding has also been observed in the marine and aerospace industry. During this failure mode, peel stresses applied to an existing facesheet/core debond or an interface low in toughness, results in the facesheet being peeled from the core material, possibly leading to a significant loss in structural integrity of the sandwich panel. In an incident during a test on a liquid hydrogen fuel tank of the X-33 prototype vehicle, the outer graphite/epoxy facesheet and honeycomb core became debonded from the inner facesheet along significant areas, leading to failure of the tank. As a consequence of the accident; significant efforts were made to characterize the toughness of the facesheet/core bond. Currently, the only standardized method available for assessing the quality of the facesheet/core interface is the climbing drum peel test (ASTM D1781). During this test a sandwich beam is removed from a panel and the lip of one of the facesheets is attached to a drum, as shown in Fig. 1. The drum is then rotated along the sandwich beam, causing the facesheet to peel from the core. This method has two major drawbacks. First, it is not possible to obtain quantitative fracture data

  1. Unveiling the Detailed Density and Velocity Structures of the Protostellar Core B335

    NASA Astrophysics Data System (ADS)

    Kurono, Yasutaka; Saito, Masao; Kamazaki, Takeshi; Morita, Koh-Ichiro; Kawabe, Ryohei

    2013-03-01

    We present an observational study of the protostellar core B335 harboring a low-mass Class 0 source. The observations of the H13CO+(J = 1-0) line emission were carried out using the Nobeyama 45 m telescope and Nobeyama Millimeter Array. Our combined image of the interferometer and single-dish data depicts detailed structures of the dense envelope within the core. We found that the core has a radial density profile of n(r)vpropr -p and a reliable difference in the power-law indices between the outer and inner regions of the core: p ≈ 2 for r >~ 4000 AU and p ≈ 1.5 for r <~ 4000 AU. The dense core shows a slight overall velocity gradient of ~1.0 km s-1 over the scale of 20, 000 AU across the outflow axis. We believe that this velocity gradient represents a solid-body-like rotation of the core. The dense envelope has a quite symmetrical velocity structure with a remarkable line broadening toward the core center, which is especially prominent in the position-velocity diagram across the outflow axis. The model calculations of position-velocity diagrams do a good job of reproducing observational results using the collapse model of an isothermal sphere in which the core has an inner free-fall region and an outer region conserving the conditions at the formation stage of a central stellar object. We derived a central stellar mass of ~0.1 M ⊙, and suggest a small inward velocity, v_{r ≥ r_inf}˜ 0 km s^{-1} in the outer core at >~ 4000 AU. We concluded that our data can be well explained by gravitational collapse with a quasi-static initial condition, such as Shu's model, or by the isothermal collapse of a marginally critical Bonnor-Ebert sphere.

  2. Hydrophobic Core Variations Provide a Structural Framework for Tyrosine Kinase Evolution and Functional Specialization

    PubMed Central

    Kwon, Annie; Byrne, Dominic P.; Ferries, Samantha; Ruan, Zheng; Hanold, Laura E.; Katiyar, Samiksha; Kennedy, Eileen J.; Eyers, Patrick A.; Kannan, Natarajan

    2016-01-01

    Protein tyrosine kinases (PTKs) are a group of closely related enzymes that have evolutionarily diverged from serine/threonine kinases (STKs) to regulate pathways associated with multi-cellularity. Evolutionary divergence of PTKs from STKs has occurred through accumulation of mutations in the active site as well as in the commonly conserved hydrophobic core. While the functional significance of active site variations is well understood, relatively little is known about how hydrophobic core variations contribute to PTK evolutionary divergence. Here, using a combination of statistical sequence comparisons, molecular dynamics simulations, mutational analysis and in vitro thermostability and kinase assays, we investigate the structural and functional significance of key PTK-specific variations in the kinase core. We find that the nature of residues and interactions in the hydrophobic core of PTKs is strikingly different from other protein kinases, and PTK-specific variations in the core contribute to functional divergence by altering the stability and dynamics of the kinase domain. In particular, a functionally critical STK-conserved histidine that stabilizes the regulatory spine in STKs is selectively mutated to an alanine, serine or glutamate in PTKs, and this loss-of-function mutation is accommodated, in part, through compensatory PTK-specific interactions in the core. In particular, a PTK-conserved phenylalanine in the I-helix appears to structurally and functionally compensate for the loss of STK-histidine by interacting with the regulatory spine, which has far-reaching effects on enzyme activity, inhibitor sensing, and stability. We propose that hydrophobic core variations provide a selective advantage during PTK evolution by increasing the conformational flexibility, and therefore the allosteric potential of the kinase domain. Our studies also suggest that Tyrosine Kinase Like kinases such as RAF are intermediates in PTK evolutionary divergence inasmuch as they

  3. Genome-wide analysis of core promoter structures in Schizosaccharomyces pombe with DeepCAGE.

    PubMed

    Li, Hua; Hou, Jingyi; Bai, Ling; Hu, Chuansheng; Tong, Pan; Kang, Yani; Zhao, Xiaodong; Shao, Zhifeng

    2015-01-01

    The core promoter, which immediately flanks the transcription start site (TSS), plays a critical role in transcriptional regulation of eukaryotes. Recent studies on higher eukaryotes have revealed an unprecedented complexity of core promoter structures that underscores diverse regulatory mechanisms of gene expression. For unicellular eukaryotes, however, the structures of core promoters have not been investigated in detail. As an important model organism, Schizosaccharomyces pombe still lacks the precise annotation for TSSs, thus hampering the analysis of core promoter structures and their relationship to higher eukaryotes. Here we used a deep sequencing-based approach (DeepCAGE) to generate 16 million uniquely mapped tags, corresponding to 93,736 positions in the S. pombe genome. The high-resolution TSS landscape enabled identification of over 8,000 core promoters, characterization of 4 promoter classes and observation of widespread alternative promoters. The landscape also allowed precise determination of the representative TSSs within core promoters, thus redefining the 5' UTR for 82.8% of S. pombe genes. We further identified the consensus initiator (Inr) sequence--PyPyPuN(A/C)(C/A), the TATA-enriched region (between position -25 and -37) and an Inr immediate downstream motif--CC(T/A)(T/C)(T/C/A)(A/G)CCA(A/T/C), all of which were associated with highly expressed promoters. In conclusion, the detailed analysis of core promoters not only significantly improves the genome annotation of S. pombe, but also reveals that this unicellular eukaryote shares a highly similar organization in the core promoters with higher eukaryotes. These findings lend additional evidence for the power of this model system in delineating complex regulatory processes in multicellular organisms, despite its perceived simplicity. PMID:25747261

  4. Genome-wide analysis of core promoter structures in Schizosaccharomyces pombe with DeepCAGE

    PubMed Central

    Li, Hua; Hou, Jingyi; Bai, Ling; Hu, Chuansheng; Tong, Pan; Kang, Yani; Zhao, Xiaodong; Shao, Zhifeng

    2015-01-01

    The core promoter, which immediately flanks the transcription start site (TSS), plays a critical role in transcriptional regulation of eukaryotes. Recent studies on higher eukaryotes have revealed an unprecedented complexity of core promoter structures that underscores diverse regulatory mechanisms of gene expression. For unicellular eukaryotes, however, the structures of core promoters have not been investigated in detail. As an important model organism, Schizosaccharomyces pombe still lacks the precise annotation for TSSs, thus hampering the analysis of core promoter structures and their relationship to higher eukaryotes. Here we used a deep sequencing-based approach (DeepCAGE) to generate 16 million uniquely mapped tags, corresponding to 93,736 positions in the S. pombe genome. The high-resolution TSS landscape enabled identification of over 8,000 core promoters, characterization of 4 promoter classes and observation of widespread alternative promoters. The landscape also allowed precise determination of the representative TSSs within core promoters, thus redefining the 5' UTR for 82.8% of S. pombe genes. We further identified the consensus initiator (Inr) sequence – PyPyPuN(A/C)(C/A), the TATA-enriched region (between position −25 and −37) and an Inr immediate downstream motif – CC(T/A)(T/C)(T/C/A)(A/G)CCA(A/T/C), all of which were associated with highly expressed promoters. In conclusion, the detailed analysis of core promoters not only significantly improves the genome annotation of S. pombe, but also reveals that this unicellular eukaryote shares a highly similar organization in the core promoters with higher eukaryotes. These findings lend additional evidence for the power of this model system in delineating complex regulatory processes in multicellular organisms, despite its perceived simplicity. PMID:25747261

  5. Structural investigations of core-shell nanowires using grazing incidence X-ray diffraction.

    PubMed

    Keplinger, Mario; Mårtensson, Thomas; Stangl, Julian; Wintersberger, Eugen; Mandl, Bernhard; Kriegner, Dominik; Holý, Václav; Bauer, Günther; Deppert, Knut; Samuelson, Lars

    2009-05-01

    The fabrication of core-shell structures is crucial for many nanowire device concepts. For the proper tailoring of their electronic properties, control of structural parameters such as shape, size, diameter of core and shell, their chemical composition, and information on their strain fields is mandatory. Using synchrotron X-ray diffraction studies and finite element simulations, we determined the chemical composition, dimensions, and strain distribution for series of InAs/InAsP core-shell wires grown on Si(111) with systematically varied growth parameters. In particular we detect initiation of plastic relaxation of these structures with increasing shell thickness and/or increasing phosphorus content. We establish a phase diagram, defining the region of parameters leading to pseudomorphic nanowire growth. This is important to avoid extended defects which are detrimental for their electronic properties. PMID:19320494

  6. What makes a protein a protein? Hydrophobic core designs that specify stability and structural properties.

    PubMed Central

    Munson, M.; Balasubramanian, S.; Fleming, K. G.; Nagi, A. D.; O'Brien, R.; Sturtevant, J. M.; Regan, L.

    1996-01-01

    Here we describe how the systematic redesign of a protein's hydrophobic core alters its structure and stability. We have repacked the hydrophobic core of the four-helix-bundle protein, Rop, with altered packing patterns and various side chain shapes and sizes. Several designs reproduce the structure and native-like properties of the wild-type, while increasing the thermal stability. Other designs, either with similar sizes but different shapes, or with decreased sizes of the packing residues, destabilize the protein. Finally, overpacking the core with the larger side chains causes a loss of native-like structure. These results allow us to further define the roles of tight residue packing and the burial of hydrophobic surface area in the construction of native-like proteins. PMID:8844848

  7. Core-satellite ZnS-Ag nanoassemblies: Synthesis, structure, and optical properties.

    PubMed

    Rohani, Parham; Sharma, Munish K; Swihart, Mark T

    2016-02-01

    We synthesized hollow core-satellite nanoassemblies comprised of hollow zinc sulfide (ZnS) shells decorated with silver nanoparticles (Ag NPs). This was achieved by solution-phase attachment of Ag NPs to hollow ZnS nanospheres (NSs) prepared by spray pyrolysis. This produces an aqueous dispersion of ZnS-Ag hybrid structures, 50-500nm in overall diameter. We characterized the nanostructures by scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (XRD), and energy dispersive X-ray spectroscopy (EDX) to elucidate the ZnS (core)-Ag (satellite) morphology and optimize conditions for producing such structures. Optical spectroscopy showed that photoluminescence of ZnS was quenched by Ag while absorbance was enhanced. This work provides a simple and general means of producing hollow core-satellite structures that could be of broad applicability. PMID:26524256

  8. Experimental and Numerical Analysis of Composite Folded Sandwich Core Structures Under Compression

    NASA Astrophysics Data System (ADS)

    Heimbs, S.; Middendorf, P.; Kilchert, S.; Johnson, A. F.; Maier, M.

    2007-11-01

    The characterisation of the mechanical behaviour of folded core structures for advanced sandwich composites under flatwise compression load using a virtual testing approach is presented. In this context dynamic compression test simulations with the explicit solvers PAM-CRASH and LS-DYNA are compared to experimental data of two different folded core structures made of aramid paper and carbon fibre-reinforced plastic (CFRP). The focus of the investigations is the constitutive modelling of the cell wall material, the consideration of imperfections and the representation of cell wall buckling, folding or crushing phenomena. The consistency of the numerical results shows that this can be a promising and efficient approach for the determination of the effective mechanical properties and a cell geometry optimisation of folded core structures.

  9. Use of existing data for public health planning: a study of the prevalence of hepatitis B surface antigen and core antibody in Al Ain Medical District, United Arab Emirates.

    PubMed Central

    al-Owais, A.; al-Suwaidi, K.; Amiri, N.; Carter, A. O.; Hossain, M. M.; Sheek-Hussein, M. M.

    2000-01-01

    INTRODUCTION: Hepatitis B is of major public health importance. Accurate information on its occurrence, with particular reference to the prevalence of immunity and chronic infection (marked by the presence of hepatitis B core antibody and surface antigen, respectively, in serum), is essential for planning public health programmes for the control of the disease. The generation of marker prevalence data through serological surveys is costly and time-consuming. The present study in Al Ain Medical District, United Arab Emirates, investigated the possibility of obtaining sufficiently accurate marker prevalence estimates from existing data to plan public health programmes. METHODS: Two antenatal screening databases, one student serological survey database, one immunization programme database and one pre-marriage screening database containing information on marker prevalence were identified. Epidemiological data were abstracted from these databases and analysed. RESULTS: The data showed that the prevalence of hepatitis B surface antigen and the prevalence of core antibody in young citizens in 1998 were approximately 2% and 14% respectively, that any immunization campaign aimed at citizens of the United Arab Emirates should target teenagers as they had the highest risk of acquiring the disease, and that pre-immunization screening of young adults would be wasteful. However, the data did not yield information on the prevalence of hepatitis B surface antigen and core antibody in other population subgroups of public health significance. DISCUSSION: While data generated by the study are sufficient to support a hepatitis B immunization programme targeted at teenaged citizens, more accurate data, generated by a well-designed serological survey, would be essential for optimal public health planning. PMID:11143192

  10. Three-Dimensional Structure and Biophysical Characterization of Staphylococcus aureus Cell Surface Antigen-Manganese Transporter MntC

    SciTech Connect

    Gribenko, Alexey; Mosyak, Lidia; Ghosh, Sharmistha; Parris, Kevin; Svenson, Kristine; Moran, Justin; Chu, Ling; Li, Sheng; Liu, Tong; Woods, Jr., Virgil L.; Jansen, Kathrin U.; Green, Bruce A.; Anderson, Annaliesa S.; Matsuka, Yury V.

    2013-08-23

    MntC is a metal-binding protein component of the Mn2 +-specific mntABC transporter from the pathogen Staphylococcus aureus. The protein is expressed during the early stages of infection and was proven to be effective at reducing both S. aureus and Staphylococcus epidermidis infections in a murine animal model when used as a vaccine antigen. MntC is currently being tested in human clinical trials as a component of a multiantigen vaccine for the prevention of S. aureus infections. To better understand the biological function of MntC, we are providing structural and biophysical characterization of the protein in this work. The three-dimensional structure of the protein was solved by X-ray crystallography at 2.2 Å resolution and suggests two potential metal binding modes, which may lead to reversible as well as irreversible metal binding. Precise Mn2 +-binding affinity of the protein was determined from the isothermal titration calorimetry experiments using a competition approach. Differential scanning calorimetry experiments confirmed that divalent metals can indeed bind to MntC reversibly as well as irreversibly. Finally, Mn2 +-induced structural and dynamics changes have been characterized using spectroscopic methods and deuterium–hydrogen exchange mass spectroscopy. Results of the experiments show that these changes are minimal and are largely restricted to the structural elements involved in metal coordination. Therefore, it is unlikely that antibody binding to this antigen will be affected by the occupancy of the metal-binding site by Mn2 +.

  11. Crystallographic Structure of the Human Leukocyte Antigen DRA, DRB3*0101: Models of a Directional Alloimmune Respone and Autoimmunity

    SciTech Connect

    Parry,C.; Gorski, J.; Stern, L.

    2007-01-01

    We describe structural studies of the human leukocyte antigen DR52a, HLA-DRA/DRB3*0101, in complex with an N-terminal human platelet integrin {alpha}II{sub B}{beta}III glycoprotein peptide which contains a Leu/Pro dimorphism. The 33:Leu dimorphism is the epitope for the T cell directed response in neonatal alloimmune thrombocytopenia and post-transfusion purpura in individuals with the {alpha}II{sub B}{beta}III 33:Pro allele, and defines the unidirectional alloimmune response. This condition is always associated with DR52a. The crystallographic structure has been refined to 2.25 {angstrom}. There are two {alpha}{beta} heterodimers to the asymmetric unit in space group P4{sub 1}2{sub 1}2. The molecule is characterized by two prominent hydrophobic pockets at either end of the peptide binding cleft and a deep, narrower and highly charged P4 opening underneath the beta 1 chain. Further, the peptide in the second molecule displays a sharp upward turn after pocket P9. The structure reveals the role of pockets and the distinctive basic P4 pocket, shared by DR52a and DR3, in selecting their respective binding peptide repertoire. We observe an interesting switch in a residue from the canonically assigned pocket 6 seen in prior class II structures to pocket 4. This occludes the P6 pocket helping to explain the distinctive '1-4-9' peptide binding motif. A {beta}57 Asp {yields} Val substitution abrogates the salt-bridge to {alpha}76 Arg and along with a hydrophobic {beta}37 is important in shaping the P9 pocket. DRB3*0101 and DRB1*0301 belong to an ancestral haplotype and are associated with many autoimmune diseases linked to antigen presentation, but whereas DR3 is susceptible to type 1 diabetes DR52a is not. This dichotomy is explored for clues to the disease.

  12. Effect of elastic center on dislocation core structure in Ni{sub 3}Al

    SciTech Connect

    Wen, M.; Lin, D.

    1997-03-01

    The dislocation core structure of 1/2[{bar 1}01] superpartials in Ni{sub 2}Al is studied, using the embedded atom method (EAM) and computer simulation techniques. It is found that the initial position of the dislocation elastic center relative to the atomistic lattice-site has pronounced effect on the dislocation core structure. Two typical cores of the 1/2[{bar 1}01] superpartials separated by an antiphase boundary (APB) on (111) planes are obtained. The most stable core is non-planar, spread on both (1{bar 1}1) and the (111) planes, while the metastable one is planar, spread only on the (111) APB plane. Three typical cores of the 1/2[{bar 1}01] superpartials separated by an APB on (010) planes are obtained. They are non-planar without any exception. The most stable core spreads again on both the (1{bar 1}1) and the (111) planes, while the metastable types spread either on the (111) or on the (1{bar 1}1) plane.

  13. Damping Properties of Sandwich Truss Core Structures by Strain Energy Method

    NASA Astrophysics Data System (ADS)

    Wesolowski, M.; Rucevskis, S.; Janeliukstis, R.; Polanski, M.

    2015-11-01

    Sandwich panel structures with stiff face sheets and cellular cores are widely used to support dynamic loads. Combining face sheets made of carbon fibre reinforced plastics (CFRPs) with an aluminium pyramidal truss improves the damping performance of the structure due to viscoelastic character of CRFP composites. To predict the damping characteristics of the pyramidal truss core sandwich panel the strain energy method is adopted. The procedure for evaluating the damping of the sandwich panel was performed using commercial finite element software NASTRAN and MATLAB. Non-contact vibration tests were performed on the real sandwich panels in order to extract the modal characteristics and compare them with the numerical predictions.

  14. Structure and function of a 40,000-molecular-weight protein antigen of Mycobacterium tuberculosis.

    PubMed Central

    Andersen, A B; Andersen, P; Ljungqvist, L

    1992-01-01

    A gene encoding a protein antigen from Mycobacterium tuberculosis with a molecular weight of 40,000 has been sequenced. On the basis of sequence homology and functional analyses, we demonstrated that the protein is an L-alanine dehydrogenase (EC 1.4.1.1). The enzyme was demonstrated in M. tuberculosis and Mycobacterium marinum but not in Mycobacterium bovis BCG. The enzyme may play a role in cell wall synthesis because L-alanine is an important constituent of the peptidoglycan layer. Although no consensus signal sequence was identified, we found evidence which suggests that the enzyme is secreted across the cell membrane. The enzyme was characterized and purified by chromatography, thus enabling further studies of its role in virulence and interaction with the immune system of M. tuberculosis-infected individuals. Images PMID:1587598

  15. Paleomagnetic Reorientation of Structural Elements in Drill Cores: an example from Tolhuaca Geothermal Field

    NASA Astrophysics Data System (ADS)

    Perez-Flores, P.; Veloso, E. E.; Cembrano, J. M.; Sánchez, P.; Iriarte, S.; Lohmar, S.

    2013-12-01

    Reorientation of mesoscopic faults, veins and fractures recovered from drilling is critical to construct reliable structural models that can account for their architecture and deformation regime. However, oriented cores are expensive and time consuming to drill. Some techniques achieve reorientation by introducing tools into the borehole. Problems arise when boreholes are unstable or collapse. One alternative technique allowing reorientation is to obtain reliable paleomagnetic vectors to reorient each core piece after drilling. Here, we present stable and reliable remnant magnetic vectors calculated from the Tol-1 core to analyze the geometry of the fracture network and its relationship to regional tectonic. Tol-1 core is a vertical, 1073 m deep geothermal well, drilled at the Tolhuaca Geothermal Field in the Southern Volcanic Zone of the Andes by MRP Geothermal Chile Ltda (formerly GGE Chile SpA) in 2009. The core consists of basaltic/andesitic volcanic rocks with subordinate pyroclastic/volcaniclastic units, with probable Pleistocene age. Fault planes with slickenlines and mineral fiber kinematic indicators are common in the upper 700 m of the core. Calcite, quartz and calcite-quartz veins are recognized along of entire core, whereas epidote-quartz and calcite-epidote veins occur in the last 350 m, minor chlorite, anhydrite and clay-minerals are present. Orientations of structural features in the core were measured with a goniometer using the core's axis and a false north for each piece; hence, orientation data has a false strike but a real dip. To achieve total reorientation of the pieces, we collected 200 standard-size paleomagnetic specimens, ensuring that at least four of them were recovered from continuous pieces. Thermal (up to 700°C) and alternating field demagnetization (up to 90mT on steps of 2mT) methods were used to isolate a stable remnant magnetization (RM) vector, and each technique yielded similar results. RM vectors were recovered between 0 to 25

  16. Hydrogen-induced change in core structures of {110}[111] edge and {110}[111] screw dislocations in iron

    PubMed Central

    Wang, Shuai; Hashimoto, Naoyuki; Ohnuki, Somei

    2013-01-01

    Employing the empirical embedded-atom method potentials, the evolution of edge and screw dislocation core structure is calculated at different hydrogen concentrations. With hydrogen, the core energy and Peierls potential are reduced for all dislocations. A broaden-core and a quasi-split core structure are observed for edge and screw dislocation respectively. The screw dislocation and hydrogen interaction in body-centred cubic iron is found to be not mainly due to the change of elastic modulus, but the variation of dislocation core structure. PMID:24067268

  17. Electronic Structure Calculations and Adaptation Scheme in Multi-core Computing Environments

    SciTech Connect

    Seshagiri, Lakshminarasimhan; Sosonkina, Masha; Zhang, Zhao

    2009-05-20

    Multi-core processing environments have become the norm in the generic computing environment and are being considered for adding an extra dimension to the execution of any application. The T2 Niagara processor is a very unique environment where it consists of eight cores having a capability of running eight threads simultaneously in each of the cores. Applications like General Atomic and Molecular Electronic Structure (GAMESS), used for ab-initio molecular quantum chemistry calculations, can be good indicators of the performance of such machines and would be a guideline for both hardware designers and application programmers. In this paper we try to benchmark the GAMESS performance on a T2 Niagara processor for a couple of molecules. We also show the suitability of using a middleware based adaptation algorithm on GAMESS on such a multi-core environment.

  18. Potential of electrospun core-shell structured gelatin-chitosan nanofibers for biomedical applications.

    PubMed

    Jalaja, K; Naskar, Deboki; Kundu, Subhas C; James, Nirmala R

    2016-01-20

    Coaxial electrospinning is an upcoming technology that has emerged from the conventional electrospinning process in order to realize the production of nanofibers of less spinnable materials with potential applications. The present work focuses on the production of chitosan nanofibers in a benign route, using natural polymer as core template, mild solvent system and naturally derived cross-linkers. Nanofibers with chitosan as shell are fabricated by coaxial electrospinning with highly spinnable gelatin as core using aqueous acetic acid as solvent. For maintaining the biocompatibility and structural integrity of the core-shell nanofibers, cross-linking is carried out using naturally derived cross-linking agents, dextran aldehyde and sucrose aldehyde. The biological evaluation of gelatin/chitosan mat is carried out using human osteoblast like cells. The results show that the cross-linked core-shell nanofibers are excellent matrices for cell adhesion and proliferation. PMID:26572452

  19. Sequence and structural analysis of surface protein antigen I/II (SpaA) of Streptococcus sobrinus.

    PubMed Central

    LaPolla, R J; Haron, J A; Kelly, C G; Taylor, W R; Bohart, C; Hendricks, M; Pyati, J P; Graff, R T; Ma, J K; Lehner, T

    1991-01-01

    Streptococcal antigen I/II or the surface protein antigen A (SpaA) of Streptococcus sobrinus is an adhesin which mediates binding of the organism to tooth surfaces. The complete sequence of the gene which encodes SpaA has been determined. The gene consists of 4,584 bp and encodes a protein of 1,528 amino acid residues. The deduced amino acid sequence shows extensive homology with those of the cell surface adhesins from Streptococcus mutans serotypes c and f and from Streptococcus sanguis. Structural analysis of the N-terminal region (residues 50 to 550), which is rich in alanine and includes four tandem repeats of an 82-residue sequence, suggests that it adopts an alpha-helical coiled-coil conformation. Cell surface hydrophobicity may be associated with this region. The C-terminal region is more conserved and includes two tandem repeats of a 39-residue proline-rich sequence. A further proline-rich sequence in this region is predicted to span the cell wall. Although a hydrophobic sequence is present in the C-terminal region, it appears to be too short to span the cell membrane. Anchoring of SpaA in the cell membrane may therefore require some form of posttranslational modification or association with another membrane protein. PMID:1855987

  20. Synthesis of Dideoxymycobactin Antigens Presented by CD1a Reveals T Cell Fine Specificity for Natural Lipopeptide Structures*

    PubMed Central

    Young, David C.; Kasmar, Anne; Moraski, Garrett; Cheng, Tan-Yun; Walz, Andrew J.; Hu, Jingdan; Xu, Yanping; Endres, Gregory W.; Uzieblo, Adam; Zajonc, Dirk; Costello, Catherine E.; Miller, Marvin J.; Moody, D. Branch

    2009-01-01

    Mycobacterium tuberculosis survival in cells requires mycobactin siderophores. Recently, the search for lipid antigens presented by the CD1a antigen-presenting protein led to the discovery of a mycobactin-like compound, dideoxymycobactin (DDM). Here we synthesize DDMs using solution phase and solid phase peptide synthesis chemistry. Comparison of synthetic standards to natural mycobacterial mycobactins by nuclear magnetic resonance and mass spectrometry allowed identification of an unexpected α-methyl serine unit in natural DDM. This finding further distinguishes these pre-siderophores as foreign compounds distinct from conventional peptides, and we provide evidence that this chemical variation influences the T cell response. One synthetic DDM recapitulated natural structures and potently stimulated T cells, making it suitable for patient studies of CD1a in infectious disease. DDM analogs differing in the stereochemistry of their butyrate or oxazoline moieties were not recognized by human T cells. Therefore, we conclude that T cells show precise specificity for both arms of the peptide, which are predicted to lie at the CD1a-T cell receptor interface. PMID:19605355

  1. Inhibition of structural changes in the simian virus 40 core origin of replication by mutation of essential origin sequences.

    PubMed Central

    Borowiec, J A

    1992-01-01

    Mutation of the simian virus 40 (SV40) origin of replication (ori) has revealed the presence of three critical domains needed for DNA replication. The outer two domains, the AT tract and early palindrome element (EP), colocalize with DNA regions that become structurally altered in the presence of the SV40 large tumor antigen (T antigen) and ATP. Mutations within each domain were examined for their effect on the distortion of ori DNA by T antigen, as assayed by the sensitivity of DNA to KMnO4 oxidation. We have found that mutations in the AT tract that inhibit SV40 DNA replication also inhibit the distortion of the AT tract. Similarly, mutations in the EP inhibited the generation of structural changes in this element by T antigen. Although AT-tract mutations or mutations on the late side of ori affected structural changes only in the AT tract, certain EP mutations or mutations on the early side of ori also inhibited AT-tract distortion. Mutation of the flanking regions did not significantly affect either the affinity of T antigen for ori or the rate of binding to ori. We conclude from these results that the primary function of the flanking ori domains is to undergo structural changes required during the initiation of SV40 DNA replication. Moreover, our results suggest that the efficiency of replication initiation is significantly affected by the degree to which the flanking elements undergo a structural transition. Images PMID:1323692

  2. The Ikaria high-temperature Metamorphic Core Complex (Cyclades, Greece): Geometry, kinematics and thermal structure

    NASA Astrophysics Data System (ADS)

    Beaudoin, Alexandre; Augier, Romain; Laurent, Valentin; Jolivet, Laurent; Lahfid, Abdeltif; Bosse, Valérie; Arbaret, Laurent; Rabillard, Aurélien; Menant, Armel

    2015-12-01

    This work attempted at clarifying the structure of Ikaria using primarily intensive geological mapping combined with structural analysis and a geothermometry approach of Raman spectrometry of carbonaceous material. Foliation over the whole island defines a structural dome cored by high-grade to partially molten rocks. Its exhumation was completed by two top-to-the-N ductile extensional shear zones, operating in the ductile and then the brittle fields, through a single extensional event coeval with progressive strain localization. The thermal structure of the dome with regard to position of ductile shear zones was retrieved using the Raman spectroscopy of carbonaceous material. Peak-metamorphic temperatures range from 390 °C in the upper parts of the structure down to 625 °C in the core of the dome in the vicinity of migmatites and S-type granite. Pioneer in situ U-Th-Pb analyses on monazite performed on the leucosome parts of these rock yielded a 15.7 ± 0.2 Ma age. Ikaria Island thus completes the series of Miocene migmatite-cored Metamorphic Core Complex in the central part of the Aegean domain where a genuine high-temperature zone can be defined as the central Aegean HT zone. There, the extreme stretching of the continental crust is associated with dominantly top-to-the-N kinematics.

  3. Fragmentation of Massive Dense Cores Down to <~ 1000 AU: Relation between Fragmentation and Density Structure

    NASA Astrophysics Data System (ADS)

    Palau, Aina; Estalella, Robert; Girart, Josep M.; Fuente, Asunción; Fontani, Francesco; Commerçon, Benoit; Busquet, Gemma; Bontemps, Sylvain; Sánchez-Monge, Álvaro; Zapata, Luis A.; Zhang, Qizhou; Hennebelle, Patrick; di Francesco, James

    2014-04-01

    In order to shed light on the main physical processes controlling fragmentation of massive dense cores, we present a uniform study of the density structure of 19 massive dense cores, selected to be at similar evolutionary stages, for which their relative fragmentation level was assessed in a previous work. We inferred the density structure of the 19 cores through a simultaneous fit of the radial intensity profiles at 450 and 850 μm (or 1.2 mm in two cases) and the spectral energy distribution, assuming spherical symmetry and that the density and temperature of the cores decrease with radius following power-laws. Even though the estimated fragmentation level is strictly speaking a lower limit, its relative value is significant and several trends could be explored with our data. We find a weak (inverse) trend of fragmentation level and density power-law index, with steeper density profiles tending to show lower fragmentation, and vice versa. In addition, we find a trend of fragmentation increasing with density within a given radius, which arises from a combination of flat density profile and high central density and is consistent with Jeans fragmentation. We considered the effects of rotational-to-gravitational energy ratio, non-thermal velocity dispersion, and turbulence mode on the density structure of the cores, and found that compressive turbulence seems to yield higher central densities. Finally, a possible explanation for the origin of cores with concentrated density profiles, which are the cores showing no fragmentation, could be related with a strong magnetic field, consistent with the outcome of radiation magnetohydrodynamic simulations. The James Clerk Maxwell Telescope is operated by the Joint Astronomy Centre on behalf of the Science and Technology Facilities Council of the United Kingdom, the Netherlands Organisation for Scientific Research, and the National Research Council of Canada.

  4. Full-length RNA structure prediction of the HIV-1 genome reveals a conserved core domain.

    PubMed

    Sükösd, Zsuzsanna; Andersen, Ebbe S; Seemann, Stefan E; Jensen, Mads Krogh; Hansen, Mathias; Gorodkin, Jan; Kjems, Jørgen

    2015-12-01

    A distance constrained secondary structural model of the ≈10 kb RNA genome of the HIV-1 has been predicted but higher-order structures, involving long distance interactions, are currently unknown. We present the first global RNA secondary structure model for the HIV-1 genome, which integrates both comparative structure analysis and information from experimental data in a full-length prediction without distance constraints. Besides recovering known structural elements, we predict several novel structural elements that are conserved in HIV-1 evolution. Our results also indicate that the structure of the HIV-1 genome is highly variable in most regions, with a limited number of stable and conserved RNA secondary structures. Most interesting, a set of long distance interactions form a core organizing structure (COS) that organize the genome into three major structural domains. Despite overlapping protein-coding regions the COS is supported by a particular high frequency of compensatory base changes, suggesting functional importance for this element. This new structural element potentially organizes the whole genome into three major domains protruding from a conserved core structure with potential roles in replication and evolution for the virus. PMID:26476446

  5. New core-pyrene π structure organophotocatalysts usable as highly efficient photoinitiators

    PubMed Central

    Telitel, Sofia; Dumur, Frédéric; Faury, Thomas; Graff, Bernadette; Tehfe, Mohamad-Ali; Fouassier, Jean-Pierre

    2013-01-01

    Summary Eleven di- and trifunctional compounds based on a core-pyrene π structure (Co_Py) were synthesized and investigated for the formation of free radicals. The application of two- and three-component photoinitiating systems (different Co_Pys with the addition of iodonium or sulfonium salts, alkyl halide or amine) was investigated in detail for cationic and radical photopolymerization reactions under near-UV–vis light. The proposed compounds can behave as new photocatalysts. Successful results in terms of rates of polymerization and final conversions were obtained. The strong MO coupling between the six different cores and the pyrene moiety was studied by DFT calculations. The different chemical intermediates are characterized by ESR and laser flash photolysis experiments. The mechanisms involved in the initiation step are discussed, and relationships between the core structure, the Co_Py absorption property, and the polymerization ability are tentatively proposed. PMID:23766803

  6. Inversion of anisotropic inner core structure from three dimensional ray tracing

    NASA Astrophysics Data System (ADS)

    Sun, X.; Song, X.

    2005-12-01

    Seismological studies have generally suggest that the Earth's inner core is anisotropic and the anisotropic structure change significantly both laterally and with depth. Previous body-wave studies of the inner core have relied on 1-D ray tracing or waveform modeling, which do not account fully the 3D anisotropic structure. Here we adopt a pseudo-bending ray tracing (PBR) method in spherical coordinates (Koketsu and Sekine, 1998) for seismic rays that traverse the inner core (PKP-DF phase). The method iteratively perturbs each discontinuity points and continuous segment of the ray through 3D (but isotropic) earth structure so that its travel time is minimum. Our implementation also includes a flexible scheme in calculating the velocity gradient needed to perturb the ray. A large volume is included in calculating the velocity gradient initially to find the global minimum, but a small volume surrounding the ray is used eventually to obtain the precise local velocity gradient that is sampled by the ray. Tests show that our implementation is very stable, reliable, and fast. We have traced the rays for over 3000 event-station pairs that we have differential PKP travel-time measurements using both the PBR method and a shooting method for a 1D model (AK135). The travel-time difference from the two methods is generally within 0.05 s with a few up to 0.07 s and the largest path difference is within 24 km; Even with a model of strong velocity gradient, the travel time difference is still less than 0.08s and the largest path difference is within 40km. Because the ray direction in the inner core does not change much (within 10 degrees even with a strong velocity gradient in the inner core), the 3D anisotropic structure of the inner core can be approximated to the first order as 3D heterogeneous (but isotropic) structure for a given ray, assuming the inner core anisotropy is axisymmetric. We are implementing the PBR method and B-spline interpolation to invert for 3D anisotropic

  7. Improved Fabrication of Ceramic Matrix Composite/Foam Core Integrated Structures

    NASA Technical Reports Server (NTRS)

    Hurwitz, Frances I.

    2009-01-01

    The use of hybridized carbon/silicon carbide (C/SiC) fabric to reinforce ceramic matrix composite face sheets and the integration of such face sheets with a foam core creates a sandwich structure capable of withstanding high-heatflux environments (150 W/cm2) in which the core provides a temperature drop of 1,000 C between the surface and the back face without cracking or delamination of the structure. The composite face sheet exhibits a bilinear response, which results from the SiC matrix not being cracked on fabrication. In addition, the structure exhibits damage tolerance under impact with projectiles, showing no penetration to the back face sheet. These attributes make the composite ideal for leading edge structures and control surfaces in aerospace vehicles, as well as for acreage thermal protection systems and in high-temperature, lightweight stiffened structures. By tailoring the coefficient of thermal expansion (CTE) of a carbon fiber containing ceramic matrix composite (CMC) face sheet to match that of a ceramic foam core, the face sheet and the core can be integrally fabricated without any delamination. Carbon and SiC are woven together in the reinforcing fabric. Integral densification of the CMC and the foam core is accomplished with chemical vapor deposition, eliminating the need for bond-line adhesive. This means there is no need to separately fabricate the core and the face sheet, or to bond the two elements together, risking edge delamination during use. Fibers of two or more types are woven together on a loom. The carbon and ceramic fibers are pulled into the same pick location during the weaving process. Tow spacing may be varied to accommodate the increased volume of the combined fiber tows while maintaining a target fiber volume fraction in the composite. Foam pore size, strut thickness, and ratio of face sheet to core thickness can be used to tailor thermal and mechanical properties. The anticipated CTE for the hybridized composite is managed by

  8. Functional and structural changes in human erythrocyte surface after irradiation by uv waves of various wavelengths. Report 1: expression of ABO and Rhesus system antigen

    SciTech Connect

    Samoylova, K.A.; Klimova, K.N.; Priyezzheva, L.S.; Artsishevskaya, R.A.

    1985-01-01

    The effect of shortwave ultraviolet (SUV) radiation ad causes change in the external surface of human erythrocytes, modifying the expression of the ABO and Rh system antigens which are related to the surface of the cells was investigated. Erythrocytes in a structurally prepared erythrocyte mass from 23 donors stabilized by glugicir or heparin were examined. Three series of experiments were performed: (1) isolated erythrocytes, before irradiation thrice washed to remove plasma with isotonic NaC1 0.9%, erythrocytes diluted to 5 x s10 to the 7th power cells per milliliter and erythrocytes on the undiluted erythrocyte mass about 7 x 5 x 109 to the 9th power cells power milliliter. The agglutinating activity of the ABO and Rh antigens was studied. Two to three hours after exposure to 248, 620, 1240 and 2480 J/m2, the degree of hemolysis of isolated erythrocytes increased by 5,10,18 and 28%. Changes were also observed in agglutinating activity of ABO antigens. The agglutinating activity of A and B antigens increased by an average factor of 2 minus H antigens by a factor of 4. The SUV radiation did not cause any activation of the Rh antigen.

  9. Modeling heterogeneous polymer-grafted nanoparticle networks having biomimetic core-shell structure

    NASA Astrophysics Data System (ADS)

    Mbanga, Badel L.; Yashin, Victor V.; Holten-Andersen, Niels; Balazs, Anna C.

    Inspired by the remarkable mechanical properties of such biological structures as mussel adhesive fibers, we use 3D computational modeling to study the behavior of heterogeneous polymer-grafted nanoparticle (PGN) networks under tensile deformation. The building block of a PGN network is a nanoparticle with grafted polymer chains whose free ends' reactive groups can form both permanent and labile bonds with the end chains on the nearby particles. The tunable behavior of cross-linked PGN networks makes them excellent candidates for designing novel materials with enhanced mechanical properties. Here, we consider the PGN networks having the core-shell structures, in which the type and strength of the inter-particle bonds in the outer shell differ from those in the core. Using the computer simulations, we obtain and compare the ultimate tensile properties (strength, toughness, ductility) and the strain recovery properties for the uniform samples and various core-shell structures. We demonstrate that the core-shell structures could be designed to obtain highly resilient self-healing materials

  10. Radiographic analysis of sedimentary structures and depositional histories in Apollo 15 cores

    NASA Technical Reports Server (NTRS)

    Coch, N. K.

    1977-01-01

    Radiographs of the Apollo 15 deepdrill drive tubes were analyzed on an SDS electronic enhancer to determine sedimentary structures in the core samples. The data obtained were compared with all other Apollo mission radiographs and used to make inferences on the character of sedimentary depositional processes on the lunar surface.

  11. Core-shell structured TiO2@polydopamine for highly active visible-light photocatalysis.

    PubMed

    Mao, Wen-Xin; Lin, Xi-Jie; Zhang, Wei; Chi, Zi-Xiang; Lyu, Rong-Wen; Cao, An-Min; Wan, Li-Jun

    2016-06-01

    This communication reports that the TiO2@polydopamine nanocomposite with a core-shell structure could be a highly active photocatalyst working under visible light. A very thin layer of polydopamine at around 1 nm was found to be critical for the degradation of Rhodamine B. PMID:27165843

  12. Core/shell structural transformation and brittle-to-ductile transition in nanowires

    NASA Astrophysics Data System (ADS)

    Yuan, Zaoshi; Nomura, Ken-ichi; Nakano, Aiichiro

    2012-04-01

    Nanowires (NWs) exhibit thermo-mechanical properties that are distinct from their bulk properties, and their understanding is critical for the reliability, manufacturability, and optimization of a wide range of devices consisting of NWs. Here, molecular-dynamics simulation reveals a rich size-temperature "phase diagram" for the mechanical response of a zinc-oxide NW under tension. For smaller diameters and higher temperatures, transitions are found from brittle cleavage to structural transformation-mediated brittle cleavage to ductile failure. Atomistic mechanisms of the unique nano-thermo-mechanical behavior are elucidated as a consequence of surface-structural relaxation, which in particular predicts spontaneous formation of a core/shell structure under tension. The nano-thermo-mechanical phase diagram resolves controversies between previous experiments and theory, and the predicted "intrinsic" core/shell structure may find device applications.

  13. Structural Optimization, Biological Evaluation and Application of Peptidomimetic Prostate Specific Antigen Inhibitors

    PubMed Central

    Kostova, Maya B.; Rosen, D. Marc; Chen, Ying; Mease, Ronnie C.; Denmeade, Samuel R.

    2013-01-01

    Prostate-Specific Antigen (PSA) is a serine protease produced at high levels by normal and malignant prostate epithelial cells that is used extensively as a biomarker in the clinical management of prostate cancer. To better understand PSA’s role in prostate cancer progression we prepared a library of peptidyl boronic acid based inhibitors. To enhance selectivity for PSA vs. other serine proteases, we modified the P1 site of the inhibitors to incorporate a bromopropylglycine group. This allowed the inhibitors to participate in halogen bond formation with the serine found at the bottom of the specificity pocket. The best of these Ahx-FSQn(boro)Bpg had PSA Ki of 72 nM and chymotrypsin Ki of 580 nM. In vivo studies using PSA-producing xenografts demonstrated that candidate inhibitors had minimal effect on growth but significantly altered serum levels of PSA. Biodistribution of 125I labeled peptides showed low levels of uptake into tumors compared to other normal tissues. PMID:23692593

  14. Fine structure of the topological defect core: Disclination in lyotropic chromonic liquid crystal

    NASA Astrophysics Data System (ADS)

    Zhou, Shuang; Shiyanovskii, Sergij; Park, Heung-Shik; Kim, Young-Ki; Hearn, Tristan; Reichel, Lothar; Lavrentovich, Oleg

    Topological defects represent an important concept in many branches of modern physics ranging from cosmology and optics to hard and soft matter. One of the most difficult problems is the fine structure of the so-called core region of defects, where the deformations of the order parameter are so strong that the phenomenological description valid in the far field becomes invalid. Experimental exploration of the fine core structure is usually hindered by the small size (atomic/molecular level) of the core, where optical or even electron microscopy techniques are invalid. In this work, we take advantage of the peculiar nature of the so-called lyotropic chromonic liquid crystals (LCLC) of a nematic type that carry disclinations with a core extending over macroscopic distances (tens of micrometers), large enough to explore their spatial variation by optical and electron microscopy. We demonstrate that the director and the scalar order parameter (associated with the degree of orientational order) show a profound change in the core region. In particular, as one approaches the center of the defect, the azimuthal dependency of the director field changes dramatically and the scalar order parameter shows a strong dependence on the strength of splay and bend deformations. This work is supported by NSF Grant DMS-1434185.

  15. One-Seeded Fruits in the Core Caryophyllales: Their Origin and Structural Diversity

    PubMed Central

    Sukhorukov, Alexander P.; Mavrodiev, Evgeny V.; Struwig, Madeleen; Nilova, Maya V.; Dzhalilova, Khalima Kh.; Balandin, Sergey A.; Erst, Andrey; Krinitsyna, Anastasiya A.

    2015-01-01

    The core Caryophyllales consist of approximately 30 families (12 000 species) distributed worldwide. Many members evolved one-seeded or conjoined fruits, but their origin and structural diversity have not been investigated. A comparative anatomical investigation of the one-seeded fruits within the core Caryophyllales was conducted. The origin of the one-seeded fruits and the evolutionary reconstructions of some carpological characters were traced using a tree based on rbcl and matK data in order to understand the ancestral characters and their changes. The one-seeded fruit type is inferred to be an ancestral character state in core Caryophyllales, with a subsequent increase in the seed number seen in all major clades. Most representatives of the ‘Earlier Diverging’ clade are distinguished in various carpological traits. The organization of the pericarp is diverse in many groups, although fruits with a dry, many-layered pericarp, consisting of sclerenchyma as outer layers and a thin-walled parenchyma below, with seeds occupying a vertical embryo position, are likely ancestral character states in the core Caryophyllales clade. Several carpological peculiarities in fruit and seed structure were discovered in obligate one-seeded Achatocarpaceae, Chenopodiaceae, Nyctaginaceae, Seguieriaceae and Sarcobataceae. The horizontal embryo evolved in only certain groups of Chenopodiaceae. The bar-thickening of endotegmen cells appears to be an additional character typical of core Caryophyllales. The syncarpy-to-lysicarpy paradigm in Caryophyllaceae needs to be reinterpreted. PMID:25710481

  16. The multifunctional wound dressing with core-shell structured fibers prepared by coaxial electrospinning

    NASA Astrophysics Data System (ADS)

    Wei, Qilin; Xu, Feiyang; Xu, Xingjian; Geng, Xue; Ye, Lin; Zhang, Aiying; Feng, Zengguo

    2016-04-01

    The non-woven wound dressing with core-shell structured fibers was prepared by coaxial electrospinning. The polycaprolactone (PCL) was electrospun as the fiber's core to provide mechanical strength whereas collagen was fabricated into the shell in order to utilize its good biocompatibility. Simultaneously, the silver nanoparticles (Ag- NPs) as anti-bacterial agent were loaded in the shell whereas the vitamin A palmitate (VA) as healing-promoting drug was encapsulated in the core. Resulting from the fiber's core-shell structure, the VA released from the core and Ag-NPs present in the shell can endow the dressing both heal-promoting and anti-bacteria ability simultaneously, which can greatly enhance the dressing's clinical therapeutic effect. The dressing can maintain high swelling ratio of 190% for 3 d indicating its potential application as wet dressing. Furthermore, the dressing's anti-bacteria ability against Staphylococcus aureus was proved by in vitro anti-bacteria test. The in vitro drug release test showed the sustainable release of VA within 72 h, while the cell attachment showed L929 cells can well attach on the dressing indicating its good biocompatibility. In conclusion, the fabricated nanofibrous dressing possesses multiple functions to benefit wound healing and shows promising potential for clinical application.

  17. The multifunctional wound dressing with core-shell structured fibers prepared by coaxial electrospinning

    NASA Astrophysics Data System (ADS)

    Wei, Qilin; Xu, Feiyang; Xu, Xingjian; Geng, Xue; Ye, Lin; Zhang, Aiying; Feng, Zengguo

    2016-06-01

    The non-woven wound dressing with core-shell structured fibers was prepared by coaxial electrospinning. The polycaprolactone (PCL) was electrospun as the fiber's core to provide mechanical strength whereas collagen was fabricated into the shell in order to utilize its good biocompatibility. Simultaneously, the silver nanoparticles (Ag-NPs) as anti-bacterial agent were loaded in the shell whereas the vitamin A palmitate (VA) as healing-promoting drug was encapsulated in the core. Resulting from the fiber's core-shell structure, the VA released from the core and Ag-NPs present in the shell can endow the dressing both heal-promoting and anti-bacteria ability simultaneously, which can greatly enhance the dressing's clinical therapeutic effect. The dressing can maintain high swelling ratio of 190% for 3 d indicating its potential application as wet dressing. Furthermore, the dressing's anti-bacteria ability against Staphylococcus aureus was proved by in vitro anti-bacteria test. The in vitro drug release test showed the sustainable release of VA within 72 h, while the cell attachment showed L929 cells can well attach on the dressing indicating its good biocompatibility. In conclusion, the fabricated nanofibrous dressing possesses multiple functions to benefit wound healing and shows promising potential for clinical application.

  18. One-seeded fruits in the core Caryophyllales: their origin and structural diversity.

    PubMed

    Sukhorukov, Alexander P; Mavrodiev, Evgeny V; Struwig, Madeleen; Nilova, Maya V; Dzhalilova, Khalima Kh; Balandin, Sergey A; Erst, Andrey; Krinitsyna, Anastasiya A

    2015-01-01

    The core Caryophyllales consist of approximately 30 families (12,000 species) distributed worldwide. Many members evolved one-seeded or conjoined fruits, but their origin and structural diversity have not been investigated. A comparative anatomical investigation of the one-seeded fruits within the core Caryophyllales was conducted. The origin of the one-seeded fruits and the evolutionary reconstructions of some carpological characters were traced using a tree based on rbcl and matK data in order to understand the ancestral characters and their changes. The one-seeded fruit type is inferred to be an ancestral character state in core Caryophyllales, with a subsequent increase in the seed number seen in all major clades. Most representatives of the 'Earlier Diverging' clade are distinguished in various carpological traits. The organization of the pericarp is diverse in many groups, although fruits with a dry, many-layered pericarp, consisting of sclerenchyma as outer layers and a thin-walled parenchyma below, with seeds occupying a vertical embryo position, are likely ancestral character states in the core Caryophyllales clade. Several carpological peculiarities in fruit and seed structure were discovered in obligate one-seeded Achatocarpaceae, Chenopodiaceae, Nyctaginaceae, Seguieriaceae and Sarcobataceae. The horizontal embryo evolved in only certain groups of Chenopodiaceae. The bar-thickening of endotegmen cells appears to be an additional character typical of core Caryophyllales. The syncarpy-to-lysicarpy paradigm in Caryophyllaceae needs to be reinterpreted. PMID:25710481

  19. Vaccination with ubiquitin-hepatitis B core antigen-cytoplasmic transduction peptide enhances the hepatitis B virus-specific cytotoxic T-lymphocyte immune response and inhibits hepatitis B virus replication in transgenic mice.

    PubMed

    Zhuo, Meng; Song, Linlin; Tang, Yuyan; Dai, Shenglan; Chen, Xiaohua; Yu, Yongsheng; Zang, Guoqing; Tang, Zhenghao

    2015-09-01

    Chronic hepatitis B virus (HBV) infection is characterized by functionally impaired type 1 T-helper cell (Thl) immunity and poor HBV‑specific T‑cell responses. Ubiquitin (Ub), a highly conserved small regulatory protein, commonly serves as a signal for target proteins that are recognized and degraded in proteasomes. The rapid degradation of Ub‑mediated antigens results in efficient stimulation of cell‑mediated immune responses. Thus, the Ub‑HBV core antigen (HBcAg)‑cytoplasmic transduction peptide (CTP) fusion protein was designed for specific delivery of a foreign modified antigen to the cytoplasm of antigen‑presenting cells. HBV transgenic mice were used to determine whether Ub‑HBcAg‑CTP would restore HBV‑specific immune responses and anti‑viral immunity in these animals. The results demonstrated that synthesized Ub‑HBcAg‑CTP not only significantly increased the levels of interleukin‑2 and interferon (IFN)‑γ compared with those in the HBcAg‑CTP, IFN‑α, Ub‑HBcAg, HBcAg and phosphate‑buffered saline groups, but additionally induced the highest IFN‑γ+ CD8+ T‑cell numbers and HBV‑specific cytotoxic T lymphocyte (CTL) responses, indicating a strong immune response. In addition, enhancement of specific CTL activity provoked by the fusion protein reduced hepatitis B surface antigen (HBsAg) and HBV DNA serum levels and diminished the expression of HBsAg and HBcAg in liver tissue of HBV transgenic mice, suggesting that there was a therapeutic effect. In conclusion, the present study provided evidence that Ub‑HBcAg‑CTP activated the Th1‑dependent immunity, triggered functional T cell responses and subsequently inhibited viral replication in HBV transgenic mice. These observations suggested that the fusion protein may represent an innovative and promising candidate for active immunotherapy during chronic and persistent HBV. PMID:26004262

  20. Re-refinement of the spliceosomal U4 snRNP core-domain structure

    PubMed Central

    Li, Jade; Leung, Adelaine K.; Kondo, Yasushi; Oubridge, Chris; Nagai, Kiyoshi

    2016-01-01

    The core domain of small nuclear ribonucleoprotein (snRNP), comprised of a ring of seven paralogous proteins bound around a single-stranded RNA sequence, functions as the assembly nucleus in the maturation of U1, U2, U4 and U5 spliceosomal snRNPs. The structure of the human U4 snRNP core domain was initially solved at 3.6 Å resolution by experimental phasing using data with tetartohedral twinning. Molecular replacement from this model followed by density modification using untwinned data recently led to a structure of the minimal U1 snRNP at 3.3 Å resolution. With the latter structure providing a search model for molecular replacement, the U4 core-domain structure has now been re-refined. The U4 Sm site-sequence AAUUUUU has been shown to bind to the seven Sm proteins SmF–SmE–SmG–SmD3–SmB–SmD1–SmD2 in an identical manner as the U1 Sm-site sequence AAUUUGU, except in SmD1 where the bound U replaces G. The progression from the initial to the re-refined structure exemplifies a tortuous route to accuracy: where well diffracting crystals of complex assemblies are initially unavailable, the early model errors are rectified by exploiting preliminary interpretations in further experiments involving homologous structures. New insights are obtained from the more accurate model. PMID:26894541

  1. Vertically aligned P(VDF-TrFE) core-shell structures on flexible pillar arrays

    PubMed Central

    Choi, Yoon-Young; Yun, Tae Gwang; Qaiser, Nadeem; Paik, Haemin; Roh, Hee Seok; Hong, Jongin; Hong, Seungbum; Han, Seung Min; No, Kwangsoo

    2015-01-01

    PVDF and P(VDF-TrFE) nano- and micro- structures have been widely used due to their potential applications in several fields, including sensors, actuators, vital sign transducers, and energy harvesters. In this study, we developed vertically aligned P(VDF-TrFE) core-shell structures using high modulus polyurethane acrylate (PUA) pillars as the support structure to maintain the structural integrity. In addition, we were able to improve the piezoelectric effect by 1.85 times from 40 ± 2 to 74 ± 2 pm/V when compared to the thin film counterpart, which contributes to the more efficient current generation under a given stress, by making an effective use of the P(VDF-TrFE) thin top layer as well as the side walls. We attribute the enhancement of piezoelectric effects to the contributions from the shell component and the strain confinement effect, which was supported by our modeling results. We envision that these organic-based P(VDF-TrFE) core-shell structures will be used widely as 3D sensors and power generators because they are optimized for current generations by utilizing all surface areas, including the side walls of core-shell structures. PMID:26040539

  2. GTfold: Enabling parallel RNA secondary structure prediction on multi-core desktops

    PubMed Central

    2012-01-01

    Background Accurate and efficient RNA secondary structure prediction remains an important open problem in computational molecular biology. Historically, advances in computing technology have enabled faster and more accurate RNA secondary structure predictions. Previous parallelized prediction programs achieved significant improvements in runtime, but their implementations were not portable from niche high-performance computers or easily accessible to most RNA researchers. With the increasing prevalence of multi-core desktop machines, a new parallel prediction program is needed to take full advantage of today’s computing technology. Findings We present here the first implementation of RNA secondary structure prediction by thermodynamic optimization for modern multi-core computers. We show that GTfold predicts secondary structure in less time than UNAfold and RNAfold, without sacrificing accuracy, on machines with four or more cores. Conclusions GTfold supports advances in RNA structural biology by reducing the timescales for secondary structure prediction. The difference will be particularly valuable to researchers working with lengthy RNA sequences, such as RNA viral genomes. PMID:22747589

  3. Vertically aligned P(VDF-TrFE) core-shell structures on flexible pillar arrays

    SciTech Connect

    Choi, Yoon-Young; Yun, Tae Gwang; Qaiser, Nadeem; Paik, Haemin; Roh, Hee Seok; Hong, Jongin; Hong, Seungbum; Han, Seung Min; No, Kwangsoo

    2015-06-04

    PVDF and P(VDF-TrFE) nano- and micro- structures are widely used due to their potential applications in several fields, including sensors, actuators, vital sign transducers, and energy harvesters. In this study, we developed vertically aligned P(VDF-TrFE) core-shell structures using high modulus polyurethane acrylate (PUA) pillars as the support structure to maintain the structural integrity. In addition, we were able to improve the piezoelectric effect by 1.85 times from 40 ± 2 to 74 ± 2 pm/V when compared to the thin film counterpart, which contributes to the more efficient current generation under a given stress, by making an effective use of the P(VDF-TrFE) thin top layer as well as the side walls. We attribute the enhancement of piezoelectric effects to the contributions from the shell component and the strain confinement effect, which was supported by our modeling results. We envision that these organic-based P(VDF-TrFE) core-shell structures will be used widely as 3D sensors and power generators because they are optimized for current generations by utilizing all surface areas, including the side walls of core-shell structures.

  4. Vertically aligned P(VDF-TrFE) core-shell structures on flexible pillar arrays

    DOE PAGESBeta

    Choi, Yoon-Young; Yun, Tae Gwang; Qaiser, Nadeem; Paik, Haemin; Roh, Hee Seok; Hong, Jongin; Hong, Seungbum; Han, Seung Min; No, Kwangsoo

    2015-06-04

    PVDF and P(VDF-TrFE) nano- and micro- structures are widely used due to their potential applications in several fields, including sensors, actuators, vital sign transducers, and energy harvesters. In this study, we developed vertically aligned P(VDF-TrFE) core-shell structures using high modulus polyurethane acrylate (PUA) pillars as the support structure to maintain the structural integrity. In addition, we were able to improve the piezoelectric effect by 1.85 times from 40 ± 2 to 74 ± 2 pm/V when compared to the thin film counterpart, which contributes to the more efficient current generation under a given stress, by making an effective use ofmore » the P(VDF-TrFE) thin top layer as well as the side walls. We attribute the enhancement of piezoelectric effects to the contributions from the shell component and the strain confinement effect, which was supported by our modeling results. We envision that these organic-based P(VDF-TrFE) core-shell structures will be used widely as 3D sensors and power generators because they are optimized for current generations by utilizing all surface areas, including the side walls of core-shell structures.« less

  5. Vertically aligned P(VDF-TrFE) core-shell structures on flexible pillar arrays.

    PubMed

    Choi, Yoon-Young; Yun, Tae Gwang; Qaiser, Nadeem; Paik, Haemin; Roh, Hee Seok; Hong, Jongin; Hong, Seungbum; Han, Seung Min; No, Kwangsoo

    2015-01-01

    PVDF and P(VDF-TrFE) nano- and micro- structures have been widely used due to their potential applications in several fields, including sensors, actuators, vital sign transducers, and energy harvesters. In this study, we developed vertically aligned P(VDF-TrFE) core-shell structures using high modulus polyurethane acrylate (PUA) pillars as the support structure to maintain the structural integrity. In addition, we were able to improve the piezoelectric effect by 1.85 times from 40 ± 2 to 74 ± 2 pm/V when compared to the thin film counterpart, which contributes to the more efficient current generation under a given stress, by making an effective use of the P(VDF-TrFE) thin top layer as well as the side walls. We attribute the enhancement of piezoelectric effects to the contributions from the shell component and the strain confinement effect, which was supported by our modeling results. We envision that these organic-based P(VDF-TrFE) core-shell structures will be used widely as 3D sensors and power generators because they are optimized for current generations by utilizing all surface areas, including the side walls of core-shell structures. PMID:26040539

  6. Structural and Functional Studies of Ig[alpha beta] and Its Assembly with the B Cell Antigen Receptor

    SciTech Connect

    Radaev, Sergei; Zou, Zhongcheng; Tolar, Pavel; Nguyen, Khanh; Nguyen, AnhThao; Krueger, Peter D.; Stutzman, Nicole; Pierce, Susan; Sun, Peter D.

    2010-11-09

    The B cell antigen receptor (BCR) plays an essential role in all phases of B cell development. Here we show that the extracellular domains of murine and human Ig{beta} form an I-set immunoglobulin-like structure with an interchain disulfide between cysteines on their G strands. Structural and sequence analysis suggests that Ig{alpha} displays a similar fold as Ig{beta}. An Ig{alpha}{beta} heterodimer model was generated based on the unique disulfide-bonded Ig{beta} dimer. Solution binding studies showed that the extracellular domains of Ig{alpha}{beta} preferentially recognize the constant region of BCR with chain specificity, suggesting a role for Ig{alpha}{beta} to enhance BCR chain signaling. Cluster mutations on Ig{alpha}, Ig{beta}, and a membrane-bound form of immunoglobulin (mIgM) based on the structural model identified distinct areas of potential contacts involving charged residues on both subunits of the coreceptor and the C4 domain of mIgM. These studies provide the first structural model for understanding BCR function.

  7. Structural Insights into the Protease-like Antigen Plasmodium falciparum SERA5 and Its Noncanonical Active-Site Serine

    SciTech Connect

    Hodder, Anthony N.; Malby, Robyn L.; Clarke, Oliver B.; Fairlie, W. Douglas; Colman, Peter M.; Crabb, Brendan S.; Smith, Brian J.

    2009-08-28

    The sera genes of the malaria-causing parasite Plasmodium encode a family of unique proteins that are maximally expressed at the time of egress of parasites from infected red blood cells. These multi-domain proteins are unique, containing a central papain-like cysteine-protease fragment enclosed between the disulfide-linked N- and C-terminal domains. However, the central fragment of several members of this family, including serine repeat antigen 5 (SERA5), contains a serine (S596) in place of the active-site cysteine. Here we report the crystal structure of the central protease-like domain of Plasmodium falciparum SERA5, revealing a number of anomalies in addition to the putative nucleophilic serine: (1) the structure of the putative active site is not conducive to binding substrate in the canonical cysteine-protease manner; (2) the side chain of D594 restricts access of substrate to the putative active site; and (3) the S{sub 2} specificity pocket is occupied by the side chain of Y735, reducing this site to a small depression on the protein surface. Attempts to determine the structure in complex with known inhibitors were not successful. Thus, despite having revealed its structure, the function of the catalytic domain of SERA5 remains an enigma.

  8. Synthesis and properties MFe2O4 (M = Fe, Co) nanoparticles and core-shell structures

    NASA Astrophysics Data System (ADS)

    Yelenich, O. V.; Solopan, S. O.; Greneche, J. M.; Belous, A. G.

    2015-08-01

    Individual Fe3-xO4 and CoFe2O4 nanoparticles, as well as Fe3-xO4/CoFe2O4 core/shell structures were synthesized by the method of co-precipitation from diethylene glycol solutions. Core/shell structure were synthesized with CoFe2O4-shell thickness of 1.0, 2.5 and 3.5 nm. X-ray diffraction patterns of individual nanoparticles and core/shell are similar and indicate that all synthesized samples have a cubic spinel structure. Compares Mössbauer studies of CoFe2O4, Fe3-xO4 nanoparticles indicate superparamagnetic properties at 300 K. It was shown that individual magnetite nanoparticles are transformed into maghemite through oxidation during the synthesis procedure, wherein the smallest nanoparticles are completely oxidized while a magnetite core does occur in the case of the largest nanoparticles. The Mössbauer spectra of core/shell nanoparticles with increasing CoFe2O4-shell thickness show a gradual decrease in the relative intensity of the quadrupole doublet and significant decrease of the mean isomer shift value at both RT and 77 K indicating a decrease of the superparamagnetic relaxation phenomena. Specific loss power for the prepared ferrofluids was experimentally calculated and it was determined that under influence of ac-magnetic field magnetic fluid based on individual CoFe2O4 and Fe3-xO4 particles are characterized by very low heating temperature, when magnetic fluids based on core/shell nanoparticles demonstrate higher heating effect.

  9. The 2.5 Å Structure of CD1c in Complex with a Mycobacterial Lipid Reveals an Open Groove Ideally Suited for Diverse Antigen Presentation

    SciTech Connect

    Scharf, Louise; Li, Nan-Sheng; Hawk, Andrew J.; Garzón, Diana; Zhang, Tejia; Fox, Lisa M.; Kazen, Allison R.; Shah, Sneha; Haddadian, Esmael J.; Gumperz, Jenny E.; Saghatelian, Alan; Faraldo-Gómez, José D.; Meredith, Stephen C.; Piccirilli, Joseph A.; Adams, Erin J.

    2011-08-24

    CD1 molecules function to present lipid-based antigens to T cells. Here we present the crystal structure of CD1c at 2.5 {angstrom} resolution, in complex with the pathogenic Mycobacterium tuberculosis antigen mannosyl-{beta}1-phosphomycoketide (MPM). CD1c accommodated MPM's methylated alkyl chain exclusively in the A pocket, aided by a unique exit portal underneath the {alpha}1 helix. Most striking was an open F pocket architecture lacking the closed cavity structure of other CD1 molecules, reminiscent of peptide binding grooves of classical major histocompatibility complex molecules. This feature, combined with tryptophan-fluorescence quenching during loading of a dodecameric lipopeptide antigen, provides a compelling model by which both the lipid and peptide moieties of the lipopeptide are involved in CD1c presentation of lipopeptides.

  10. Bacterial community structure in the hyperarid core of the Atacama Desert, Chile

    USGS Publications Warehouse

    Drees, Kevin P.; Neilson, Julia W.; Betancourt, Julio L.; Quade, Jay; Henderson, David A.; Pryor, Barry M.; Maier, Raina M.

    2006-01-01

    Soils from the hyperarid Atacama Desert of northern Chile were sampled along an east-west elevational transect (23.75 to 24.70 degrees S) through the driest sector to compare the relative structure of bacterial communities. Analysis of denaturing gradient gel electrophoresis (DGGE) profiles from each of the samples revealed that microbial communities from the extreme hyperarid core of the desert clustered separately from all of the remaining communities. Bands sequenced from DGGE profiles of two samples taken at a 22-month interval from this core region revealed the presence of similar populations dominated by bacteria from the Gemmatimonadetes and Planctomycetes phyla.

  11. Cycle 0(CY1991) NLS trade studies and analyses report. Book 1: Structures and core vehicle

    NASA Technical Reports Server (NTRS)

    1992-01-01

    This report (SR-1: Structures, Trades, and Analysis), documents the Core Tankage Trades and analyses performed in support of the National Launch System (NLS) Cycle 0 preliminary design activities. The report covers trades that were conducted on the Vehicle Assembly, Fwd Skirt, LO2 Tank, Intertank, LH2 Tank, and Aft Skirt of the NLS Core Tankage. For each trade study, a two page executive summary and the detail trade study are provided. The trade studies contain study results, recommended changes to the Cycle 0 Baselines, and suggested follow on tasks to be performed during Cycle 1.

  12. Core structures of haemosiderins deposited in various organs in β-thalassaemia/haemoglobin e disease

    NASA Astrophysics Data System (ADS)

    St. Pierre, T. G.; Tran, K. C.; Webb, J.; Macey, D. J.; Pootrakul, P.; Dickson, D. P. E.

    1992-04-01

    Mössbauer spectra were recorded of tissue from β-thalassaemia/haemoglobin E spleen, liver, pancreas and heart and of crude haemosiderins (insoluble iron fractions) isolated from the organs. Iron in the crude haemosiderins from the spleen and heart remains paramagnetic below 4.2K indicating that the iron is in a non-crystalline form. Superparamagnetic behaviour of the crude haemosiderins from the pancreas and liver indicate the presence of ferrihydrite cores with some cores with a structure based on defect-goethite.

  13. Exploring meso-/microporous composite molecular sieves with core-shell structures.

    PubMed

    Qian, Xufang F; Li, Bin; Hu, Yuanyuan Y; Niu, Guoxing X; Zhang, D Yahong H; Che, Renchao C; Tang, Yi; Su, Dangsheng S; Asiri, Abdullah M; Zhao, Dongyuan Y

    2012-01-16

    A series of core-shell-structured composite molecular sieves comprising zeolite single crystals (i.e., ZSM-5) as a core and ordered mesoporous silica as a shell were synthesized by means of a surfactant-directed sol-gel process in basic medium by using cetyltrimethylammonium bromide (CTAB) as a template and tetraethylorthosilicate (TEOS) as silica precursor. Through this coating method, uniform mesoporous silica shells closely grow around the anisotropic zeolite single crystals, the shell thickness of which can easily be tuned in the range of 15-100 nm by changing the ratio of TEOS/zeolite. The obtained composite molecular sieves have compact meso-/micropore junctions that form a hierarchical pore structure from ordered mesopore channels (2.4-3.0 nm in diameter) to zeolite micropores (≈0.51 nm). The short-time kinetic diffusion efficiency of benzene molecules within pristine ZSM-5 (≈7.88×10(-19)  m(2)  s(-1)) is almost retainable after covering with 75 nm-thick mesoporous silica shells (≈7.25×10(-19)  m(2)  s(-1)), which reflects the greatly opened junctions between closely connected mesopores (shell) and micropores (core). The core-shell composite shows greatly enhanced adsorption capacity (≈1.35 mmol  g(-1)) for large molecules such as 1,3,5-triisopropylbenzene relative to that of pristine ZSM-5 (≈0.4 mmol  g(-1)) owing to the mesoporous silica shells. When Al species are introduced during the coating process, the core-shell composite molecular sieves demonstrate a graded acidity distribution from weak acidity of mesopores (predominant Lewis acid sites) to accessible strong acidity of zeolite cores (Lewis and Brønsted acid sites). The probe catalytic cracking reaction of n-dodecane shows the superiority of the unique core-shell structure over pristine ZSM-5. Insight into the core-shell composite structure with hierarchical pore and graded acidity distribution show great potential for petroleum catalytic processes. PMID

  14. Bacterial Community Structure in the Hyperarid Core of the Atacama Desert, Chile▿

    PubMed Central

    Drees, Kevin P.; Neilson, Julia W.; Betancourt, Julio L.; Quade, Jay; Henderson, David A.; Pryor, Barry M.; Maier, Raina M.

    2006-01-01

    Soils from the hyperarid Atacama Desert of northern Chile were sampled along an east-west elevational transect (23.75 to 24.70°S) through the driest sector to compare the relative structure of bacterial communities. Analysis of denaturing gradient gel electrophoresis (DGGE) profiles from each of the samples revealed that microbial communities from the extreme hyperarid core of the desert clustered separately from all of the remaining communities. Bands sequenced from DGGE profiles of two samples taken at a 22-month interval from this core region revealed the presence of similar populations dominated by bacteria from the Gemmatimonadetes and Planctomycetes phyla. PMID:17028238

  15. Structural aspects of antibody-antigen interaction revealed through small random peptide libraries.

    PubMed

    Slootstra, J W; Puijk, W C; Ligtvoet, G J; Langeveld, J P; Meloen, R H

    1996-02-01

    Two small random peptide libraries, one composed of 4550 dodecapeptides and one of 8000 tripeptides, were synthesized in newly developed credit-card format miniPEPSCAN cards (miniPEPSCAN libraries). Each peptide was synthesized in a discrete well (455 peptides/card). The two miniPEPSCAN libraries were screened with three different monoclonal antibodies (Mabs). Two other random peptide libraries, expressed on the wall of bacteria (recombinant libraries) and composed of 10(7) hexa- and octapeptides, were screened with the same three Mabs. The aim of this study was to compare the amino acid sequence of peptides selected from small and large pools of random peptides and, in this way, investigate the potential of small random peptide libraries. The screening of the two miniPEPSCAN libraries resulted in the identification of a surprisingly large number of antibody-binding peptides, while the screening of the large recombinant libraries, using the same Mabs, resulted in the identification of only a small number of peptides. The large number of peptides derived from the small random peptide libraries allowed the determination of consensus sequences. These consensus sequences could be related to small linear and nonlinear parts of the respective epitopes. The small number of peptides derived from the large random peptide libraries could only be related to linear epitopes that were previously mapped using small libraries of overlapping peptides covering the antigenic protein. Thus, with respect to the cost and speed of identifying peptides that resemble linear and nonlinear parts of epitopes, small diversity libraries based on synthetic peptides appear to be superior to large diversity libraries based on expression systems. PMID:9237197

  16. Structure and antigenicity analysis of the IgG gene for Nyctereutes procyonoides

    PubMed Central

    Zhao, Cui; Guo, Shuyuan; Pang, Xiaoru; Song, Daozhen; Fu, Shijun

    2015-01-01

    Objective Nyctereutes procyonoides immunoglobulin G (IgG) gene is partially cloned. Material and methods In order to obtain a certain length (966bp) of Nyctereutes procyonoides immunoglobulin G (IgG), two pairs of primers are designed according to the conserved nucleotide sequence of canine (GenBank:AF354265, AF354265, AF354266, AF354267) and mink (GenBank: L07789). Using Bioinformatics technology and Western-blot to analyze antigenicity of Nyctereutes procyonoides IgG-B gene. Results The homology for nucleotide sequence of IgG between Nyctereutes procyonoides and canine (IgG A, IgG B, IgG C, IgG D), mink, Homo sapiens, Oryctolagus cuniculus, Mus musculus, Anas platyrhynchos and gallus were respectively (88.1%, 93.6%, 85.4%, 87.2%), 83.7%, 74.8%, 71.8%, 69.2%, 51.6%, 48.4%. It can be seen that there was high homology of aminoacid sequence between IgG of Nyctereutes procyonoides and IgG (A, B, C, D) of canine. And the serum antibody of Nyctereutes procyonoides had obviously cross-reaction with HRP conjugated rabbit anti-dog IgG, compared with those of canine, oryctolagus cuniculus, mus musculus, mink, gallus. Conclusions We successfully got Nyctereutes procyonoides immuneglobulin G (IgG) gene (Gen- Bank: KM010191). There is the closest ties of consanguinity of IgG exist between Nyctereutes procyonoides and canine among the mammal through the genetic evolution. The detection and treament of canine distemper can be used on Nyctereutes procyonoides. PMID:26648768

  17. Molecular dynamics study of crater formation by core-shell structured cluster impact

    NASA Astrophysics Data System (ADS)

    Aoki, Takaaki; Seki, Toshio; Matsuo, Jiro

    2012-07-01

    Crater formation processes by the impacts of large clusters with binary atomic species were studied using molecular dynamics (MD) simulations. Argon and xenon atoms are artificially organized in core-shell cluster structures with various component ratios and irradiated on a Si(1 0 0) target surface. When the cluster has Xe1000 core covered with 1000 Ar atoms, and impacts at a total of 20 keV, the core Xe cluster penetrates into the deep area, and a crater with a conical shape is left on the target. On the other hand, in the case of a cluster with the opposite structure, Ar1000 core covered with 1000 Xe atoms, the cluster stops at a shallow area of the target. The incident cluster atoms are mixed and tend to spread in a lateral direction, which results in a square shaped crater with a shallower hole and wider opening. The MD simulations suggest that large cluster impacts cause different irradiation effects by changing the structure, even if the component ratio is the same.

  18. Coercivity enhancement in Ce-Fe-B based magnets by core-shell grain structuring

    NASA Astrophysics Data System (ADS)

    Ito, M.; Yano, M.; Sakuma, N.; Kishimoto, H.; Manabe, A.; Shoji, T.; Kato, A.; Dempsey, N. M.; Givord, D.; Zimanyi, G. T.

    2016-05-01

    Ce-based R2Fe14B (R= rare-earth) nano-structured permanent magnets consisting of (Ce,Nd)2Fe14B core-shell grains separated by a non-magnetic grain boundary phase, in which the relative amount of Nd to Ce is higher in the shell of the magnetic grain than in its core, were fabricated by Nd-Cu infiltration into (Ce,Nd)2Fe14B hot-deformed magnets. The coercivity values of infiltrated core-shell structured magnets are superior to those of as-hot-deformed magnets with the same overall Nd content. This is attributed to the higher value of magnetocrystalline anisotropy of the shell phase in the core-shell structured infiltrated magnets compared to the homogeneous R2Fe14B grains of the as-hot-deformed magnets, and to magnetic isolation of R2Fe14B grains by the infiltrated grain boundary phase. First order reversal curve (FORC) diagrams suggest that the higher anisotropy shell suppresses initial magnetization reversal at the edges and corners of the R2Fe14B grains.

  19. The core structure of Mars as expected to be seen by InSight's VBB seismometer

    NASA Astrophysics Data System (ADS)

    Hempel, Stefanie; Garcia, Raphael; Wieczorek, Mark; Murdoch, Naomi

    2016-04-01

    The question of the Martian core concerns our basic understanding of the planet's thermal evolution, dynamo models for the past and present, the composition of the Martian mantle, especially in regards to its iron content and prevalent phase transitions, which in turn constrain possible regimes of mantle convection. So far the (outer) core radius of Mars is uncertain to about 250 kilometers (Sohl et al., 2005), and evidence neither supports nor falsifies the existence of an inner core (Defraigne et al., 2003). We apply our extensions of the ray tracing toolbox TauP (Crotwell et al., 1999) to compute amplitude loss, ellipticity, crustal and topography corrections in combination with existing models of seismic activity on Mars (Golombek, 1992, Knapmeyer et al., 2006), crustal thickness models (Wieczorek, 2007) and structure models (e.g. Okal and Anderson, 1978, Zharkov and Gudkova, 2000, Rivoldini et al., 2011). In preparation for NASA's discovery mission InSight, we simulate the detected relative travel-time curves at a single seismic station in Elysium Planitia for several models of Martian structure, seismicity, environmental and instrumental noise. We discuss possibilities and difficulties of considering the effects of Martian ellipticity and topography up to degree 8 and 30, respectively. Furthermore, we demonstrate the effect of low velocity layers, as well as the relevance of modeling the effects of ellipticity and crustal thickness during the interpretation of seismic data acquired by InSight's SEIS instrument on Mars, especially concerning seismic phases which provide direct evidence on the core structure of Mars.

  20. Structures of MART-126/27-35Peptide/HLA-A2 Complexes Reveal a Remarkable Disconnect between Antigen Structural Homology and T Cell Recognition

    SciTech Connect

    Borbulevych, Oleg Y; Insaidoo, Francis K; Baxter, Tiffany K; Powell, Jr., Daniel J.; Johnson, Laura A; Restifo, Nicholas P; Baker, Brian M

    2008-09-17

    Small structural changes in peptides presented by major histocompatibility complex (MHC) molecules often result in large changes in immunogenicity, supporting the notion that T cell receptors are exquisitely sensitive to antigen structure. Yet there are striking examples of TCR recognition of structurally dissimilar ligands. The resulting unpredictability of how T cells will respond to different or modified antigens impacts both our understanding of the physical bases for TCR specificity as well as efforts to engineer peptides for immunomodulation. In cancer immunotherapy, epitopes and variants derived from the MART-1/Melan-A protein are widely used as clinical vaccines. Two overlapping epitopes spanning amino acid residues 26 through 35 are of particular interest: numerous clinical studies have been performed using variants of the MART-1 26-35 decamer, although only the 27-35 nonamer has been found on the surface of targeted melanoma cells. Here, we show that the 26-35 and 27-35 peptides adopt strikingly different conformations when bound to HLA-A2. Nevertheless, clonally distinct MART-1{sub 26/27-35}-reactive T cells show broad cross-reactivity towards these ligands. Simultaneously, however, many of the cross-reactive T cells remain unable to recognize anchor-modified variants with very subtle structural differences. These dichotomous observations challenge our thinking about how structural information on unligated peptide/MHC complexes should be best used when addressing questions of TCR specificity. Our findings also indicate that caution is warranted in the design of immunotherapeutics based on the MART-1 26/27-35 epitopes, as neither cross-reactivity nor selectivity is predictable based on the analysis of the structures alone.

  1. Lowering of ground state induced by core-shell structure in strontium titanate

    NASA Astrophysics Data System (ADS)

    Kiat, J. M.; Hehlen, B.; Anoufa, M.; Bogicevic, C.; Curfs, C.; Boyer, B.; Al-Sabbagh, M.; Porcher, F.; Al-Zein, A.

    2016-04-01

    A new ground state of textbook compound strontium titanate (SrTi O3) is obtained by inducing a specific core-shell structure of the particles. Using a combination of high energy synchrotron and neutron diffraction, we demonstrate a lowering of the ferroelastic ground state towards a new antiferrodistortive phase, accompanied with strong shifts of the critical temperature. This new phase is discussed within the Landau theory and compared with the situation in thin films and during pressure experiments. The crucial competition between particle shape anisotropy, surface tension, and shear strain is analyzed. Inducing a specific core-shell structure is therefore an easy way to tailor structural properties and to stabilize new phases that cannot exist in bulk material, just like film deposition on a substrate.

  2. Raman spectroscopic characterization of the core-rim structure in reaction bonded boron carbide ceramics

    SciTech Connect

    Jannotti, Phillip; Subhash, Ghatu; Zheng, James Q.; Halls, Virginia; Karandikar, Prashant G.; Salamone, S.; Aghajanian, Michael K.

    2015-01-26

    Raman spectroscopy was used to characterize the microstructure of reaction bonded boron carbide ceramics. Compositional and structural gradation in the silicon-doped boron carbide phase (rim), which develops around the parent boron carbide region (core) due to the reaction between silicon and boron carbide, was evaluated using changes in Raman peak position and intensity. Peak shifting and intensity variation from the core to the rim region was attributed to changes in the boron carbide crystal structure based on experimental Raman observations and ab initio calculations reported in literature. The results were consistent with compositional analysis determined by energy dispersive spectroscopy. The Raman analysis revealed the substitution of silicon atoms first into the linear 3-atom chain, and then into icosahedral units of the boron carbide structure. Thus, micro-Raman spectroscopy provided a non-destructive means of identifying the preferential positions of Si atoms in the boron carbide lattice.

  3. Raman spectroscopic characterization of the core-rim structure in reaction bonded boron carbide ceramics

    NASA Astrophysics Data System (ADS)

    Jannotti, Phillip; Subhash, Ghatu; Zheng, James Q.; Halls, Virginia; Karandikar, Prashant G.; Salamone, S.; Aghajanian, Michael K.

    2015-01-01

    Raman spectroscopy was used to characterize the microstructure of reaction bonded boron carbide ceramics. Compositional and structural gradation in the silicon-doped boron carbide phase (rim), which develops around the parent boron carbide region (core) due to the reaction between silicon and boron carbide, was evaluated using changes in Raman peak position and intensity. Peak shifting and intensity variation from the core to the rim region was attributed to changes in the boron carbide crystal structure based on experimental Raman observations and ab initio calculations reported in literature. The results were consistent with compositional analysis determined by energy dispersive spectroscopy. The Raman analysis revealed the substitution of silicon atoms first into the linear 3-atom chain, and then into icosahedral units of the boron carbide structure. Thus, micro-Raman spectroscopy provided a non-destructive means of identifying the preferential positions of Si atoms in the boron carbide lattice.

  4. Seismic anisotropy in the Earth's innermost inner core: Testing structural models against mineral physics predictions

    NASA Astrophysics Data System (ADS)

    Romanowicz, Barbara; Cao, Aimin; Godwal, Budhiram; Wenk, Rudy; Ventosa, Sergi; Jeanloz, Raymond

    2016-01-01

    Using an updated data set of ballistic PKIKP travel time data at antipodal distances, we test different models of anisotropy in the Earth's innermost inner core (IMIC) and obtain significantly better fits for a fast axis aligned with Earth's rotation axis, rather than a quasi-equatorial direction, as proposed recently. Reviewing recent results on the single crystal structure and elasticity of iron at core conditions, we find that an hcp structure with the fast c axis parallel to Earth's rotation is more likely but a body-centered cubic structure with the [111] axis aligned in that direction results in very similar predictions for seismic anisotropy. These models are therefore not distinguishable based on current seismological data. In addition, to match the seismological observations, the inferred strength of anisotropy in the IMIC (6-7%) implies almost perfect alignment of iron crystals, an intriguing, albeit unlikely situation, especially in the presence of heterogeneity, which calls for further studies.

  5. Orientation of aromatic residues in amyloid cores: Structural insights into prion fiber diversity

    PubMed Central

    Reymer, Anna; Frederick, Kendra K.; Rocha, Sandra; Beke-Somfai, Tamás; Kitts, Catherine C.; Lindquist, Susan; Nordén, Bengt

    2014-01-01

    Structural conversion of one given protein sequence into different amyloid states, resulting in distinct phenotypes, is one of the most intriguing phenomena of protein biology. Despite great efforts the structural origin of prion diversity remains elusive, mainly because amyloids are insoluble yet noncrystalline and therefore not easily amenable to traditional structural-biology methods. We investigate two different phenotypic prion strains, weak and strong, of yeast translation termination factor Sup35 with respect to angular orientation of tyrosines using polarized light spectroscopy. By applying a combination of alignment methods the degree of fiber orientation can be assessed, which allows a relatively accurate determination of the aromatic ring angles. Surprisingly, the strains show identical average orientations of the tyrosines, which are evenly spread through the amyloid core. Small variations between the two strains are related to the local environment of a fraction of tyrosines outside the core, potentially reflecting differences in fibril packing. PMID:25404291

  6. Manson impact structure, Iowa: First geochemical results for drill core M-1

    NASA Technical Reports Server (NTRS)

    Koeberl, Christian; Anderson, Raymond R.; Hartung, Jack B.; Reimold, Wolf Uwe

    1993-01-01

    The Manson Impact Structure is a large complex impact crater centered ca. S km north of the town of Manson, Iowa. It is the largest intact impact structure recognized in the United States (35 km in diameter). Its Ar-40/Ar-39 age is indistinguishable from that of the Cretaceous-Tertiary (K-T) boundary. The Manson structure may be one element of the events at the K-T boundary. The crater is completely covered by Quaternary glacial sedimentary deposits that are normally underlain by Cretaceous clastic sediments and flat-lying carbonate sediments of Phanerozoic age, as well as Proterozoic red clastic, metamorphic, volcanic, and plutonic rock sequences. The study of a reflection seismic profile, provided by Amoco, was critical in interpreting the structure. In the 35 km diameter zone that marks the extension of the crater the normal rock sequence is disturbed due to the impact, and at the center of the structure granitic basement rocks are present that have been uplifted from about 4 km depth. Our studies consist of detailed petrological and geochemical characterization of all cores, with emphasis on a detailed description of all rock types found in the core samples and their relationship to target rocks. Geochemical data on samples from the Manson M-1 core are presented.

  7. Manson impact structure, Iowa: First geochemical results for drill core M-1

    NASA Astrophysics Data System (ADS)

    Koeberl, Christian; Anderson, Raymond R.; Hartung, Jack B.; Reimold, Wolf Uwe

    1993-03-01

    The Manson Impact Structure is a large complex impact crater centered ca. S km north of the town of Manson, Iowa. It is the largest intact impact structure recognized in the United States (35 km in diameter). Its Ar-40/Ar-39 age is indistinguishable from that of the Cretaceous-Tertiary (K-T) boundary. The Manson structure may be one element of the events at the K-T boundary. The crater is completely covered by Quaternary glacial sedimentary deposits that are normally underlain by Cretaceous clastic sediments and flat-lying carbonate sediments of Phanerozoic age, as well as Proterozoic red clastic, metamorphic, volcanic, and plutonic rock sequences. The study of a reflection seismic profile, provided by Amoco, was critical in interpreting the structure. In the 35 km diameter zone that marks the extension of the crater the normal rock sequence is disturbed due to the impact, and at the center of the structure granitic basement rocks are present that have been uplifted from about 4 km depth. Our studies consist of detailed petrological and geochemical characterization of all cores, with emphasis on a detailed description of all rock types found in the core samples and their relationship to target rocks. Geochemical data on samples from the Manson M-1 core are presented.

  8. UNVEILING THE DETAILED DENSITY AND VELOCITY STRUCTURES OF THE PROTOSTELLAR CORE B335

    SciTech Connect

    Kurono, Yasutaka; Saito, Masao; Kamazaki, Takeshi; Morita, Koh-Ichiro; Kawabe, Ryohei

    2013-03-10

    We present an observational study of the protostellar core B335 harboring a low-mass Class 0 source. The observations of the H{sup 13}CO{sup +}(J = 1-0) line emission were carried out using the Nobeyama 45 m telescope and Nobeyama Millimeter Array. Our combined image of the interferometer and single-dish data depicts detailed structures of the dense envelope within the core. We found that the core has a radial density profile of n(r){proportional_to}r {sup -p} and a reliable difference in the power-law indices between the outer and inner regions of the core: p Almost-Equal-To 2 for r {approx}> 4000 AU and p Almost-Equal-To 1.5 for r {approx}< 4000 AU. The dense core shows a slight overall velocity gradient of {approx}1.0 km s{sup -1} over the scale of 20, 000 AU across the outflow axis. We believe that this velocity gradient represents a solid-body-like rotation of the core. The dense envelope has a quite symmetrical velocity structure with a remarkable line broadening toward the core center, which is especially prominent in the position-velocity diagram across the outflow axis. The model calculations of position-velocity diagrams do a good job of reproducing observational results using the collapse model of an isothermal sphere in which the core has an inner free-fall region and an outer region conserving the conditions at the formation stage of a central stellar object. We derived a central stellar mass of {approx}0.1 M{sub Sun }, and suggest a small inward velocity, v{sub r{>=}r{sub i{sub n{sub f}}}}{approx}0 km s{sup -1} in the outer core at {approx}> 4000 AU. We concluded that our data can be well explained by gravitational collapse with a quasi-static initial condition, such as Shu's model, or by the isothermal collapse of a marginally critical Bonnor-Ebert sphere.

  9. Transforming powder mechanical properties by core/shell structure: compressible sand.

    PubMed

    Shi, Limin; Sun, Changquan Calvin

    2010-11-01

    Some active pharmaceutical ingredients possess poor mechanical properties and are not suitable for tableting. Using fine sand (silicon dioxide), we show that a core/shell structure, where a core particle (sand) is coated with a thin layer of polyvinylpyrrolidone (PVP), can profoundly improve powder compaction properties. Sand coated with 5% PVP could be compressed into intact tablets. Under a given compaction pressure, tablet tensile strength increases dramatically with the amount of coating. This is in sharp contrast to poor compaction properties of physical mixtures, where intact tablets cannot be made when PVP content is 20% or less. The profoundly improved tabletability of core/shell particles is attributed to the formation of a continuous three-dimensional bonding network in the tablet. PMID:20845444

  10. Upper-ocean velocity structure of Gulf Stream warm-core ring 82B

    NASA Technical Reports Server (NTRS)

    Joyce, T. M.; Kennelly, M. A.

    1985-01-01

    Acoustic-Doppler current profiling of warm-core ring (WCR) 82B revealed changes in the velocity structure over much of the ring's 7-month lifespan. As ring diameter decreased, peak speeds in the high-velocity region decreased from 0.8 m/s in April 1982 to 0.5 m/s in August 1982. Azimuthally averaged velocities revealed the core of WCR 82B to be in near solid-body rotation, with little measurable horizontal divergence at 100 m. In addition, potential vorticity was conserved in the ring core despite interactions with the Gulf Stream and large changes in ring size. Deviations from symmetry in WCR 82B were caused by superposition with the shelf-slope front, small cyclonic eddies, and upper-layer mean flow.

  11. Structural Analysis of the Synthetic Duffy Binding Protein (DBP) Antigen DEKnull Relevant for Plasmodium vivax Malaria Vaccine Design

    PubMed Central

    Chen, Edwin; Salinas, Nichole D.; Ntumngia, Francis B.; Adams, John H.; Tolia, Niraj H.

    2015-01-01

    The Plasmodium vivax vaccine candidate Duffy Binding Protein (DBP) is a protein necessary for P. vivax invasion of reticulocytes. The polymorphic nature of DBP induces strain-specific immune responses that pose unique challenges for vaccine development. DEKnull is a synthetic DBP based antigen that has been engineered through mutation to enhance induction of blocking inhibitory antibodies. We determined the x-ray crystal structure of DEKnull to identify if any conformational changes had occurred upon mutation. Computational and experimental analyses assessed immunogenicity differences between DBP and DEKnull epitopes. Functional binding assays with monoclonal antibodies were used to interrogate the available epitopes in DEKnull. We demonstrate that DEKnull is structurally similar to the parental Sal1 DBP. The DEKnull mutations do not cause peptide backbone shifts within the polymorphic loop, or at either the DBP dimerization interface or DARC receptor binding pockets, two important structurally conserved protective epitope motifs. All B-cell epitopes, except for the mutated DEK motif, are conserved between DEKnull and DBP. The DEKnull protein retains binding to conformationally dependent inhibitory antibodies. DEKnull is an iterative improvement of DBP as a vaccine candidate. DEKnull has reduced immunogenicity to polymorphic regions responsible for strain-specific immunity while retaining conserved protein folds necessary for induction of strain-transcending blocking inhibitory antibodies. PMID:25793371

  12. Structural characterization of the N-glycans of a recombinant hepatitis B surface antigen derived from yeast

    SciTech Connect

    Ip, C.C.Y.; Miller, W.J.; Kubek, D.J. ); Strang, A.M.; van Halbeek, H. ); Piesecki, S.J.; Alhadeff, J.A. )

    1992-01-14

    The N-glycans of purified recombinant middle surface protein (preS2+S) from hepatitis B virus, a candidate vaccine antigen expressed in a mnn9 mutant strain of Saccharomyces cerevisiae, have been characterized structurally. The glycans were released by N-glycanase treatment, isolated by size-exclusion chromatography on Sephadex G-50 and Bio-Gel P-4 columns, and analyzed by 500-MHz {sup 1}H NMR spectroscopy and fast atom bombardment mass spectrometry. The mixture of oligosaccharides was fractionated by HPLC, the major subfractions were isolated, and their carbohydrate compositions were determined by high-pH anion-exchange chromatography with pulsed amperometric detection. The combined results suggest that high-mannose oligosaccharides account for all the N-glycans released from preS2+S: structures include Man{sub 7}GlcNAc{sub 2}, Man{sub 8}GlcNAc{sub 2} isomers in the ratios of 3:6:1. Approximately 80% of the oligosaccharides contain the C2, C6-branched trimannosyl structural element typical of yeast high-mannose oligosaccharides but not usually found in high-mannose oligosaccharides in animal glycoproteins.

  13. THE DEPENDENCE OF PRESTELLAR CORE MASS DISTRIBUTIONS ON THE STRUCTURE OF THE PARENTAL CLOUD

    SciTech Connect

    Parravano, Antonio; Sanchez, Nestor; Alfaro, Emilio J.

    2012-08-01

    The mass distribution of prestellar cores is obtained for clouds with arbitrary internal mass distributions using a selection criterion based on the thermal and turbulent Jeans mass and applied hierarchically from small to large scales. We have checked this methodology by comparing our results for a log-normal density probability distribution function with the theoretical core mass function (CMF) derived by Hennebelle and Chabrier, namely a power law at large scales and a log-normal cutoff at low scales, but our method can be applied to any mass distributions representing a star-forming cloud. This methodology enables us to connect the parental cloud structure with the mass distribution of the cores and their spatial distribution, providing an efficient tool for investigating the physical properties of the molecular clouds that give rise to the prestellar core distributions observed. Simulated fractional Brownian motion (fBm) clouds with the Hurst exponent close to the value H = 1/3 give the best agreement with the theoretical CMF derived by Hennebelle and Chabrier and Chabrier's system initial mass function. Likewise, the spatial distribution of the cores derived from our methodology shows a surface density of companions compatible with those observed in Trapezium and Ophiucus star-forming regions. This method also allows us to analyze the properties of the mass distribution of cores for different realizations. We found that the variations in the number of cores formed in different realizations of fBm clouds (with the same Hurst exponent) are much larger than the expected root N statistical fluctuations, increasing with H.

  14. Switching of the core structures of glycosphingolipids from globo- and lacto- to ganglio-series upon human embryonic stem cell differentiation

    PubMed Central

    Liang, Yuh-Jin; Kuo, Huan-Hsien; Chen, Yen-Ying; Yang, Bei-Chia; Cheng, Yuan-Yuan; Yu, Alice L.; Khoo, Kay-Hooi; Yu, John

    2010-01-01

    A systematic survey of expression profiles of glycosphingolipids (GSLs) in two hESC lines and their differentiated embryoid body (EB) outgrowth with three germ layers was carried out using immunofluorescence, flow cytometry, and MALDI-MS and MS/MS analyses. In addition to the well-known hESC-specific markers stage-specific embryonic antigen 3 (SSEA-3) and SSEA-4, we identified several globosides and lacto-series GSLs, previously unrevealed in hESCs, including Gb4Cer, Lc4Cer, fucosyl Lc4Cer, Globo H, and disialyl Gb5Cer. During hESC differentiation into EBs, MS analysis revealed a clear-cut switch in the core structures of GSLs from globo- and lacto- to ganglio-series, which was not as evident by immunostaining with antibodies against SSEA-3 and SSEA-4, owing to their cross-reactivities with various glycosphingolipids. Such a switch was attributable to altered expression of key glycosyltransferases (GTs) in the biosynthetic pathways by the up-regulation of ganglio-series–related GTs with simultaneous down-regulation of globo- and lacto-series–related GTs. Thus, these results provide insights into the unique stage-specific transition and mechanism for alterations of GSL core structures during hESC differentiation. In addition, unique glycan structures uncovered by MS analyses may serve as surface markers for further delineation of hESCs and help identify of their functional roles not only in hESCs but also in cancers. PMID:21149694

  15. Antigenic and 3D structural characterization of soluble X4 and hybrid X4-R5 HIV-1 Env trimers

    PubMed Central

    2014-01-01

    Background HIV-1 is decorated with trimeric glycoprotein spikes that enable infection by engaging CD4 and a chemokine coreceptor, either CCR5 or CXCR4. The variable loop 3 (V3) of the HIV-1 envelope protein (Env) is the main determinant for coreceptor usage. The predominant CCR5 using (R5) HIV-1 Env has been intensively studied in function and structure, whereas the trimeric architecture of the less frequent, but more cytopathic CXCR4 using (X4) HIV-1 Env is largely unknown, as are the consequences of sequence changes in and near V3 on antigenicity and trimeric Env structure. Results Soluble trimeric gp140 Env constructs were used as immunogenic mimics of the native spikes to analyze their antigenic properties in the context of their overall 3D structure. We generated soluble, uncleaved, gp140 trimers from a prototypic T-cell line-adapted (TCLA) X4 HIV-1 strain (NL4-3) and a hybrid (NL4-3/ADA), in which the V3 spanning region was substituted with that from the primary R5 isolate ADA. Compared to an ADA (R5) gp140, the NL4-3 (X4) construct revealed an overall higher antibody accessibility, which was most pronounced for the CD4 binding site (CD4bs), but also observed for mAbs against CD4 induced (CD4i) epitopes and gp41 mAbs. V3 mAbs showed significant binding differences to the three constructs, which were refined by SPR analysis. Of interest, the NL4-3/ADA construct with the hybrid NL4-3/ADA CD4bs showed impaired CD4 and CD4bs mAb reactivity despite the presence of the essential elements of the CD4bs epitope. We obtained 3D reconstructions of the NL4-3 and the NL4-3/ADA gp140 trimers via electron microscopy and single particle analysis, which indicates that both constructs inherit a propeller-like architecture. The first 3D reconstruction of an Env construct from an X4 TCLA HIV-1 strain reveals an open conformation, in contrast to recently published more closed structures from R5 Env. Exchanging the X4 V3 spanning region for that of R5 ADA did not alter the open

  16. Crystal Structure of TDP-Fucosamine Acetyl Transferase (WECD) from Escherichia Coli, an Enzyme Required for Enterobacterial Common Antigen Synthesis

    SciTech Connect

    Hung,M.; Rangarajan, E.; Munger, C.; Nadeau, G.; Sulea, T.; Matte, A.

    2006-01-01

    Enterobacterial common antigen (ECA) is a polysaccharide found on the outer membrane of virtually all gram-negative enteric bacteria and consists of three sugars, N-acetyl-D-glucosamine, N-acetyl-D-mannosaminuronic acid, and 4-acetamido-4,6-dideoxy-D-galactose, organized into trisaccharide repeating units having the sequence {yields}(3)-{alpha}-D-Fuc4NAc-(1{yields}4)-{beta}-D-ManNAcA-(1{yields}4)-{alpha}-D-GlcNAc-(1{yields}). While the precise function of ECA is unknown, it has been linked to the resistance of Shiga-toxin-producing Escherichia coli (STEC) O157:H7 to organic acids and the resistance of Salmonella enterica to bile salts. The final step in the synthesis of 4-acetamido-4,6-dideoxy-D-galactose, the acetyl-coenzyme A (CoA)-dependent acetylation of the 4-amino group, is carried out by TDP-fucosamine acetyltransferase (WecD). We have determined the crystal structure of WecD in apo form at a 1.95-Angstroms resolution and bound to acetyl-CoA at a 1.66-Angstroms resolution. WecD is a dimeric enzyme, with each monomer adopting the GNAT N-acetyltransferase fold, common to a number of enzymes involved in acetylation of histones, aminoglycoside antibiotics, serotonin, and sugars. The crystal structure of WecD, however, represents the first structure of a GNAT family member that acts on nucleotide sugars. Based on this cocrystal structure, we have used flexible docking to generate a WecD-bound model of the acetyl-CoA-TDP-fucosamine tetrahedral intermediate, representing the structure during acetyl transfer. Our structural data show that WecD does not possess a residue that directly functions as a catalytic base, although Tyr208 is well positioned to function as a general acid by protonating the thiolate anion of coenzyme A.

  17. Structures and contribution to the antigenicity of oligosaccharides of Japanese cedar (Cryptomeria japonica) pollen allergen Cry j I: relationship between the structures and antigenic epitopes of plant N-linked complex-type glycans.

    PubMed

    Ogawa, H; Hijikata, A; Amano, M; Kojima, K; Fukushima, H; Ishizuka, I; Kurihara, Y; Matsumoto, I

    1996-08-01

    The oligosaccharide structures of Cry j I, a major allergenic glycoprotein of Cryptomeria japonica (Japanese cedar, sugi), were analysed by 400 MHz 1H-NMR and two-dimensional sugar mapping analyses. The four major fractions comprised a series of biantennary complex type N-linked oligosaccharides that share a fucose/xylose-containing core and glucosamine branches including a novel structure with a nongalactosylated fucosylglucosamine branch. Rabbit polyclonal anti-Cry j I IgG antibodies cross-reacted with three different plant glycoproteins having the same or shorter N-linked oligosaccharides as Cry j I. ELISA and ELISA inhibition studies with intact glycoproteins, glycopeptides and peptides indicated that both anti-Cry j I IgGs and anti-Sophora japonica bark lectin II (B-SJA-II) IgGs included oligosaccharide-specific antibodies with different specificities, and that the epitopic structures against anti-Cry j I IgGs include a branch containing alpha 1-6 linked fucose and a core containing fucose/xylose, while those against anti-B-SJA-II IgGs include nonreducing terminal mannose residues. The cross-reactivities of human allergic sera to miraculin and Clerodendron Trichotomum lectin (CTA) were low, and inhibition studies suggested that the oligosaccharides on Cry j I contribute little or only conformationally to the reactivity of specific IgE antibodies. PMID:8872112

  18. Structural requirements for assembly and homotypic interactions of the hepatitis C virus core protein.

    PubMed

    Kim, Meehyein; Ha, Youngju; Park, Hae-Joon

    2006-12-01

    The hepatitis C virus (HCV) core protein is involved in the assembly of nucleocapsid particles, as well as regulation of cellular and viral gene expression. To investigate the biological properties of the viral core protein and viral RNA assembly, two recombinant core proteins, the mature core protein (named C179) and a C-terminal truncated protein (named C124), were expressed and purified. To confirm their ability to generate viral particles, the production of nucleocapsid-like particles was monitored using transmission electron microscopy (EM). The EM analysis revealed that exposure of these proteins to the 5' untranslated region (5' UTR) of the viral RNA resulted in generation of spherical particles of 30-140nm in diameter. Interestingly, a cross-linking analysis revealed that C124 required an RNA component for homotypic interactions. In contrast, C179 successfully assembled in the absence of nucleic acids. Additionally, RNA-mediated conversion of the C124 structure into a more stable state was maintained even after RNase treatment. Therefore, our results indicate that the basic N-terminal domain of the viral core protein utilizes RNA components to induce conformational changes or efficient homotypic interactions, while the C-terminal domain may contain key peptide sequences for initiating spontaneous multimerization at the early stages of viral assembly. PMID:16949699

  19. Stability of the inner structure constituting a 'kernel' in ribosomal cores probed by dielectric spectroscopy

    NASA Astrophysics Data System (ADS)

    Blasi, M.; Bonincontro, A.; Calandrini, V.; Onori, G.; Risuleo, G.

    2001-05-01

    In this communication we present an investigation on ribosomal cores, i.e. ribosomes deprived of a select group of ribosomal proteins by LiCl treatment. This study was conducted by dielectric spectroscopy technique. The aim was to elucidate the role of ribosomal proteins in the stabilization of a very stable structural nucleus previously observed within the ribosome. The results show that this structure withstands relatively high concentrations of LiCl and is demolished within a limited range of salt concentration. The data discussed here corroborate the idea that this structure constitutes the ribosomal kernel.

  20. Structural Analysis of a Highly Glycosylated and Unliganded gp120-Based Antigen Using Mass Spectrometry

    SciTech Connect

    L Wang; Y Qin; S Ilchenko; J Bohon; W Shi; M Cho; K Takamoto; M Chance

    2011-12-31

    Structural characterization of the HIV-1 envelope protein gp120 is very important for providing an understanding of the protein's immunogenicity and its binding to cell receptors. So far, the crystallographic structure of gp120 with an intact V3 loop (in the absence of a CD4 coreceptor or antibody) has not been determined. The third variable region (V3) of the gp120 is immunodominant and contains glycosylation signatures that are essential for coreceptor binding and entry of the virus into T-cells. In this study, we characterized the structure of the outer domain of gp120 with an intact V3 loop (gp120-OD8) purified from Drosophila S2 cells utilizing mass spectrometry-based approaches. We mapped the glycosylation sites and calculated the glycosylation occupancy of gp120-OD8; 11 sites from 15 glycosylation motifs were determined as having high-mannose or hybrid glycosylation structures. The specific glycan moieties of nine glycosylation sites from eight unique glycopeptides were determined by a combination of ECD and CID MS approaches. Hydroxyl radical-mediated protein footprinting coupled with mass spectrometry analysis was employed to provide detailed information about protein structure of gp120-OD8 by directly identifying accessible and hydroxyl radical-reactive side chain residues. Comparison of gp120-OD8 experimental footprinting data with a homology model derived from the ligated CD4-gp120-OD8 crystal structure revealed a flexible V3 loop structure in which the V3 tip may provide contacts with the rest of the protein while residues in the V3 base remain solvent accessible. In addition, the data illustrate interactions between specific sugar moieties and amino acid side chains potentially important to the gp120-OD8 structure.

  1. Importin β Can Bind Hepatitis B Virus Core Protein and Empty Core-Like Particles and Induce Structural Changes.

    PubMed

    Chen, Chao; Wang, Joseph Che-Yen; Pierson, Elizabeth E; Keifer, David Z; Delaleau, Mildred; Gallucci, Lara; Cazenave, Christian; Kann, Michael; Jarrold, Martin F; Zlotnick, Adam

    2016-08-01

    Hepatitis B virus (HBV) capsids are found in many forms: immature single-stranded RNA-filled cores, single-stranded DNA-filled replication intermediates, mature cores with relaxed circular double-stranded DNA, and empty capsids. A capsid, the protein shell of the core, is a complex of 240 copies of core protein. Mature cores are transported to the nucleus by a complex that includes both importin α and importin β (Impα and Impβ), which bind to the core protein's C-terminal domains (CTDs). Here we have investigated the interactions of HBV core protein with importins in vitro. Strikingly, empty capsids and free core protein can bind Impβ without Impα. Cryo-EM image reconstructions show that the CTDs, which are located inside the capsid, can extrude through the capsid to be bound by Impβ. Impβ density localized on the capsid exterior near the quasi-sixfold vertices, suggested a maximum of 30 Impβ per capsid. However, examination of complexes using single molecule charge-detection mass spectrometry indicate that some complexes include over 90 Impβ molecules. Cryo-EM of capsids incubated with excess Impβ shows a population of damaged particles and a population of "dark" particles with internal density, suggesting that Impβ is effectively swallowed by the capsids, which implies that the capsids transiently open and close and can be destabilized by Impβ. Though the in vitro complexes with great excess of Impβ are not biological, these results have implications for trafficking of empty capsids and free core protein; activities that affect the basis of chronic HBV infection. PMID:27518410

  2. Importin β Can Bind Hepatitis B Virus Core Protein and Empty Core-Like Particles and Induce Structural Changes

    PubMed Central

    Pierson, Elizabeth E.; Keifer, David Z.; Delaleau, Mildred; Gallucci, Lara; Cazenave, Christian; Kann, Michael; Jarrold, Martin F.; Zlotnick, Adam

    2016-01-01

    Hepatitis B virus (HBV) capsids are found in many forms: immature single-stranded RNA-filled cores, single-stranded DNA-filled replication intermediates, mature cores with relaxed circular double-stranded DNA, and empty capsids. A capsid, the protein shell of the core, is a complex of 240 copies of core protein. Mature cores are transported to the nucleus by a complex that includes both importin α and importin β (Impα and Impβ), which bind to the core protein’s C-terminal domains (CTDs). Here we have investigated the interactions of HBV core protein with importins in vitro. Strikingly, empty capsids and free core protein can bind Impβ without Impα. Cryo-EM image reconstructions show that the CTDs, which are located inside the capsid, can extrude through the capsid to be bound by Impβ. Impβ density localized on the capsid exterior near the quasi-sixfold vertices, suggested a maximum of 30 Impβ per capsid. However, examination of complexes using single molecule charge-detection mass spectrometry indicate that some complexes include over 90 Impβ molecules. Cryo-EM of capsids incubated with excess Impβ shows a population of damaged particles and a population of “dark” particles with internal density, suggesting that Impβ is effectively swallowed by the capsids, which implies that the capsids transiently open and close and can be destabilized by Impβ. Though the in vitro complexes with great excess of Impβ are not biological, these results have implications for trafficking of empty capsids and free core protein; activities that affect the basis of chronic HBV infection. PMID:27518410

  3. A facile route to synthesize core/shell structured carbon/magnetic nanoparticles hybrid and their magnetic properties

    SciTech Connect

    Qi, Xiaosi; Xu, Jianle; Zhong, Wei; Du, Youwei

    2015-07-15

    Graphical abstract: Controllable synthesis of core/shell structured carbon/magnetic nanoparticles hybrid and their tunable magnetic properties. - Highlights: • The paper reports a simple route for core/shell structured carbon/magnetic nanoparticles hybrid. • By controlling the temperature, Fe{sub 3}O{sub 4}@CNCs, Fe@HCNTs and Fe@LCNTs were produced selectively. • The magnetic properties of the obtained core/shell structured hybrid could be tuned effectively. - Abstract: By controlling the pyrolysis temperature, core/shell structured Fe{sub 3}O{sub 4}/carbon nanocages, Fe/helical carbon nanotubes and Fe/low helicity of carbon nanotubes could be synthesized selectively over Fe{sub 2}O{sub 3} nanotubes generated by a hydrothermal method. The transmission electron microscopic and scanning electron microscopic investigations revealed that the efficiency of generating core/shell structured hybrid was high, exceeding 90%. Because of the magnetic nanoparticles tightly wrapped in graphitic layers, the obtained core/shell structured hybrids showed high stability and good magnetic properties. And the magnetic properties of the obtained core/shell structured hybrid could be tuned by the decomposition temperature and time. Therefore, a simple, inexpensive and environment-benign route was proposed to produce magnetism-tunable core/shell structured hybrid in large quantities.

  4. Core level shifts in Cu-Pd alloys as a function of bulk composition and structure

    NASA Astrophysics Data System (ADS)

    Boes, Jacob R.; Kondratyuk, Peter; Yin, Chunrong; Miller, James B.; Gellman, Andrew J.; Kitchin, John R.

    2015-10-01

    CuPd alloys are important materials in hydrogen purification, where they are used as dense Pd-based separation membranes. Cu is added to impart sulfur tolerance and improved mechanical properties. At intermediate compositions and T < 873 K, a BCC alloy (B2) phase occurs, which has superior separation characteristics to those of the FCC phases that form at high Cu and high Pd compositions. Identifying the composition and temperature window where the B2 phase forms is a critical need to enable the design of improved alloys. A composition spread alloy film of Cu and Pd was synthesized. The film was characterized by electron back scatter diffraction and X-ray photoelectron spectroscopy, providing the core level shifts as a function of bulk composition and bulk structure. An anomalous deviation in the Cu core level shift was observed in the composition range 0.33 < xPd < 0.55 over which the B2 phase occurs. Density functional theory calculations were used to simulate core level shifts in the FCC and B2 alloy structures. They suggest that the anomalous deviation in core level shift is due to formation of the ordered B2 phase in this composition range.

  5. Shape-variable sandwich structure with SMA honeycomb core and CFRP skins

    NASA Astrophysics Data System (ADS)

    Okabe, Yoji; Sugiyama, Hiroshi

    2009-03-01

    The authors proposed a sandwich structure that consists of a shape memory alloy (SMA) honeycomb core and carbon fiber reinforced plastic (CFRP) skins as a lightweight geometric-variable structure. This method has the better ability to bend skins with high in-plane stiffness, because the SMA honeycomb core generates a recovery-shear-force and applies the force uniformly to the skins. Hence, although this sandwich beam is really lightweight and has a moderate specific bending stiffness, the beam can be bent by raising the temperature. The honeycomb core was made of thin Ti-Ni SMA foils, and skins were thin unidirectional CFRP laminates. Pre-shear-strain was applied to the SMA honeycomb core, and the both ends of the two skins were fixed. When the beam was heated, it was bent upward taking the form of a sigmoid curve. Furthermore, it was verified that the beam was able to generate the sufficient actuation force. Then, when the specimen was cooled down to the room temperature, the specimen returned to the straight beam again. Hence the twoway actuation is possible by heating and cooling. Also the mechanism of this bending deformation could be clarified by a numerical simulation using the finite element method.

  6. Comparative structural and chemical studies of ferritin cores with gradual removal of their iron contents.

    PubMed

    Gálvez, Natividad; Fernández, Belén; Sánchez, Purificación; Cuesta, Rafael; Ceolín, Marcelo; Clemente-León, Miguel; Trasobares, Susana; López-Haro, Miguel; Calvino, Jose J; Stéphan, Odile; Domínguez-Vera, José M

    2008-06-25

    Transmission Electron Microscopy (TEM), X-ray Absorption Near Edge Spectroscopy (XANES), Electron Energy-Loss Spectroscopy (EELS), Small-Angle X-ray Scattering (SAXS), and SQUID magnetic studies were performed in a batch of horse spleen ferritins from which iron had been gradually removed, yielding samples containing 2200, 1200, 500, and 200 iron atoms. Taken together, findings obtained demonstrate that the ferritin iron core consists of a polyphasic structure (ferrihydrite, magnetite, hematite) and that the proportion of phases is modified by iron removal. Thus, the relative amount of magnetite in ferritin containing 2200 to 200 iron atoms rose steadily from approximately 20% to approximately 70% whereas the percentage of ferrihydrite fell from approximately 60% to approximately 20%. These results indicate a ferrihydrite-magnetite core-shell structure. It was also found that the magnetite in the ferritin iron core is not a source of free toxic ferrous iron, as previously believed. Therefore, the presence of magnetite in the ferritin cores of patients with Alzheimer's disease is not a cause of their increased brain iron(II) concentration. PMID:18507465

  7. Controllable synthesis of a novel hedgehog-like core/shell structure

    NASA Astrophysics Data System (ADS)

    Wang, Shumin; Tian, Hongwei; Pei, Yanhui; Meng, Qingnan; Chen, Jianli; Wang, Huan; Zeng, Yi; Zheng, Weitao; Liu, Yichun

    2012-02-01

    A novel hedgehog-like core/shell structure, consisting of a high density of vertically aligned graphene sheets and a thin graphene shell/a copper core (VGs-GS/CC), has been synthesized via a simple one-step synthesis route using radio-frequency plasma-enhanced chemical vapor deposition (RF-PECVD). Scanning and transmission electron microscopy investigations show that the morphology of this core/shell material could be controlled by deposition time. For a short deposition time, only multilayer graphene shell tightly surrounds the copper particle, while as the deposition time is relative long, graphene sheets extend from the surface of GS/CC. The GS can protect CC particles from oxidation. The growth mechanism for the obtained GS/CC and VGs-GS/CC has been revealed. Compared to VGs, VGs-GS/CC material exhibits a better electron field emission property. This investigation opens a possibility for designing a core/shell structure of different carbon-metal hybrid materials for a wide variety of practical applications.

  8. The structural elucidation of the Salmonella enterica subsp. enterica, reveals that it contains both O-factors 4 and 5 on the LPS antigen.

    PubMed

    De Castro, Cristina; Lanzetta, Rosa; Leone, Serena; Parrilli, Michelangelo; Molinaro, Antonio

    2013-04-01

    Spectroscopic investigation of the O-antigen from Salmonella enterica subsp. enterica revealed fine details on the acetylation pattern, the biological repeating unit and the polymerization degree. Acetylation at O-2 of the abequose residue, defined both O-factors 4 and 5 in the O-antigen chain of the lipopolysaccharide. NMR observation of the terminal non-reducing end of the polymer confirmed previous data regarding the biological repeating unit and showed an average polymerization degree of 5. The information about these structural elements might contribute to the understanding of key features of the biology of this pathogen, as phase variation and/or adaptation to the external environment. PMID:23419941

  9. Efficient Design and Analysis of Lightweight Reinforced Core Sandwich and PRSEUS Structures

    NASA Technical Reports Server (NTRS)

    Bednarcyk, Brett A.; Yarrington, Phillip W.; Lucking, Ryan C.; Collier, Craig S.; Ainsworth, James J.; Toubia, Elias A.

    2012-01-01

    Design, analysis, and sizing methods for two novel structural panel concepts have been developed and incorporated into the HyperSizer Structural Sizing Software. Reinforced Core Sandwich (RCS) panels consist of a foam core with reinforcing composite webs connecting composite facesheets. Boeing s Pultruded Rod Stitched Efficient Unitized Structure (PRSEUS) panels use a pultruded unidirectional composite rod to provide axial stiffness along with integrated transverse frames and stitching. Both of these structural concepts are ovencured and have shown great promise applications in lightweight structures, but have suffered from the lack of efficient sizing capabilities similar to those that exist for honeycomb sandwich, foam sandwich, hat stiffened, and other, more traditional concepts. Now, with accurate design methods for RCS and PRSEUS panels available in HyperSizer, these concepts can be traded and used in designs as is done with the more traditional structural concepts. The methods developed to enable sizing of RCS and PRSEUS are outlined, as are results showing the validity and utility of the methods. Applications include several large NASA heavy lift launch vehicle structures.

  10. Structural Performance of a Compressively Loaded Foam-Core Hat-Stiffened Textile Composite Panel

    NASA Technical Reports Server (NTRS)

    Ambur, Damodar R.; Dexter, Benson H.

    1996-01-01

    A structurally efficient hat-stiffened panel concept that utilizes a structural foam as a stiffener core material has been designed and developed for aircraft primary structural applications. This stiffener concept is fabricated from textile composite material forms with a resin transfer molding process. This foam-filled hat-stiffener concept is structurally more efficient than most other prismatically stiffened panel configurations in a load range that is typical for both fuselage and wing structures. The panel design is based on woven/stitched and braided graphite-fiber textile preforms, an epoxy resin system, and Rohacell foam core. The structural response of this panel design was evaluated for its buckling and postbuckling behavior with and without low-speed impact damage. The results from single-stiffener and multi-stiffener specimen tests suggest that this structural concept responds to loading as anticipated and has excellent damage tolerance characteristics compared to a similar panel design made from preimpregnated graphite-epoxy tape material.

  11. [Surface structure of the macrophages and lymphocytes in their interaction under conditions of antigenic stimulation observed with the scanning electron microscope].

    PubMed

    Favorskaia, Iu N; Krymskiĭ, L D; Nestaĭko, G V

    1975-01-01

    The surface structure of macrophages, lymphocytes of peritoneal exudate and lymphocytes from the lymphatic node of intact, stimulated with meat-pentone broth and induced with antigen mice was studied using raster electron microscopy. Lymphocytes outwardly did not differ from each other irrespective the source of their origin. Macrophages obtained from the peritoneal cavity of the stimulated mice morphologically differed from those isolated from intact mice. Antigenic stimulation of macrophages made it possible to investigate the dynamics of absorption and digestion of sheep corpuscles, as well as the morphology of this process. It was established that in combined cultivation of macrophages and lymphocytes under conditions of antigenic stimulation the number of contacts between lymphocytes and between lymphocytes and macrophages considerably increased. The cytoplasmic ponticulus connecting cells was formed mostly at the expense of a single finger-shaped growth of the lymphocyte membrane. PMID:1167113

  12. Valency and density matter: Deciphering impacts of immunogen structures on immune responses against a tumor associated carbohydrate antigen using synthetic glycopolymers.

    PubMed

    Qin, Qian; Yin, Zhaojun; Wu, Xuanjun; Haas, Karen M; Huang, Xuefei

    2016-09-01

    For successful carbohydrate based anti-cancer vaccines, it is critical that B cells are activated to secret antibodies targeting the tumor associated carbohydrate antigens (TACAs). Despite the availability of many TACA based constructs, systematic understanding of the effects of structural features on anti-glycan antibody responses is lacking. In this study, a series of defined synthetic glyco-polymers bearing a representative TACA, i.e., the Thomsen-nouveau (Tn) antigen, have been prepared to probe the induction of early B cell activation and antibody production via a T cell independent mechanism. Valency and density of the antigen in the polymers turned out to be critical. An average of greater than 6 Tn per chain was needed to induce antibody production. Glycopolymers with 40 antigens per chain and backbone molecular weight of 450 kDa gave the strongest stimulation to B cells in vitro, which correlated well with its in vivo activity. Deviations from the desired valency and density led to decreased antibody production or even antigen specific B cell non-responsiveness. These findings provide important insights on how to modulate anti-TACA immune responses facilitating the development of TACA based anti-cancer vaccines using glycopolymers. PMID:27294537

  13. Antibodies recognizing a variety of different structural motifs on meningococcal Lip antigen fail to demonstrate bactericidal activity.

    PubMed

    Tinsley, C R; Virji, M; Heckels, J E

    1992-11-01

    The neisserial Lip antigen is a conserved antigen associated with the pathogenic Neisseria species, and is composed of multiple repeats of a consensus pentapeptide. A series of monoclonal antibodies reacting with meningococcal Lip antigen were subjected to epitope mapping, using solid-phase synthetic peptides based on the consensus repeat sequence. The antibodies were found to recognize different continuous epitopes based on the consensus sequence. One monoclonal antibody was utilized in affinity chromatography to obtain purified Lip antigen and the antigen was used for immunization of mice. The resulting antisera did not recognize Lip antigen on Western blots but reacted specifically with Lip antigen in immune precipitation experiments, indicating that the predominant polyclonal immune response was directed against conformational epitopes. Despite the diversity of both continuous and conformational epitopes recognized by the antibodies produced, none of the antibodies demonstrated the ability to promote complement-mediated bactericidal activity. Thus despite its initial apparent promise as a potential vaccine candidate the case for the inclusion of Lip antigen in vaccine formulation cannot be supported at present. PMID:1282535

  14. Hypervelocity Impact Performance of Open Cell Foam Core Sandwich Panel Structures

    NASA Technical Reports Server (NTRS)

    Ryan, Shannon; Christiansen, Eric; Lear, Dana

    2009-01-01

    Metallic foams are a relatively new class of materials with low density and novel physical, mechanical, thermal, electrical and acoustic properties. Although incompletely characterized, they offer comparable mechanical performance to traditional spacecraft structural materials (i.e. honeycomb sandwich panels) without detrimental through-thickness channeling cells. There are two competing types of metallic foams: open cell and closed cell. Open cell foams are considered the more promising technology due to their lower weight and higher degree of homogeneity. Leading micrometeoroid and orbital debris shields (MMOD) incorporate thin plates separated by a void space (i.e. Whipple shield). Inclusion of intermediate fabric layers, or multiple bumper plates have led to significant performance enhancements, yet these shields require additional non-ballistic mass for installation (fasteners, supports, etc.) that can consume up to 35% of the total shield weight [1]. Structural panels, such as open cell foam core sandwich panels, that are also capable of providing sufficient MMOD protection, represent a significant potential for increased efficiency in hypervelocity impact shielding from a systems perspective through a reduction in required non-ballistic mass. In this paper, the results of an extensive impact test program on aluminum foam core sandwich panels are reported. The effect of pore density, and core thickness on shielding performance have been evaluated over impact velocities ranging from 2.2 - 9.3 km/s at various angles. A number of additional tests on alternate sandwich panel configurations of comparable-weight have also been performed, including aluminum honeycomb sandwich panels (see Figure 1), Nomex honeycomb core sandwich panels, and 3D aluminum honeycomb sandwich panels. A total of 70 hypervelocity impact tests are reported, from which an empirical ballistic limit equation (BLE) has been derived. The BLE is in the standard form suitable for implementation in

  15. Structural insights into the adaptation of proliferating cell nuclear antigen (PCNA) from Haloferax volcanii to a high-salt environment

    SciTech Connect

    Morgunova, Ekaterina; Gray, Fiona C.; MacNeill, Stuart A.; Ladenstein, Rudolf

    2009-10-01

    The crystal structure of PCNA from the halophilic archaeon H. volcanii reveals specific features of the charge distribution on the protein surface that reflect adaptation to a high-salt environment and suggests a different type of interaction with DNA in halophilic PCNAs. The sliding clamp proliferating cell nuclear antigen (PCNA) plays vital roles in many aspects of DNA replication and repair in eukaryotic cells and in archaea. Realising the full potential of archaea as a model for PCNA function requires a combination of biochemical and genetic approaches. In order to provide a platform for subsequent reverse genetic analysis, PCNA from the halophilic archaeon Haloferax volcanii was subjected to crystallographic analysis. The gene was cloned and expressed in Escherichia coli and the protein was purified by affinity chromatography and crystallized by the vapour-diffusion technique. The structure was determined by molecular replacement and refined at 3.5 Å resolution to a final R factor of 23.7% (R{sub free} = 25%). PCNA from H. volcanii was found to be homotrimeric and to resemble other homotrimeric PCNA clamps but with several differences that appear to be associated with adaptation of the protein to the high intracellular salt concentrations found in H. volcanii cells.

  16. Study of thermal diffusivity of nanofluids with bimetallic nanoparticles with Au(core)/Ag(shell) structure

    NASA Astrophysics Data System (ADS)

    Gutierrez Fuentes, R.; Pescador Rojas, J. A.; Jiménez-Pérez, J. L.; Sanchez Ramirez, J. F.; Cruz-Orea, A.; Mendoza-Alvarez, J. G.

    2008-11-01

    The thermal diffusivity of Au/Ag nanoparticles with core/shell structure, at different compositions (Au/Ag = 3/1, 1/1, 1/3, 1/6), was measured by using the mismatched mode of the dual-beam thermal lens (TL) technique. This study determines the effect of the bimetallic composition on the thermal diffusivity of the nanofluids. In these results we find a lineal increment of the nanofluid it thermal diffusivity when the Ag shell thickness is increased. Our results show that the nanoparticle structure is an important parameter to improve the heat transport in composites and nanofluids. These results could have importance for applications in therapies and photothermal deliberation of drugs. Complementary measurements with UV-vis spectroscopy and TEM, were used to characterize the Au(core)/Ag(shell) nanoparticles.

  17. Structure of RCC1 chromatin factor bound to the nucleosome core particle

    SciTech Connect

    Makde, Ravindra D.; England, Joseph R.; Yennawar, Hemant P.; Tan, Song

    2010-11-11

    The small GTPase Ran enzyme regulates critical eukaryotic cellular functions including nuclear transport and mitosis through the creation of a RanGTP gradient around the chromosomes. This concentration gradient is created by the chromatin-bound RCC1 (regulator of chromosome condensation) protein, which recruits Ran to nucleosomes and activates Ran's nucleotide exchange activity. Although RCC1 has been shown to bind directly with the nucleosome, the molecular details of this interaction were not known. Here we determine the crystal structure of a complex of Drosophila RCC1 and the nucleosome core particle at 2.9 {angstrom} resolution, providing an atomic view of how a chromatin protein interacts with the histone and DNA components of the nucleosome. Our structure also suggests that the Widom 601 DNA positioning sequence present in the nucleosomes forms a 145-base-pair nucleosome core particle, not the expected canonical 147-base-pair particle.

  18. Crystal Structure of the Protease-Resistant Core Domain of Yersinia Pestis Virulence Factor Yopr

    SciTech Connect

    Schubot,F.; Cherry, S.; Austin, B.; Tropea, J.; Waugh, D.

    2005-01-01

    Yersinia pestis, the causative agent of the plague, employs a type III secretion system (T3SS) to secrete and translocate virulence factors into the cytoplasm of mammalian host cells. One of the secreted virulence factors is YopR. Little is known about the function of YopR other than that it is secreted into the extracellular milieu during the early stages of infection and that it contributes to virulence. Hoping to gain some insight into the function of YopR, we determined the crystal structure of its protease-resistant core domain, which consists of residues 38--149 out of 165 amino acids. The core domain is composed of five {alpha}-helices that display unexpected structural similarity with one domain of YopN, a central regulator of type III secretion in Y. pestis. This finding raises the possibility that YopR may play a role in the regulation of type III secretion.

  19. High-Pressure Core Structures of Si Nanoparticles for Solar Energy Conversion

    NASA Astrophysics Data System (ADS)

    Wippermann, S.; Vörös, M.; Rocca, D.; Gali, A.; Zimanyi, G.; Galli, G.

    2013-01-01

    We present density functional and many body perturbation theory calculations of the electronic, optical, and impact ionization properties of Si nanoparticles (NPs) with core structures based on high-pressure bulk Si phases. Si particles with a BC8 core structure exhibit significantly lower optical gaps and multiple exciton generation (MEG) thresholds, and an order of magnitude higher MEG rate than diamondlike ones of the same size. Several mechanisms are discussed to further reduce the gap, including surface reconstruction and chemistry, excitonic effects, and embedding pressure. Experiments reported the formation of BC8 NPs embedded in amorphous Si and in amorphous regions of femtosecond-laser doped “black silicon.” For all these reasons, BC8 nanoparticles may be promising candidates for MEG-based solar energy conversion.

  20. Cometary cores with multiple structure from the oort cloud and the general scheme of origin of unusually active comets

    SciTech Connect

    Davydov, V.D.

    1986-03-01

    A newly conceived scheme is constructed which synthesizes consistent solutions to several principal problems concerning multiple-core comets: a power mechanism, a place and epoch of formation of the multiple core structure, the qualitative differences between current structure and younger structure, the origin of two types of cometary orbits, and a trigger mechanism for recent ignition of cometary activity of a multiple core. This scheme uses a new explanation of the ejection of dust (including icy dust) from various cometary cores as evidence that the material of multiple-core comets may be collisionally ablated at the expense of the comet-centered orbital energy of a multitude of massive boulders (see Kosm. Issled., No. 6 (1984)). Natural mechanisms are shown which preserve this important feature of multiple cores. The concept consists of the following elements: evolution of a system of satellites of the core toward a colli sionless structure; preservation of internal kinetic energy in the collisionless system over astro nomically lengthy time scales; tidal initiation of a collisional mechanism with the first revolution of the ancient multiple core in the zone of visibility. It is possible that such revoltions correspond to the existence of especially active comets in nearly parabolic orbits. Multiple structure in the core of active short-period comets might be descended from a nearly parabolic comet (if the theory holds on perturbational multistage transformation of near-parabolic orbits into contemporary short-period orbits).

  1. Current and Historical Drivers of Landscape Genetic Structure Differ in Core and Peripheral Salamander Populations

    PubMed Central

    Dudaniec, Rachael Y.; Spear, Stephen F.; Richardson, John S.; Storfer, Andrew

    2012-01-01

    With predicted decreases in genetic diversity and greater genetic differentiation at range peripheries relative to their cores, it can be difficult to distinguish between the roles of current disturbance versus historic processes in shaping contemporary genetic patterns. To address this problem, we test for differences in historic demography and landscape genetic structure of coastal giant salamanders (Dicamptodon tenebrosus) in two core regions (Washington State, United States) versus the species' northern peripheral region (British Columbia, Canada) where the species is listed as threatened. Coalescent-based demographic simulations were consistent with a pattern of post-glacial range expansion, with both ancestral and current estimates of effective population size being much larger within the core region relative to the periphery. However, contrary to predictions of recent human-induced population decline in the less genetically diverse peripheral region, there was no genetic signature of population size change. Effects of current demographic processes on genetic structure were evident using a resistance-based landscape genetics approach. Among core populations, genetic structure was best explained by length of the growing season and isolation by resistance (i.e. a ‘flat’ landscape), but at the periphery, topography (slope and elevation) had the greatest influence on genetic structure. Although reduced genetic variation at the range periphery of D. tenebrosus appears to be largely the result of biogeographical history rather than recent impacts, our analyses suggest that inherent landscape features act to alter dispersal pathways uniquely in different parts of the species' geographic range, with implications for habitat management. PMID:22590604

  2. Gap state related blue light emitting boron-carbon core shell structures

    NASA Astrophysics Data System (ADS)

    Singh, Paviter; Kaur, Manpreet; Singh, Bikramjeet; Kaur, Gurpreet; Singh, Kulwinder; Kumar, Manjeet; Bala, Rajni; Thakur, Anup; Kumar, Akshay

    2016-05-01

    Boron- carbon core shell structures have been synthesized by solvo-thermal synthesis route. The synthesized material is highly pure. X-ray diffraction analysis confirms the reduction of reactants in to boron and carbon. Scanning Electron Microscopy (SEM) analysis showed that the shell is uniform with average thickness of 340 nm. Photo luminescence studies showed that the material is blue light emitting with CIE color coordinates: x=0.16085, y=0.07554.

  3. Physical Properties of Suevite Section of the Eyreville Core, Chesapeake Bay Impact Structure

    NASA Astrophysics Data System (ADS)

    Elbra, T.; Pesonen, L. J.

    2007-12-01

    Chesapeake is a 35 Ma old shallow marine, complex impact structure with a diameter of ca. 85 km. The structure has previously been mapped with shallow drillings. Recently, the deep drilling into inner crater zone near Cape Charles was carried out in order to provide constraints on cratering processes in multi-layered marine targets. The Eyreville-1 core includes three holes with total depth of 1766m (Gohn et al. 2006). We are analyzing the fragments of the Eyreville core including post-impact, impact and basement units of the structure. The sampling interval was chosen dense enough to allow high-resolution petrophysical, paleomagnetic and rock magnetic data to be extracted from the core. Hereby we report the preliminary petrophysical and rock-magnetic data from suevite section of Eyreville core B. Results obtained so far show large variations in magnetic susceptibility data of suevite section. Polymict lithic breccias and cataclasites in lower part of the section are characterized by low magnetic susceptibility (below 0.0003 SI). The upper part, however, consists of more magnetic (susceptibility up to 0.006 SI) suevites. The rock- magnetic measurements (including thermal behavior of magnetic susceptibility and magnetic hysteresis) show the presence of magnetites in lower part of the section. Upper part shows additionally a distinct change in the slope of the susceptibility curve also near 350C, which may indicate the presence of pyrrhotites or maghemites. More extensive studies will be applied in near future in order to clarify the magnetomineralogy and will be presented. References: G. S. Gohn, C. Koeberl, K. G. Miller, W. U. Reimold, C. S. Cockell, J. W. Horton, W. E. Sanford, M. A. Voytek, 2006. Chesapeake Bay Impact Structure Drilled. EOS, vol 87. nr 35

  4. Direct atomic resolution imaging of dislocation core structures in a 300 kV stem

    SciTech Connect

    McGibbon, A.J.; Pennycook, S.J.

    1995-05-01

    By employing the incoherent imaging technique of Z-contrast imaging in a 300kV STEM, the authors show that it is possible to provide directly interpretable, atomic resolution images of the sublattice in compound semiconductors. Using this approach, analysis of dislocations at an interface in the CdTe(001)/GaAs(001) system reveals unexpected core structures at Lomer dislocations.

  5. Microfluidic fabrication of cholesteric liquid crystal core-shell structures toward magnetically transportable microlasers.

    PubMed

    Chen, Lu-Jian; Gong, Ling-Li; Lin, Ya-Li; Jin, Xin-Yi; Li, Han-Ying; Li, Sen-Sen; Che, Kai-Jun; Cai, Zhi-Ping; Yang, Chaoyong James

    2016-04-01

    We report a magnetically transportable microlaser with cholesteric liquid crystal (CLC) core-shell structure, operating in band-edge mode. The dye doped CLC shells as a water-in-oil-in-water (W/O/W) double emulsion were fabricated by microfluidics. Water-dispersible Fe3O4 magnetic nanoparticles were incorporated in the inner aqueous phase by taking advantage of the immiscibility with the middle CLC oil phase. The influence of temperature and shell thickness on laser properties was discussed in detail. The non-invasive manipulation of microlasers was realized under a magnetic field. The dependence of velocity on the viscosity of the carrying fluid and size of the core-shell structure was theoretically analyzed and experimentally investigated using a prototype electromagnetic platform. We also discussed the design principles for this type of DDCLC core-shell structure. Such magnetically transportable microlasers offer promise in in-channel illumination applications requiring active control inside micro-channels. PMID:26923221

  6. On the mineral core of ferritin-like proteins: structural and magnetic characterization.

    PubMed

    García-Prieto, A; Alonso, J; Muñoz, D; Marcano, L; Abad Díaz de Cerio, A; Fernández de Luis, R; Orue, I; Mathon, O; Muela, A; Fdez-Gubieda, M L

    2016-01-14

    It is generally accepted that the mineral core synthesized by ferritin-like proteins consists of a ferric oxy-hydroxide mineral similar to ferrihydrite in the case of horse spleen ferritin (HoSF) and an oxy-hydroxide-phosphate phase in plant and prokaryotic ferritins. The structure reflects a dynamic process of deposition and dissolution, influenced by different biological, chemical and physical variables. In this work we shed light on this matter by combining a structural (High Resolution Transmission Electron Microscopy (HRTEM) and Fe K-edge X-ray Absorption Spectroscopy (XAS)) and a magnetic study of the mineral core biomineralized by horse spleen ferritin (HoSF) and three prokaryotic ferritin-like proteins: bacterial ferritin (FtnA) and bacterioferritin (Bfr) from Escherichia coli and archaeal ferritin (PfFtn) from Pyrococcus furiosus. The prokaryotic ferritin-like proteins have been studied under native conditions and inside the cells for the sake of preserving their natural attributes. They share with HoSF a nanocrystalline structure rather than an amorphous one as has been frequently reported. However, the presence of phosphorus changes drastically the short-range order and magnetic response of the prokaryotic cores with respect to HoSF. The superparamagnetism observed in HoSF is absent in the prokaryotic proteins, which show a pure atomic-like paramagnetic behaviour attributed to phosphorus breaking the Fe-Fe exchange interaction. PMID:26666195

  7. Structure of Protein Phosphatase 2A Core Enzyme Bound to Tumor-Inducing Toxins

    SciTech Connect

    Xing,Y.; Xu, Y.; Chen, Y.; Jeffrey, P.; Chao, Y.; Lin, Z.; Li, Z.; Strack, S.; Stock, J.; Shi, Y.

    2006-01-01

    The serine/threonine phosphatase protein phosphatase 2A (PP2A) plays an essential role in many aspects of cellular functions and has been shown to be an important tumor suppressor. The core enzyme of PP2A comprises a 65 kDa scaffolding subunit and a 36 kDa catalytic subunit. Here we report the crystal structures of the PP2A core enzyme bound to two of its inhibitors, the tumor-inducing agents okadaic acid and microcystin-LR, at 2.6 and 2.8 {angstrom} resolution, respectively. The catalytic subunit recognizes one end of the elongated scaffolding subunit by interacting with the conserved ridges of HEAT repeats 11-15. Formation of the core enzyme forces the scaffolding subunit to undergo pronounced structural rearrangement. The scaffolding subunit exhibits considerable conformational flexibility, which is proposed to play an essential role in PP2A function. These structures, together with biochemical analyses, reveal significant insights into PP2A function and serve as a framework for deciphering the diverse roles of PP2A in cellular physiology.

  8. POLARIZATION STRUCTURE IN THE CORE OF 1803+784: A SIGNATURE OF RECOLLIMATION SHOCKS?

    SciTech Connect

    Cawthorne, T. V.; Jorstad, S. G.; Marscher, A. P.

    2013-07-20

    The extragalactic radio source 1803+784 is a BL Lac object that shows rapid variability and strong linear polarization. Very long baseline interferometry observations reveal that the core possesses a distinctive structure in polarized intensity with two maxima on axis and two minima symmetrically placed on either side. The approximately radial pattern of electric field polarization rods is reminiscent of the results obtained earlier by Cawthorne for conical shocks, but, individually, these do not reproduce the main features of the polarized intensity images. In numerical simulations and experiments, these shocks occur in pairs and help to stabilize jets as they adjust to changes in environment. Here, the polarization resulting from such structures is investigated using an approximate, analytical approach, by making some simple assumptions about the nature of the flow between two such shock waves. For fairly small viewing angles, it is found that a reasonable representation of the core polarization of 1803+784 can be obtained. The similarity between the observed and model polarizations supports the view that the core structure in 1803+784 represents a recollimation shock, and that such shock waves may be responsible for the first disturbance and hence brightening of the quiescent flow in astrophysical jets.

  9. Insert Design and Manufacturing for Foam-Core Composite Sandwich Structures

    NASA Astrophysics Data System (ADS)

    Lares, Alan

    Sandwich structures have been used in the aerospace industry for many years. The high strength to weight ratios that are possible with sandwich constructions makes them desirable for airframe applications. While sandwich structures are effective at handling distributed loads such as aerodynamic forces, they are prone to damage from concentrated loads at joints or due to impact. This is due to the relatively thin face-sheets and soft core materials typically found in sandwich structures. Carleton University's Uninhabited Aerial Vehicle (UAV) Project Team has designed and manufactured a UAV (GeoSury II Prototype) which features an all composite sandwich structure fuselage structure. The purpose of the aircraft is to conduct geomagnetic surveys. The GeoSury II Prototype serves as the test bed for many areas of research in advancing UAV technologies. Those areas of research include: low cost composite materials manufacturing, geomagnetic data acquisition, obstacle detection, autonomous operations and magnetic signature control. In this thesis work a methodology for designing and manufacturing inserts for foam-core sandwich structures was developed. The results of this research work enables a designer wishing to design a foam-core sandwich airframe structure, a means of quickly manufacturing optimized inserts for the safe introduction of discrete loads into the airframe. The previous GeoSury II Prototype insert designs (v.1 & v.2) were performance tested to establish a benchmark with which to compare future insert designs. Several designs and materials were considered for the new v.3 inserts. A plug and sleeve design was selected, due to its ability to effectively transfer the required loads to the sandwich structure. The insert material was chosen to be epoxy, reinforced with chopped carbon fibre. This material was chosen for its combination of strength, low mass and also compatibility with the face-sheet material. The v.3 insert assembly is 60% lighter than the

  10. Bending Response of Sandwiched Double Tube Structures with Aluminum Foam Core

    NASA Astrophysics Data System (ADS)

    Guo, L. W.; Yu, J. L.

    2010-05-01

    Three point bending response of sandwiched double cylindrical tube structures with aluminum foam core was studied numerically using the explicit finite element method. The numerical results are in good agreement with the corresponding experimental results and display the advantage of this new structure in load carrying capacity and energy absorption efficiency over the traditional foam-filled single tube structure. The deformation and failure mechanism is revealed by comparisons of the strain and stress distributions and the history of the maximum strain. The influence of the inner tube diameter for the structure was explored. It is found that increasing the inner tube diameter enhances the maximum deflection at failure of the foam-filled double tube within the diameter range considered. With a proper inner tube diameter, a steady load carrying capacity of the foam-filled double tube structure can be achieved, which shows an excellent crashworthiness with high energy absorption efficiency.

  11. TEM Study of the Growth Mechanism, Phase Transformation, and Core/shell Structure of Semiconductor Nanowires

    NASA Astrophysics Data System (ADS)

    Wong, Tai Lun

    In this thesis, the fabrication and characterization of one-dimensional nanostructures have been studied systematically to understand the growth mechanism and structure transformation of one-dimensional nanostructures. The growth behavior of the ultrathin ZnSe nanowires with diameter less than 60 nm was found to be different from classical vapor-liquid-solid (VLS) process. The growth rate increases when the diameter of nanowires decreases, in contrast to the classical VLS process in which the growth rate increases with the diameter. The nucleation, initial growth, growth rates, defects, interface structures and growth direction of the nanowires were investigated by high resolution transmission electron microscopy (HRTEM). We found the structure and growth direction of ultra-thin nanowires are highly sensitive to growth temperatures and diameters of nanowires. At a low growth temperature (380°C), the growth direction for most nanowires is along <111>. Planar defects were found throughout the nanowires. At a high growth temperature (530°C), uniform nanowires with diameters around 10nm were grown along <110> and <112> directions, and the nanowires with diameters larger than 20nm were mainly grown along <111> direction. The possible growth mechanism of ultrathin nanowires was proposed by combining the solid catalytic growth with the interface diffusion theory, in order to explain how the growth temperature and the size of the catalysts influent the morphology, growth direction and growth rate of ultrathin nanowires. Structural and phase transformation of a nickel coated Si nanowire to NiSi2/SiC core-shell nanowire heterostructures has been investigated by the in-situ Transmission Electron Microscope (TEM). The phase transformation is a single-site nucleation process and therefore a single crystalline NiSi2 core resulted in the core-shell nanowire heterostructures. The transformation of the Si nanowire to NiSi2/SiC core-shell nanowire heterostructures was extremely

  12. Simulation Based Optimization of Complex Monolithic Composite Structures Using Cellular Core Technology

    NASA Astrophysics Data System (ADS)

    Hickmott, Curtis W.

    Cellular core tooling is a new technology which has the capability to manufacture complex integrated monolithic composite structures. This novel tooling method utilizes thermoplastic cellular cores as inner tooling. The semi-rigid nature of the cellular cores makes them convenient for lay-up, and under autoclave temperature and pressure they soften and expand providing uniform compaction on all surfaces including internal features such as ribs and spar tubes. This process has the capability of developing fully optimized aerospace structures by reducing or eliminating assembly using fasteners or bonded joints. The technology is studied in the context of evaluating its capabilities, advantages, and limitations in developing high quality structures. The complex nature of these parts has led to development of a model using the Finite Element Analysis (FEA) software Abaqus and the plug-in COMPRO Common Component Architecture (CCA) provided by Convergent Manufacturing Technologies. This model utilizes a "virtual autoclave" technique to simulate temperature profiles, resin flow paths, and ultimately deformation from residual stress. A model has been developed simulating the temperature profile during curing of composite parts made with the cellular core technology. While modeling of composites has been performed in the past, this project will look to take this existing knowledge and apply it to this new manufacturing method capable of building more complex parts and develop a model designed specifically for building large, complex components with a high degree of accuracy. The model development has been carried out in conjunction with experimental validation. A double box beam structure was chosen for analysis to determine the effects of the technology on internal ribs and joints. Double box beams were manufactured and sectioned into T-joints for characterization. Mechanical behavior of T-joints was performed using the T-joint pull-off test and compared to traditional

  13. Radioimmunoassays of hidden viral antigens

    SciTech Connect

    Neurath, A.R.; Strick, N.; Baker, L.; Krugman, S.

    1982-07-01

    Antigens corresponding to infectious agents may be present in biological specimens only in a cryptic form bound to antibodies and, thus, may elude detection. We describe a solid-phase technique for separation of antigens from antibodies. Immune complexes are precipitated from serum by polyethylene glycol, dissociated with NaSCN, and adsorbed onto nitrocellulose or polystyrene supports. Antigens remain topographically separated from antibodies after removal of NaSCN and can be detected with radiolabeled antibodies. Genomes from viruses immobilized on nitrocellulose can be identified by nucleic acid hybridization. Nanogram quantities of sequestered hepatitis B surface and core antigens and picogram amounts of hepatitis B virus DNA were detected. Antibody-bound adenovirus, herpesvirus, and measles virus antigens were discerned by the procedure.

  14. The structure of melting mushy zones, with implications for Earth's inner core (Invited)

    NASA Astrophysics Data System (ADS)

    Bergman, M. I.; Huguet, L.; Alboussiere, T.

    2013-12-01

    Seismologists have inferred hemispherical differences in the isotropic wavespeed, the elastic anisotropy, the attenuation, and the attenuation anisotropy of Earth's inner core. One hypothesis for these hemispherical differences involves an east-west translation of the inner core, with enhanced solidification on one side and melting on the other. Another hypothesis is that long term mantle control over outer core convection can lead to hemispherical variations in solidification that could even result in melting in some regions of the inner core boundary. It has also been hypothesized that the inner core is growing dendritically, resulting in an inner core that has the structure of a mushy zone (albeit one with a high solid fraction). It would therefore be helpful to understand how the structure of a melting mushy zone might look in comparison with one that is solidifying, in an effort to help interpret the seismic inferences. We have carried out experiments on the solidification of ammonium chloride from an aqueous solution, yielding a mushy zone. The experiments run in a centrifuge, in order to reach a more realistic ratio of convective velocity to phase change rate, expected to be very large at the boundary of the inner core. Hypergravity thus increases the experimental solid fraction of the mush. So far the maximum gravity we have achieved is 200 g. A Peltier cell provides cooling at one end of the cell, and after the mushy zone has grown we turn on a heater at the other end. Probes monitor the temperature along the height of the cell. As ammonium chloride in the mushy zone melts it produces more dense fluid, which results in convection in the mushy zone, a greater ammonium chloride concentration deeper in the mushy zone, and hence enhanced solidification there. This thus changes the solid fraction profile from that during solidification, which may be observable in the lab experiments using ultrasonic transducers and post-mortem under a microscope. The melting

  15. Crystallization of ion clouds in octupole traps: Structural transitions, core melting, and scaling laws

    SciTech Connect

    Calvo, F.; Champenois, C.; Yurtsever, E.

    2009-12-15

    The stable structures and melting properties of ion clouds in isotropic octupole traps are investigated using a combination of semianalytical and numerical models, with a particular emphasis at finite-size scaling effects. Small-size clouds are found to be hollow and arranged in shells corresponding approximately to the solutions of the Thomson problem. The shell structure is lost in clusters containing more than a few thousands of ions, the inner parts of the cloud becoming soft and amorphous. While melting is triggered in the core shells, the melting temperature follows the rule expected for three-dimensional dense particles, with a depression scaling linearly with the inverse radius.

  16. Hepatitis B Core IgM antibody (anti-HBcIgM) among hepatitis B Surface antigen (HBsAg) negative blood donors in Nigeria

    PubMed Central

    2011-01-01

    Background Transfusion associated Hepatitis B virus (TAHBV) continues to be a major problem despite mandatory screening for Hepatitis B surface Antigen (HBsAg). Presence of HBsAg is the common method for detecting hepatitis B infection. Unfortunately, this marker is not detected during the window period of the infection. Nigeria being a developing country cannot afford DNA testing of all collected units of blood which serve as the only possibility of achieving zero risk of transfusion associated HBV. Five different serological makers of hepatitis B virus (HBV) infection were therefore assessed to evaluate the reliability of using HBsAg marker alone in diagnosis of HBV infection among blood donors and to detect the serological evidence of the infection at the window period. This will preclude the possibility of transmitting hepatitis B through transfusion of Hepatitis B surface antigen (HBsAg) negative blood in Nigeria. Methods Between July and August 2009, 92 blood donors were enrolled for the study. The prevalence of 5 different markers of Hepatitis B virus infection was detected using Enzyme Linked Immunosorbent Assay (ELISA). Demographic factors were assessed during the study. Results HBsAg and its antibody (anti-HBs) was detected in 18 (19.6%) and 14(15.2%) of the 92 blood donors respectively. Anti-HBc IgM was found in 12(13.0%) of the 92 blood donors while Hepatitis B envelope antigen (HBeAg) and its antibody (anti-HBe) were detected in 4(8.9%) and 12(26.7%) respectively from 45 donors sampled. HBeAg is a marker of high infectivity and appears after HBsAg. At least one serological marker was detected in 30(32.6%) of the blood donors. Five (5.4%) of the 92 donors had anti-HBc IgM as the only serological evidence of hepatitis B virus infection. Conclusions The result of this study shows that five donors have anti-HBcIgM as the only serological evidence of HBV infection. Inclusion of anti-HBcIgM in routine screening of blood donors in Nigeria should be encouraged

  17. The structure of Fe-Si alloy in Earth's inner core

    NASA Astrophysics Data System (ADS)

    Tateno, Shigehiko; Kuwayama, Yasuhiro; Hirose, Kei; Ohishi, Yasuo

    2015-05-01

    Phase relations of iron-silicon alloy (Fe-6.5 wt.% Si and Fe-9 wt.% Si) were investigated up to 407 GPa and 5960 K in a laser-heated diamond-anvil cell, which likely covers the entire pressure and temperature conditions of the Earth's inner core. Synchrotron X-ray diffraction measurements show that Fe-9 wt.% Si with a hexagonal close-packed (hcp) structure is stable to 4800 K at 330 GPa, corresponding to the pressure at the inner/outer core boundary, and decomposes into a mixture of Si-poor hcp and Si-rich CsCl-type (B2) phases at higher temperatures. We also found that the solubility of silicon in solid iron is relatively insensitive to temperature, decreasing from 9 to >6.5 wt.% over a range of 1500 K at 70 GPa. These suggest that the inner core is composed solely of the hcp phase, when the silicon content is up to 7 wt.% that likely accounts for the inner core density deficit as well as for the Mg/Si ratio and the Si isotopic composition of the mantle. Additionally, the present experiments demonstrate that the incorporation of silicon in iron expands the stability of hcp with respect to that of fcc.

  18. Contamination assessment in microbiological sampling of the Eyreville core, Chesapeake Bay impact structure

    USGS Publications Warehouse

    Gronstal, A.L.; Voytek, M.A.; Kirshtein, J.D.; Von der, Heyde, N. M.; Lowit, M.D.; Cockell, C.S.

    2009-01-01

    Knowledge of the deep subsurface biosphere is limited due to difficulties in recovering materials. Deep drilling projects provide access to the subsurface; however, contamination introduced during drilling poses a major obstacle in obtaining clean samples. To monitor contamination during the 2005 International Continental Scientific Drilling Program (ICDP)-U.S. Geological Survey (USGS) deep drilling of the Chesapeake Bay impact structure, four methods were utilized. Fluorescent microspheres were used to mimic the ability of contaminant cells to enter samples through fractures in the core material during retrieval. Drilling mud was infused with a chemical tracer (Halon 1211) in order to monitor penetration of mud into cores. Pore water from samples was examined using excitation-emission matrix (EEM) fl uorescence spectroscopy to characterize dissolved organic carbon (DOC) present at various depths. DOC signatures at depth were compared to signatures from drilling mud in order to identify potential contamination. Finally, microbial contaminants present in drilling mud were identified through 16S ribosomal deoxyribonucleic acid (rDNA) clone libraries and compared to species cultured from core samples. Together, these methods allowed us to categorize the recovered core samples according to the likelihood of contamination. Twenty-two of the 47 subcores that were retrieved were free of contamination by all the methods used and were subsequently used for microbiological culture and culture-independent analysis. Our approach provides a comprehensive assessment of both particulate and dissolved contaminants that could be applied to any environment with low biomass. ?? 2009 The Geological Society of America.

  19. Genetic structure and a selected core set of Brazilian soybean cultivars

    PubMed Central

    Priolli, Regina Helena Geribello; Wysmierski, Philip Traldi; da Cunha, Camila Pinto; Pinheiro, José Baldin; Vello, Natal Antonio

    2013-01-01

    Soybean is one of the most valuable and profitable oil crop species and a thorough knowledge of the genetic structure of this crop is necessary for developing the best breeding strategies. In this study, a representative collection of soybean cultivars recommended for farming in all Brazilian regions was genotyped using 27 simple sequence repeat (SSR) loci. A total of 130 alleles were detected, with an average allelic number of 4.81 per locus. These alleles determined the core set that best represented this soybean germplasm. The Bayesian analysis revealed the presence of two clusters or subgroups within the whole collection (435 soybean cultivars) and the core set (31 entries). Cultivars of similar origin (ancestral) were clustered into the same groups in both analyses. The genetic diversity parameters, based on the SSR loci, revealed high similarity between the whole collection and core set. Differences between the two clusters detected in the core set were attributed more to the frequency of their ancestors than to their genetic base. In terms of ancestry, divergent groups were presented and a panel is shown which may foster efficient breeding programs and aid soybean breeders in planning reliable crossings in the development of new varieties. PMID:24130446

  20. Micromagnetic Modeling of Reversal Nucleation in Core/Shell Exchange-Spring Structures

    NASA Astrophysics Data System (ADS)

    Jiang, J. S.; Bader, Sam

    2015-03-01

    Nanocomposite exchange-spring permanent magnet materials promise superior performance and are a potential solution to the supply criticality in rare earth elements. The nucleation of magnetization reversal in cylindrical and spherical soft core/hard shell exchange-spring structures has been investigated by solving the linearized Brown's equation perturbatively, and has been verified with numerical simulations. Accounting for the magnetostatic self-interaction field leads to a modification to the proposed quasi-coherent ``bulging'' mode of nucleation for small core sizes. The modified curling mode, where the magnetization configuration is vortex-like and flux-closed, becomes favored at large core sizes. The mode crossover occurs at a core diameter of approximately twice the exchange length for the cylindrical geometry. Since flux-closure allows magnetic elements to be densely packed without affecting the nucleation field, a potential direction for improving permanent magnet materials is to induce the modified curling mode by creating a soft-cylinder-in-hard-matrix exchange-spring microstructure. This work was supported by the U.S. Department of Energy, Office of Science, Basic Energy Sciences, Materials Sciences and Engineering Division.

  1. Empirical transfer functions: Application to determination of outermost core velocity structure using SmKS phases

    NASA Astrophysics Data System (ADS)

    Alexandrakis, Catherine; Eaton, David W.

    2007-11-01

    SmKS waves provide good resolution of outer-core velocity structure, but are affected by heterogeneity in the D'' region. We have developed an Empirical Transfer Function (ETF) technique that transforms a reference pulse (here, SmKS) into a target waveform (SKKS) by: (1) time-windowing the respective pulses, (2) applying Wiener deconvolution, and (3) convolving the output with a Gaussian waveform. Common source and path effects are implicitly removed by this process. We combine ETFs from 446 broadband seismograms to produce a global stack, from which S3KS-SKKS differential time can be measured accurately. As a result of stacking, the scatter in our measurements (0.43 s) is much less than the 1.29 s scatter in previous compilations. Although our data do not uniquely constrain outermost core velocities, we show that the fit of most standard models can be improved by perturbing the outermost core velocity. Our best-fitting model is formed using IASP91 with PREM-like velocity at the top of the core.

  2. Structures of a pan-specific antagonist antibody complexed to different isoforms of TGFβ reveal structural plasticity of antibody–antigen interactions

    PubMed Central

    Moulin, Aaron; Mathieu, Magali; Lawrence, Catherine; Bigelow, Russell; Levine, Mark; Hamel, Christine; Marquette, Jean-Piere; Le Parc, Josiane; Loux, Christophe; Ferrari, Paul; Capdevila, Cecile; Dumas, Jacques; Dumas, Bruno; Rak, Alexey; Bird, Julie; Qiu, Huawei; Pan, Clark Q; Edmunds, Tim; Wei, Ronnie R

    2014-01-01

    Various important biological pathways are modulated by TGFβ isoforms; as such they are potential targets for therapeutic intervention. Fresolimumab, also known as GC1008, is a pan-TGFβ neutralizing antibody that has been tested clinically for several indications including an ongoing trial for focal segmental glomerulosclerosis. The structure of the antigen-binding fragment of fresolimumab (GC1008 Fab) in complex with TGFβ3 has been reported previously, but the structural capacity of fresolimumab to accommodate tight interactions with TGFβ1 and TGFβ2 was insufficiently understood. We report the crystal structure of the single-chain variable fragment of fresolimumab (GC1008 scFv) in complex with target TGFβ1 to a resolution of 3.00 Å and the crystal structure of GC1008 Fab in complex with TGFβ2 to 2.83 Å. The structures provide further insight into the details of TGFβ recognition by fresolimumab, give a clear indication of the determinants of fresolimumab pan-specificity and provide potential starting points for the development of isoform-specific antibodies using a fresolimumab scaffold. 4KV5; 4KXZ PMID:25209176

  3. Massive Quiescent Cores in Orion. VI. The Internal Structures and a Candidate of Transiting Core in NGC 2024 Filament

    NASA Astrophysics Data System (ADS)

    Ren, Zhiyuan; Li, Di

    2016-06-01

    We present a multiwavelength observational study of the NGC 2024 filament using infrared to submillimeter continuum and the {{NH}}3 (1,1) and (2,2) inversion transitions centered on FIR-3, the most massive core therein. FIR-3 is found to have no significant infrared point sources in the Spitzer/IRAC bands. But the {{NH}}3 kinetic temperature map shows a peak value at the core center with {T}{{k}}=25 K, which is significantly higher than the surrounding level ({T}{{k}}\\quad = 15–19 K). Such internal heating signature without an infrared source suggests an ongoing core collapse possibly at a transition stage from first hydrostatic core (FHSC) to protostar. The eight dense cores in the filament have dust temperatures between 17.5 and 22 K. They are much cooler than the hot ridge ({T}{{d}}∼ 55 K) around the central heating star IRS-2b. Comparison with a dust heating model suggests that the filament should have a distance of 3–5 pc from IRS-2b. This value is much larger than the spatial extent of the hot ridge, suggesting that the filament is spatially separated from the hot region along the line of sight.

  4. A novel multiple drug release system in vitro based on adjusting swelling core of emulsion electrospun nanofibers with core-sheath structure.

    PubMed

    Wang, Yazhou; Li, Zong; Shao, Pengyu; Hao, Shilei; Wang, Wei; Yang, Qian; Wang, Bochu

    2014-11-01

    We have developed a novel drug delivery system with the swelling core for differential release of multiple drugs by emulsion electrospinning, in which the aqueous phase is composed of polyvinyl alcohol and the oil phase consists of poly(ε-caprolactone). The microscopy images indicate that the W/O nanofibers with swelling core structure are successfully prepared and the model drugs, Rhodamine B and bovine serum albumin, were encapsulated in the fibers. In vitro drug release study demonstrated that this core-sheath structure could significantly alleviate the initial drug burst release and provided a differential diffusion pathway to release. It could be found that the postponement of the maximum accumulated release of bovine serum albumin was found due to the presence of sodium citrate and different types of polyvinyl alcohol. This study would provide a basis for optimization of encapsulation conditions to control the release of multiple agents and ultimately be applied in cancer chemotherapy. PMID:25280686

  5. MAGNETIC CORE SHELL STRUCTURES: from 0D to 1D assembling.

    PubMed

    Ficai, Denisa; Ficai, Anton; Dinu, Elena; Oprea, Ovidiu; Sonmez, Maria; Keler, Memduh Kagan; Sahin, Yesim Muge; Ekren, Nazmi; Inan, Ahmet Talat; Daglilar, Sibel; Gunduz, Oguzhan

    2015-01-01

    Material research and development studies are focused on different techniques of bringing out nanomaterials with desired characteristics and properties. From the point of view of materials development, nowadays scientists are strongly focused on obtaining materials with predefined characteristics and properties. The morphology control seems to be a determinant factor and increasing attention is devoted to this aspect. At this moment it is possible to engineer the material's features by using different methods and materials combination for both medical and industrial applications. In the applications of chemistry and synthesis, biology, mechanics, optics solar cells and microelectronics tailoring the adjustable parameters of stoichiometry, chemical structure, shape and segregation are evaluated and opens new fields. Because of the magnetic features of nanoparticles and durable particle size, less than 100 nm, this study is aiming to describe their uses in practical applications. That's why the whole hydrodynamic magnetic core shell topic will be reviewed on this paper. Additionally, the properties acting in general sight in solid-state physics are utilized for material selection and for defining issue connecting the core, shell structure and their producing properties. Here, in the study of core/shell nanoparticle various physical and chemical synthesis routes and the effect of electrospun method are briefly discussed. Starting from a real void of the scientific literature, the existent data related to the 1D magnetic electrospun materials are reviewed. The perspectives in the medical, environmental or energetic sector is great and bring some real advantages related to the 0D core@shell structures because both mechanical and biological properties are dependent on the morphology of the materials. PMID:26377653

  6. Fine Seismic Velocity Structure of the Lowermost Outer Core (F-layer) Beneath the Eastern Pacific

    NASA Astrophysics Data System (ADS)

    Ohtaki, T.; Kaneshima, S.

    2014-12-01

    Solidification or melting at the inner core boundary, the phenomena that have been suggested to occur reflecting the dynamical processes either of the inner core or of the outer core, might cause a Fe-rich or Fe-poor layer in the lowermost outer core (F-layer). Such a compositional anomaly might be detectable by investigating fine seismic structure of the F-layer. In our previous study we determined the overall Vp structure near the inner core boundary beneath Antarctica using differential traveltimes between PKIKP and PKPbc, waveform modeling of PKIKP and PKiKP, and amplitude ratios between PKIKP and PKPbc. But the fine structure of the F-layer remained poorly constrained.In this presentation, we examined the Vp structure of the F-layer beneath the eastern Pacific using differential traveltimes between PKiKP and PKPbc as well as frequency dependence of differential traveltimes between PKIKP and PKPbc, because these two analyses are particularly sensitive to the F-layer structure. We analyzed broadband seismograms of South American earthquakes observed at HI-NET in Japan. The differential traveltime residuals (observed minus calculated) between PKiKP and PKPbc are sensitive to the Vp excess relative to the reference model that is summed over the F-layer below the turning depth of PKPbc. For between 147 and 150 degrees the observed differential residuals show larger negative values and no noticeable dependence on distance compared to that for AK135. PREM that has larger Vp values in the F-layer than AK135 gives smaller differentials than the observations. On the other hand frequency dependence of differential traveltimes between PKIKP and PKPbc has unique sensitivity to the Vp slope in the F-layer, and low sensitivity to the Vp value on the ICB. We measured differential traveltimes for two different frequency bands for between 150 and 157 degrees, and then calculated the difference of the differentials between the two frequency bands. The observed differences show

  7. Inhibitory and neutral antibodies to Plasmodium falciparum MSP119 form ring structures with their antigen.

    PubMed

    Dekker, Carien; Uthaipibull, Chairat; Calder, Lesley J; Lock, Matthew; Grainger, Munira; Morgan, William D; Dodson, Guy G; Holder, Anthony A

    2004-09-01

    Blood-stage malaria vaccine candidates include surface proteins of the merozoite. Antibodies to these proteins may either block essential steps during invasion or render the merozoite susceptible to phagocytosis or complement-mediated degradation. Structural information on merozoite surface proteins complexed to antibodies provides crucial information for knowledge-based vaccine design. The major merozoite surface protein MSP1 is an abundant surface molecule in Plasmodium falciparum. Only a subset of antibodies against MSP119 inhibits invasion (inhibitory antibodies), whereas other antibodies binding to MSP119 have no effect on invasion (neutral antibodies). Here we report on the complex of MSP119 with both inhibitory monoclonal antibody 12.10 and neutral monoclonal antibody 2F10. The complexes were established using both whole IgG's and Fab fragments, and analysed by dynamic light scattering, electron microscopy and analytical ultra centrifugation. Specific ring structures were formed in the ternary complex with the two antibodies, providing direct evidence of non-overlapping epitopes on MSP119. Mutational studies also indicated that the epitopes of the inhibitory and neutral antibodies are spatially remote. PMID:15279960

  8. Conserved structure of amphibian T-cell antigen receptor beta chain.

    PubMed

    Fellah, J S; Kerfourn, F; Guillet, F; Charlemagne, J

    1993-07-15

    All jawed vertebrates possess well-differentiated thymuses and elicit T-cell-like cell-mediated responses; however, no surface T-cell receptor (TCR) molecules or TCR genes have been identified in ectothermic vertebrate species. Here we describe cDNA clones from an amphibian species, Ambystoma mexicanum (the Mexican axolotl), that have sequences highly homologous to the avian and mammalian TCR beta chains. The cloned amphibian beta chain variable region (V beta) shares most of the structural characteristics with the more evolved vertebrate V beta and presents approximately 56% amino acid identities with the murine V beta 14 and human V beta 18 families. The two different cloned axolotl beta chain joining regions (J beta) were found to have conserved all the invariant mammalian J beta residues, and in addition, the presence of a conserved glycine at the V beta-J beta junction suggests the existence of diversity elements. The extracellular domains of the two axolotl beta chain constant region isotypes C beta 1 and C beta 2 show an impressively high degree of identity, thus suggesting that a very efficient mechanism of gene correction has been in operation to preserve this structure at least from the early tetrapod evolution. The transmembrane axolotl C beta domains have been less well conserved when compared to the mammalian C beta but they do maintain the lysine residue that is thought to be involved in the charged interaction between the TCR alpha beta heterodimer and the CD3 complex. PMID:8341702

  9. Direct observation of Σ7 domain boundary core structure in magnetic skyrmion lattice.

    PubMed

    Matsumoto, Takao; So, Yeong-Gi; Kohno, Yuji; Sawada, Hidetaka; Ikuhara, Yuichi; Shibata, Naoya

    2016-02-01

    Skyrmions are topologically protected nanoscale magnetic spin entities in helical magnets. They behave like particles and tend to form hexagonal close-packed lattices, like atoms, as their stable structure. Domain boundaries in skyrmion lattices are considered to be important as they affect the dynamic properties of magnetic skyrmions. However, little is known about the fine structure of such skyrmion domain boundaries. We use differential phase contrast scanning transmission electron microscopy to directly visualize skyrmion domain boundaries in FeGe1-x Si x induced by the influence of an "edge" of a crystal grain. Similar to hexagonal close-packed atomic lattices, we find the formation of skyrmion "Σ7" domain boundary, whose orientation relationship is predicted by the coincidence site lattice theory to be geometrically stable. On the contrary, the skyrmion domain boundary core structure shows a very different structure relaxation mode. Individual skyrmions can flexibly change their size and shape to accommodate local coordination changes and free volumes formed at the domain boundary cores. Although atomic rearrangement is a common structural relaxation mode in crystalline grain boundaries, skyrmions show very unique and thus different responses to such local lattice disorders. PMID:26933690

  10. Crystal Structure of the Heterotrimer Core of Saccharomyces cerevisiae AMPK Homologue SNF1

    SciTech Connect

    Amodeo,G.; Rudolph, M.; Tong, L.

    2007-01-01

    AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis in mammals and is an attractive target for drug discovery against diabetes, obesity and other diseases. The AMPK homologue in Saccharomyces cerevisiae, known as SNF1, is essential for responses to glucose starvation as well as for other cellular processes, although SNF1 seems to be activated by a ligand other than AMP. Here we report the crystal structure at 2.6 resolution of the heterotrimer core of SNF1. The ligand-binding site in the {gamma}-subunit (Snf4) has clear structural differences from that of the Schizosaccharomyces pombe enzyme, although our crystallographic data indicate that AMP can also bind to Snf4. The glycogen-binding domain in the {beta}-subunit (Sip2) interacts with Snf4 in the heterotrimer but should still be able to bind carbohydrates. Our structure is supported by a large body of biochemical and genetic data on this complex. Most significantly, the structure reveals that part of the regulatory sequence in the {alpha}-subunit (Snf1) is sequestered by Snf4, demonstrating a direct interaction between the {alpha}- and {gamma}-subunits and indicating that our structure may represent the heterotrimer core of SNF1 in its activated state.

  11. Direct observation of Σ7 domain boundary core structure in magnetic skyrmion lattice

    PubMed Central

    Matsumoto, Takao; So, Yeong-Gi; Kohno, Yuji; Sawada, Hidetaka; Ikuhara, Yuichi; Shibata, Naoya

    2016-01-01

    Skyrmions are topologically protected nanoscale magnetic spin entities in helical magnets. They behave like particles and tend to form hexagonal close-packed lattices, like atoms, as their stable structure. Domain boundaries in skyrmion lattices are considered to be important as they affect the dynamic properties of magnetic skyrmions. However, little is known about the fine structure of such skyrmion domain boundaries. We use differential phase contrast scanning transmission electron microscopy to directly visualize skyrmion domain boundaries in FeGe1−xSix induced by the influence of an “edge” of a crystal grain. Similar to hexagonal close-packed atomic lattices, we find the formation of skyrmion “Σ7” domain boundary, whose orientation relationship is predicted by the coincidence site lattice theory to be geometrically stable. On the contrary, the skyrmion domain boundary core structure shows a very different structure relaxation mode. Individual skyrmions can flexibly change their size and shape to accommodate local coordination changes and free volumes formed at the domain boundary cores. Although atomic rearrangement is a common structural relaxation mode in crystalline grain boundaries, skyrmions show very unique and thus different responses to such local lattice disorders. PMID:26933690

  12. On the body centered structure of iron at Earth Core Conditions

    NASA Astrophysics Data System (ADS)

    Jeanloz, R.; Stixrude, L.; Verma, A.; Modak, P.; Godwal, B.

    2007-12-01

    The stability of the body-centered cubic (bcc) phase of iron is considered at Earth-core conditions (V = 7.2 Å3, T = 5500 K) by way of ab-initio molecular-dynamics simulations and electronic-structure calculations using the density-functional approach. Tetragonal strain splits a peak in the electronic density of states at the Fermi level, lowering the energy of the structure with distortion and therefore documenting the metastability of the bcc structure. As temperature is increased from zero to 5500 K, the bcc structure satisfies the condition of hydrostaticity, with vanishing of stress anisotropy, but it remains energetically unstable with respect to the tetragonal distortion; an increase in elastic anisotropy is documented with increasing tetragonal strain. An energy minimum is observed around c/a = 0.9 in a Bain-path plot, and has previously been interpreted as evidence of an elastically-stable body-centered tetragonal (bct) structure. However, we find from static total-energy calculations as a function of b/a and c/a that this is a local minimum in energy corresponding to a metastable structure. Analysis of the structure with tetragonal strain reveals the presence of anomalous shear stresses that, coupled with phonon instability, suggest a tendency toward formation of a hexagonal closed-packed (hcp) structure. Overall, these results argue against bcc or even bct structures of Fe being present in Earth's core, and instead highlight the importance of the known hcp (ɛ) high-pressure phase of iron.

  13. Core structure, internal osmotic pressure and irreversible structural changes of chromaffin granules during osmometer behaviour.

    PubMed

    Südhof, T C

    1982-01-01

    In the adrenal medullary cells, catecholamines are stored in and secreted from specialized secretory vesicles, the chromaffin granules. In order to gain some understanding of both functions of chromaffin granules, it is important to characterize their biophysical organization. Using isolated bovine chromaffin granules we have investigated the osmometer behaviour of chromaffin granules by 31P-NMR and fluorescence spectroscopy, by turbidity measurements and by electron-microscopic determination of chromaffin granule size distributions. On the basis of the osmometer model we have formulated equations predicting the behaviour of the native catecholamine fluorescence quenching and of the size of chromaffin granules a a function of osmolarity and have shown experimentally that the granules' behaviour conforms to these. It was possible to estimate the osmotic activity of the chromaffin granule core solution and the mean absolute water space in chromaffin granules from the determination of the size distributions as a function of osmotic pressure. With NMR spectroscopy a selective line-broadening of the alpha-resonances was observed with increasing osmolarities, while the gamma-phosphorus resonances remained virtually unchanged. Possibly there is an increase in core viscosity with osmolarity which affects only the alpha- and beta-phosphorus groups. While suspending chromaffin granules from lower to higher osmolarities causes no lysis, moving them back to their original osmolarity at which they were previously stable lyses them, thereby releasing a maximum of 70% of their releasable protein. This 'hyperosmolar' lysis is independent of preincubation times in the higher osmolarities and of the absolute dilution applied but depends on dilution beyond the 405 to 322 mosM sucrose range. Under the experiment conditions no uptake of sucrose from the medium into the granules could be measured, thereby suggesting that hyperosmolar lysis is a phenomenon not due to solute penetration

  14. Structure of a TCR with High Affinity for Self-antigen Reveals Basis for Escape from Negative Selection

    SciTech Connect

    Y Yin; Y Li; M Kerzic; R Martin; R Mariuzza

    2011-12-31

    The failure to eliminate self-reactive T cells during negative selection is a prerequisite for autoimmunity. To escape deletion, autoreactive T-cell receptors (TCRs) may form unstable complexes with self-peptide-MHC by adopting suboptimal binding topologies compared with anti-microbial TCRs. Alternatively, escape can occur by weak binding between self-peptides and MHC. We determined the structure of a human autoimmune TCR (MS2-3C8) bound to a self-peptide from myelin basic protein (MBP) and the multiple sclerosis-associated MHC molecule HLA-DR4. MBP is loosely accommodated in the HLA-DR4-binding groove, accounting for its low affinity. Conversely, MS2-3C8 binds MBP-DR4 as tightly as the most avid anti-microbial TCRs. MS2-3C8 engages self-antigen via a docking mode that resembles the optimal topology of anti-foreign TCRs, but is distinct from that of other autoreactive TCRs. Combined with a unique CDR3 conformation, this docking mode compensates for the weak binding of MBP to HLA-DR4 by maximizing interactions between MS2-3C8 and MBP. Thus, the MS2-3C8-MBP-DR4 complex reveals the basis for an alternative strategy whereby autoreactive T cells escape negative selection, yet retain the ability to initiate autoimmunity.

  15. Crystal structural basis for Rv0315, an immunostimulatory antigen and inactive beta-1,3-glucanase of Mycobacterium tuberculosis

    PubMed Central

    Dong, Wanyu; Huang, Junhua; Li, Yanan; Tan, Yubei; Shen, Zhou; Song, Yunfeng; Wang, Dang; Xiao, Shaobo; Chen, Huanchun; Fu, Zhen F.; Peng, Guiqing

    2015-01-01

    Mycobacterium tuberculosis (Mtb) remains a leading cause of morbidity and mortality worldwide, as two billion people are latently infected with Mtb. To address Mtb drug resistance and the limitations of current vaccines, the characteristics of candidate Mtb vaccines need to be explored. Here, we report the three-dimensional structure of Rv0315 at 1.70 Å resolution, a novel immunostimulatory antigen of Mtb, and demonstrate that Rv0315 is an inactive β-1,3-glucanase of the glycoside hydrolase 16 (GH16) family. Our study further elaborates the molecular basis for the lack of glucan recognition by Rv0315. Rv0315 has a large open groove, and this particular topology cannot bind oligosaccharide chains in solution, thus explaining the lack of detectable hydrolytic activity towards its substrate. Additionally, we identified Glu-176, a conserved catalytic residue in GH16 endo-β-1,3-glucanases, as essential for Rv0315 to induce immunological responses. These results indicate that Rv0315 likely diverged from a broad-specificity ancestral GH16 glucanase, and this inactive member of the GH16 family offers new insights into the GH16 glucanase. Together, our findings suggest that an inactive β-1,3-glucanase in Mtb drives T-helper 1 (Th1) immune responses, which may help develop more effective vaccines against Mtb infection. PMID:26469317

  16. Structural Identity of Human Histocompatibility Leukocyte Antigen-B27 Molecules from Patients with Ankylosing Spondylitis and Normal Individuals

    PubMed Central

    Karr, Robert W.; Hahn, Yaffa; Schwartz, Benjamin D.

    1982-01-01

    Although the association between human histocompatibility leukocyte antigen (HLA) B27 and ankylosing spondylitis is the prototype of HLA-disease association, the mechanism underlying these associations has not been determined. We have investigated the possibility that the B27 molecules from patients with ankylosing spondylitis are different from those of normals, and only the “different” molecules predispose the individual to disease. Biosynthetically radiolabeled HLA-B27 molecules from patients with ankylosing spondylitis and normal individuals were compared by two-dimensional gel electrophoresis and tryptic peptide mapping with high pressure liquid chromatography. Extensive charge heterogeneity in the 45,000-dalton heavy chain was detected when B27 molecules were analyzed by two-dimensional gel electrophoresis; the charge heterogeneity was reduced, but not eliminated, when the B27 molecules were treated with neuraminidase to remove sialic acid residues before analysis. No structural difference in the B27 molecules from an ankylosing spondylitis patient and a normal individual were detected by two-dimensional gel electrophoresis. Analysis of [3H]leucine-labeled and [3H]arginine-labeled tryptic peptides and chymotryptic peptides of the trypsin insoluble material by reverse-phase high pressure liquid chromatography revealed identity of the B27 molecules from ankylosing spondylitis patients and normal individuals. These studies indicate that development of akylosing spondylitis in only some B27 positive individuals is not attributable to those individuals possessing variant B27 molecules. Images PMID:7056855

  17. Structural Basis for Antigen Recognition by Transglutaminase 2-specific Autoantibodies in Celiac Disease*

    PubMed Central

    Chen, Xi; Hnida, Kathrin; Graewert, Melissa Ann; Andersen, Jan Terje; Iversen, Rasmus; Tuukkanen, Anne; Svergun, Dmitri; Sollid, Ludvig M.

    2015-01-01

    Antibodies to the autoantigen transglutaminase 2 (TG2) are a hallmark of celiac disease. We have studied the interaction between TG2 and an anti-TG2 antibody (679-14-E06) derived from a single gut IgA plasma cell of a celiac disease patient. The antibody recognizes one of four identified epitopes targeted by antibodies of plasma cells of the disease lesion. The binding interface was identified by small angle x-ray scattering, ab initio and rigid body modeling using the known crystal structure of TG2 and the crystal structure of the antibody Fab fragment, which was solved at 2.4 Å resolution. The result was confirmed by testing binding of the antibody to TG2 mutants by ELISA and surface plasmon resonance. TG2 residues Arg-116 and His-134 were identified to be critical for binding of 679-14-E06 as well as other epitope 1 antibodies. In contrast, antibodies directed toward the two other main epitopes (epitopes 2 and 3) were not affected by these mutations. Molecular dynamics simulations suggest interactions of 679-14-E06 with the N-terminal domain of TG2 via the CDR2 and CDR3 loops of the heavy chain and the CDR2 loop of the light chain. In addition there were contacts of the framework 3 region of the heavy chain with the catalytic domain of TG2. The results provide an explanation for the biased usage of certain heavy and light chain gene segments by epitope 1-specific antibodies in celiac disease. PMID:26160175

  18. Structural Basis for Antigen Recognition by Transglutaminase 2-specific Autoantibodies in Celiac Disease.

    PubMed

    Chen, Xi; Hnida, Kathrin; Graewert, Melissa Ann; Andersen, Jan Terje; Iversen, Rasmus; Tuukkanen, Anne; Svergun, Dmitri; Sollid, Ludvig M

    2015-08-28

    Antibodies to the autoantigen transglutaminase 2 (TG2) are a hallmark of celiac disease. We have studied the interaction between TG2 and an anti-TG2 antibody (679-14-E06) derived from a single gut IgA plasma cell of a celiac disease patient. The antibody recognizes one of four identified epitopes targeted by antibodies of plasma cells of the disease lesion. The binding interface was identified by small angle x-ray scattering, ab initio and rigid body modeling using the known crystal structure of TG2 and the crystal structure of the antibody Fab fragment, which was solved at 2.4 Å resolution. The result was confirmed by testing binding of the antibody to TG2 mutants by ELISA and surface plasmon resonance. TG2 residues Arg-116 and His-134 were identified to be critical for binding of 679-14-E06 as well as other epitope 1 antibodies. In contrast, antibodies directed toward the two other main epitopes (epitopes 2 and 3) were not affected by these mutations. Molecular dynamics simulations suggest interactions of 679-14-E06 with the N-terminal domain of TG2 via the CDR2 and CDR3 loops of the heavy chain and the CDR2 loop of the light chain. In addition there were contacts of the framework 3 region of the heavy chain with the catalytic domain of TG2. The results provide an explanation for the biased usage of certain heavy and light chain gene segments by epitope 1-specific antibodies in celiac disease. PMID:26160175

  19. Structure and stability of nickel/nickel oxide core-shell nanoparticles

    NASA Astrophysics Data System (ADS)

    D'Addato, S.; Grillo, V.; Altieri, S.; Tondi, R.; Valeri, S.; Frabboni, S.

    2011-05-01

    The results of a combined x-ray photoelectron spectroscopy (XPS) and high resolution transmission electron microscopy (HR-TEM) study of Ni nanoparticles (NP), before and after oxidation, are presented. An experimental set-up was realized for the preparation and study of pre-formed NP films, concentrating the attention on Ni NP in the diameter range between 4 and 8 nm. The XPS data were taken in situ from NPs after different stages of oxidation, including controlled dosing of O2 gas in the experimental system and exposure to the atmosphere. The Ni 2p structure is a combination of spectra from metallic Ni in the NP core and from the oxide shell. The signal from the NP core was observed even for samples after exposure to air. From the comparison of HR-TEM experimental images with theoretical simulations, it was found that the Ni NP core has a regular multitwinned icosahedral structure, composed of single-crystal tetrahedra with (111) faces. The NiO phase is clearly observed forming islands on the NP surface.

  20. Potassium dependent rescue of a myopathy with core-like structures in mouse

    PubMed Central

    Hanson, M Gartz; Wilde, Jonathan J; Moreno, Rosa L; Minic, Angela D; Niswander, Lee

    2015-01-01

    Myopathies decrease muscle functionality. Mutations in ryanodine receptor 1 (RyR1) are often associated with myopathies with microscopic core-like structures in the muscle fiber. In this study, we identify a mouse RyR1 model in which heterozygous animals display clinical and pathological hallmarks of myopathy with core-like structures. The RyR1 mutation decreases sensitivity to activated calcium release and myoplasmic calcium levels, subsequently affecting mitochondrial calcium and ATP production. Mutant muscle shows a persistent potassium leak and disrupted expression of regulators of potassium homeostasis. Inhibition of KATP channels or increasing interstitial potassium by diet or FDA-approved drugs can reverse the muscle weakness, fatigue-like physiology and pathology. We identify regulators of potassium homeostasis as biomarkers of disease that may reveal therapeutic targets in human patients with myopathy of central core disease (CCD). Altogether, our results suggest that amelioration of potassium leaks through potassium homeostasis mechanisms may minimize muscle damage of myopathies due to certain RyR1 mutations. DOI: http://dx.doi.org/10.7554/eLife.02923.001 PMID:25564733

  1. Synthesis, structural characterization and magnetic properties of Fe/Pt core-shell nanoparticles

    NASA Astrophysics Data System (ADS)

    Pisane, K. L.; Singh, Sobhit; Seehra, M. S.

    2015-05-01

    Structural and magnetic properties of Fe/Pt core-shell nanostructure prepared by a sequential reduction process are reported. Transmission electron microscopy shows nearly spherical particles fitting a lognormal size distribution with Do = 3.0 nm and distribution width λD = 0.31. In x-ray diffraction, Bragg lines only from the Pt shell are clearly identified with line-widths yielding crystallite size = 3.1 nm. Measurements of magnetization M vs. T (2 K-350 K) in magnetic fields up to 90 kOe show a blocking temperature TB = 13 K below which hysteresis loops are observed with coercivity HC increasing with decreasing T reaching HC = 750 Oe at 2 K. Temperature dependence of the ac susceptibilities at frequencies fm = 10 Hz-5 kHz is measured to determine the change in TB with fm using the Vogel-Fulcher law. This analysis shows the presence of significant interparticle interaction, the Neel-Brown relaxation frequency fo = 5.3 × 1010 Hz and anisotropy constant Ka = 3.6 × 106 ergs/cm3. A fit of the M vs. H data up to H = 90 kOe for T > TB to the modified Langevin function taking particle size distribution into account yields magnetic moment per particle consistent with the proposed core-shell structure; Fe core of 2.2 nm diameter and Pt shell of 0.4 nm thickness.

  2. Modulation of protein release from biodegradable core-shell structured fibers prepared by coaxial electrospinning.

    PubMed

    Jiang, Hongliang; Hu, Yingqian; Zhao, Pengcheng; Li, Yan; Zhu, Kangjie

    2006-10-01

    Biodegradable core-shell structured fibers with poly(epsilon-caprolactone) as shell and bovine serum albumin (BSA)-containing dextran as core were prepared by coaxial electrospinning for incorporation and controlled release of proteins. BSA loading percent in the fibers and its release rate could be conveniently varied by the feed rate of the inner dope during electrospinning. With the increase in the feed rate of the inner dope, there was an associated increase in the loading percent and accelerated release of BSA. Poly(ethylene glycol) (PEG) was added to the shell section of the fibers to further finely modulate the release behavior of BSA. It was revealed that the release rate of BSA increased with the PEG percent in the shell section. By varying the feed rate of the inner dope and PEG content, most of BSA could be released from the core-shell structured fibers within the period of time ranging from 1 week to more than 1 month. The effect of the feed rate of the inner dope and addition of PEG into the shell section on the fiber morphology was also examined by scanning electron microscope. PMID:16544305

  3. Nature-inspired design of tetraindoles: Optimization of the core structure and evaluation of structure-activity relationship.

    PubMed

    Abdu-Allah, Hajjaj H M; Huang, Shih-Ting; Chang, Tzu Ting; Chen, Chia-Ling; Wu, Han-Chung; Li, Wen-Shan

    2016-09-15

    Building on the initial successful optimization of a novel series of tetraindoles, a second generation of the compounds with changes in the core phenyl ring was synthesized to improve anticancer properties. 17 new compounds with different rigidity, planarity, symmetry and degree of conjugation of their core structures to 5-hydroxyindole units were synthesized. All the compounds were fully characterized and tested against breast cancer cell line (MDA-MB-231). The results revealed that the core structure is required for activity and it should be aromatic, rigid, planar, symmetrical and conjugated for optimal activity. Compound 29, which has strong anticancer activity against various tumor-derived cell lines, including Mahlavu (hepatocellular), SK-HEP-1 (hepatic), HCT116 (colon), MIA PaCa-2 (pancreatic), H441 (lung papillary), A549 (lung), H460 (non-small cell lung) and CL1-5 (lung carcinoma) with IC50 values ranging from 0.19 to 3.50μM, was generated after series of successive optimizations. It was found to induce cell cycle arrest and apoptosis in vitro and inhibit tumor growth in the non-obese diabetic-severe combined immunodeficiency (NOD/SCID) mice bearing xenografted MIA PaCa-2 human pancreatic cancer. PMID:27503685

  4. Phase Diagrams of Iron Rich Alloys and Their Influence on the Chemical Structure of Planetary Cores

    NASA Astrophysics Data System (ADS)

    Campbell, A. J.; Miller, N. A.; Fischer, R. A.; Seagle, C. T.; Prakapenka, V. B.

    2008-12-01

    Many planetary bodies are thought to have metallic, iron rich cores, with a significant component of some 'light' alloying element(s). The identity of this light alloying component has a profound effect on the chemical properties of the core, including its melting/crystallization behavior, partitioning of minor and trace elements during core/mantle segregation and core crystallization, and other phase relations. Despite this importance, the light element component(s) of planetary bodies generally remain unknown, apart from those of a few iron meteorite parent bodies. Experimentally determined physical and chemical properties of iron-rich systems can be compared to observations and models of planetary interiors to constrain compositions of planetary cores. Here we summarize our recent high pressure, high temperature experiments on the phase diagrams of iron+light element (Fe-X) binaries, specifically iron-sulfide, iron-silicide, and iron-oxide systems. Melting as well as subsolidus phase relations have been determined in the laser heated diamond anvil cell, using either synchrotron X-ray diffraction or optical methods to establish phase boundaries. X-ray diffraction while laser heating the sample reveals the nature of structural transitions (including partial melting), and optical methods (such as temperature vs. emissivity and related methods) establish the phase boundaries with finer precision. Drawing on these and other recent experimental results, we compare and contrast the binary Fe-X phase diagrams to address such questions as: Which candidate light elements (S, Si, O, C) cause the largest melting point depression, and how does this change with pressure? Which can produce large density constrasts against crystallizing iron metal? and others. These results are compared to thermal and chemical models of terrestrial planet interiors (including Earth's), and important gaps and discrepancies in the available experimental data are highlighted.

  5. The thermal structure of the cool core in the Phoenix cluster

    NASA Astrophysics Data System (ADS)

    Tozzi, Paolo

    2012-10-01

    The SZ-selected cluster SPT-CLJ2344-4243 at z~0.56 (the Phoenix cluster) shows for the first time a hint of a massive cooling-flow-induced starburst, suggesting that the feedback source responsible for preventing runaway cooling may not yet be fully established. We propose to robustly estimate the emission measure distribution of the cool core in the Phoenix cluster, and its temperature and abundance profiles out to 500 kpc, with a medium-deep (210 ks) EPIC observation, in order to investigate the actual structure of the cool core. The proposed study will provide secure science results with a relatively modest exposure, paving the way to an eventual deeper observation of this exceptional and puzzling source.

  6. Sizing Single Cantilever Beam Specimens for Characterizing Facesheet/Core Peel Debonding in Sandwich Structure

    NASA Technical Reports Server (NTRS)

    Ratcliffe, James G.

    2010-01-01

    This paper details part of an effort focused on the development of a standardized facesheet/core peel debonding test procedure. The purpose of the test is to characterize facesheet/core peel in sandwich structure, accomplished through the measurement of the critical strain energy release rate associated with the debonding process. The specific test method selected for the standardized test procedure utilizes a single cantilever beam (SCB) specimen configuration. The objective of the current work is to develop a method for establishing SCB specimen dimensions. This is achieved by imposing specific limitations on specimen dimensions, with the objectives of promoting a linear elastic specimen response, and simplifying the data reduction method required for computing the critical strain energy release rate associated with debonding. The sizing method is also designed to be suitable for incorporation into a standardized test protocol. Preliminary application of the resulting sizing method yields practical specimen dimensions.

  7. TiN/VN composites with core/shell structure for supercapacitors

    SciTech Connect

    Dong, Shanmu; Chen, Xiao; Gu, Lin; Zhou, Xinhong; Wang, Haibo; Liu, Zhihong; Han, Pengxian; Yao, Jianhua; Wang, Li; Cui, Guanglei; Chen, Liquan

    2011-06-15

    Research highlights: {yields} Vanadium and titanium nitride nanocomposite with core-shell structure was prepared. {yields} TiN/VN composites with different V:Ti molar ratios were obtained. {yields} TiN/VN composites can provide promising electronic conductivity and favorable capacity storage. -- Abstract: TiN/VN core-shell composites are prepared by a two-step strategy involving coating of commercial TiN nanoparticles with V{sub 2}O{sub 5}.nH{sub 2}O sols followed by ammonia reduction. The highest specific capacitance of 170 F g{sup -1} is obtained when scanned at 2 mV s{sup -1} and a promising rate capacity performance is maintained at higher voltage sweep rates. These results indicate that these composites with good electronic conductivity can deliver a favorable capacity performance.

  8. Size-dependent structural evolution of the biomineralized iron-core nanoparticles in ferritins

    NASA Astrophysics Data System (ADS)

    Lee, Eunsook; Kim, D. H.; Hwang, Jihoon; Lee, Kiho; Yoon, Sungwon; Suh, B. J.; Hyun Kim, Kyung; Kim, J.-Y.; Jang, Z. H.; Kim, Bongjae; Min, B. I.; Kang, J.-S.

    2013-04-01

    The structural identity of the biomineralized iron core nanoparticles in Helicobacter pylori ferritins (Hpf's) has been determined by employing soft x-ray absorption spectroscopy and soft x-ray magnetic circular dichroism. Valence states of Fe ions are nearly trivalent in all Hpf's, indicating that the amount of magnetite (Fe3O4) is negligible. With increasing filling of Fe ions, the local configurations of Fe3+ ions change from the mixture of the tetrahedral and octahedral symmetries to the octahedral symmetry. These results demonstrate that the biomineralization of the ferritin core changes from maghemite-like (γ-Fe2O3) formation to hematite-like (α-Fe2O3) formation with increasing Fe content.

  9. Open structure ZnO/CdSe core/shell nanoneedle arrays for solar cells

    PubMed Central

    2012-01-01

    Open structure ZnO/CdSe core/shell nanoneedle arrays were prepared on a conducting glass (SnO2:F) substrate by solution deposition and electrochemical techniques. A uniform CdSe shell layer with a grain size of approximately several tens of nanometers was formed on the surface of ZnO nanoneedle cores after annealing at 400°C for 1.5 h. Fabricated solar cells based on these nanostructures exhibited a high short-circuit current density of about 10.5 mA/cm2 and an overall power conversion efficiency of 1.07% with solar illumination of 100 mW/cm2. Incident photo-to-current conversion efficiencies higher than 75% were also obtained. PMID:22995031

  10. Spiral-like structure in the core of nearby galaxy clusters

    SciTech Connect

    Lagana, Tatiana F.; Andrade-Santos, Felipe; Lima Neto, Gastao B.

    2010-07-15

    Not surprisingly, with the very high angular resolution of the Chandra telescope, results revealed fairly complex structures in cluster cores to be more common than expected. In particular, understanding the nature of spiral-like features at the center of some clusters is the major motivation of this work. We present results from Chandra deep observations of 15 nearby galaxy clusters (0.01core of 7 clusters: A85, A426, A496, Hydra A, Centaurus, A1644 and Ophiuchus. Comparing our results to numerical simulations, our investigation lends support to the fact that these patterns are due to nonzero impact parameter mergers.

  11. The structure, morphology, and the metal-enhanced fluorescence of nano-Ag/ZnO core-shell structure

    NASA Astrophysics Data System (ADS)

    Zhao, Yue; Ding, Yanli; Peng, Xiang; Zhou, Mingtao; Liang, Xiaoyan; Min, Jiahua; Wang, Linjun; Shi, Weimin

    2015-06-01

    Nano-polyc rystalline silver (Ag) particles with the diameter of 60 nm were synthesized by the reducing agent sodium citrate. An amorphous zinc oxide (ZnO) shell layer was then coated on the surface of silver particles using wet chemical method. The Ag/ZnO core-shell structure was characterized by scanning electron microscope, transmission electron microscopy, ultraviolet-visible spectroscopy and fluorescence (FL) measurement. The results showed that nano-Ag/ZnO core-shell particles with an average diameter of ~100 nm were prepared successfully, and the FL intensity of Rhodamine 6G (R6G) mixed with Ag/ZnO nanoparticle was 53 % greater than that of the same amount of R6G without any nanoparticles, which may be related to the effect of surface plasmon resonance.

  12. The structure, morphology, and the metal-enhanced fluorescence of nano-Ag/ZnO core-shell structure

    NASA Astrophysics Data System (ADS)

    Zhao, Yue; Ding, Yanli; Peng, Xiang; Zhou, Mingtao; Liang, Xiaoyan; Min, Jiahua; Wang, Linjun; Shi, Weimin

    2014-09-01

    Nano-polyc rystalline silver (Ag) particles with the diameter of 60 nm were synthesized by the reducing agent sodium citrate. An amorphous zinc oxide (ZnO) shell layer was then coated on the surface of silver particles using wet chemical method. The Ag/ZnO core-shell structure was characterized by scanning electron microscope, transmission electron microscopy, ultraviolet-visible spectroscopy and fluorescence (FL) measurement. The results showed that nano-Ag/ZnO core-shell particles with an average diameter of ~100 nm were prepared successfully, and the FL intensity of Rhodamine 6G (R6G) mixed with Ag/ZnO nanoparticle was 53 % greater than that of the same amount of R6G without any nanoparticles, which may be related to the effect of surface plasmon resonance.

  13. Insight into the core-shell structures of Cu-In-S microspheres

    NASA Astrophysics Data System (ADS)

    Wochnik, Angela S.; Frank, Anna; Heinzl, Christoph; Häusler, Jonas; Schneider, Julian; Hoffmann, Ramona; Matich, Sonja; Scheu, Christina

    2013-12-01

    In this study we report about the inner and outer structure of CuInS2 microspheres which might be used e.g. in pastes for simple, low-cost solar cell preparation, as well as in electrodes for light-driven water splitting. The microspheres are synthesized via a mild, template-free solvothermal synthesis route and characterised by electron and focused ion beam microscopy, X-ray diffraction, inductively coupled plasma atomic emission and energy dispersive X-ray spectroscopy. The investigations of cross sections prepared by focused ion beam showed that the spheres consist of compact cores and flaky surface structures. Depending on the reaction time, the core possesses a stoichiometric or Cu-rich chemical composition surrounded by an In-rich shell. The flaky surface always comprises a stoichiometric composition in tetragonal chalcopyrite crystal structure, whereas the other areas additionally show minor contributions of CuS, and CuInS2 in hexagonal wurtzite structure. The presence of different phases can be beneficial for future applications since they offer different absorption behaviour in the visible range.

  14. Hypervelocity Impact Performance of Open Cell Foam Core Sandwich Panel Structures

    NASA Technical Reports Server (NTRS)

    Ryan, S.; Ordonez, E.; Christiansen, E. L.; Lear, D. M.

    2010-01-01

    Open cell metallic foam core sandwich panel structures are of interest for application in spacecraft micrometeoroid and orbital debris shields due to their novel form and advantageous structural and thermal performance. Repeated shocking as a result of secondary impacts upon individual foam ligaments during the penetration process acts to raise the thermal state of impacting projectiles ; resulting in fragmentation, melting, and vaporization at lower velocities than with traditional shielding configurations (e.g. Whipple shield). In order to characterize the protective capability of these structures, an extensive experimental campaign was performed by the Johnson Space Center Hypervelocity Impact Technology Facility, the results of which are reported in this paper. Although not capable of competing against the protection levels achievable with leading heavy shields in use on modern high-risk vehicles (i.e. International Space Station modules), metallic foam core sandwich panels are shown to provide a substantial improvement over comparable structural panels and traditional low weight shielding alternatives such as honeycomb sandwich panels and metallic Whipple shields. A ballistic limit equation, generalized in terms of panel geometry, is derived and presented in a form suitable for application in risk assessment codes.

  15. The Dependence of ITCZ Structure on Model Resolution and Dynamical Core in Aquaplanet Simulations

    SciTech Connect

    Landu, Kiranmayi; Leung, Lai-Yung R.; Hagos, Samson M.; Vinoj, V.; Rauscher, Sara; Ringler, Todd; Taylor, Mark

    2014-03-15

    Aqua-planet simulations using the Community Atmosphere Model version 4 (CAM4) with the Model for Prediction Across Scales Atmosphere (MPAS-A) and Higher Order Method Modeling Environment (HOMME) dynamical cores and zonally symmetric sea surface temperature (SST) structure are studied to understand the dependence of the inter-tropical convergence zone (ITCZ) structure on resolution and dynamical core. While all resolutions in HOMME and the low-resolution MPAS-A simulations give a single equatorial peak in zonal mean precipitation, the high-resolution MPAS-A simulations give a double ITCZ with precipitation peaking around 2° to 3° on either side of the equator. This study reveals that the structure of ITCZ is dependent on the feedbacks among convection and large-scale circulation and surface heat fluxes. We show that, by increasing convective available potential energy (CAPE) off the equator, the simulations with higher wind induced surface heat fluxes result in double ITCZ structure. This in turn leads to stronger convection and positive feedback with the large-scale circulation. We further show that the dominance of anti-symmetric waves in a model is not enough to cause double ITCZ, and the lateral extent of equatorial waves does not play an important role in determining the width of the ITCZ but rather the latter may influence the former.

  16. Structural optical correlated properties of SnO2/Al2O3 core@ shell heterostructure

    NASA Astrophysics Data System (ADS)

    Heiba, Zein K.; Imam, N. G.; Bakr Mohamed, Mohamed

    2016-07-01

    Nano size polycrystalline samples of the core@shell heterostructure of SnO2 @ xAl2O3 (x = 0, 25, 50, 75 wt.%) were synthesized by sol-gel technique. The resulting samples were characterized with fourier transform infrared spectroscopy (FT-IR), photoluminescence (PL) and X-ray powder diffraction (XRD). The XRD patterns manifest diffraction peaks of SnO2 as main phase with weak peaks corresponding to Al2O3 phase. The formation of core@ shell structure is confirmed by TEM images and Rietveld quantitative phase analysis which revealed that small part of Al2O3 is incorporated into the SnO2 lattice while the main part (shell) remains as a separate phase segregated on the grain boundary surface of SnO2 (core). It is found that the grain size of the mixed oxides SnO2 @ xAl2O3 is below 10 nm while for pure SnO2 it is over 41 nm, indicating that alumina can effectively prevent SnO2 from further growing up in the process of calcination. This is confirmed by the large increase in the specific surface area for mixed oxide samples. The PL emission showed great dependence on the structure properties analyzed by XRD and FTIR. The PL results recommend Al2O3@SnO2 core@shell heterostructure to be a promising short-wavelength luminescent optoelectronic devices for blue, UV, and laser light-emitting diodes.

  17. Structural and antigenic types of cell wall polysaccharides from viridans group streptococci with receptors for oral actinomyces and streptococcal lectins.

    PubMed

    Cisar, J O; Sandberg, A L; Reddy, G P; Abeygunawardana, C; Bush, C A

    1997-12-01

    Lectin-mediated interactions between oral viridans group streptococci and actinomyces may play an important role in microbial colonization of the tooth surface. The presence of two host-like motifs, either GalNAc beta1-->3Gal (Gn) or Gal beta1-->3GalNAc (G), in the cell wall polysaccharides of five streptococcal strains accounts for the lactose-sensitive coaggregations of these bacteria with Actinomyces naeslundii. Three streptococcal strains which have Gn-containing polysaccharides also participate in GalNAc-sensitive coaggregations with strains of Streptococcus gordonii and S. sanguis. Each Gn- or G-containing polysaccharide is composed of a distinct phosphodiester-linked hexa- or heptasaccharide repeating unit. The occurrence of these polysaccharides on 19 additional viridans group streptococcal strains that participate in lactose-sensitive coaggregations with actinomyces was examined. Negatively charged polysaccharides that reacted with Bauhinia purpurea agglutinin, a Gal and GalNAc binding plant lectin, were isolated from 17 strains by anion exchange column chromatography of mutanolysin-cell wall digests. Results from nuclear magnetic resonance and immunodiffusion identified each of 16 polysaccharides as a known Gn- or G-containing structural type and one polysaccharide as a new but closely related Gn-containing type. Unlike the reactions of lectins, the cross-reactions of most rabbit antisera with these polysaccharides were correlated with structural features other than the host-like motifs. Gn-containing polysaccharides occurred primarily on the strains of S. sanguis and S. oralis while G-containing polysaccharides were more common among the strains of S. gordonii and S. mitis examined. The findings strongly support the hypothesis that lectin-mediated recognition of these streptococci by other oral bacteria depends on a family of antigenically diverse Gn- and G-containing cell wall polysaccharides, the occurrence of which may differ between streptococcal

  18. Structural and antigenic types of cell wall polysaccharides from viridans group streptococci with receptors for oral actinomyces and streptococcal lectins.

    PubMed Central

    Cisar, J O; Sandberg, A L; Reddy, G P; Abeygunawardana, C; Bush, C A

    1997-01-01

    Lectin-mediated interactions between oral viridans group streptococci and actinomyces may play an important role in microbial colonization of the tooth surface. The presence of two host-like motifs, either GalNAc beta1-->3Gal (Gn) or Gal beta1-->3GalNAc (G), in the cell wall polysaccharides of five streptococcal strains accounts for the lactose-sensitive coaggregations of these bacteria with Actinomyces naeslundii. Three streptococcal strains which have Gn-containing polysaccharides also participate in GalNAc-sensitive coaggregations with strains of Streptococcus gordonii and S. sanguis. Each Gn- or G-containing polysaccharide is composed of a distinct phosphodiester-linked hexa- or heptasaccharide repeating unit. The occurrence of these polysaccharides on 19 additional viridans group streptococcal strains that participate in lactose-sensitive coaggregations with actinomyces was examined. Negatively charged polysaccharides that reacted with Bauhinia purpurea agglutinin, a Gal and GalNAc binding plant lectin, were isolated from 17 strains by anion exchange column chromatography of mutanolysin-cell wall digests. Results from nuclear magnetic resonance and immunodiffusion identified each of 16 polysaccharides as a known Gn- or G-containing structural type and one polysaccharide as a new but closely related Gn-containing type. Unlike the reactions of lectins, the cross-reactions of most rabbit antisera with these polysaccharides were correlated with structural features other than the host-like motifs. Gn-containing polysaccharides occurred primarily on the strains of S. sanguis and S. oralis while G-containing polysaccharides were more common among the strains of S. gordonii and S. mitis examined. The findings strongly support the hypothesis that lectin-mediated recognition of these streptococci by other oral bacteria depends on a family of antigenically diverse Gn- and G-containing cell wall polysaccharides, the occurrence of which may differ between streptococcal

  19. Structural Metals in the Group I Intron: A Ribozyme with a Multiple Metal Ion Core

    SciTech Connect

    Stahley,M.; Adams, P.; Wang, J.; Strobel, S.

    2007-01-01

    Metal ions play key roles in the folding and function for many structured RNAs, including group I introns. We determined the X-ray crystal structure of the Azoarcus bacterial group I intron in complex with its 5' and 3' exons. In addition to 222 nucleotides of RNA, the model includes 18 Mg2+ and K+ ions. Five of the metals bind within 12 Angstroms of the scissile phosphate and coordinate the majority of the oxygen atoms biochemically implicated in conserved metal-RNA interactions. The metals are buried deep within the structure and form a multiple metal ion core that is critical to group I intron structure and function. Eight metal ions bind in other conserved regions of the intron structure, and the remaining five interact with peripheral structural elements. Each of the 18 metals mediates tertiary interactions, facilitates local bends in the sugar-phosphate backbone or binds in the major groove of helices. The group I intron has a rich history of biochemical efforts aimed to identify RNA-metal ion interactions. The structural data are correlated to the biochemical results to further understand the role of metal ions in group I intron structure and function.

  20. The Interior Structure of the G31.41+0.31 Hot Molecular Core

    NASA Astrophysics Data System (ADS)

    Araya, Esteban; Hofner, Peter; Olmi, Luca; Linz, Hendrik; Kurtz, Stan; Cesaroni, Riccardo

    We present interferometric images at 7mm and 3.6cm with a resolution of 1500 AU of the G31.41+0.31 Hot Molecular Core. Our observations show an elongated structure which is oriented perpendicular to the bipolar flow observed by Olmi et al. (1996). If the 7mm emission is entirely due to dust then the total mass in this structure is on the order of 500 solar masses which implies densities of order 1010 cm-3. The 3.6cm emission is unresolved and coincident with the 7mm peak and likely marks the position of the central object. We discuss the elongated structure in terms of an accretion disk scenario as well as a binary scenario. This work is partially supported by Research Corporation grant Nr. CC4996 and NSF grant AST-0098524.

  1. On the mineral core of ferritin-like proteins: structural and magnetic characterization

    NASA Astrophysics Data System (ADS)

    García-Prieto, A.; Alonso, J.; Muñoz, D.; Marcano, L.; Abad Díaz de Cerio, A.; Fernández de Luis, R.; Orue, I.; Mathon, O.; Muela, A.; Fdez-Gubieda, M. L.

    2015-12-01

    It is generally accepted that the mineral core synthesized by ferritin-like proteins consists of a ferric oxy-hydroxide mineral similar to ferrihydrite in the case of horse spleen ferritin (HoSF) and an oxy-hydroxide-phosphate phase in plant and prokaryotic ferritins. The structure reflects a dynamic process of deposition and dissolution, influenced by different biological, chemical and physical variables. In this work we shed light on this matter by combining a structural (High Resolution Transmission Electron Microscopy (HRTEM) and Fe K-edge X-ray Absorption Spectroscopy (XAS)) and a magnetic study of the mineral core biomineralized by horse spleen ferritin (HoSF) and three prokaryotic ferritin-like proteins: bacterial ferritin (FtnA) and bacterioferritin (Bfr) from Escherichia coli and archaeal ferritin (PfFtn) from Pyrococcus furiosus. The prokaryotic ferritin-like proteins have been studied under native conditions and inside the cells for the sake of preserving their natural attributes. They share with HoSF a nanocrystalline structure rather than an amorphous one as has been frequently reported. However, the presence of phosphorus changes drastically the short-range order and magnetic response of the prokaryotic cores with respect to HoSF. The superparamagnetism observed in HoSF is absent in the prokaryotic proteins, which show a pure atomic-like paramagnetic behaviour attributed to phosphorus breaking the Fe-Fe exchange interaction.It is generally accepted that the mineral core synthesized by ferritin-like proteins consists of a ferric oxy-hydroxide mineral similar to ferrihydrite in the case of horse spleen ferritin (HoSF) and an oxy-hydroxide-phosphate phase in plant and prokaryotic ferritins. The structure reflects a dynamic process of deposition and dissolution, influenced by different biological, chemical and physical variables. In this work we shed light on this matter by combining a structural (High Resolution Transmission Electron Microscopy (HRTEM

  2. Extremely high energy hadron and gamma-ray families(3). Core structure of the halo of superfamily

    NASA Technical Reports Server (NTRS)

    Yamashita, S.; Ohsawa, A.; Chinellato, J. A.; Shibuya, E. H.

    1985-01-01

    The study of the core structure seen in the halo of Mini-Andromeda 3(M.A.3), which was observed in the Chacaltaya emulsion chamber, is presented. On the assumption that lateral distribution of darkness of the core is exponential type, i.e., D=D0exp(-R/r0), subtraction of D from halo darkness is performed until the cores are gone. The same quantity on cores obtained by this way are summarized. The analysis is preliminary and is going to be developed.

  3. CCD photometry of globular cluster core structure. I - NGC 6388, NGC 6624, and M15: One flat core and two cusps

    NASA Technical Reports Server (NTRS)

    Lugger, Phyllis M.; Cohn, Haldan; Grindlay, Jonathan E.; Bailyn, Charles D.; Hertz, Paul

    1987-01-01

    The first results of a major survey of globular cluster core structure are reported. Surface brightness profiles for three clusters are presented: one with a normal flat core profile (NGC 6388), and two with central cusps (NGC 6624 and M15). The profiles are fitted with both seeing-convolved King models and seeing-convolved power laws. A King model provides a reasonable fit to the entire profile of NGC 6388, but there are no acceptable King profiles for NGC 6624 and M15. For these two clusters, a seeing-convolved power law provides a good fit to the inner part of the profile, while a King model gives a good fit to the outer part of the profile. The interpretation of the measured power-law slopes of the central surface brightness cusps of NGC 6624 and M15 are discussed in terms of models for core collapse in a multicomponent cluster.

  4. Au@SiO2 core-shell structure involved with methotrexate: Fabrication, biodegradation process and bioassay explore.

    PubMed

    Huo, Xiaolei; Dai, Chaofan; Tian, Deying; Li, Shuping; Li, Xiaodong

    2015-12-30

    A new strategy is proposed to synthesize a kind of Au@SiO2 core-shell structure with methotrexate (MTX) loaded within it. Firstly, MTX molecules are attracted to the surface and vicinity of Au nanoparticles (NPs). Then the enriched MTX molecules on the surface of Au NPs have a good chance to be wrapped into the core-shell structure when SiO2 is uniformly deposited on the Au core. Secondly, the effect of Au amount and MTX content on the drug-loading capacity is emphatically studied and the result shows that core-shell structure plays a vital role in drug loading. In addition, the biodegradation process is also examined in phosphate buffer solution (PBS) at 37°C. The results show that the biodegradation of Au-MTX@SiO2 core-shell structure can be divided into two stages: the release of drug together with the fragmentation of core-shell structure and the subsequent dissolution of SiO2 layers. Lastly, in vitro bioassay tests give the evidence that obvious tumor inhibition can be achieved in presence of Au-MTX@SiO2 NPs even at low concentration and the efficacy can be greatly enhanced by the photothermal therapy on Au cores. PMID:26516099

  5. Physical properties of the drill core from the El'gygytgyn impact structure, NE Russia

    NASA Astrophysics Data System (ADS)

    Maharaj, Dharmindar; Elbra, Tiiu; Pesonen, Lauri J.

    2013-07-01

    The El'gygytgyn impact structure in northeast Russia was drilled in 2008/2009. The 3.5 Ma old structure has a rim-to-rim diameter of 18 km and is the only known impact structure that has been formed on a siliceous volcanic target. The petrophysical, rock- and paleomagnetic properties, including attempted reorientation of samples, along the El'gygytgyn drill core were analyzed. Physical properties, such as bulk density, porosity, seismic velocity, and electrical conductivity, clearly showed the propagation of shock and the associated fracturing. The grain density, however, was probably influenced by the postimpact hydrothermal activity and/or the distribution of impact melt. The highest values of electrical conductivity coincided with higher concentrations of particular metals as indicated by Raschke et al. (2012a). The rock- and paleomagnetic investigations showed iron-titanium oxides with varying oxidation/reduction states as the main magnetic fraction in the core samples and indicated them as carriers for remanent magnetization. With few exceptions, most samples showed normal polarity of characteristic remanent magnetization and confirmed that the impact occurred after the Gauss/Gilbert (approximately 3.596 Ma) reversal. Shallower inclinations than that expected for a 3.5 Ma dipole field were probably due to impact-related block movements and/or compaction.

  6. Maturation of phage T7 involves structural modification of both shell and inner core components.

    PubMed

    Agirrezabala, Xabier; Martín-Benito, Jaime; Castón, José R; Miranda, Roberto; Valpuesta, José María; Carrascosa, José L

    2005-11-01

    The double-stranded DNA bacteriophages are good model systems to understand basic biological processes such as the macromolecular interactions that take place during the virus assembly and maturation, or the behavior of molecular motors that function during the DNA packaging process. Using cryoelectron microscopy and single-particle methodology, we have determined the structures of two phage T7 assemblies produced during its morphogenetic process, the DNA-free prohead and the mature virion. The first structure reveals a complex assembly in the interior of the capsid, which involves the scaffolding, and the core complex, which plays an important role in DNA packaging and is located in one of the phage vertices. The reconstruction of the mature virion reveals important changes in the shell, now much larger and thinner, the disappearance of the scaffolding structure, and important rearrangements of the core complex, which now protrudes the shell and interacts with the tail. Some of these changes must originate by the pressure exerted by the DNA in the interior of the head. PMID:16211007

  7. Maturation of phage T7 involves structural modification of both shell and inner core components

    PubMed Central

    Agirrezabala, Xabier; Martín-Benito, Jaime; Castón, José R; Miranda, Roberto; Valpuesta, José María; Carrascosa, José L

    2005-01-01

    The double-stranded DNA bacteriophages are good model systems to understand basic biological processes such as the macromolecular interactions that take place during the virus assembly and maturation, or the behavior of molecular motors that function during the DNA packaging process. Using cryoelectron microscopy and single-particle methodology, we have determined the structures of two phage T7 assemblies produced during its morphogenetic process, the DNA-free prohead and the mature virion. The first structure reveals a complex assembly in the interior of the capsid, which involves the scaffolding, and the core complex, which plays an important role in DNA packaging and is located in one of the phage vertices. The reconstruction of the mature virion reveals important changes in the shell, now much larger and thinner, the disappearance of the scaffolding structure, and important rearrangements of the core complex, which now protrudes the shell and interacts with the tail. Some of these changes must originate by the pressure exerted by the DNA in the interior of the head. PMID:16211007

  8. Role of core support material in veneer failure of brittle layer structures.

    PubMed

    Hermann, Ilja; Bhowmick, Sanjit; Lawn, Brian R

    2007-07-01

    A study is made of veneer failure by cracking in all-ceramic crown-like layer structures. Model trilayers consisting of a 1 mm thick external glass layer (veneer) joined to a 0.5 mm thick inner stiff and hard ceramic support layer (core) by epoxy bonding or by fusion are fabricated for testing. The resulting bilayers are then glued to a thick compliant polycarbonate slab to simulate a dentin base. The specimens are subjected to cyclic contact (occlusal) loading with spherical indenters in an aqueous environment. Video cameras are used to record the fracture evolution in the transparent glass layer in situ during testing. The dominant failure mode is cone cracking in the glass veneer by traditional outer (Hertzian) cone cracks at higher contact loads and by inner (hydraulically pumped) cone cracks at lower loads. Failure is deemed to occur when one of these cracks reaches the veneer/core interface. The advantages and disadvantages of the alumina and zirconia core materials are discussed in terms of mechanical properties-strength and toughness, as well as stiffness. Consideration is also given to the roles of interface strength and residual thermal expansion mismatch stresses in relation to the different joining methods. PMID:17078086

  9. Detectability of temporal changes in fine structures near the inner core boundary beneath the eastern hemisphere

    NASA Astrophysics Data System (ADS)

    Yu, W.

    2016-07-01

    The inner core boundary (ICB), where melting and solidification of the core occur, plays a crucial role in the dynamics of the Earth's interior. To probe temporal changes near the ICB beneath the eastern hemisphere, I analyze differential times of PKiKP (dt(PKiKP)), double differential times of PKiKP-PKPdf, and PKiKP coda waves from repeating earthquakes in the southwest Pacific subduction zones. dt(PKiKP) values are mostly within ±30 ms of one another, without systematic temporal dependence. Some observations of PKiKP coda waves have absolute time shifts of >50 ms relative to their main phases. The combination of temporal changes in PKiKP coda arrivals and negligible changes in PKiKP arrivals favors a smooth ICB with fine-scale structures in the upper inner core. dt(PKiKP) values are interpreted in the context of melting- or growth-induced ICB topography, based on dynamic models. Uncertainties in dt(PKiKP) prevent verification of ICB melting or growth on decadal time scales.

  10. Petrophysical and paleomagnetic data of drill cores from the Bosumtwi impact structure, Ghana

    NASA Astrophysics Data System (ADS)

    Elbra, T.; Kontny, A.; Pesonen, L. J.; Schleifer, N.; Schell, C.

    Physical properties from rocks of the Bosumtwi impact structure, Ghana, Central Africa, are essential to understand the formation of the relatively young (1.07 Ma) and small (10.5 km) impact crater and to improve its geophysical modeling. Results of our petrophysical studies of deep drill cores LB-07A and LB-08A reveal distinct lithological patterns but no depth dependence. The most conspicuous difference between impactites and target lithologies are the lower bulk densities and significantly higher porosities of the suevite and lithic breccia units compared to meta-graywacke and metapelites of target lithologies. Magnetic susceptibility shows mostly paramagnetic values (200-500 × 10-6 SI) throughout the core, with an exception of a few metasediment samples, and correlates positively with natural remanent magnetization (NRM) and Q values. These data indicate that magnetic parameters are related to inhomogeneously distributed ferrimagnetic pyrrhotite. The paleomagnetic data reveals that the characteristic direction of NRM has shallow normal (in a few cases shallow reversed) polarity, which is in agreement with the Lower Jaramillo N-polarity chron direction, and is carried by ferrimagnetic pyrrhotite. However, our study has not revealed the expected high magnetization body required from previous magnetic modeling. Furthermore, the LB-07A and LB08-A drill cores did not show the predicted high content of melt in the rocks, requiring a new interpretation model for magnetic data.

  11. Structuring a written examination to assess ASBH health care ethics consultation core knowledge competencies.

    PubMed

    White, Bruce D; Jankowski, Jane B; Shelton, Wayne N

    2014-01-01

    As clinical ethics consultants move toward professionalization, the process of certifying individual consultants or accrediting programs will be discussed and debated. With certification, some entity must be established or ordained to oversee the standards and procedures. If the process evolves like other professions, it seems plausible that it will eventually include a written examination to evaluate the core knowledge competencies that individual practitioners should possess to meet peer practice standards. The American Society for Bioethics and Humanities (ASBH) has published core knowledge competencies for many years that are accepted by experts as the prevailing standard. Probably any written examination will be based upon the ASBH core knowledge competencies. However, much remains to be done before any examination may be offered. In particular, it seems likely that a recognized examining board must create and validate examination questions and structure the examination so as to establish meaningful, defensible parameters after dealing with such challenging questions as: Should the certifying examination be multiple choice or short-answer essay? How should the test be graded? What should the pass rate be? How may the examination be best administered? To advance the field of health care ethics consultation, thought leaders should start to focus on the written examination possibilities, to date unaddressed carefully in the literature. Examination models-both objective and written-must be explored as a viable strategy about how the field of health care ethics consultations can grow toward professionalization. PMID:24422920

  12. Structures of two novel, serologically nonrelated core oligosaccharides of Yokenella regensburgei lipopolysaccharides differing only by a single hexose substitution.

    PubMed

    Niedziela, Tomasz; Jachymek, Wojciech; Lukasiewicz, Jolanta; Maciejewska, Anna; Andersson, Rolf; Kenne, Lennart; Lugowski, Czeslaw

    2010-02-01

    Immunochemical analysis of the Yokenella regensburgei lipopolysaccharides (LPS) indicated the presence of the core oligosaccharide-related immunotypes among the investigated strains. The structure of the core oligosaccharide segment of the Y. regensburgei LPS has been investigated using chemical methods, mass spectrometry, and (1)H, (13)C NMR spectroscopy. It was concluded that the core oligosaccharides of the strains PCM 2476 and PCM 2477 are composed of an undecasaccharide. The combined data revealed two immunotypes of the core oligosaccharide recognized by antibodies against the whole bacterial cells. The structural differences between the core oligosaccharides are limited to the outermost terminal hexopyranose residue. In the core oligosaccharide of the strain PCM 2476, it was identified as alpha-d-Glcp and in that of the strain PCM 2477 as alpha-d-Galp. This subtle difference between the glycoforms of the LPS core appeared to be essential for formation of the epitopes recognized by the specific antibodies directed against the Y. regensburgei whole bacterial cells. The oligosaccharides are not substituted by phosphate groups. Instead, the carboxyl groups of Kdo and galacturonic acid residues present in the core provide the negative charges. The undecasaccharides represent a novel core type of bacterial LPS, which is characteristic for Y. regensburgei. PMID:19880424

  13. Nematic liquid crystals with a tetrafluoroethylene bridge in the mesogenic core structure.

    PubMed

    Kirsch, P; Bremer, M; Huber, F; Lannert, H; Ruhl, A; Lieb, M; Wallmichrath, T

    2001-06-13

    A dramatic increase of the clearing temperatures of liquid crystals based on bis(cyclohexyl)ethane 1 by 50 to 70 K can be achieved by the perfluorination of the central ethylene link. Conformational analysis indicates that this effect is due to the increased rigidity of the mesogenic core structure and to the suppression of conformers with a bent shape. Materials based on bis(cylohexyl)tetrafluoroethane 2 might play a crucial role as materials for the next generation of active matrix LCDs with reduced power consumption. PMID:11389620

  14. Optimal design of hollow core-shell structural active materials for lithium ion batteries

    NASA Astrophysics Data System (ADS)

    Jiang, Wenjuan; Li, Tingting; Ma, Zengsheng; Lin, Jianguo; Lu, Chunsheng

    To mitigate mechanical and chemical degradation of active materials, hollow core-shell structures have been applied in lithium ion batteries. Without embedding of lithium ions, the rigid coating shell can constrain the inward volume deformation. In this paper, optimal conditions for the full use of inner hollow space are identified in terms of the critical ratio of shell thickness and inner size and the state of charge. It is shown that the critical ratios are 0.10 and 0.15 for Si particle and tube (0.12 and 0.18 for Sn particle and tube), and above which there is lack of space for further lithiation.

  15. Single-step in situ synthesis of double bond-grafted yttrium-hydroxide nanotube core-shell structures.

    PubMed

    Li, Weijia; Wang, Xun; Li, Yadong

    2004-01-21

    Novel MMA-Y(OH)(3) nanotube core-shell structures have been successfully prepared with double bonds successfully grafted on the surface through a single-step in-situ hydrothermal method. PMID:14737530

  16. Diverse melting modes and structural collapse of hollow bimetallic core-shell nanoparticles: a perspective from molecular dynamics simulations.

    PubMed

    Huang, Rao; Shao, Gui-Fang; Zeng, Xiang-Ming; Wen, Yu-Hua

    2014-01-01

    Introducing hollow structures into metallic nanoparticles has become a promising route to improve their catalytic performances. A fundamental understanding of thermal stability of these novel nanostructures is of significance for their syntheses and applications. In this article, molecular dynamics simulations have been employed to offer insights into the thermodynamic evolution of hollow bimetallic core-shell nanoparticles. Our investigation reveals that for hollow Pt-core/Au-shell nanoparticle, premelting originates at the exterior surface, and a typical two-stage melting behavior is exhibited, similar to the solid ones. However, since the interior surface provides facilitation for the premelting initiating at the core, the two-stage melting is also observed in hollow Au-core/Pt-shell nanoparticle, remarkably different from the solid one. Furthermore, the collapse of hollow structure is accompanied with the overall melting of the hollow Pt-core/Au-shell nanoparticle while it occurs prior to that of the hollow Au-core/Pt-shell nanoparticle and leads to the formation of a liquid-core/solid-shell structure, although both of them finally transform into a mixing alloy with Au-dominated surface. Additionally, the existence of stacking faults in the hollow Pt-core/Au-shell nanoparticle distinctly lowers its melting point. This study could be of great importance to the design and development of novel nanocatalysts with both high activity and excellent stability. PMID:25394424

  17. Diverse Melting Modes and Structural Collapse of Hollow Bimetallic Core-Shell Nanoparticles: A Perspective from Molecular Dynamics Simulations

    PubMed Central

    Huang, Rao; Shao, Gui-Fang; Zeng, Xiang-Ming; Wen, Yu-Hua

    2014-01-01

    Introducing hollow structures into metallic nanoparticles has become a promising route to improve their catalytic performances. A fundamental understanding of thermal stability of these novel nanostructures is of significance for their syntheses and applications. In this article, molecular dynamics simulations have been employed to offer insights into the thermodynamic evolution of hollow bimetallic core-shell nanoparticles. Our investigation reveals that for hollow Pt-core/Au-shell nanoparticle, premelting originates at the exterior surface, and a typical two-stage melting behavior is exhibited, similar to the solid ones. However, since the interior surface provides facilitation for the premelting initiating at the core, the two-stage melting is also observed in hollow Au-core/Pt-shell nanoparticle, remarkably different from the solid one. Furthermore, the collapse of hollow structure is accompanied with the overall melting of the hollow Pt-core/Au-shell nanoparticle while it occurs prior to that of the hollow Au-core/Pt-shell nanoparticle and leads to the formation of a liquid-core/solid-shell structure, although both of them finally transform into a mixing alloy with Au-dominated surface. Additionally, the existence of stacking faults in the hollow Pt-core/Au-shell nanoparticle distinctly lowers its melting point. This study could be of great importance to the design and development of novel nanocatalysts with both high activity and excellent stability. PMID:25394424

  18. Core size determination and structural characterization of intravenous iron complexes by cryogenic transmission electron microscopy.

    PubMed

    Wu, Yong; Petrochenko, Peter; Chen, Lynn; Wong, Sook Yee; Absar, Mohammad; Choi, Stephanie; Zheng, Jiwen

    2016-05-30

    Understanding physicochemical properties of intravenous (IV) iron drug products is essential to ensure the manufacturing process is consistent and streamlined. The history of physicochemical characterization of IV iron complex formulations stretches over several decades, with disparities in iron core size and particle morphology as the major source of debate. One of the main reasons for this controversy is room temperature sample preparation artifacts, which affect accurate determination of size, shape and agglomeration/aggregation of nanoscale iron particles. The present study is first to report the ultra-fine iron core structures of four IV iron complex formulations, sodium ferric gluconate, iron sucrose, low molecular weight iron dextran and ferumoxytol, using a cryogenic transmission electron microscopy (cryo-TEM) preservation technique, as opposed to the conventional room temperature (RT-TEM) technique. Our results show that room temperature preparation causes nanoparticle aggregation and deformation, while cryo-TEM preserves IV iron colloidal suspension in their native frozen-hydrated and undiluted state. In contrast to the current consensus in literature, all four IV iron colloids exhibit a similar morphology of their iron oxide cores with a spherical shape, narrow size distribution and an average size of 2nm. Moreover, out of the four tested formulations, ferumoxytol exhibits a cluster-like community of several iron carbohydrate particles which likely accounts for its large hydrodynamic size of 25nm, measured with dynamic light scattering. Our findings outline a suitable method for identifying colloidal nanoparticle core size in the native state, which is increasingly important for manufacturing and design control of complex drug formulations, such as IV iron drug products. PMID:27001529

  19. Crystal Structure of Plasmodium knowlesi Apical Membrane Antigen 1 and Its Complex with an Invasion-Inhibitory Monoclonal Antibody

    PubMed Central

    van der Eijk, Marjolein; Thomas, Alan W.; Singh, Balbir; Kocken, Clemens H. M.

    2015-01-01

    The malaria parasite Plasmodium knowlesi, previously associated only with infection of macaques, is now known to infect humans as well and has become a significant public health problem in Southeast Asia. This species should therefore be targeted in vaccine and therapeutic strategies against human malaria. Apical Membrane Antigen 1 (AMA1), which plays a role in Plasmodium merozoite invasion of the erythrocyte, is currently being pursued in human vaccine trials against P. falciparum. Recent vaccine trials in macaques using the P. knowlesi orthologue PkAMA1 have shown that it protects against infection by this parasite species and thus should be developed for human vaccination as well. Here, we present the crystal structure of Domains 1 and 2 of the PkAMA1 ectodomain, and of its complex with the invasion-inhibitory monoclonal antibody R31C2. The Domain 2 (D2) loop, which is displaced upon binding the Rhoptry Neck Protein 2 (RON2) receptor, makes significant contacts with the antibody. R31C2 inhibits binding of the Rhoptry Neck Protein 2 (RON2) receptor by steric blocking of the hydrophobic groove and by preventing the displacement of the D2 loop which is essential for exposing the complete binding site on AMA1. R31C2 recognizes a non-polymorphic epitope and should thus be cross-strain reactive. PkAMA1 is much less polymorphic than the P. falciparum and P. vivax orthologues. Unlike these two latter species, there are no polymorphic sites close to the RON2-binding site of PkAMA1, suggesting that P. knowlesi has not developed a mechanism of immune escape from the host’s humoral response to AMA1. PMID:25886591

  20. Influence of shape, size and internal structure on magnetic properties of core-edge nanodots with perpendicular anisotropy

    SciTech Connect

    Milińska, E. Wawro, A.

    2014-11-21

    The properties of perpendicularly magnetized isolated nanodots different in shape, size, and internal structure are simulated by micromagnetic calculations. Investigated dots are magnetically uniform, or they are composed of a core and an edge characterized by different anisotropy—stronger or weaker than that of the core. Based on calculated hysteresis loops, we discuss in details the magnetization reversal processes, stability of magnetic structures, and spin configurations in the dots.

  1. Conservation of distantly related membrane proteins: photosynthetic reaction centers share a common structural core.

    PubMed

    Sadekar, Sumedha; Raymond, Jason; Blankenship, Robert E

    2006-11-01

    Photosynthesis was established on Earth more than 3 billion years ago. All available evidences suggest that the earliest photosynthetic organisms were anoxygenic and that oxygen-evolving photosynthesis is a more recent development. The reaction center complexes that form the heart of the energy storage process are integral membrane pigment proteins that span the membrane in vectorial fashion to carry out electron transfer. The origin and extent of distribution of these proteins has been perplexing from a phylogenetic point of view mostly because of extreme sequence divergence. A series of integral membrane proteins of known structure and varying degrees of sequence identity have been compared using combinatorial extension-Monte Carlo methods. The proteins include photosynthetic reaction centers from proteobacteria and cyanobacterial photosystems I and II, as well as cytochrome oxidase, bacteriorhodopsin, and cytochrome b. The reaction center complexes show a remarkable conservation of the core structure of 5 transmembrane helices, strongly implying common ancestry, even though the residual sequence identity is less than 10%, whereas the other proteins have structures that are unrelated. A relationship of sequence with structure was derived from the reaction center structures; with characteristic decay length of 1.6 A. Phylogenetic trees derived from the structural alignments give insights into the earliest photosynthetic reaction center, strongly suggesting that it was a homodimeric complex that did not evolve oxygen. PMID:16887904

  2. Methionine Oxidation Perturbs the Structural Core of the Prion Protein and Suggests a Generic Misfolding Pathway*

    PubMed Central

    Younan, Nadine D.; Nadal, Rebecca C.; Davies, Paul; Brown, David R.; Viles, John H.

    2012-01-01

    Oxidative stress and misfolding of the prion protein (PrPC) are fundamental to prion diseases. We have therefore probed the effect of oxidation on the structure and stability of PrPC. Urea unfolding studies indicate that H2O2 oxidation reduces the thermodynamic stability of PrPC by as much as 9 kJ/mol. 1H-15N NMR studies indicate methionine oxidation perturbs key hydrophobic residues on one face of helix-C as follows: Met-205, Val-209, and Met-212 together with residues Val-160 and Tyr-156. These hydrophobic residues pack together and form the structured core of the protein, stabilizing its ternary structure. Copper-catalyzed oxidation of PrPC causes a more significant alteration of the structure, generating a monomeric molten globule species that retains its native helical content. Further copper-catalyzed oxidation promotes extended β-strand structures that lack a cooperative fold. This transition from the helical molten globule to β-conformation has striking similarities to a misfolding intermediate generated at low pH. PrP may therefore share a generic misfolding pathway to amyloid fibers, irrespective of the conditions promoting misfolding. Our observations support the hypothesis that oxidation of PrP destabilizes the native fold of PrPC, facilitating the transition to PrPSc. This study gives a structural and thermodynamic explanation for the high levels of oxidized methionine in scrapie isolates. PMID:22654104

  3. Preliminary Descriptions of Impact Rocks Recovered by Recent Core Drilling in the Manson Impact Structure

    NASA Astrophysics Data System (ADS)

    Anderson, R. R.; Witzke, B. J.; Hartung, J. B.

    1993-07-01

    In a recent drilling program 12 cores totaling over 1200 m were recovered from the Manson Impact Structure. Four principal impact rock types were encountered (1) Sedimentary Clast Breccia (SCB), (2) Crystalline Clast Breccia with Sandy Matrix (CCB-S) and Melt Rock Matrix (CCB-M), (3) Central Peak Igneous and Metamorphic Rocks (CP), and (4) an overturned flap of Impact Ejecta (IE). The SCB is dominated by clasts of Cretaceous marine shale and mudstone, with subordinate Cretaceous sandstones, Paleozoic carbonates, minor Proterozoic Red Clastics, and rare crystalline rock and impact melt-rock clasts in a medium gray, calcareous, sandy shale matrix. Parallel deformation features (PDFs) and other evidence of impact metamorphism are extremely rare. The SCB reaches a maximum thickness in excess of 200 m and is interpreted as a post-impact debris flow that originated at the crater margins. The abundance, large clasts (up to 75 m) and pervasive occurrence of SCB (cored in all regions of the Manson Impact Structure including the Central Peak pit) suggests a high energy emplacement mechanism, possibly water rushing into the crater following an impact in a shallow marine environment. The uppermost unit on the Central Peak, the CCB-M, displays abundant clasts, dominated by quartz grains, most displaying PDFs, shock isotropism, and/or partial melting. Some clasts display accretionary mantling by melt materials, apparently while airborne, with subsequent mixing into the CCB-M. An isotropic melt matrix frequently displays flow-banding and devitrification textures. The CCB-M is interpreted as an impact melt layer, derived primarily from crystalline basement rocks, and may represent CCB-S that experienced sufficient heat to melt the matrix grains. A central zone of the CCB-M displays clusters of sanidine crystals, recrystalized from impact melt in a region that apparently cooled more slowly. The CCB-S is dominated by clasts of basement gneiss and granite in a matrix of sand- to silt

  4. Kupffer Cells Support Hepatitis B Virus-Mediated CD8+ T Cell Exhaustion via Hepatitis B Core Antigen-TLR2 Interactions in Mice.

    PubMed

    Li, Min; Sun, Rui; Xu, Long; Yin, Wenwei; Chen, Yongyan; Zheng, Xiaodong; Lian, Zhexiong; Wei, Haiming; Tian, Zhigang

    2015-10-01

    Hepatitis B virus (HBV) persistence is a fundamental process in chronic HBV infection and a key factor in all related liver diseases; however, the mechanisms have yet to be elucidated. We studied the role of TLR2 in HBV persistence using a well-established HBV-carrier mouse model generated by hydrodynamically injecting a phospho-adeno-associated virus/HBV1.2 plasmid into mice. We found that a genetic deficiency in TLR2 improves HBV elimination, whereas activating TLR2 led to more stable HBV persistence, suggesting that TLR2 activation is critical in HBV persistence. Furthermore, we noted that TLR2 activation could inhibit CD8(+) T cell function, causing the exhaustion phenotype in HBV-carrier mice, because TLR2 deficiency might rescue CD8(+) T cell function in a cellular adoptive experiment. TLR2 expression on Kupffer cells (KCs) was upregulated in HBV-carrier mice, which accounts for HBV persistence, because the difference in anti-HBV immunity between HBV-carrier wild-type and Tlr2(-/-) mice did not exist after KC depletion. In addition, similar to TLR2 deficiency, after KC depletion, CD8(+) T cells were more efficiently activated in HBV-carrier mice, leading to rapid HBV elimination. KCs produced more IL-10 upon TLR2 activation in response to direct hepatitis B core Ag stimulation, and the elevated IL-10 inhibited CD8(+) T cell function in HBV-carrier mice, because IL-10 deficiency or anti-IL-10R treatment resulted in CD8(+) T cells with stronger antiviral function. In conclusion, KCs support liver tolerance by inducing anti-HBV CD8(+) T cell exhaustion via IL-10 production after TLR2 activation by hepatitis B core Ag stimulation. PMID:26304988

  5. Synthesis of human parainfluenza virus 2 nucleocapsid protein in yeast as nucleocapsid-like particles and investigation of its antigenic structure.

    PubMed

    Bulavaitė, Aistė; Lasickienė, Rita; Vaitiekaitė, Aušra; Sasnauskas, Kęstutis; Žvirblienė, Aurelija

    2016-05-01

    The aim of this study was to investigate the suitability of yeast Saccharomyces cerevisiae expression system for the production of human parainfluenza virus type 2 (HPIV2) nucleocapsid (N) protein in the form of nucleocapsid-like particles (NLPs) and to characterize its antigenic structure. The gene encoding HPIV2 N amino acid (aa) sequence RefSeq NP_598401.1 was cloned into the galactose-inducible S. cerevisiae expression vector and its high-level expression was achieved. However, this recombinant HPIV2 N protein did not form NLPs. The PCR mutagenesis was carried out to change the encoded aa residues to the ones conserved across HPIV2 isolates. Synthesis of the modified proteins in yeast demonstrated that the single aa substitution NP_598401.1:p.D331V was sufficient for the self-assembly of NLPs. The significance of certain aa residues in this position was confirmed by analysing HPIV2 N protein structure models. To characterize the antigenic structure of NLP-forming HPIV2 N protein, a panel of monoclonal antibodies (MAbs) was generated. The majority of the MAbs raised against the recombinant NLPs recognized HPIV2-infected cells suggesting the antigenic similarity between the recombinant and virus-derived HPIV2 N protein. Fine epitope mapping revealed the C-terminal part (aa 386-504) as the main antigenic region of the HPIV2 N protein. In conclusion, the current study provides new data on the impact of HPIV2 N protein sequence variants on the NLP self-assembly and demonstrates an efficient production of recombinant HPIV2 N protein in the form of NLPs. PMID:26821928

  6. Structural Analysis of Histo-Blood Group Antigen Binding Specificity in a Norovirus GII.4 Epidemic Variant: Implications for Epochal Evolution

    SciTech Connect

    Shanker, Sreejesh; Choi, Jae-Mun; Sankaran, Banumathi; Atmar, Robert L.; Estes, Mary K.; Prasad, B.V. Venkataram

    2012-03-23

    Susceptibility to norovirus (NoV), a major pathogen of epidemic gastroenteritis, is associated with histo-blood group antigens (HBGAs), which are also cell attachment factors for this virus. GII.4 NoV strains are predominantly associated with worldwide NoV epidemics with a periodic emergence of new variants. The sequence variations in the surface-exposed P domain of the capsid protein resulting in differential HBGA binding patterns and antigenicity are suggested to drive GII.4 epochal evolution. To understand how temporal sequence variations affect the P domain structure and contribute to epochal evolution, we determined the P domain structure of a 2004 variant with ABH and secretor Lewis HBGAs and compared it with the previously determined structure of a 1996 variant. We show that temporal sequence variations do not affect the binding of monofucosyl ABH HBGAs but that they can modulate the binding strength of difucosyl Lewis HBGAs and thus could contribute to epochal evolution by the potentiated targeting of new variants to Lewis-positive, secretor-positive individuals. The temporal variations also result in significant differences in the electrostatic landscapes, likely reflecting antigenic variations. The proximity of some of these changes to the HBGA binding sites suggests the possibility of a coordinated interplay between antigenicity and HBGA binding in epochal evolution. From the observation that the regions involved in the formation of the HBGA binding sites can be conformationally flexible, we suggest a plausible mechanism for how norovirus disassociates from salivary mucin-linked HBGA before reassociating with HBGAs linked to intestinal epithelial cells during its passage through the gastrointestinal tract.

  7. Mutagenicity in a Molecule: Identification of Core Structural Features of Mutagenicity Using a Scaffold Analysis

    PubMed Central

    Hsu, Kuo-Hsiang; Su, Bo-Han; Tu, Yi-Shu; Lin, Olivia A.; Tseng, Yufeng J.

    2016-01-01

    With advances in the development and application of Ames mutagenicity in silico prediction tools, the International Conference on Harmonisation (ICH) has amended its M7 guideline to reflect the use of such prediction models for the detection of mutagenic activity in early drug safety evaluation processes. Since current Ames mutagenicity prediction tools only focus on functional group alerts or side chain modifications of an analog series, these tools are unable to identify mutagenicity derived from core structures or specific scaffolds of a compound. In this study, a large collection of 6512 compounds are used to perform scaffold tree analysis. By relating different scaffolds on constructed scaffold trees with Ames mutagenicity, four major and one minor novel mutagenic groups of scaffold are identified. The recognized mutagenic groups of scaffold can serve as a guide for medicinal chemists to prevent the development of potentially mutagenic therapeutic agents in early drug design or development phases, by modifying the core structures of mutagenic compounds to form non-mutagenic compounds. In addition, five series of substructures are provided as recommendations, for direct modification of potentially mutagenic scaffolds to decrease associated mutagenic activities. PMID:26863515

  8. Protein 4.1R core domain structure and insights into regulation of cytoskeletal organization.

    PubMed

    Han, B G; Nunomura, W; Takakuwa, Y; Mohandas, N; Jap, B K

    2000-10-01

    The crystal structure of the core domain (N-terminal 30 kDa domain) of cytoskeletal protein 4.1R has been determined and shows a cloverleaf-like architecture. Each lobe of the cloverleaf contains a specific binding site for either band 3, glycophorin C/D or p55. At a central region of the molecule near where the three lobes are joined are two separate calmodulin (CaM) binding regions. One of these is composed primarily of an alpha-helix and is Ca 2+ insensitive; the other takes the form of an extended structure and its binding with CaM is dramatically enhanced by the presence of Ca 2+, resulting in the weakening of protein 4.1R binding to its target proteins. This novel architecture, in which the three lobes bind with three membrane associated proteins, and the location of calmodulin binding sites provide insight into how the protein 4.1R core domain interacts with membrane proteins and dynamically regulates cell shape in response to changes in intracellular Ca2+ levels. PMID:11017195

  9. Rich club analysis in the Alzheimer's disease connectome reveals a relatively undisturbed structural core network

    PubMed Central

    Daianu, Madelaine; Jahanshad, Neda; Nir, Talia M.; Jack, Clifford R.; Weiner, Michael W.; Bernstein, Matthew; Thompson, Paul M.

    2015-01-01

    Diffusion imaging can assess the white matter connections within the brain, revealing how neural pathways break down in Alzheimer's disease (AD). We analyzed 3-Tesla whole-brain diffusion-weighted images from 202 participants scanned by the Alzheimer's Disease Neuroimaging Initiative – 50 healthy controls, 110 with mild cognitive impairment (MCI) and 42 AD patients. From whole-brain tractography, we reconstructed structural brain connectivity networks to map connections between cortical regions. We tested whether AD disrupts the ‘rich-club’ – a network property where high-degree network nodes are more interconnected than expected by chance. We calculated the rich-club properties at a range of degree thresholds, as well as other network topology measures including global degree, clustering coefficient, path length and efficiency. Network disruptions predominated in the low-degree regions of the connectome in patients, relative to controls. The other metrics also showed alterations, suggesting a distinctive pattern of disruption in AD, less pronounced in MCI, targeting global brain connectivity, and focusing on more remotely connected nodes rather than the central core of the network. AD involves severely reduced structural connectivity; our step-wise rich club coefficients analyze points to disruptions predominantly in the peripheral network components; other modalities of data are needed to know if this indicates impaired communication among non rich-club regions. The highly connected core was relatively preserved, offering new evidence on the neural basis of progressive risk for cognitive decline. PMID:26037224

  10. Rich club analysis in the Alzheimer's disease connectome reveals a relatively undisturbed structural core network.

    PubMed

    Daianu, Madelaine; Jahanshad, Neda; Nir, Talia M; Jack, Clifford R; Weiner, Michael W; Bernstein, Matt A; Thompson, Paul M

    2015-08-01

    Diffusion imaging can assess the white matter connections within the brain, revealing how neural pathways break down in Alzheimer's disease (AD). We analyzed 3-Tesla whole-brain diffusion-weighted images from 202 participants scanned by the Alzheimer's Disease Neuroimaging Initiative-50 healthy controls, 110 with mild cognitive impairment (MCI) and 42 AD patients. From whole-brain tractography, we reconstructed structural brain connectivity networks to map connections between cortical regions. We tested whether AD disrupts the "rich club" - a network property where high-degree network nodes are more interconnected than expected by chance. We calculated the rich club properties at a range of degree thresholds, as well as other network topology measures including global degree, clustering coefficient, path length, and efficiency. Network disruptions predominated in the low-degree regions of the connectome in patients, relative to controls. The other metrics also showed alterations, suggesting a distinctive pattern of disruption in AD, less pronounced in MCI, targeting global brain connectivity, and focusing on more remotely connected nodes rather than the central core of the network. AD involves severely reduced structural connectivity; our step-wise rich club coefficients analyze points to disruptions predominantly in the peripheral network components; other modalities of data are needed to know if this indicates impaired communication among non rich club regions. The highly connected core was relatively preserved, offering new evidence on the neural basis of progressive risk for cognitive decline. PMID:26037224

  11. Synthesis of Core-shell Structured Amorphous Si Nanoparticles by Induction Thermal Plasmas

    NASA Astrophysics Data System (ADS)

    Okamoto, Daisuke; Kageyama, Takuya; Tanaka, Manabu; Sone, Hirotaka; Watanabe, Takayuki

    2015-09-01

    Core-shell structured amorphous Si nanoparticles were synthesized by induction thermal plasma. Crystalline Si powder with 3 μm of average diameter was injected into the induction thermal plasma at 4 MHz. The Si raw materials immediately evaporate in the high temperature plasma region and nanoparticles were produced through the quenching process. Counterflow quenching gas was injected from downstream of the torch with its direction against the plasma flow. The effect of the operating parameter such as flow rate of quenching gas and input power was investigated. Collected particles were characterized by X-ray diffraction, transmission electron microscopy, electron energy-loss spectroscopy, and Raman spectroscopy. Obtained results indicate that amorphization degree of the synthesized nanoparticles is more than 90% when additional quenching gas of 20 L/min is injected. The quenching rate of the prepared nanoparticles in the growth region have an important role on determining the amorphization degree. Moreover, EELS and Raman analyses showed the synthesized nanoparticles were coated by the SiO2 shell with thickness of 2-4 nm. These findings indicated that amorphous Si/SiO2 core-shell structured nanoparticles were successfully synthesized by induction thermal plasma in single step.

  12. Focused ion beam fabrication of novel core-shell nanowire structures.

    PubMed

    He, Li; Johansson, Jonas; Murayama, Mitsuhiro; Hull, Robert

    2008-11-01

    A novel method of indirect deposition by means of a focused ion beam (FIB) is utilized to develop metal/insulator/semiconductor nanowire core-shell structures. This method is based upon depositing an annular pattern centered on a nanowire, with secondary deposition then coating the wire. Typical cross-sectional deposition area increments as a function of ion doses are 1.3 × 10(-2) µm(2) nC(-1) for Pt and 3.5 × 10(-2) µm(2) nC(-1) for SiO(2). The structures are examined with a transmission electron microscope (TEM) using a new nanowire TEM sample preparation method that allows direct examinations of individually selected core-shell nanowires fabricated under different indirect FIB deposition conditions. Elemental analyses by means of energy dispersive x-ray spectroscopy and electron energy filtered TEM imaging verify the deposition of SiO(2) and Pt layers. Relatively uniform Pt and SiO(2) coatings on individual GaP nanowires can be achieved with overall thickness deviation of about 10% for deposition up to 25-30 nm thick Pt or SiO(2) shells. It should be possible to extend this approach to any nanowire/nanotube system, and to a wide range of coatings in any desired layer sequences. PMID:21832742

  13. Supersolid structure and excitation spectrum of soft-core bosons in three dimensions

    NASA Astrophysics Data System (ADS)

    Ancilotto, Francesco; Rossi, Maurizio; Toigo, Flavio

    2013-09-01

    By means of a mean-field method, we have studied the zero-temperature structure and excitation spectrum of a three-dimensional soft-core bosonic system for a value of the interaction strength that favors a crystal structure made of atomic nanoclusters arranged with fcc ordering. In addition to the longitudinal and transverse phonon branches expected for a normal crystal, the excitation spectrum shows a soft mode related to the breaking of gauge symmetry, which signals a partial superfluid character of the solid. Additional evidence of supersolidity is provided by the calculation of the superfluid fraction, which shows a first-order drop, from 1 to 0.4, at the liquid-supersolid transition and a monotonic decrease as the interaction strength parameter is increased. The conditions for the coexistence of the supersolid with the homogeneous superfluid are discussed, and the surface tension of a representative solid-liquid interface is calculated.

  14. Death Domain Assembly Mechanism Revealed by Crystal Structure of the Oligomeric PIDDosome Core Complex

    SciTech Connect

    Park,H.; Logette, E.; Raunser, S.; Cuenin, S.; Walz, T.; Tschopp, J.; Wu, H.

    2007-01-01

    Proteins of the death domain (DD) superfamily mediate assembly of oligomeric signaling complexes for the activation of caspases and kinases via unknown mechanisms. Here we report the crystal structure of the PIDD DD and RAIDD DD complex, which forms the core of the caspase-2-activating complex PIDDosome. Although RAIDD DD and PIDD DD are monomers, they assemble into a complex that comprises seven RAIDD DDs and five PIDD DDs. Despite the use of an asymmetric assembly mechanism, all DDs in the complex are in quasi-equivalent environments. The structure provided eight unique asymmetric interfaces, which can be classified into three types. These three types of interactions together cover a majority of the DD surface. Mutagenesis on almost all interfaces leads to disruption of the assembly, resulting in defective caspase-2 activation. The three types of interactions may represent most, if not all, modes of interactions in the DD superfamily for assembling complexes of different stoichiometry.

  15. Death Domain Assembly Mechanism Revealed by Crystal Structure of the Oligomeric PIDDosome Core Complex

    PubMed Central

    Park, Hyun Ho; Logette, Emmanuelle; Raunser, Stefan; Cuenin, Solange; Walz, Thomas; Tschopp, Jurg; Wu, Hao

    2010-01-01

    SUMMARY Proteins of the death domain (DD) superfamily mediate assembly of oligomeric signaling complexes for the activation of caspases and kinases via unknown mechanisms. Here we report the crystal structure of the PIDD DD and RAIDD DD complex, which forms the core of the caspase-2 activating complex PIDDosome. While RAIDD DD and PIDD DD are monomers, they assemble into a complex that comprises seven RAIDD DDs and five PIDD DDs. Despite the use of an asymmetric assembly mechanism, all DDs in the complex are in quasi-equivalent environments. The structure provided eight unique asymmetric interfaces, which can be classified into three types. These three types of interactions together cover a majority of the DD surface. Mutagenesis on almost all interfaces leads to disruption of the assembly resulting in defective caspase-2 activation. The three types of interactions may represent most, if not all, modes of interactions in the DD superfamily for assembling complexes of different stoichiometry. PMID:17289572

  16. An enhanced sine dwell method as applied to the Galileo core structure modal survey

    NASA Technical Reports Server (NTRS)

    Smith, Kenneth S.; Trubert, Marc

    1990-01-01

    An incremental modal survey performed in 1988 on the core structure of the Galileo spacecraft with its adapters with the purpose of assessing the dynamics of the new portions of the structure is considered. Emphasis is placed on the enhancements of the sine dwell method employed in the test. For each mode, response data is acquired at 32 frequencies in a narrow band enclosing the resonance, utilizing the SWIFT technique. It is pointed out that due to the simplicity of the data processing involved, the diagnostic and modal-parameter data is available within several minutes after data acquisition; however, compared with straight curve-fitting approaches, the method requires more time for data acquisition.

  17. Structure of the TatC core of the twin-arginine protein transport system.

    PubMed

    Rollauer, Sarah E; Tarry, Michael J; Graham, James E; Jääskeläinen, Mari; Jäger, Franziska; Johnson, Steven; Krehenbrink, Martin; Liu, Sai-Man; Lukey, Michael J; Marcoux, Julien; McDowell, Melanie A; Rodriguez, Fernanda; Roversi, Pietro; Stansfeld, Phillip J; Robinson, Carol V; Sansom, Mark S P; Palmer, Tracy; Högbom, Martin; Berks, Ben C; Lea, Susan M

    2012-12-13

    The twin-arginine translocation (Tat) pathway is one of two general protein transport systems found in the prokaryotic cytoplasmic membrane and is conserved in the thylakoid membrane of plant chloroplasts. The defining, and highly unusual, property of the Tat pathway is that it transports folded proteins, a task that must be achieved without allowing appreciable ion leakage across the membrane. The integral membrane TatC protein is the central component of the Tat pathway. TatC captures substrate proteins by binding their signal peptides. TatC then recruits TatA family proteins to form the active translocation complex. Here we report the crystal structure of TatC from the hyperthermophilic bacterium Aquifex aeolicus. This structure provides a molecular description of the core of the Tat translocation system and a framework for understanding the unique Tat transport mechanism. PMID:23201679

  18. Hinterland-to-foreland structural evolution of the base of the Himalayan metamorphic core, west Nepal

    NASA Astrophysics Data System (ADS)

    Braden, Z.; Godin, L.; Yakymchuk, C.; Kellett, D.; Cottle, J. M.

    2015-12-01

    The base of the Himalayan metamorphic core is a folded reverse-sense shear zone exposed extensively along its transport direction. In west Nepal, along-transport exposures show a transition in structural style from hinterland to foreland, and sampled quartzite and pelite show variations in thermobarometry, quartz crystallographic preferred orientation (CPO), monazite Th-Pb ages and 40Ar/39Ar thermochronology. In the hinterland region, the shear zone yields a deformation temperature gradient from > 700°C at the top of the shear zone down to 400°C at the base. Metamorphic grade also decreases downwards through the shear zone. Muscovite 40Ar/39Ar ages are ca. 6 Ma. In the transition zone separating hinterland and foreland on the north flank of the Karnali klippe, a comparable structural section yields a deformation temperature gradient that similarly decreases down structural level from ~700 to 500°C. Muscovite 40Ar/39Ar dating yield ca. 14-12 Ma cooling ages. In-situ monazite geochronology indicates prograde metamorphism at ca. 43-34 Ma and melt crystallization at ca. 26-18 Ma. In the foreland, deformation is not strictly brittle; CPO analyses on sheared quartzite on the south flank of the Karnali klippe suggest deformation temperatures decreasing from 500 to 400°C downwards through the shear zone. Muscovite from the foreland yields 40Ar/39Ar ages of ca. 17 Ma. Deformation temperatures decrease marginally from hinterland to foreland and structurally downward within the shear zone, and estimates suggest ductile deformation prevails well into the foreland. Hinterland 40Ar/39Ar muscovite ages in west Nepal are anomalously young, and are possibly related to recent exhumation due to the SE-propagating mid-Miocene Gurla Mandhata-Humla system. Alternatively, they could be linked to the activation of a young duplex in the footwall of the Himalayan metamorphic core due to along-strike variation in geometry of the Main Himalayan thrust ramp.

  19. Optimal design at inner core of the shaped pyramidal truss structure

    SciTech Connect

    Lee, Sung-Uk; Yang, Dong-Yol

    2013-12-16

    Sandwich material is a type of composite material with lightweight, high strength,