Science.gov

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

    PubMed Central

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

    1989-01-01

    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. The single conformational determinant responsible for HBc antigenicity in the assembled core (HBc) and a linear HBe-related determinant (HBe1) were both mapped to an overlapping hydrophilic sequence around amino acid 80; a second HBe determinant (HBe2) was assigned to a location in the vicinity of amino acid 138 but found to require for its antigenicity the intramolecular participation of the extended sequence between amino acids 10 and 140. 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 B virus nucleocapsid. Images PMID:2463383

  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

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

    2014-10-01

    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.

  5. The complete structure of the core of the LPS from Plesiomonas shigelloides 302-73 and the identification of its O-antigen biological repeating unit.

    PubMed

    Pieretti, Giuseppina; Carillo, Sara; Lindner, Buko; Lanzetta, Rosa; Parrilli, Michelangelo; Jimenez, Natalia; Regué, Miguel; Tomás, Juan M; Corsaro, M Michela

    2010-11-22

    Plesiomonas shigelloides is a Gram-negative opportunistic pathogen associated with gastrointestinal and extraintestinal infections, which especially invades immunocompromised patients and neonates. The lipopolysaccharides are one of the major virulence determinants in Gram-negative bacteria and are structurally composed of three different domains: the lipid A, the core oligosaccharide and the O-antigen polysaccharide. In the last few years we elucidated the structures of the O-chain and the core oligosaccharide from the P. shigelloides strain 302-73. In this paper we now report the characterization of the linkage between the core and the O-chain. The LPS obtained after PCP extraction contained a small number of O-chain repeating units. The product obtained by hydrazinolysis was analysed by FTICR-ESIMS and suggested the presence of an additional Kdo in the core oligosaccharide. Furthermore, the LPS was hydrolysed under mild acid conditions and a fraction that contained one O-chain repeating unit linked to a Kdo residue was isolated and characterized by FTICR-ESIMS and NMR spectroscopy. Moreover, after an alkaline reductive hydrolysis, a disaccharide α-Kdo-(2→6)-GlcNol was isolated and characterized. The data obtained proved the presence of an α-Kdo in the outer core and allowed the identification of the O-antigen biological repeating unit as well as its linkage with the core oligosaccharide.

  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. Flaviviruses and their antigenic structure.

    PubMed

    Heinz, F X; Stiasny, Karin

    2012-12-01

    Flaviviruses comprise important arthropod-transmitted human pathogens, including yellow fever (YF), dengue (Den), Japanese encephalitis (JE), West Nile (WN) and tick-borne encephalitis (TBE) viruses that have the potential of expanding their endemic areas due to global climatic, ecological and socio-economic changes. While effective vaccines against YF, JE and TBE are in widespread use, the development of a dengue vaccine has been hampered for a long time because of concerns of immunopathological consequences of vaccination. Phase III clinical trials with a recombinant chimeric live vaccine are now ongoing and will show whether the enormous problem of dengue can be resolved or at least reduced by vaccination in the future. Unprecedented details of the flavivirus particle structure have become available through the combined use of X-ray crystallography and cryo-electron microscopy that led to novel and surprising insights into the antigenic structure of these viruses. Recent studies provided evidence for an important role of virus maturation as well as particle dynamics in virus neutralization by antibodies and thus added previously unknown layers of complexity to our understanding of flavivirus immune protection. This information is invaluable for interpreting current investigations on the functional activities of polyclonal antibody responses to flavivirus infections and vaccinations and may open new avenues for studies on flavivirus cell biology and vaccine design.

  10. Red cell antigens: Structure and function

    PubMed Central

    Pourazar, Abbasali

    2007-01-01

    Landsteiner and his colleagues demonstrated that human beings could be classified into four groups depending on the presence of one (A) or another (B) or both (AB) or none (O) of the antigens on their red cells. The number of the blood group antigens up to 1984 was 410. In the next 20 years, there were 16 systems with 144 antigens and quite a collection of antigens waiting to be assigned to systems, pending the discovery of new information about their relationship to the established systems. The importance of most blood group antigens had been recognized by immunological complications of blood transfusion or pregnancies; their molecular structure and function however remained undefined for many decades. Recent advances in molecular genetics and cellular biochemistry resulted in an abundance of new information in this field of research. In this review, we try to give some examples of advances made in the field of ‘structure and function of the red cell surface molecules.’ PMID:21938229

  11. [Clinical benefit of HCV core antigen assay in patients receiving interferon and ribavirin combination therapy].

    PubMed

    Higashimoto, Makiko; Takahashi, Masahiko; Jokyu, Ritsuko; Saito, Hidetsugu

    2006-02-01

    A highly sensitive second generation HCV core antigen assay has recently been developed. We compared viral disappearance and kinetics data between commercially available core antigen assays, Lumipulse Ortho HCV Ag, and a quantitative HCV RNA PCR assay, Cobas Amplicor HCV Monitor Test, Version 2 to estimate the predictive benefit of sustained viral response (SVR) and non-SVR in 59 patients treated with interferon and ribavirin combination therapy. We found a good correlation between HCV core Ag and HCV RNA level regardless of genotype. Although the sensitivity of the core antigen assay was lower than PCR, the dynamic range was broader than that of the PCR assay, so that we did not need to dilute the samples in 59 patients. We detected serial decline of core Ag levels in 24 hrs, 7 days and 14 days after interferon combination therapy. The decline of core antigen levels was significant in SVR patients compared to non-SVR as well as in genotype 2a, 2b patients compared to 1b. Core antigen-negative on day 1 could predict all 10 SVR patients (PPV = 100%), whereas RNA-negative could predict 22 SVR out of 25 on day 14 (PPV = 88.0%). None of the patients who had detectable serum core antigen on day 14 became SVR(NPV = 100%), although NPV was 91.2% on RNA negativity. An easy, simple, low cost new HCV core antigen detecting system seems to be useful for assessing and monitoring IFN treatment for HCV.

  12. Structural determinants of GAD antigenicity.

    PubMed

    Arafat, Yasir; Fenalti, Gustavo; Whisstock, James C; Mackay, Ian R; Garcia de la Banda, Maria; Rowley, Merrill J; Buckle, Ashley M

    2009-12-01

    Our aim was to ascertain structural determinants of autoantigenicity based on the model of the diabetes autoantigen glutamic acid decarboxylase 65 kDa isoform (GAD65) in comparison with that of the non-autoantigenic isoform GAD67. This difference exists despite the two isoforms having the same fold and high sequence identity. Autoantibodies to GAD65 precede the development of type 1 diabetes and are clinical markers of this and certain neural autoimmune diseases. To date, epitope mapping has been based on particular amino acid differences between the two isoforms, and there is no explanation as to why autoantibodies that react with GAD65 only infrequently cross-react with GAD67. To characterize each isoform of the enzyme and gain insights into their contrasting autoantigenic properties, we have used the recently determined crystal structures of GAD65 and GAD67 to compare their structure, hydrophobicity, electrostatics, flexibility and physiochemical properties. The results revealed striking differences which appear almost exclusively at the C-terminal domain of the isoforms. Whereas GAD65 displayed a highly charged and flexible C-terminal domain containing numerous patches of high electrostatic and solvation energies, these characteristics were absent in the GAD67 molecule. Additionally, analysis indicated potential N-terminal and PLP domain binding sites surrounding the C-terminal domain of GAD65, a major region of autoantigenic activity, but not of GAD67. These features agree with good accuracy with published epitope-mapping data. Our analysis suggests that the high flexibility and charge of GAD65 in the C-terminal domain is coupled with the mobility of its catalytic loop, a property that is absolutely required for its enzymatic function. Thus, the structural features that distinguish GAD65 from GAD67 as a B cell autoantigen are related to functional requirements for its enzymatic mechanism. This could well apply to the various other enzyme autoantigens and, if

  13. Antigenic variation in ciliates: antigen structure, function, expression.

    PubMed

    Simon, Martin C; Schmidt, Helmut J

    2007-01-01

    In the past decades, the major focus of antigen variation research has been on parasitic protists. However, antigenic variation occurs also in free-living protists. The antigenic systems of the ciliates Paramecium and Tetrahymena have been studied for more than 100 yr. In spite of different life strategies and distant phylogenetic relationships of free-living ciliates and parasitic protists, their antigenic systems have features in common, such as the presence of repeated protein motifs and multigene families. The function of variable surface antigens in free-living ciliates is still unknown. Up to now no detailed monitoring of antigen expression in free-living ciliates in natural habitats has been performed. Unlike stochastic switching in parasites, antigen expression in ciliates can be directed, e.g. by temperature, which holds great advantages for research on the expression mechanism. Regulated expression of surface antigens occurs in an exclusive way and the responsible mechanism is complex, involving both transcriptional and post-transcriptional features. The involvement of homology-dependent effects has been proposed several times but has not been proved yet.

  14. The Structure and Function of the Rh antigen Complex

    PubMed Central

    Westhoff, Connie M.

    2007-01-01

    The Rh system is one of the most important and complex blood group systems because of the large number of antigens and the serious complications for the fetus of a woman sensitized by transfusion or pregnancy. Major advances in our understanding of the Rh system have occurred with the cloning of the genes and with functional evidence that the Rh blood group proteins belong to an ancient family of membrane proteins involved in ammonia transport. The arrangement and configuration of the genes at the RH locus promotes genetic exchange, generating new antigens. Importantly, RH genetic testing can now be applied to clinical transfusion medicine and prenatal practice. This includes testing for RHD zygosity, confirmation or resolution of D antigen status, and detection of altered RHD and RHCE genes in individuals at risk for producing antibodies to high incidence Rh antigens, particularly sickle cell disease patients. The Rh proteins form a core complex that is critical to the structure of the erythrocyte membrane, and may play a physiologically role in the sequestration of blood ammonia. The Rh family of proteins now includes non-erythroid Rh homologs present in many other tissues, and comparative genomics reveals Rh homologs in all domains of life. PMID:17198846

  15. Common antigenic structures of HL-A antigens

    PubMed Central

    Nakamuro, K.; Tanigaki, N.; Kreiter, V. P.; Pressman, D.

    1974-01-01

    Spent culture media of all the human cell lines tested have been found to contain the antigenic activity present on the 11,000-Dalton HL-A common portion fragment of the HL-A antigen molecule that appears to be a characteristic, invariant portion of HL-A antigen molecules. From the culture medium of one of these lines, RPMI 1788, a lymphoid cell line, the substance carrying HL-A common activity was isolated, which was shown to be identical to the HL-A common portion fragment with respect to molecular size, electrophoretic mobility, isoelectric focusing patterns, and certain antigenic characteristics. By an isolation procedure involving differential ultrafiltration, gel filtration, and column electrophoresis, 8 litres of the culture medium yielded 1.5–2.0 A280 units of the substance representing 15–20 per cent of the HL-A common antigenic activity originally present. A single protein band with a Rf of 0.47 was obtained by disc electrophoresis. The molecular size was shown to be about 11,000 Daltons by gel filtration and by sodium dodecyl sulphate—acrylamide gel electrophoresis. Upon isoelectric focusing two bands were obtained which corresponded exactly to those obtained with HL-A common portion fragment prepared from papain-solubilized HL-A antigen preparations by acid dissociation. The isoelectric point of the major band was 5.0. The reactions of this substance with rabbit antisera against human lymphoid cell membrane and against the substance were essentially identical to the reactions of HL-A common portion fragment with these same antisera. ImagesFIG. 3Fig. 4Fig. 5 PMID:4476726

  16. Structure and function of the Ca antigen.

    PubMed Central

    Bramwell, M. E.; Bhavanandan, V. P.; Wiseman, G.; Harris, H.

    1983-01-01

    The Ca antigen, which can be detected in a wide range of malignant human tumours by means of the Cal antibody, is a glycoprotein of the mucin type. At least 95% of the carbohydrate is 0-glycosidically linked to the polypeptide which contains high proportions of glycine, serine and glutamic acid. The carbohydrate has a very simple structure: it is composed almost entirely of tetra- tri- and disaccharides having the general formula (NeuNac)n leads to [Gal leads to GalNac] alpha leads to, where n = 0, 1 or 2. In many malignant cell lines, the antigen is produced constitutively in vitro; but in one that has been examined, its synthesis can be induced by high concentrations of lactate. Evidence is presented for the view that a primary function of this glycoprotein is to shield the cells that produce it from hydrogen ion concentrations outside of the physiological range. The presence of the Ca antigen in malignant tumours may thus be a reflection of metabolic conditions that are known to be characteristics of such tumours. Images Figure 1 Figure 2 PMID:6349673

  17. 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

  18. 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

  19. Determination of immunoglobulin M antibodies for hepatitis B core antigen with a capture enzyme immunoassay and biotin-labeled core antigen produced in Escherichia coli.

    PubMed Central

    Vilja, P; Turunen, H J; Leinikki, P O

    1985-01-01

    A new capture enzyme immunoassay for the determination of immunoglobulin M (IgM) antibodies against hepatitis B core antigen (HBcAg) is described. Core antigen produced in Escherichia coli was labeled with biotin and subsequently detected by an avidin-biotin-peroxidase complex. The biotin-labeled core antigen was effective at concentrations as low as 20 ng/ml. Of 561 serum samples from different groups of patients that were tested, 465 samples were negative for other hepatitis B virus markers and also for anti-HBcAg IgM. Sera from the early stages of hepatitis B infection had high levels of anti-HBcAg IgM, and a clear correlation with the acuteness of the disease was observed in 45 follow-up sera from 23 patients with acute or recent hepatitis B. Sera from 21 patients with past hepatitis B were all negative for anti-HBcAg IgM. Twenty serum samples from chronic carriers of hepatitis B surface antigen showed slightly elevated antibody levels for anti-HBcAg IgM. Ten sera which were positive for anti-HBcAg IgG antibodies and had high levels of rheumatoid factor were negative for anti-HBcAg IgM. PMID:3908476

  20. Bacterial cell surface display for epitope mapping of hepatitis C virus core antigen.

    PubMed

    Kang, Su-Min; Rhee, Jin-Kyu; Kim, Eui-Joong; Han, Kwang-Hyub; Oh, Jong-Won

    2003-09-26

    Cell surface expression of protein has been widely used to display enzymes and antigens. Here we show that Pseudomonas syringae ice nucleation protein with a deletion of internal repeating domain (INC) can be used in Escherichia coli to display peptide in a conformationally active form on the outside of the folded protein by fusing to the C-terminus of INC. Diagnostic potential of this technology was demonstrated by effective mapping of antigenic epitopes derived from hepatitis C virus (HCV) core protein. Amino acids 1-38 and 26-53 of HCV core protein were found to react more sensitively in a native conformation with the HCV patient sera than commercial diagnostic antigen, c22p (amino acids 10-53) by display-ELISA. These results demonstrate that the bacterial cell surface display using INC is useful for peptide presentation and thus epitope mapping of antigen. PMID:14553932

  1. 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

  2. Characterization of the core oligosaccharide and the O-antigen biological repeating unit from Halomonas stevensii lipopolysaccharide: the first case of O-antigen linked to the inner core.

    PubMed

    Pieretti, Giuseppina; Carillo, Sara; Lindner, Buko; Kim, Kwang Kyu; Lee, Keun Chul; Lee, Jung-Sook; Lanzetta, Rosa; Parrilli, Michelangelo; Corsaro, Maria Michela

    2012-03-19

    A novel core structure among bacterial lipopolysaccharides (LPS) that belong to the genus Halomonas has been characterized. H. stevensii is a moderately halophilic microorganism, as are the majority of the Halomonadaceae. It brought to light the pathogenic potential of this genus. On account of their role in immune system elicitation, elucidation of LPS structure is the mandatory starting point for a deeper understanding of the interaction mechanisms between host and pathogen. In this paper we report the structure of the complete saccharidic portion of the LPS from H. stevensii. In contrast to the finding that the O-antigen is usually covalently linked to the outer core oligosaccharide, we could demonstrate that the O-polysaccharide of H. stevensii is linked to the inner core of an LPS. By means of high-performance anion-exchange chromatography with pulsed amperometric detection we were able to isolate the core decasaccharide as well as a tridecasaccharide constituted by the core region plus one O-repeating unit after alkaline degradation of the LPS. The structure was elucidated by one- and two-dimensional NMR spectroscopy, ESI Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry, and chemical analysis.

  3. 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

  4. [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

  5. [Hepatitis B virus core antigen as a carrier for virus-like partical vaccine: a review].

    PubMed

    Yang, Xing-Yu; Bo, Hong; Shu, Yue-Long

    2012-05-01

    Hepatitis B virus core antigen (HBcAg) is a major viral nucleocapsid protein of HBV. It is a 21-22kD protein consisting of 183-185 amino acids. Because of its easy purification, strong immunogenicity, high expression level, and self-assembles into the virus-like particles (VLP), HBcAg could be an efficient and safe VLP carrier for developing vaccines for various pathogens. Up to now, HBcAg VLP carrier has been an important system to develop novel vaccines and many antigen epitope genes from viruses, bacteria and parasites were expressed successfully using the system.

  6. 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.

  7. 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.

  8. Linearized hepatitis B surface antigen and hepatitis B core-related antigen in the natural history of chronic hepatitis B.

    PubMed

    Seto, W-K; Wong, D K-H; Fung, J; Huang, F-Y; Liu, K S-H; Lai, C-L; Yuen, M-F

    2014-11-01

    Changes in two novel HBV serological markers, linearized hepatitis B surface antigen (HQ-HBsAg) and hepatitis B core-related antigen (HBcrAg), in the natural history of chronic hepatitis B (CHB) have not been well characterized. Serum HQ-HBsAg and HBcrAg levels of 404 Asian treatment-naïve CHB patients were analysed in a cross-sectional manner. Patients were categorized into five groups: immune tolerant (IT group, n=52), immune clearance (IC group, n=105), hepatitis B e antigen (HBeAg)-negative hepatitis (ENH group, n=97), HBeAg-negative quiescent group (ENQ group, n=95) and CHB with hepatitis B surface antigen (HBsAg) seroclearance (SC group, n=55). HQ-HBsAg and HBcrAg were measured and correlated with HBV DNA, HBsAg, HBV genotype and clinical parameters. HQ-HBsAg showed good correlation with HBsAg, especially in the ENQ group (r=0.874, p<0.001). Correlation of HQ-HBsAg with HBV DNA was less prominent and weakest in the ENH group (r=0.268, p 0.008). HBcrAg correlated best with HBV DNA in the ENQ group (r=0.537, p<0.001). In the ENQ group, 42.1% of patients had undetectable HBcrAg; this subgroup of patients, when compared with those with detectable HBcrAg, had significantly lower median HBV DNA (3.17/4.48 log IU/mL, p<0.001) and HBsAg (5.05/5.96 log mIU/mL, p<0.001) levels. Forty per cent of the SC group patients had detectable HQ-HBsAg and/or HBcrAg up to 42 months after HBsAg seroclearance. When comparing anti-HBs positivity and median time after HBsAg seroclearance in the SC group with and without detectable HQ-HBsAg/HBcrAg, there was no significant difference (22.7% and 36.4%, respectively, p 0.284, and 76.5 and 93.2 months, respectively, p 0.245). HQ-HBsAg and HBcrAg showed unique patterns of distribution throughout the five disease phases of CHB, including high detectability rates after HBsAg seroclearance, opening up different possibilities for their applicability.

  9. 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

  10. 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.

  11. Structural Basis for Distinct Binding Properties of the Human Galectins to Thomsen-Friedenreich Antigen

    PubMed Central

    Bian, Cheng-Feng; Zhang, Ying; Sun, Hui; Li, De-Feng; Wang, Da-Cheng

    2011-01-01

    The Thomsen-Friedenreich (TF or T) antigen, Galβ1-3GalNAcα1-O-Ser/Thr, is the core 1 structure of O-linked mucin type glycans appearing in tumor-associated glycosylation. The TF antigen occurs in about 90% of human cancer cells and is a potential ligand for the human endogenous galectins. It has been reported that human galectin-1 (Gal-1) and galectin-3 (Gal-3) can perform their cancer-related functions via specifically recognizing TF antigen. However, the detailed binding properties have not been clarified and structurally characterized. In this work, first we identified the distinct TF-binding abilities of Gal-1 and Gal-3. The affinity to TF antigen for Gal-3 is two orders of magnitude higher than that for Gal-1. The structures of Gal-3 carbohydrate recognition domain (CRD) complexed with TF antigen and derivatives, TFN and GM1, were then determined. These structures show a unique Glu-water-Arg-water motif-based mode as previously observed in the mushroom galectin AAL. The observation demonstrates that this recognition mode is commonly adopted by TF-binding galectins, either as endogenous or exogenous ones. The detailed structural comparisons between Gal-1 and Gal-3 CRD and mutagenesis experiments reveal that a pentad residue motif (51AHGDA55) at the loop (g1-L4) connecting β-strands 4 and 5 of Gal-1 produces a serious steric hindrance for TF binding. This motif is the main structural basis for Gal-1 with the low affinity to TF antigen. These findings provide the intrinsic structural elements for regulating the TF-binding activity of Gal-1 in some special conditions and also show certain target and approach for mediating some tumor-related bioactivities of human galectins. PMID:21949831

  12. Characterization of the Streptococcus adjacens group antigen structure.

    PubMed Central

    Sieling, P A; Thomas, M J; van de Rijn, I

    1992-01-01

    Serological classification of bacteria requires the presence of an antigen unique to the organism of interest. Streptococci are serologically differentiated by group antigens, many of which are carbohydrates, although some are amphiphiles. This report describes the chemical characterization of the Streptococcus adjacens group antigen structure. Previous studies demonstrated that the amphiphile contained phosphorus, ribitol, galactose, galactosamine, alanine, and fatty acids. Phosphodiester bonds present in the purified group antigen were identified as part of a poly(ribitol phosphate), since ribitol phosphate was the only organic phosphate detected after acid hydrolysis. Hydrofluoric acid cleavage of the phosphodiester bonds generated oligosaccharide repeating units. Gas chromatography-mass spectrometric analysis of the methylated, acetylated oligosaccharide suggested that the repeating unit is a trisaccharide of Galp beta 1-3Galp beta 1-4GalNac with N-acetylgalactosamine attached in beta-linkage to either the number two or the number four carbon of ribitol. The lipid- and carbohydrate-substituted poly(ribitol phosphate) of the S. adjacens group antigen therefore is a unique amphiphile structure, differing in its repeating-unit structure from the polyglycerophosphate structure of the more common gram-positive amphiphile lipoteichoic acid. PMID:1309524

  13. Mitotic evolution of Plasmodium falciparum shows a stable core genome but recombination in antigen families.

    PubMed

    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 evade

  14. 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

  15. Complement fixing hepatitis B core antigen immune complexes in the liver of patients with HBs antigen positive chronic disease.

    PubMed Central

    Rizzetto, M; Bonino, F; Crivelli, O; Canese, M G; Verme, G

    1976-01-01

    One hundred and fifty-two biopsies from serologically HBsAg positive and negative patients with liver disease were studied in immunofluorescence: for the presence of the surface (HBs) and the core (HBc) antigenic determinants foeterminants of the hepatitis B virus, of immunoglobulins and complement (C) deposits, and for the capacity to fix human C. Circumstantial evidence is presented suggesting that HBc immune-complexes are a relevant feature in the establishment and progression of chronic HBSAg liver disease. C fixation by liver cells was shown in all HBC positive patients with chronic hepatitis; an active form was present in every case, except two with a persistent hepatitis, an inverse ratio of HBc to C binding fluorescence being noted between active chronic hepatitis and cirrhotic patients. HBc without C fixation was observed in only three patients in the incubation phase of infectious hepatitis. IgG deposits were often found in HBc containing, C fixing nuclei. No C binding or IgG deposits were observed in acute self-limited type B hepatitis, in serologically positive patients with normal liver or minimal histological lesions, with and without HBs cytoplasmic fluorescence in their biopsy, or in serologically negative individuals. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:1001973

  16. Hepatitis B Virus Core-Related Antigens as Markers for Monitoring Chronic Hepatitis B Infection▿

    PubMed Central

    Wong, Danny Ka-Ho; Tanaka, Yasuhito; Lai, Ching-Lung; Mizokami, Masashi; Fung, James; Yuen, Man-Fung

    2007-01-01

    A sensitive chemiluminescence enzyme immunoassay has been developed for hepatitis B virus (HBV) core-related antigen (HBcrAg) detection. We aimed to investigate the usefulness of HBcrAg measurement for monitoring chronic hepatitis B disease. HBcrAg levels were measured by a chemiluminescence enzyme immunoassay in 54 untreated patients and 39 patients treated with either entecavir or lamivudine. The HBcrAg concentration correlated positively with the levels of serum HBV DNA (r = 0.820), intrahepatic total HBV DNA (r = 0.700), and covalently closed circular DNA (cccDNA) (r = 0.664; for all, P values were <0.001). A higher HBcrAg concentration was associated with a greater proportion of hepatitis B core antigen immunostaining. Although the differences were not statistically significant, patients with higher Knodell necroinflammation and fibrosis scores tended to have higher serum HBcrAg concentration levels. In the treated patients, the logarithmic reduction in HBcrAg at week 48 correlated positively with the logarithmic reduction of serum HBV DNA, intrahepatic total HBV DNA, and cccDNA. Of the 31 patients with undetectable serum HBV DNA (<300 copies/ml) at the end of treatment, 20 (65%) still had detectable HBcrAg. A greater reduction in posttreatment HBcrAg concentration was associated with histological improvement and a decrease in hepatitis B core antigen immunostaining. HBcrAg concentrations of <40,000 kU/ml at baseline and <200 kU/ml at week 24 were associated with a higher chance of having undetectable HBV DNA at week 48. In conclusion, serum HBcrAg levels correlated with HBV virological markers and reflected the chronic hepatitis B disease activity in the liver. PMID:17942661

  17. Hepatitis B virus core-related antigens as markers for monitoring chronic hepatitis B infection.

    PubMed

    Wong, Danny Ka-Ho; Tanaka, Yasuhito; Lai, Ching-Lung; Mizokami, Masashi; Fung, James; Yuen, Man-Fung

    2007-12-01

    A sensitive chemiluminescence enzyme immunoassay has been developed for hepatitis B virus (HBV) core-related antigen (HBcrAg) detection. We aimed to investigate the usefulness of HBcrAg measurement for monitoring chronic hepatitis B disease. HBcrAg levels were measured by a chemiluminescence enzyme immunoassay in 54 untreated patients and 39 patients treated with either entecavir or lamivudine. The HBcrAg concentration correlated positively with the levels of serum HBV DNA (r = 0.820), intrahepatic total HBV DNA (r = 0.700), and covalently closed circular DNA (cccDNA) (r = 0.664; for all, P values were <0.001). A higher HBcrAg concentration was associated with a greater proportion of hepatitis B core antigen immunostaining. Although the differences were not statistically significant, patients with higher Knodell necroinflammation and fibrosis scores tended to have higher serum HBcrAg concentration levels. In the treated patients, the logarithmic reduction in HBcrAg at week 48 correlated positively with the logarithmic reduction of serum HBV DNA, intrahepatic total HBV DNA, and cccDNA. Of the 31 patients with undetectable serum HBV DNA (<300 copies/ml) at the end of treatment, 20 (65%) still had detectable HBcrAg. A greater reduction in posttreatment HBcrAg concentration was associated with histological improvement and a decrease in hepatitis B core antigen immunostaining. HBcrAg concentrations of <40,000 kU/ml at baseline and <200 kU/ml at week 24 were associated with a higher chance of having undetectable HBV DNA at week 48. In conclusion, serum HBcrAg levels correlated with HBV virological markers and reflected the chronic hepatitis B disease activity in the liver.

  18. [Stability of the structure and antigenic determinants of adenovirus type 1 native hexon to proteases].

    PubMed

    Kiseleva, E K; Khil'ko, S N; Grigor'ev, V G; Diachenko, N S; Vantsak, N P

    1986-08-01

    Hexon capsomers of human adenovirus type 1 (h1) labeled by iodine 125 were digested in a native state (trimers) by trypsin, chymotrypsin or papain, and the resulting hydrolysates were analyzed by SDS-PAGE. In each case, a discrete and temporally stable pattern of relatively large fragments was revealed. The degree of hexon polypeptide hydrolysis was maximal for papain, intermediate for chymotrypsin and minimal for trypsin, the largest fragments in the digest being 32, 40 and 80 kD, respectively. At room temperature, all the electrophoretically discernible hexon proteolytical fragments were held together in structures resembling intact hexon trimers and could be regarded as "hexon cores", of which papain hexon cores were the most stable during SDS-PAGE. Radioimmunoprecipitation analysis revealed a complete absence of native hexon antigenicity in thermodenaturated fragments of hexon protease digests, while native trypsin, chymotrypsin and papain hexon cores could be precipitated by hexon-specific antibodies. The immunoprecipitated material contained all of the hexon fragments found in appropriate hexon cores and retained the structure of the original cores. Trypsin, chymotrypsin and papain hexon cores were shown to possess at least part of native Ad h1 hexon antigenic determinants of each of the following specificities: species-specific (epsilon), cross-reactive with hexon of human adenoviruses (h3 and h6), simian adenovirus (sim 16), bovine adenoviruses (bos 3 and bos 7) and avian adenovirus (Aviadenovirus gal 1 or CELO). Thus, the full spectrum of known hexon antigenic determinants (species-specific to intergenus-crossreactive) is at least portly stable against protease attack of native hexon capsomers.

  19. Changes in the antigenic and molecular structure of. gamma. -irradiated bacterial lipopolysaccharide (LPS)

    SciTech Connect

    Csako, G.; Suba, E.A.; Tsai, C.M.; Elin, R.J.

    1986-03-01

    Ionization radiation is known to alter the biological properties of LPS. The author treated a highly purified LPS from E. coli in aqueous medium with /sup 60/Co-radiation. The changes in the antigenic and molecular structure of LPS were studied in double immunodiffusion/immunoelectrophoresis (rabbit antiserum) and sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE), respectively. Untreated LPS revealed two major antigenic components and, due to varying lengths of the O-polysaccharide side chain, a series of homopolymers (SDS-PAGE). High doses of ..gamma..-radiation destroyed all antigenic reactivities and all stainable bands on SDS-PAGE. However, lower doses of radiation were selective. Disappearance of the more radiation-sensitive, electrophoretically fast-migrating antigenic component paralleled elimination of the long O-side chain containing molecules. The relatively radiation-resistant, less anodic second antigenic component cross-reacted with LPS of another E. coli strain and corresponded to LPS molecules composed of R-core and lipid A (SDS-PAGE). These findings explain the in vivo loss of antibody protection from shock before non-specific resistance with ..gamma..-irradiation of LPS.

  20. A recombinant hepatitis B core antigen polypeptide with the protamine-like domain deleted self-assembles into capsid particles but fails to bind nucleic acids.

    PubMed Central

    Gallina, A; Bonelli, F; Zentilin, L; Rindi, G; Muttini, M; Milanesi, G

    1989-01-01

    We have cloned in Escherichia coli both the complete core gene of hepatitis B virus and a truncated version of it, leading to the synthesis of high levels of a core-antigen-equivalent polypeptide (r-p22) and of an e-antigen-equivalent polypeptide (r-p16), respectively. We then compared the structural and antigenic properties of the two polypeptides, as well as their ability to bind viral nucleic acids. r-p16 was found to self-assemble into capsid-like particles that appeared similar, when observed under the electron microscope, to those formed by r-p22. In r-p16 particles, disulfide bonds linked the truncated polypeptides in dimers, assembled in the particle by noncovalent interactions. In r-p22 capsids, further disulfide bonds, conceivably involving the carboxy-terminal cysteines of r-p22 polypeptides, joined the dimers together, converting the structure into a covalently closed lattice. The protamine-like domain was at least partly exposed on the surface of r-p22 particles, since it was accessible to selective proteolysis. Finally, r-p22, but not r-p16, was shown to bind native and denatured DNA as well as RNA. Taken together, these results suggest that the protamine-like domain in core polypeptides is a nucleic acid-binding domain and is dispensable for the correct folding and assembly of amino-terminal and central regions. Images PMID:2677399

  1. Structural modeling of sandwich structures with lightweight cellular cores

    NASA Astrophysics Data System (ADS)

    Liu, T.; Deng, Z. C.; Lu, T. J.

    2007-10-01

    An effective single layered finite element (FE) computational model is proposed to predict the structural behavior of lightweight sandwich panels having two dimensional (2D) prismatic or three dimensional (3D) truss cores. Three different types of cellular core topology are considered: pyramidal truss core (3D), Kagome truss core (3D) and corrugated core (2D), representing three kinds of material anisotropy: orthotropic, monoclinic and general anisotropic. A homogenization technique is developed to obtain the homogenized macroscopic stiffness properties of the cellular core. In comparison with the results obtained by using detailed FE model, the single layered computational model can give acceptable predictions for both the static and dynamic behaviors of orthotropic truss core sandwich panels. However, for non-orthotropic 3D truss cores, the predictions are not so well. For both static and dynamic behaviors of a 2D corrugated core sandwich panel, the predictions derived by the single layered computational model is generally acceptable when the size of the unit cell varies within a certain range, with the predictions for moderately strong or strong corrugated cores more accurate than those for weak cores.

  2. The lipopolysaccharide of the mastitis isolate Escherichia coli strain 1303 comprises a novel O-antigen and the rare K-12 core type.

    PubMed

    Duda, Katarzyna A; Lindner, Buko; Brade, Helmut; Leimbach, Andreas; Brzuszkiewicz, Elzbieta; Dobrindt, Ulrich; Holst, Otto

    2011-06-01

    Mastitis represents one of the most significant health problems of dairy herds. The two major causative agents of this disease are Escherichia coli and Staphylococcus aureus. Of the first, its lipopolysaccharide (LPS) is thought to play a prominent role during infection. Here, we report the O-antigen (OPS, O-specific polysaccharide) structure of the LPS from bovine mastitis isolate E. coli 1303. The structure was determined utilizing chemical analyses, mass spectrometry, and 1D and 2D NMR spectroscopy methods. The O-repeating unit was characterized as -[→4)-β-D-Quip3NAc-(1→3)-α-L-Fucp2OAc-(1→4)-β-D-Galp-(1→3)-α-D-GalpNAc-(1→]- in which the O-acetyl substitution was non-stoichiometric. The nucleotide sequence of the O-antigen gene cluster of E. coli 1303 was also determined. This cluster, located between the gnd and galF genes, contains 13 putative open reading frames, most of which represent unknown nucleotide sequences that have not been described before. The O-antigen of E. coli 1303 was shown to substitute O-7 of the terminal LD-heptose of the K-12 core oligosaccharide. Interestingly, the non-OPS-substituted core oligosaccharide represented a truncated version of the K-12 outer core - namely terminal LD-heptose and glucose were missing; however, it possessed a third Kdo residue in the inner core. On the basis of structural and genetic data we show that the mastitis isolate E. coli 1303 represents a new serotype and possesses the K-12 core type, which is rather uncommon among human and bovine isolates.

  3. The role of adjuvant in mediating antigen structure and stability.

    PubMed

    Braun, Latoya Jones; Eldridge, Aimee M; Cummiskey, Jessica; Arthur, Kelly K; Wuttke, Deborah S

    2012-04-01

    The purpose of this study was to probe the fate of a model antigen, a cysteine-free mutant of bacteriophage T4 lysozyme, to the level of fine structural detail, as a consequence of its interaction with an aluminum (Al)-containing adjuvant. Fluorescence spectroscopy and differential scanning calorimetry were used to compare the thermal stability of the protein in solution versus adsorbed onto an Al-containing adjuvant. Differences in accessible hydrophobic surface areas were investigated using an extrinsic fluorescence probe, 8-Anilino-1-naphthalenesulfonic acid (ANS). As has been observed with other model antigens, the apparent thermal stability of the protein decreased following adsorption onto the adjuvant. ANS spectra suggested that adsorption onto the adjuvant caused an increase in exposure of hydrophobic regions of the protein. Electrostatic interactions drove the adsorption, and disruption of these interactions with high ionic strength buffers facilitated the collection of two-dimensional (15) N heteronuclear single quantum coherence nuclear magnetic resonance data of protein released from the adjuvant. Although the altered stability of the adsorbed protein suggested changes to the protein's structure, the fine structure of the desorbed protein was nearly identical to the protein's structure in the adjuvant-free formulation. Thus, the adjuvant-induced changes to the protein that were responsible for the reduced thermal stability were not observed upon desorption.

  4. Protease-like sequence in hepatitis B virus core antigen is not involved in the cleavage processes of core protein in Escherichia coli.

    PubMed

    Hwang, L H; Lin, Y J; Lai, W C; Lo, M S

    1991-02-01

    A DNA fragment, coding for hepatitis core antigen (HBcAg), was amplified by polymerase chain reaction and inserted into a lambda PL promoter-derived expression vector. The recombinant plasmid was transformed into Escherichia coli and proteins produced after heat induction were analyzed. In addition to the 21 kDa HBcAg protein, several smaller related polypeptides, particularly one of 17 kDa in size, were also detected with rabbit anti-HBcAg antiserum. Whether the protease-like sequence of core protein involved in the self-cleavage process to form the 17 kDa polypeptide was investigated by a deletion experiment. Our results with a mutant in which 7 amino acids of the conserved protease-like region in the core protein have been deleted suggest that the cleavage does not depend on the presence of these protease-like sequence. In addition, the core protein synthesized from in vitro translation reaction was not cleaved. Core particles from E. coli lysate were purified by sucrose and cesium chloride density gradient centrifugations and subsequently treated with 0.2% of SDS and 0.2% of beta-mecaptoethanol. Immunoblotting analysis, however, did not reveal any conversion of the 21 kDa protein to smaller ones. In conclusion, our results suggest that the protease-like domain at the N-terminus of the core protein does not contain intrinsic autocleavage activity, nor could the HBcAg be converted to smaller antigens by detergent treatment. PMID:1935370

  5. 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

  6. 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.

  7. Crystal structure of the jacalin-T-antigen complex and a comparative study of lectin-T-antigen complexes.

    PubMed

    Jeyaprakash, A Arockia; Geetha Rani, P; Banuprakash Reddy, G; Banumathi, S; Betzel, C; Sekar, K; Surolia, A; Vijayan, M

    2002-08-23

    Thomsen-Friedenreich antigen (Galbeta1-3GalNAc), generally known as T-antigen, is expressed in more than 85% of human carcinomas. Therefore, proteins which specifically bind T-antigen have potential diagnostic value. Jacalin, a lectin from jack fruit (Artocarpus integrifolia) seeds, is a tetramer of molecular mass 66kDa. It is one of the very few proteins which are known to bind T-antigen. The crystal structure of the jacalin-T-antigen complex has been determined at 1.62A resolution. The interactions of the disaccharide at the binding site are predominantly through the GalNAc moiety, with Gal interacting only through water molecules. They include a hydrogen bond between the anomeric oxygen of GalNAc and the pi electrons of an aromatic side-chain. Several intermolecular interactions involving the bound carbohydrate contribute to the stability of the crystal structure. The present structure, along with that of the Me-alpha-Gal complex, provides a reasonable qualitative explanation for the known affinities of jacalin to different carbohydrate ligands and a plausible model of the binding of the lectin to T-antigen O-linked to seryl or threonyl residues. Including the present one, the structures of five lectin-T-antigen complexes are available. GalNAc occupies the primary binding site in three of them, while Gal occupies the site in two. The choice appears to be related to the ability of the lectin to bind sialylated sugars. In either case, most of the lectin-disaccharide interactions are at the primary binding site. The conformation of T-antigen in the five complexes is nearly the same.

  8. [Fundamental and clinical evaluation of hepatitis B virus core-related antigen assay by LUMIPULSE f].

    PubMed

    Tanaka, Yasuhito; Takagi, Kazumi; Hiramatsu, Kumiko; Naganuma, Hatsue; Iida, Takayasu; Takasaka, Yoshimitsu; Mizokami, Masashi

    2006-07-01

    A sensitive chemiluminescence enzyme immunoassay (CLEIA) has been developed for hepatitis B virus (HBV) core-related antigens (HBcrAg) detection. The HBcrAg is designated as the precore/core gene products including HBeAg. The aim of this study is to evaluate reproducibility of HBcrAg and correlation with HBV-DNA in serum using the automatic LUMIPULSE f to estimate an assay suitable for general laboratory use. In this study, we demonstrated that HBcrAg assay had highly intra-assay reproducible [coefficients of variation(CVs); 2.8-5.2%] and inter-assay reproducible [CVs; 3.9-9.1%]. When the cutoff value was tentatively set at 1 kU/ml, all healthy controls (HBsAg/HBV-DNA negative; n=100) and anti-HCV antibody-positive (n=50) sera were identified as negative. The assay showed a detection limit of 0.5 kU/ml using four serially diluted HBV high-titer sera, indicating higher sensitivity than HBV-DNA (transcription-mediated amplification). The HBcrAg concentration correlated positively with serum HBV-DNA (n=125, r = 0.860, p < 0.0001) regardless of HBeAg, although the HBcrAg levels were higher in HBeAg-positive group than in HBeAg-negative group. In the natural course of HBV infection, the HBcrAg concentration usually changed in accordance with HBV-DNA levels, however during lamivudine therapy the change of HBcrAg was more gradual than that of HBV-DNA. In conclusion, HBcrAg concentration provides a reflection of HBV virus load equivalent to HBV-DNA level, and the assay therefore offers a simple method for monitoring hepatitis B patients.

  9. Antibody to Hepatitis B Core Antigen Levels in the Natural History of Chronic Hepatitis B

    PubMed Central

    Jia, Wei; Song, Liu-Wei; Fang, Yu-Qing; Wu, Xiao-Feng; Liu, Dan-Yang; Xu, Chun; Wang, Xiao-Mei; Wang, Wen; Lv, Dong-Xia; Li, Jun; Deng, Yong-Qiong; Wang, Yan; Huo, Na; Yu, Min; Xi, Hong-Li; Liu, Dan; Zhou, Yi-Xing; Wang, Gui-Qiang; Xia, Ning-Shao; Zhang, Ming-Xiang

    2014-01-01

    Abstract Previous studies have revealed antibody to hepatitis B core antigen (anti-HBc) levels as a predictor of treatment response in hepatitis B early antigen (HBeAg)-positive chronic hepatitis B (CHB) patients in both interferon and nucleos(t)ide analog therapy cohorts. However, there is no information about anti-HBc levels in the natural history of CHB. This study aimed to define anti-HBc levels of different phases in the natural history of CHB. Two hundred eleven treatment-naive CHB patients were included in the study. They were classified into 4 phases: immune tolerance (IT) phase (n = 39), immune clearance (IC) phase (n = 48), low or no-replicative (LR) phase (n = 55), and HBeAg-negative hepatitis (ENH, n = 69). Fifty patients who were HBsAg negative and anti-HBc positive were also recruited as past HBV infection (PBI) control group. Anti-HBc levels were measured by a newly developed double-sandwich immunoassay. Correlation of anti-HBc levels with alanine aminotransferase (ALT) and other HBV-related markers within each phase was performed. Serum anti-HBc levels were statistically significant between patients in different phases of CHB (P < 0.001). The median anti-HBc levels were: IT (3.17 log10 IU/mL), IC (4.39 log10 IU/mL), LR (3.29 log10 IU/mL), ENH (4.12 log10 IU/mL), and PBI (0.61 log10 IU/mL). There existed a strong correlation in IC (r = 0.489, P < 0.001), a poor correlation in ENH (r = 0.275, P = 0.042), and no correlation in patients with ALT reached 5 times upper limit of normal (r = 0.120, P = 0.616). Anti-HBc levels show significant differences during the natural course of CHB. These results may provide some potentially useful insights into hepatitis B pathogenesis and immune activation against hepatitis B virus. PMID:25546679

  10. 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.

  11. Sensitive enzyme immunoassay for hepatitis B virus core-related antigens and their correlation to virus load.

    PubMed

    Kimura, Tatsuji; Rokuhara, Akinori; Sakamoto, Yoko; Yagi, Shintaro; Tanaka, Eiji; Kiyosawa, Kendo; Maki, Noboru

    2002-02-01

    A sensitive enzyme immunoassay (EIA) specific for hepatitis B virus core antigen (HBcAg) and hepatitis B e antigen (HBeAg) was developed. We designated the precore/core gene products as hepatitis B virus (HBV) core-related antigens (HBcrAg). In order to detect HBcrAg even in anti-HBc/e antibody-positive specimens, the specimens were pretreated in detergents. The antibodies are inactivated by this pretreatment and, simultaneously, the antigens are released and the epitopes are exposed. The assay demonstrated 71 to 112% recovery using HBcrAg-positive sera. We observed no interference from the tested anticoagulants or blood components. When the cutoff value was tentatively set at 10(3) U/ml, all healthy control (HBsAg/HBV-DNA negative; n = 108) and anti-HCV antibody-positive (n = 59) sera were identified as negative. The assay showed a detection limit of 4 x 10(2) U/ml using recombinant antigen. Detection limits were compared in four serially diluted HBV high-titer sera. The HBcrAg assay demonstrated higher sensitivity than HBV-DNA transcription-mediated amplification (TMA) or HBeAg radio immunoassay (RIA) in the dilution test. HBcrAg concentrations correlated well with HBV-DNA TMA (r = 0.91, n = 29) and in-house real-time detection-PCR (r = 0.93, n = 47) in hepatitis B patients. On HBeAg/anti-HBe antibody seroconversion panels, the HBcrAg concentration changed in accordance with HBV-DNA levels. HBcrAg concentration provides a reflection of HBV virus load equivalent to HBV-DNA level, and the assay therefore offers a simple method for monitoring hepatitis B patients.

  12. Sensitive Enzyme Immunoassay for Hepatitis B Virus Core-Related Antigens and Their Correlation to Virus Load

    PubMed Central

    Kimura, Tatsuji; Rokuhara, Akinori; Sakamoto, Yoko; Yagi, Shintaro; Tanaka, Eiji; Kiyosawa, Kendo; Maki, Noboru

    2002-01-01

    A sensitive enzyme immunoassay (EIA) specific for hepatitis B virus core antigen (HBcAg) and hepatitis B e antigen (HBeAg) was developed. We designated the precore/core gene products as hepatitis B virus (HBV) core-related antigens (HBcrAg). In order to detect HBcrAg even in anti-HBc/e antibody-positive specimens, the specimens were pretreated in detergents. The antibodies are inactivated by this pretreatment and, simultaneously, the antigens are released and the epitopes are exposed. The assay demonstrated 71 to 112% recovery using HBcrAg-positive sera. We observed no interference from the tested anticoagulants or blood components. When the cutoff value was tentatively set at 103 U/ml, all healthy control (HBsAg/HBV-DNA negative; n = 108) and anti-HCV antibody-positive (n = 59) sera were identified as negative. The assay showed a detection limit of 4 × 102 U/ml using recombinant antigen. Detection limits were compared in four serially diluted HBV high-titer sera. The HBcrAg assay demonstrated higher sensitivity than HBV-DNA transcription-mediated amplification (TMA) or HBeAg radio immunoassay (RIA) in the dilution test. HBcrAg concentrations correlated well with HBV-DNA TMA (r = 0.91, n = 29) and in-house real-time detection-PCR (r = 0.93, n = 47) in hepatitis B patients. On HBeAg/anti-HBe antibody seroconversion panels, the HBcrAg concentration changed in accordance with HBV-DNA levels. HBcrAg concentration provides a reflection of HBV virus load equivalent to HBV-DNA level, and the assay therefore offers a simple method for monitoring hepatitis B patients. PMID:11825954

  13. 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

  14. Expression in yeast of amino-terminal peptide fusions to hepatitis B core antigen and their immunological properties.

    PubMed

    Beesley, K M; Francis, M J; Clarke, B E; Beesley, J E; Dopping-Hepenstal, P J; Clare, J J; Brown, F; Romanos, M A

    1990-07-01

    Hepatitis B core protein (HBcAg) is a potent antigen that gives both a T-cell-dependent and a T-cell-independent antibody response. It has been shown that a foreign epitope can be fused to the amino terminus of HBcAg without affecting particle integrity, and that the resulting chimaeric cores retain the immunogenicity of the foreign epitope. Here we describe the efficient expression in yeast of two different chimaeric cores, carrying epitopes of Foot and Mouth Disease Virus (FMDV) or human chorionic gonadotrophin (hCG), which are candidates for FMD and contraceptive vaccines, respectively. These cores could not be produced in E. coli in soluble form but were expressed to high levels in yeast. We constructed a yeast expression vector that allows rapid production of different chimaeric cores by cloning in cassettes encoding foreign epitopes. Both FMDV and hCG-cores were shown to present the epitopes at the surface of the particles. The FMDV-cores produced in yeast were efficient inducers of neutralising antibodies in guinea-pigs after one low dose.

  15. 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

    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

  16. Clinical relevance of total HCV core antigen testing for hepatitis C monitoring and for predicting patients' response to therapy.

    PubMed

    Maynard, M; Pradat, P; Berthillon, P; Picchio, G; Voirin, N; Martinot, M; Marcellin, P; Trepo, C

    2003-07-01

    To study the correlation between total Hepatitis C virus (HCV) Core antigen (Ag) and HCV-RNA, and to assess the proficiency of HCV Core Ag testing in monitoring and predicting virologic response during and after pegylated interferon (PEG-IFN) and ribavirin combination therapy. A total of 307 samples from treated and untreated patients were used to assess the correlation between the total HCV Core Ag test and quantitative HCV-RNA assays (Superquant, and Quantiplex branched DNA 2.0 assay). Twenty-four patients received combination therapy for 48 weeks. Blood samples were collected at day 0, and week 2, 4, 12, 24, 48 and 72 for virologic evaluation. A linear relation exists between total HCV Core Ag and HCV-RNA levels. At 3 months the positive predictive value (PPV) of response to therapy was 100% with either HCV Core Ag or HCV-RNA. For HCV Core Ag the negative predictive value (NPV) was 100% whereas for HCV-RNA the NPV was 80% (P > 0.05). At month 1, the PPV was 95% and 100% when determined by HCV Core Ag and HCV-RNA, respectively. The NPV value was 100% for HCV Core Ag and 33% for HCV-RNA (P = 0.005). HCV Core Ag quantification could be useful in clinical practice to predict a sustained virological response early during therapy (4 weeks), reaching an optimal performance at month 3. The determination of total HCV Core Ag levels in serum, constitutes an accurate and reliable alternative to HCV-RNA for monitoring and predicting treatment outcome in patients receiving PEG-IFN/Ribavirin combination therapy.

  17. Hepatitis C core antigen testing: a reliable, quick, and potentially cost-effective alternative to hepatitis C polymerase chain reaction in diagnosing acute hepatitis C virus infection.

    PubMed

    Cresswell, Fiona V; Fisher, Martin; Hughes, Daniel J; Shaw, Simon G; Homer, Gary; Hassan-Ibrahim, Mohammed O

    2015-01-15

    Hepatitis C virus (HCV) is increasingly common among human immunodeficiency virus (HIV)-infected men who have sex with men. We evaluated the efficacy of HCV core antigen in diagnosing acute HCV in an HIV-infected cohort. Compared with HCV polymerase chain reaction, core antigen proved sensitive (100%) and specific (97.9%). As a quick, simple, and cost-effective test, it has considerable utility in screening for acute HCV.

  18. 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.

  19. 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

  20. Performance evaluation of new automated hepatitis B viral markers in the clinical laboratory: two quantitative hepatitis B surface antigen assays and an HBV core-related antigen assay.

    PubMed

    Park, Yongjung; Hong, Duck Jin; Shin, Saeam; Cho, Yonggeun; Kim, Hyon-Suk

    2012-05-01

    We evaluated quantitative hepatitis B surface antigen (qHBsAg) assays and a hepatitis B virus (HBV) core-related antigen (HBcrAg) assay. A total of 529 serum samples from patients with hepatitis B were tested. HBsAg levels were determined by using the Elecsys (Roche Diagnostics, Indianapolis, IN) and Architect (Abbott Laboratories, Abbott Park, IL) qHBsAg assays. HBcrAg was measured by using Lumipulse HBcrAg assay (Fujirebio, Tokyo, Japan). Serum aminotransferases and HBV DNA were respectively quantified by using the Hitachi 7600 analyzer (Hitachi High-Technologies, Tokyo, Japan) and the Cobas AmpliPrep/Cobas TaqMan test (Roche). Precision of the qHBsAg and HBcrAg assays was assessed, and linearity of the qHBsAg assays was verified. All assays showed good precision performance with coefficients of variation between 4.5% and 5.3% except for some levels. Both qHBsAg assays showed linearity from 0.1 to 12,000.0 IU/mL and correlated well (r = 0.9934). HBsAg levels correlated with HBV DNA (r = 0.3373) and with HBcrAg (r = 0.5164), and HBcrAg also correlated with HBV DNA (r = 0.5198; P < .0001). This observation could provide impetus for further research to elucidate the clinical usefulness of the qHBsAg and HBcrAg assays.

  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. 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.

  3. [Improvement of sensitivity in the second generation HCV core antigen assay by a novel concentration method using polyethylene glycol (PEG)].

    PubMed

    Higashimoto, Makiko; Takahashi, Masahiko; Jokyu, Ritsuko; Syundou, Hiromi; Saito, Hidetsugu

    2007-11-01

    A HCV core antigen (Ag) detection assay system, Lumipulse Ortho HCV Ag has been developed and is commercially available in Japan with a lower detection level limit of 50 fmol/l, which is equivalent to 20 KIU/ml in PCR quantitative assay. HCV core Ag assay has an advantage of broader dynamic range compared with PCR assay, however the sensitivity is lower than PCR. We developed a novel HCV core Ag concentration method using polyethylene glycol (PEG), which can improve the sensitivity five times better than the original assay. The reproducibility was examined by consecutive five-time measurement of HCV patients serum, in which the results of HCV core Ag original and concentrated method were 56.8 +/- 8.1 fmol/l (mean +/- SD), CV 14.2% and 322.9 +/- 45.5 fmol/l CV 14.0%, respectively. The assay results of HCV negative samples in original HCV core Ag were all 0.1 fmol/l and the results were same even in the concentration method. The results of concentration method were 5.7 times higher than original assay, which was almost equal to theoretical rate as expected. The assay results of serially diluted samples were also as same as expected data in both original and concentration assay. We confirmed that the sensitivity of HCV core Ag concentration method had almost as same sensitivity as PCR high range assay in the competitive assay study using the serially monitored samples of five HCV patients during interferon therapy. A novel concentration method using PEG in HCV core Ag assay system seems to be useful for assessing and monitoring interferon treatment for HCV.

  4. Epidemiological analysis of the significance of low-positive test results for antibody to hepatitis B surface and core antigens.

    PubMed Central

    Hadler, S C; Murphy, B L; Schable, C A; Heyward, W L; Francis, D P; Kane, M A

    1984-01-01

    To determine the significance of certain serological test results commonly encountered in hepatitis B virus testing, we reviewed serological test data from nine studies of hepatitis B conducted between 1980 and 1982. Three tests, for hepatitis B surface antigen and for antibodies to hepatitis B surface antigen and hepatitis B core antigen (anti-HBs and anti-HBc), were used to measure hepatitis B virus infection risk in various populations. Two results, low levels of anti-HBs alone and low levels of anti-HBc alone, occurred at constant frequencies (2.72 and 0.4%, respectively), regardless of the prevalence of HBV infection in the population. Positivity for low levels of anti-HBs alone persisted for 1 year in less than one-half of those studied; in addition, response to hepatitis B virus vaccine was augmented in only one-third of this group. Positivity for low levels of anti-HBc alone did not persist in any of 11 persons studied. These findings indicate that presently available tests for anti-HBs and anti-HBc at low levels are often nonspecific and should be interpreted with caution. PMID:6715519

  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. Heat treatment of unclarified Escherichia coli homogenate improved the recovery efficiency of recombinant hepatitis B core antigen.

    PubMed

    Ng, Michelle Y T; Tan, Wen Siang; Abdullah, Norhafizah; Ling, Tau Chuan; Tey, Beng Ti

    2006-10-01

    Heat precipitation procedure has been regularly incorporated as a selective purification step in various thermostable proteins expressed in different hosts. This method is efficient in precipitation of most of the host proteins and also deactivates various host proteases that can be harmful to the desired gene products. In this study, introduction of heat treatment procedure in the purification of hepatitis B core antigen (HBcAg) produced in Escherichia coli has been investigated. Thermal treatment of the cell homogenate at 60 degrees C for 30 min prior to subsequent clarification steps has resulted in 1.4 times and 18% higher in purity and recovery yield, respectively, compared to the non-heat-treated cell homogenate. In direct capture of HBcAg by using anion-exchangers from unclarified feedstock, pre-conditioning the feedstock by heat treatment at 60 degrees C for 45 min has increased the recovery yield of HBcAg by 2.9-fold and 42% in purity compared to that treated for 10 min. Enzyme-linked immunosorbent assay (ELISA) analysis showed that the antigenicity of the core particles was not affected by the heat treatment process. PMID:16860402

  7. Functional Characterization of WaaL, a Ligase Associated with Linking O-Antigen Polysaccharide to the Core of Pseudomonas aeruginosa Lipopolysaccharide

    PubMed Central

    Abeyrathne, Priyanka D.; Daniels, Craig; Poon, Karen K. H.; Matewish, Mauricia J.; Lam, Joseph S.

    2005-01-01

    The O antigen of Pseudomonas aeruginosa B-band lipopolysaccharide is synthesized by assembling O-antigen-repeat units at the cytoplasmic face of the inner membrane by nonprocessive glycosyltransferases, followed by polymerization on the periplasmic face. The completed chains are covalently attached to lipid A core by the O-antigen ligase, WaaL. In P. aeruginosa the process of ligating these O-antigen molecules to lipid A core is not clearly defined, and an O-antigen ligase has not been identified until this study. Using the sequence of waaL from Salmonella enterica as a template in a BLAST search, a putative waaL gene was identified in the P. aeruginosa genome. The candidate gene was amplified and cloned, and a chromosomal knockout of PAO1 waaL was generated. Lipopolysaccharide (LPS) from this mutant is devoid of B-band O-polysaccharides and semirough (SR-LPS, or core-plus-one O-antigen). The mutant PAO1waaL is also deficient in the production of A-band polysaccharide, a homopolymer of d-rhamnose. Complementation of the mutant with pPAJL4 containing waaL restored the production of both A-band and B-band O antigens as well as SR-LPS, indicating that the knockout was nonpolar and waaL is required for the attachment of O-antigen repeat units to the core. Mutation of waaL in PAO1 and PA14, respectively, could be complemented with waaL from either strain to restore wild-type LPS production. The waaL mutation also drastically affected the swimming and twitching motilities of the bacteria. These results demonstrate that waaL in P. aeruginosa encodes a functional O-antigen ligase that is important for cell wall integrity and motility of the bacteria. PMID:15838026

  8. Structure and gene cluster of the O-antigen of Escherichia coli O68.

    PubMed

    Jiang, Lingyan; Perepelov, Andrei V; Filatov, Andrei V; Liu, Bin; Shashkov, Alexander S; Senchenkova, Sof'ya N; Wang, Lei; Knirel, Yuriy A

    2014-10-01

    The O-polysaccharide (O-antigen) of Escherichia coli O68 was studied by sugar analysis, partial solvolysis with anhydrous trifluoroacetic acid, and 1D and 2D (1)H and (13)C NMR spectroscopies. The following structure of the branched heptasaccharide repeating unit was established: [structure: see text]. The O-antigen gene cluster of E. coli O68 was sequenced. The gene functions were tentatively assigned by comparison with sequences in the available databases and found to be in full agreement with the O-antigen structure.

  9. 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

  10. [Duffy blood group antigens: structure, serological properties and function].

    PubMed

    Łukasik, Ewa; Waśniowska, Kazimiera

    2016-01-01

    Duffy (Fy) blood group antigens are located on seven-transmembrane glycoprotein expressed on erythrocytes and endothelial cells, which acts as atypical chemokine receptor (ACKR1) and malarial receptor. The biological role of the Duffy glycoprotein has not been explained yet. It is suggested that Duffy protein modulate the intensity of the inflammatory response. The Duffy blood group system consists of two major antigens, Fy(a) and Fy(b), encoded by two codominant alleles designated FY*A and FY*B which differ by a single nucleotide polymorphism (SNP) at position 125G>A of the FY gene that results in Gly42Asp amino acid change in the Fy(a) and Fy(b) antigens, respectively. The presence of antigen Fy(a) and/or Fy(b) on the erythrocytes determine three Duffy-positive phenotypes: Fy(a+b-), Fy(a-b+) and Fy(a+b+), identified in Caucasian population. The Duffy-negative phenotype Fy(a-b-), frequent in Africans, but very rare in Caucasians, is defined by the homozygous state of FY*B-33 alleles. The FY*B-33 allele is associated with a SNP -33T>C in the promoter region of the FY gene, which suppresses erythroid expression of this gene without affecting its expression in other tissues. The FY*X allele, found in Caucasians, is correlated with weak expression of Fy(b) antigen. Fy(x) antigen differs from the native Fy(b) by the Arg89Cys and Ala100Thr amino acid substitutions due to SNPs: 265C>T and 298G>A in FY*B allele. The frequency of the FY alleles shows marked geographic disparities, the FY*B-33 allele is predominant in Africans, the FY*B in Caucasians, while the FY*A allele is dominant in Asians and it is the most prevalent allele globally. PMID:26943312

  11. Japanese Reference Panel of Blood Specimens for Evaluation of Hepatitis C Virus RNA and Core Antigen Quantitative Assays

    PubMed Central

    Murayama, Asako; Sugiyama, Nao; Watashi, Koichi; Masaki, Takahiro; Suzuki, Ryosuke; Aizaki, Hideki; Mizuochi, Toshiaki; Wakita, Takaji

    2012-01-01

    An accurate and reliable quantitative assay for hepatitis C virus (HCV) is essential for measuring viral propagation and the efficacy of antiviral therapy. There is a growing need for domestic reference panels for evaluation of clinical assay kits because the performance of these kits may vary with region-specific genotypes or polymorphisms. In this study, we established a reference panel by selecting 80 donated blood specimens in Japan that tested positive for HCV. Using this panel, we quantified HCV viral loads using two HCV RNA kits and five core antigen (Ag) kits currently available in Japan. The data from the two HCV RNA assay kits showed excellent correlation. All RNA titers were distributed evenly across a range from 3 to 7 log IU/ml. Although the data from the five core Ag kits also correlated with RNA titers, the sensitivities of individual kits were not sufficient to quantify viral load in all samples. As calculated by the correlation with RNA titers, the theoretical lower limits of detection by these core Ag assays were higher than those for the detection of RNA. Moreover, in several samples in our panel, core Ag levels were underestimated compared to RNA titers. Sequence analysis in the HCV core region suggested that polymorphisms at amino acids 47 to 49 of the core Ag were responsible for this underestimation. The panel established in this study will be useful for estimating the quality of currently available and upcoming HCV assay kits; such quality control is essential for clinical usage of these kits. PMID:22495557

  12. Structural Performance of Eco-Core Sandwich Panels

    NASA Astrophysics Data System (ADS)

    Shivakumar, Kunigal; Chen, Huanchun

    Eco-Core, a fire resistant core material for sandwich composite structures developed under the US Navy (ONR) program, was used to study its performance as a sandwich beam with glass/vinyl ester face sheet. Performance of Eco-Core was compared with balsa and PVC core sandwich panels. Test specimens were designed to simulate shear, flexural, and edgewise compression loadings. These tests were conducted on Eco-Core as well as balsa and PVC sandwich composite specimens. Failure loads and modes were compared with each other and the analytical prediction. Both Eco-Core and balsa cored sandwich beams had similar failure modes in all three test conditions. In the case of transversely loaded (four-point) beams Eco-Core specimens failed by core shear for span/depth (S/d) ratio less than 4 and the failure mode changed to core tension for S/d >4. This is attributed to weak tensile strength of the core material. An expression for core tension failure load based on beam theory was derived. On the other hand, ductile materials like PVC failed by core indentation. Under edgewise compression, face sheet microbuckling and general buckling are the two potential failure modes for Eco-Core and balsa core sandwich composites. For specimen length/depth ratio L/d <7 the failure is by face sheet microbuckling, for 7 ≤L/d ≤13 the failure is a combination of face sheet microbuckling, debonding and buckling, and for L/d >13 the failure is by general buckling. Predictions from the existing equations agreed well with the experiment for both core materials. For PVC core, wrinkling/shear buckling and general buckling are the potential failure modes. For L/d ≤8.5 the failure is wrinkling and for L/d >8.5 the failure is general buckling.

  13. Crystal structure of c5321: a protective antigen present in uropathogenic Escherichia coli strains displaying an SLR fold

    PubMed Central

    2013-01-01

    Background Increasing rates of antimicrobial resistance among uropathogens led, among other efforts, to the application of subtractive reverse vaccinology for the identification of antigens present in extraintestinal pathogenic E. coli (ExPEC) strains but absent or variable in non-pathogenic strains, in a quest for a broadly protective Escherichia coli vaccine. The protein coded by locus c5321 from CFT073 E. coli was identified as one of nine potential vaccine candidates against ExPEC and was able to confer protection with an efficacy of 33% in a mouse model of sepsis. c5321 (known also as EsiB) lacks functional annotation and structurally belongs to the Sel1-like repeat (SLR) family. Herein, as part of the general characterization of this potential antigen, we have focused on its structural properties. Results We report the 1.74 Å-resolution crystal structure of c5321 from CFT073 E. coli determined by Se-Met SAD phasing. The structure is composed of 11 SLR units in a topological organisation that highly resembles that found in HcpC from Helicobacter pylori, with the main difference residing in how the super-helical fold is stabilised. The stabilising effect of disulfide bridges in HcpC is replaced in c5321 by a strengthening of the inter-repeat hydrophobic core. A metal-ion binding site, uncharacteristic of SLR proteins, is detected between SLR units 3 and 4 in the region of the inter-repeat hydrophobic core. Crystal contacts are observed between the C-terminal tail of one molecule and the C-terminal amphipathic groove of a neighbouring one, resembling interactions between ligand and proteins containing tetratricopeptide-like repeats. Conclusions The structure of antigen c5321 presents a mode of stabilization of the SLR fold different from that observed in close homologs of known structure. The location of the metal-ion binding site and the observed crystal contacts suggest a potential role in regulation of conformational flexibility and interaction with yet

  14. Inner core structure - probing the African hemisphere boundary

    NASA Astrophysics Data System (ADS)

    Irving, J. C.

    2013-12-01

    The inner core is Earth's deepest region and many of its properties still remain elusive - the exact composition of the iron-nickel alloy of which is it formed, the crystalline phase or phases present and its age and dynamical history. One of the more mysterious properties of the inner core is the presence of a seismologically observable hemispherical structure in the inner core, which persists through at least half if its depth. Hemispherical inner core structure requires that there be parts of the inner core where either a gradual or rapid transition between the two hemispheres takes place. A sharp boundary has been observed in the uppermost 100km of the inner core; here I investigate the nature of the boundary under Africa. By using PKPbc-PKPdf differential travel times, I am able to seismologically image the nature of the hemisphere boundary region under Africa. Core sensitive waves generated by earthquakes in the Americas, the polar regions, Asia and the Indian Ocean are used to discern the perturbations to PKPdf travel times though the inner core. The PKPdf waves used sample the inner core under Africa with a range of ray angles, permitting the investigation of the variations present in both anisotropic and isotropic P-wave velocity in the inner core. The PKPdf waves are sensitive to the upper 360km of the inner core, allowing us to image a region which could have been growing for hundreds of millions of years. A stronger understanding of the seismological properties of the inner core will help us to better distinguish between possible mechanisms for the formation of both hemispherical structure and anisotropic texture in the inner core.

  15. Synthesis of the Common Core Structure of the Stemofoline Alkaloids.

    PubMed

    Ideue, Eiji; Shimokawa, Jun; Fukuyama, Tohru

    2015-10-16

    A novel synthetic route to the common core structural motif of the stemofoline alkaloids has been developed. The key transformations include (1) an intramolecular 1,3-dipolar cycloaddition reaction of a highly functionalized nitrone, (2) the subsequent formation of a caged structure via lithiated allylic sulfoxide, and (3) the concomitant sila-Pummerer reaction of α-silylalkenyl sulfoxide to prepare a thioester precursor. A series of stereochemistries on the highly caged core structure characteristic of the stemofoline alkaloids was successfully assembled.

  16. 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.

  17. Structural proteins of ribonucleic acid tumor viruses. Purification of envelope, core, and internal components.

    PubMed

    Strand, M; August, J T

    1976-01-25

    Murine type C virus structural proteins, the envelope glycopeptides, 30,000 dalton major core protein, and 15,000 dalton internal protein have each been purified to near homogeneity and in high yield from the smae batch of virus by use of phosphocellulose column chromatography and gel filtration procedures. Evidence that these proteins are specified by the viral genome was obtained by competition radioimmunoassay analysis, comparing these polypeptides from Rauscher virus cultivated in a variety of mammalian cell lines; all of the reactive antigenic determinants of these proteins appeared to be virus-specific.

  18. 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.

  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. Photon management with core-shell nanowire structures.

    PubMed

    Lai, Kun-Yu; Chang, Hung-Chih; Dai, Yu-An; He, Jr-Hau

    2012-03-12

    Antireflective Si/oxide core-shell nanowire arrays (NWAs) were fabricated by galvanic etching and subsequent annealing process. The excellent light-harvesting characteristics of the core-shell NWAs, such as broadband working ranges, omnidirectionality, and polarization-insensitivity, ascribed to the smooth index transition from air to the substrates, have been demonstrated. By tuning core-shell volume ratios, we obtained enhanced light trapping regions implemented in either the planar Si underneath NWAs or the core regions of NWAs, greatly benefiting the geometry design of planar and radial p-n junction cell structures, respectively. This photon management scheme indicates the potential use in nanostructured photovoltaic applications. PMID:22418674

  1. Comparative studies on the antigenic structures of five subspecies of Oncomelania snails by immunoelectrophoresis.

    PubMed

    Iwanaga, Y

    1997-03-01

    To approach the biochemical relationships of five subspecies of Oncomelania snails, antigenic structures among the subspecies were compared using immunoelectrophoresis. The results obtained are summarized as follows: 1) For five subspecies of Oncomelania hupensis snails (Oncomelania hupensis hupensis, O.h.nosophora, O.h. formosana, O.h. chiui and O.h. quadrasi), 23-24 precipitin bands were observed between the antigens and their homologous antisera, while 18-22 bands were observed in the heterologous reactions. 2) For each subspecies, residual bands observed after absorption procedure demonstrated the presence of antigens unique to each subspecies except O.h. chiui. Based on the immunological antigenic structures among the Oncomelania subspecies, it is suggested that O.h. nosophora and O.h. hupensis forms are closely related group, while O.h. formosana, O.h. chiui and O.h. quadrasi forms are another group.

  2. Biosynthesis and Structure of the Burkholderia cenocepacia K56-2 Lipopolysaccharide Core Oligosaccharide

    PubMed Central

    Ortega, Ximena; Silipo, Alba; Saldías, M. Soledad; Bates, Christa C.; Molinaro, Antonio; Valvano, Miguel A.

    2009-01-01

    Burkholderia cenocepacia is an opportunistic pathogen that displays a remarkably high resistance to antimicrobial peptides. We hypothesize that high resistance to antimicrobial peptides in these bacteria is because of the barrier properties of the outer membrane. Here we report the identification of genes for the biosynthesis of the core oligosaccharide (OS) moiety of the B. cenocepacia lipopolysaccharide. We constructed a panel of isogenic mutants with truncated core OS that facilitated functional gene assignments and the elucidation of the core OS structure in the prototypic strain K56-2. The core OS structure consists of three heptoses in the inner core region, 3-deoxy-d-manno-octulosonic acid, d-glycero-d-talo-octulosonic acid, and 4-amino-4-deoxy-l-arabinose linked to d-glycero-d-talo-octulosonic acid. Also, glucose is linked to heptose I, whereas heptose II carries a second glucose and a terminal heptose, which is the site of attachment of the O antigen. We established that the level of core truncation in the mutants was proportional to their increased in vitro sensitivity to polymyxin B (PmB). Binding assays using fluorescent 5-dimethylaminonaphthalene-1-sulfonyl-labeled PmB demonstrated a correlation between sensitivity and increased binding of PmB to intact cells. Also, the mutant producing a heptoseless core OS did not survive in macrophages as compared with the parental K56-2 strain. Together, our results demonstrate that a complete core OS is required for full PmB resistance in B. cenocepacia and that resistance is due, at least in part, to the ability of B. cenocepacia to prevent binding of the peptide to the bacterial cell envelope. PMID:19525227

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

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

    PubMed

    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

  13. Structure and gene cluster of the O-antigen of Escherichia coli O140.

    PubMed

    Perepelov, Andrei V; Wang, Quan; Senchenkova, Sof'ya N; Mei, Zhu; Shashkov, Alexander S; Wang, Lei; Knirel, Yuriy A

    2015-06-26

    An acidic O-polysaccharide (O-antigen) was isolated from the lipopolysaccharide of Escherichia coli O140 and studied by sugar analysis along with 1D and 2D (1)H and (13)C NMR spectroscopy. The following structure of the branched hexasaccharide repeating unit was established: [Formula: see text]. The O-antigen gene cluster of E. coli O140 was sequenced. The gene functions were tentatively assigned by a comparison with sequences in the available databases and found to be in full agreement with the E. coli O140 polysaccharide structure.

  14. Structure and gene cluster of the O-antigen of Escherichia coli O43.

    PubMed

    Perepelov, Andrei V; Guo, Xi; Filatov, Andrei V; Liu, Bin; Knirel, Yuriy A

    2015-10-30

    The O-polysaccharide (O-antigen) of Escherichia coli O43 was isolated from the lipopolysaccharide and studied by chemical methods, including sugar analyses, Smith degradation, and solvolysis with anhydrous trifluoroacetic acid, along with (1)H and (13)C NMR spectroscopy. The following structure of the pentasaccharide repeating unit of the O-polysaccharide was established: [Formula: see text] Functions of genes in the O-antigen gene cluster of E. coli O43 were assigned by a comparison with sequences in the available databases and found to be in agreement with the O-polysaccharide structure.

  15. High performance carbon nanotube-Si core-shell wires with a rationally structured core for lithium ion battery anodes.

    PubMed

    Fan, Yu; Zhang, Qing; Lu, Congxiang; Xiao, Qizhen; Wang, Xinghui; Tay, Beng Kang

    2013-02-21

    Core-shell Si nanowires are very promising anode materials. Here, we synthesize vertically aligned carbon nanotubes (CNTs) with relatively large diameters and large inter-wire spacing as core wires and demonstrate a CNT-Si core-shell wire composite as a lithium ion battery (LIB) anode. Owing to the rationally engineered core structure, the composite shows good capacity retention and rate performance. The excellent performance is superior to most core-shell nanowires previously reported.

  16. 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

  17. 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

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

    PubMed

    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.

  19. 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

  20. 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

  1. 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)-

  2. Effects of core perturbations on the structure of the sun

    NASA Technical Reports Server (NTRS)

    Sweigart, A. V.

    1983-01-01

    The effects of perturbing the inner part of the solar core where the hydrogen abundance has been partially depleted by nuclear burning are investigated. Small regions are mixed within the core and the evolution of the resulting luminosity and radius perturbations is followed. The sensitivity of the solar luminosity and radius to mixing events of different sizes and at different locations in the core is determined and several relationships between the luminosity and radius perturbations are examined to see if the value of one of these perturbations can be inferred from a measurement of the other. It is found that any core perturbation which alters the hydrostatic structures will immediately affect the solar luminosity and radius. The behavior of these perturbations depends on the location of the mixing event within the core. Mixing events cannot produce the decrease in the solar radius without leading to a homogeneous evolution of the solar core and/or to a prohibitively large change in the solar luminosity.

  3. 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.

  4. Detection of antibody to hepatitis B core antigen (anti-HBc) using a direct (antiglobulin) format and development of a confirmatory assay for anti-HBc.

    PubMed

    Nelles, M J; Taylor, L; Filer, S; Wellerson, R; Haberzettl, C; Sito, A; Geltosky, J E

    1988-07-01

    A direct (antiglobulin) solid-phase enzyme immunoassay for the detection of antibody to hepatitis B core antigen (anti-HBc) is described. The assay utilizes recombinant hepatitis B core antigen as the solid-phase 'capture' reagent and a mixture of monoclonal antibodies specific for human IgG and IgM conjugated to horseradish peroxidase as the 'detector' reagent. The direct assay demonstrated excellent sensitivity and specificity when compared with a commercially available competitive enzyme immunoassay. The direct assay format lends itself to a confirmatory assay for anti-HBc by addition of monoclonal anti-HBc to the reaction mixture. Feasibility of the confirmatory assay for anti-HBc was demonstrated using specimens reactive for anti-HBc as documented by both the direct and competitive assays.

  5. 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

  6. The constant region affects antigen binding of antibodies to DNA by altering secondary structure.

    PubMed

    Xia, Yumin; Janda, Alena; Eryilmaz, Ertan; Casadevall, Arturo; Putterman, Chaim

    2013-11-01

    We previously demonstrated an important role of the constant region in the pathogenicity of anti-DNA antibodies. To determine the mechanisms by which the constant region affects autoantibody binding, a panel of isotype-switch variants (IgG1, IgG2a, IgG2b) was generated from the murine PL9-11 IgG3 autoantibody. The affinity of the PL9-11 antibody panel for histone was measured by surface plasmon resonance (SPR). Tryptophan fluorescence was used to determine wavelength shifts of the antibody panel upon binding to DNA and histone. Finally, circular dichroism spectroscopy was used to measure changes in secondary structure. SPR analysis revealed significant differences in histone binding affinity between members of the PL9-11 panel. The wavelength shifts of tryptophan fluorescence emission were found to be dependent on the antibody isotype, while circular dichroism analysis determined that changes in antibody secondary structure content differed between isotypes upon antigen binding. Thus, the antigen binding affinity is dependent on the particular constant region expressed. Moreover, the effects of antibody binding to antigen were also constant region dependent. Alteration of secondary structures influenced by constant regions may explain differences in fine specificity of anti-DNA antibodies between antibodies with similar variable regions, as well as cross-reactivity of anti-DNA antibodies with non-DNA antigens.

  7. 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.

  8. 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

  9. 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

  10. Stapled HIV-1 Peptides Recapitulate Antigenic Structures and Engage Broadly Neutralizing Antibodies

    PubMed Central

    Bird, Gregory H.; Irimia, Adriana; Ofek, Gilad; Kwong, Peter D.; Wilson, Ian A.; Walensky, Loren D.

    2014-01-01

    Hydrocarbon stapling can restore bioactive, α-helical structure to natural peptides, yielding research tools and prototype therapeutics to dissect and target protein interactions. Here, we explore the capacity of peptide stapling to generate high fidelity, protease-resistant mimics of antigenic structures for vaccine development. HIV-1 has been refractory to vaccine technologies thus far, although select human antibodies can broadly neutralize HIV-1 by targeting sequences of the gp41 juxtamembrane fusion apparatus. To develop candidate HIV-1 immunogens, we generated and characterized stabilized α-helices of the membrane proximal external region (SAH-MPER) of gp41. SAH-MPER peptides were remarkably protease-resistant and bound to the broadly neutralizing 4E10 and 10E8 antibodies with high affinity, recapitulating the structure of the MPER epitope when differentially engaged by the two anti-HIV Fabs. Thus, stapled peptides may provide a new opportunity to develop chemically-stabilized antigens for vaccination. PMID:25420104

  11. 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.

  12. Effect of Silicon Alloying on the Structure of Exoplanetary Cores

    NASA Astrophysics Data System (ADS)

    Wicks, J. K.; Smith, R.; Coppari, F.; Kraus, R. G.; Newman, M.; Duffy, T. S.

    2015-12-01

    The composition of cores of terrestrial planets are expected to be broadly similar to that of Earth in that they are comprised of a Fe-Ni alloy with variable amounts of light elements such as O, Si, C, S, and H. With the increasing number of discoveries of Super-Earths (rocky planets many times the mass of our own), the properties of terrestrial phases at ultrahigh pressures are required to understand and interpret the variability of large-scale exoplanet observations. The properties of the cores of these bodies are important for understanding the bulk chemistry, thermal evolution, magnetic fields, and, ultimately, habitability of a planet. Recent diamond anvil cell studies interrogating the structure of iron generally agree that Fe should be hcp at core pressures and temperatures, although other structures have been proposed. At higher pressures and with the addition of light elements, the structure is less understood. The addition of large amounts of Si, for example, stabilizes the cubic B2 structure with respect to hcp at outer core pressures. Our goal in this study is to explore the effect of Si-alloying at inner core and exoplanetary-core pressures. Dynamic compression experiments were carried out at the Omega Laser at the Laboratory for Laser Energetics, University of Rochester. High pressures were achieved by focusing laser drives onto target packages containing Fe-Si alloys. Pressures within the sample were determined by monitoring the velocity history at the sample/window interface. Quasi-monochromatic X-rays, timed with maximum compression of the Fe-alloy sample, were generated via laser irradiation of iron or germanium foils arranged in a backlighter configuration and collected on image plates lining the inner walls of a box attached to the target package. In this presentation we will report on the effect of Si-alloying on the structure and density of Fe over the pressure range 100-1000 GPa. We find that while Fe with 7 wt.% Si remains in the hcp

  13. Structure and stability of complex coacervate core micelles with lysozyme.

    PubMed

    Lindhoud, Saskia; Vries, Renko de; Norde, Willem; Stuart, Martien A Cohen

    2007-07-01

    Encapsulation of enzymes by polymers is a promising method to influence their activity and stability. Here, we explore the use of complex coacervate core micelles for encapsulation of enzymes. The core of the micelles consists of negatively charged blocks of the diblock copolymer PAA42PAAm417 and the positively charged homopolymer PDMAEMA150. For encapsulation, part of the positively charged homopolymer was replaced by the positively charged globular protein lysozyme. We have studied the formation, structure, and stability of the resulting micelles for three different mixing ratios of homopolymer and lysozyme: a system predominantly consisting of homopolymer, a system predominantly consisting of lysozyme, and a system where the molar ratio between the two positively charged molecules was almost one. We also studied complexes made of only lysozyme and PAA42PAAm417. Complex formation and the salt-induced disintegration of the complexes were studied using dynamic light-scattering titrations. Small-angle neutron scattering was used to investigate the structures of the cores. We found that micelles predominantly consisting of homopolymer are spherical but that complex coacervate core micelles predominantly consisting of lysozyme are nonspherical. The stability of the micelles containing a larger fraction of lysozyme is lower.

  14. Structure and gene cluster of the o-antigen of Escherichia coli o96.

    PubMed

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

    2016-02-01

    Mild acid degradation of the lipopolysaccharide of Escherichia coli O96 afforded a mixture of two polysaccharides. The following structure of the pentasaccharide repeating unit of the major polymer was established by sugar analysis, Smith degradation, and (1)H and (13)C NMR spectroscopy: [Formula: see text]. The O-antigen gene cluster of E. coli O96 between conserved galF and gnd genes was found to be consistent with this structure, and hence, the major polysaccharide represents the O96-antigen. The O96-antigen structure and gene cluster are similar to those of E. coli O170, and two proteins encoded in the gene clusters of both bacteria were putatively assigned a function of galactofuranosyltransferases. The minor polymer has the same structure as a peptidoglycan-related polysaccharide reported earlier in Providencia alcalifeciens O45 and several other O-serogoups of this species (Ovchinnikova OG, Liu B, Kocharova NA, Shashkov AS, Kondakova AN, Siwinska M, Feng L, Rozalski A, Wang L, Knirel YA. Biochemistry (Moscow) 2012;77:609-15) → 4)-β-D-GlcpNAc-(1 → 4)-β-D-GlcpNAc3(Rlac-lAla)-(1 → where Rlac-lAla indicates (R)-1-[(S)-1-carboxyethylaminocarbonyl]ethyl.

  15. Vortex-dominated flow with viscous core structure

    NASA Technical Reports Server (NTRS)

    Liu, C. H.; Krause, E.; Ting, L.

    1985-01-01

    Recent theoretical studies of vortex-dominated flows are reviewed with special emphasis on those for which the viscous core structures play an important role. The problems to be described are: The interaction and merging of two-dimensional vortices and of curved vortex filaments, the roll-up and decay of trailing far wakes, and the initiation of vortex breakdown. The analysis utilizes finite-difference solutions of the Navier-Stokes equations complemented by asymptotic expansion techniques.

  16. cDNA cloning and primary structure of a white-face hornet venom allergen, antigen 5.

    PubMed Central

    Fang, K S; Vitale, M; Fehlner, P; King, T P

    1988-01-01

    A major allergen of white-face hornet (Dolichovespula maculata) venom is antigen 5 (also designated Dol m V). We have determined the primary structures of two forms of this protein by cDNA and protein sequencings. These two forms with 204 and 205 amino acid residues differ in 23% of their sequences but they are antigenically similar. Both forms have sequence similarity with a pathogenesis-related protein of tobacco leaf. In a 130-residue overlap of these proteins, 35-39 residues were identical. Hornet antigen 5 cDNAs were isolated from an expression library in lambda gt11 phage using antibody probes. Several of the cDNAs were not full length, but the fusion fragments expressed were immunoreactive. These results suggest that antigenic determinants of the sequential type are distributed throughout the entire molecule of antigen 5. After subcloning, antigen 5 was also expressed in pKK233-2 plasmid. Images PMID:3422469

  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. 5'-structural analysis of genes encoding polymorphic antigens of chemically induced tumors

    SciTech Connect

    Srivastava, R.K.; Chen, Y.T.; Old, L.J.

    1987-06-01

    The authors have proposed that the distinct tumor rejection antigens of chemically induced sarcomas in inbred mice belong to a family of M/sub r/ 96,000 glycoproteins (gp96). An identical 14-amino acid sequence was found at the amino terminus of gp96 from two antigenically distinct BALB/c sarcomas. Oligonucleotide probes, end-labeled with (/sup 12/P)-ATP, derived from this sequence permitted isolation of 5' cDNA and genomic fragments coding for gp96. Three short exons interrupted by relatively long introns were identified at the 5' terminus of the gp96 gene. The first exon encodes a signal peptide, which is consistent with gp96 being a cell surface antigen. Southern blot analysis indicated that the gp96 family is encoded by a single gene, and 3-kilobase transcripts were detected in all normal and tumor cells tested. Nucleotide and deduced amino acid sequences from 311 base pairs at the 5' terminus showed no homology with any know protein. The availability of molecular probes for the gp96 system permits analysis of the structural polymorphism of these antigens.

  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.

  20. Structural Characterization of Closely Related O-antigen Lipopolysaccharide (LPS) Chain Length Regulators*

    PubMed Central

    Kalynych, Sergei; Yao, Deqiang; Magee, James; Cygler, Miroslaw

    2012-01-01

    The surface O-antigen polymers of Gram-negative bacteria exhibit a modal length distribution that depends on dedicated chain length regulator periplasmic proteins (polysaccharide co-polymerases, PCPs) anchored in the inner membrane by two transmembrane helices. In an attempt to determine whether structural changes underlie the O-antigen modal length specification, we have determined the crystal structures of several closely related PCPs, namely two chimeric PCP-1 family members solved at 1.6 and 2.8 Å and a wild-type PCP-1 from Shigella flexneri solved at 2.8 Å. The chimeric proteins form circular octamers, whereas the wild-type WzzB from S. flexneri was found to be an open trimer. We also present the structure of a WzzFepE mutant, which exhibits severe attenuation in its ability to produce very long O-antigen polymers. Our findings suggest that the differences in the modal length distribution depend primarily on the surface-exposed amino acids in specific regions rather than on the differences in the oligomeric state of the PCP protomers. PMID:22437828

  1. Hepatitis B core-related antigen levels are associated with response to entecavir and peginterferon add-on therapy in hepatitis B e antigen-positive chronic hepatitis B patients.

    PubMed

    van Campenhout, M J H; Brouwer, W P; van Oord, G W; Xie, Q; Zhang, Q; Zhang, N; Guo, S; Tabak, F; Streinu-Cercel, A; Wang, J; Pas, S D; Sonneveld, M J; de Knegt, R J; Boonstra, A; Hansen, B E; Janssen, H L A

    2016-06-01

    Hepatitis B core-related antigen (HBcrAg), a new serum marker, may be useful in monitoring chronic hepatitis B infection. HBcrAg was measured in 175 hepatitis B e antigen-positive patients treated with entecavir (ETV) with or without peginterferon (PEG-IFN) add-on therapy. Decline in HBcrAg was stronger in patients with vs. without combined response (ETV: -3.22 vs. -1.71 log U/mL, p <0.001; PEG-IFN add-on: -3.16 vs. -1.83 IU/mL, p <0.001) and in patients with vs. without hepatitis B surface antigen (HBsAg) response (ETV: -2.60 vs. -1.74 log U/mL, p <0.001; PEG-IFN add-on: -2.38 vs. -2.15 log U/mL, p = 0.31). HBcrAg was associated with combined response (adjusted odds ratio 0.3, 95% confidence interval 0.2-0.5, p <0.001), but was not superior to quantitative HBsAg (qHBsAg).

  2. Crystal structure of the anti-(carcinoembryonic antigen) single-chain Fv antibody MFE-23 and a model for antigen binding based on intermolecular contacts.

    PubMed

    Boehm, M K; Corper, A L; Wan, T; Sohi, M K; Sutton, B J; Thornton, J D; Keep, P A; Chester, K A; Begent, R H; Perkins, S J

    2000-03-01

    MFE-23 is the first single-chain Fv antibody molecule to be used in patients and is used to target colorectal cancer through its high affinity for carcinoembryonic antigen (CEA), a cell-surface member of the immunoglobulin superfamily. MFE-23 contains an N-terminal variable heavy-chain domain joined by a (Gly(4)Ser)(3) linker to a variable light-chain (V(L)) domain (kappa chain) with an 11-residue C-terminal Myc-tag. Its crystal structure was determined at 2.4 A resolution by molecular replacement with an R(cryst) of 19.0%. Five of the six antigen-binding loops, L1, L2, L3, H1 and H2, conformed to known canonical structures. The sixth loop, H3, displayed a unique structure, with a beta-hairpin loop and a bifurcated apex characterized by a buried Thr residue. In the crystal lattice, two MFE-23 molecules were associated back-to-back in a manner not seen before. The antigen-binding site displayed a large acidic region located mainly within the H2 loop and a large hydrophobic region within the H3 loop. Even though this structure is unliganded within the crystal, there is an unusually large region of contact between the H1, H2 and H3 loops and the beta-sheet of the V(L) domain of an adjacent molecule (strands DEBA) as a result of intermolecular packing. These interactions exhibited remarkably high surface and electrostatic complementarity. Of seven MFE-23 residues predicted to make contact with antigen, five participated in these lattice contacts, and this model for antigen binding is consistent with previously reported site-specific mutagenesis of MFE-23 and its effect on CEA binding.

  3. 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.

  4. 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.

  5. 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

  6. Clinical evaluation of a new enzyme immunoassay for hepatitis B virus core-related antigen; a marker distinct from viral DNA for monitoring lamivudine treatment.

    PubMed

    Rokuhara, A; Tanaka, E; Matsumoto, A; Kimura, T; Yamaura, T; Orii, K; Sun, X; Yagi, S; Maki, N; Kiyosawa, K

    2003-07-01

    We aimed to assess the clinical performance of a newly developed chemiluminescence enzyme immunoassay (CLEIA) for the detection of hepatitis B virus (HBV) core-related antigen (HBcrAg) in patients with chronic HBV infection. A total of 82 patients with chronic HBV infection and 167 HBV-negative controls were studied. HBcrAg was measured by CLEIA with monoclonal antibodies to hepatitis B e antigen (HBeAg) and hepatitis B core antigen (HBcAg), and HBV DNA was measured by transcription-mediated amplification assay (TMA) and in-house real-time detection polymerase chain reaction (RTD-PCR). The HBcrAg assay detected viremia in 189 of 216 samples (88%) collected from 72 patients whilst the TMA assay detected viremia in 178 of the 216 samples (82%) (P = 0.019). The HBcrAg concentration correlated linearly with the HBV DNA concentration (P < 0.001) over a range which varied 100 000-fold. The accuracy in the measurement of the patients' HBV load obtained using the HBcrAg assay was not affected by the absence of hepatitis B e antigen from the serum or the presence of precore mutations in the HBV genome. In patients without anti-viral drugs, changes in their serum HBcrAg concentration over time corresponded to their HBV DNA concentration. In six additional patients who were later treated with lamivudine, HBV DNA concentration declined more rapidly than their HBcrAg concentration. Three months after treatment commenced, the ratio of HBcrAg: HBV DNA had increased in all six patients (P = 0.031). The HBcrAg assay is a sensitive and useful test for the assessment of a patient's HBV load. When monitoring the anti-viral effect of lamivudine, HBcrAg provides a viral marker which is independent of HBV DNA.

  7. 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

  8. 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

  9. Volcano structure in atomic resolution core-loss images.

    PubMed

    D'Alfonso, A J; Findlay, S D; Oxley, M P; Allen, L J

    2008-06-01

    A feature commonly present in simulations of atomic resolution electron energy loss spectroscopy images in the scanning transmission electron microscope is the volcano or donut structure. In the past this has been understood in terms of a geometrical perspective using a dipole approximation. It is shown that the dipole approximation for core-loss spectroscopy begins to break down as the probe forming aperture semi-angle increases, necessitating the inclusion of higher order terms for a quantitative understanding of volcano formation. Using such simulations we further investigate the mechanisms behind the formation of such structures in the single atom case and extend this to the case of crystals. The cubic SrTiO3 crystal is used as a test case to show the effects of nonlocality, probe channelling and absorption in producing the volcano structure in crystal images.

  10. 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.

  11. SplitCore: An exceptionally versatile viral nanoparticle for native whole protein display regardless of 3D structure

    PubMed Central

    Walker, Andreas; Skamel, Claudia; Nassal, Michael

    2011-01-01

    Nanoparticles displaying native proteins are attractive for many applications, including vaccinology. Virus-based nanoparticles are easily tailored by genetic means, commonly by inserting heterologous sequences into surface-exposed loops. The strategy works well with short peptides but is incompatible with the structures of most native proteins, except those with closely juxtaposed termini. Here we overcome this constraint by splitting the capsid protein of hepatitis B virus, one of the most advanced and most immunogenic display platforms, inside the insertion loop (SplitCore). The split parts, coreN and coreC, efficiently form capsid-like particles (CLPs) in E. coli and so do numerous fusions to coreN and/or coreC of differently structured proteins, including human disease related antigens of >300 amino acids in length. These CLPs induced high-titer antibodies, including neutralizing ones, in mice. The concept was easily expanded to triple-layer CLPs carrying reporter plus targeting domains, and should be applicable to protein-based nanoparticle design in general. PMID:22355524

  12. 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.

  13. 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

  14. 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

  15. 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

    2015-11-13

    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.

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. Serospecific antigens of Legionella pneumophila.

    PubMed Central

    Otten, S; Iyer, S; Johnson, W; Montgomery, R

    1986-01-01

    Serospecific antigens isolated by EDTA extraction from four serogroups of Legionella pneumophila were analyzed for their chemical composition, molecular heterogeneity by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunological properties. The antigens were shown to be lipopolysaccharides and to differ from the lipopolysaccharides of other gram-negative bacteria. The serospecific antigens contained rhamnose, mannose, glucosamine, and two unidentified sugars together with 2-keto-3-deoxyoctonate, phosphate, and fatty acids. The fatty acid composition was predominantly branched-chain acids with smaller amounts of 3-hydroxymyristic acid. The antigens contain periodate-sensitive groups; mannosyl residues were completely cleaved by periodate oxidation. Hydrolysis of the total lipopolysaccharide by acetic acid resulted in the separation of a lipid A-like material that cross-reacted with the antiserum to lipid A from Salmonella minnesota but did not comigrate with it on sodium dodecyl sulfate gels. None of the four antigens contained heptose. All of the antigen preparations showed endotoxicity when tested by the Limulus amebocyte lysate assay. The results of this study indicate that the serogroup-specific antigens of L. pneumophila are lipopolysaccharides containing an unusual lipid A and core structure and different from those of other gram-negative bacteria. Images PMID:3017918

  3. Galactoxylomannans from Cryptococcus neoformans Varieties neoformans and grubii Are Structurally and Antigenically Variable▿

    PubMed Central

    De Jesus, Magdia; Chow, Siu-Kei; Cordero, Radames J. B.; Frases, Susana; Casadevall, Arturo

    2010-01-01

    Prior studies have established that the Cryptococcus neoformans capsular polysaccharide component galactoxylomannan (GalXM) manifests serotype-related structural differences that translate into antigenic differences. We analyzed GalXM from acapsular serotype A and D strains by carbohydrate analysis and static and dynamic light scattering to determine mass, effective diameter, polydispersity, and diffusion coefficients. Multiangle laser light scattering showed that GalXM from C. neoformans var. grubii strain cap59 (serotype A) had larger molecular mass (4.21 × 106 ± 0.95 × 106 g/mol) and radius of gyration (207 ± 27 nm) than GalXM from C. neoformans var. neoformans cap67 (serotype D). cap67 GalXM had corresponding values of 0.70 × 106 ± 0.05 × 106 g/mol and 120 ± 22 nm, respectively. The effective diameter for GalXM and polydispersity from the two strains varied depending on temperature and medium growth conditions, indicating that GalXM structure can vary within a strain, depending on its environment. Zeta potential determinations were negative for GalXM from both strains under all conditions, consistent with the recently reported presence of glucuronic acid. These results imply that C. neoformans GalXM, like glucuronoxylomannan, can manifest variety- and growth condition-related variations. Analysis of 16 C. neoformans and 7 Cryptococcus gattii strains with polyclonal antibody to a GalXM strain revealed antigenic similarities among the C. neoformans variety neoformans and grubii strains and no reactivity with C. gattii. As a result of the deleterious effects of GalXM on immune function, structural and antigenic variability between serotypes may translate into differences in immunomodulatory effects. PMID:20061411

  4. Galactoxylomannans from Cryptococcus neoformans varieties neoformans and grubii are structurally and antigenically variable.

    PubMed

    De Jesus, Magdia; Chow, Siu-Kei; Cordero, Radames J B; Frases, Susana; Casadevall, Arturo

    2010-07-01

    Prior studies have established that the Cryptococcus neoformans capsular polysaccharide component galactoxylomannan (GalXM) manifests serotype-related structural differences that translate into antigenic differences. We analyzed GalXM from acapsular serotype A and D strains by carbohydrate analysis and static and dynamic light scattering to determine mass, effective diameter, polydispersity, and diffusion coefficients. Multiangle laser light scattering showed that GalXM from C. neoformans var. grubii strain cap59 (serotype A) had larger molecular mass (4.21 x 10(6) +/- 0.95 x 10(6) g/mol) and radius of gyration (207 +/- 27 nm) than GalXM from C. neoformans var. neoformans cap67 (serotype D). cap67 GalXM had corresponding values of 0.70 x 10(6) +/- 0.05 x 10(6) g/mol and 120 +/- 22 nm, respectively. The effective diameter for GalXM and polydispersity from the two strains varied depending on temperature and medium growth conditions, indicating that GalXM structure can vary within a strain, depending on its environment. Zeta potential determinations were negative for GalXM from both strains under all conditions, consistent with the recently reported presence of glucuronic acid. These results imply that C. neoformans GalXM, like glucuronoxylomannan, can manifest variety- and growth condition-related variations. Analysis of 16 C. neoformans and 7 Cryptococcus gattii strains with polyclonal antibody to a GalXM strain revealed antigenic similarities among the C. neoformans variety neoformans and grubii strains and no reactivity with C. gattii. As a result of the deleterious effects of GalXM on immune function, structural and antigenic variability between serotypes may translate into differences in immunomodulatory effects.

  5. 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.

  6. 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

  7. Francisella tularensis Schu S4 Lipopolysaccharide Core Sugar and O-Antigen Mutants Are Attenuated in a Mouse Model of Tularemia

    PubMed Central

    Rasmussen, Jed A.; Post, Deborah M. B.; Gibson, Bradford W.; Lindemann, Stephen R.; Apicella, Michael A.; Meyerholz, David K.

    2014-01-01

    The virulence factors mediating Francisella pathogenesis are being investigated, with an emphasis on understanding how the organism evades innate immunity mechanisms. Francisella tularensis produces a lipopolysaccharide (LPS) that is essentially inert and a polysaccharide capsule that helps the organism to evade detection by components of innate immunity. Using an F. tularensis Schu S4 mutant library, we identified strains that are disrupted for capsule and O-antigen production. These serum-sensitive strains lack both capsule production and O-antigen laddering. Analysis of the predicted protein sequences for the disrupted genes (FTT1236 and FTT1238c) revealed similarity to those for waa (rfa) biosynthetic genes in other bacteria. Mass spectrometry further revealed that these proteins are involved in LPS core sugar biosynthesis and the ligation of O antigen to the LPS core sugars. The 50% lethal dose (LD50) values of these strains are increased 100- to 1,000-fold for mice. Histopathology revealed that the immune response to the F. tularensis mutant strains was significantly different from that observed with wild-type-infected mice. The lung tissue from mutant-infected mice had widespread necrotic debris, but the spleens lacked necrosis and displayed neutrophilia. In contrast, the lungs of wild-type-infected mice had nominal necrosis, but the spleens had widespread necrosis. These data indicate that murine death caused by wild-type strains occurs by a mechanism different from that by which the mutant strains kill mice. Mice immunized with these mutant strains displayed >10-fold protective effects against virulent type A F. tularensis challenge. PMID:24452684

  8. Analysis of Structures and Epitopes of Surface Antigen Glycoproteins Expressed in Bradyzoites of Toxoplasma gondii

    PubMed Central

    Cong, Hua; Zhang, Min; Zhang, Qingli; Gong, Jing; Cong, Haizi; Xin, Qing; He, Shenyi

    2013-01-01

    Toxoplasma gondii is a protozoan parasite capable of infecting humans and animals. Surface antigen glycoproteins, SAG2C, -2D, -2X, and -2Y, are expressed on the surface of bradyzoites. These antigens have been shown to protect bradyzoites against immune responses during chronic infections. We studied structures of SAG2C, -2D, -2X, and -2Y proteins using bioinformatics methods. The protein sequence alignment was performed by T-Coffee method. Secondary structural and functional domains were predicted using software PSIPRED v3.0 and SMART software, and 3D models of proteins were constructed and compared using the I-TASSER server, VMD, and SWISS-spdbv. Our results showed that SAG2C, -2D, -2X, and -2Y are highly homologous proteins. They share the same conserved peptides and HLA-I restricted epitopes. The similarity in structure and domains indicated putative common functions that might stimulate similar immune response in hosts. The conserved peptides and HLA-restricted epitopes could provide important insights on vaccine study and the diagnosis of this disease. PMID:23586017

  9. 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

  10. 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.

  11. Core-shell strain structure of zeolite microcrystals.

    PubMed

    Cha, Wonsuk; Jeong, Nak Cheon; Song, Sanghoon; Park, Hyun-jun; Thanh Pham, Tung Cao; Harder, Ross; Lim, Bobae; Xiong, Gang; Ahn, Docheon; McNulty, Ian; Kim, Jungho; Yoon, Kyung Byung; Robinson, Ian K; Kim, Hyunjung

    2013-08-01

    Zeolites are crystalline aluminosilicate minerals featuring a network of 0.3-1.5-nm-wide pores, used in industry as catalysts for hydrocarbon interconversion, ion exchangers, molecular sieves and adsorbents. For improved applications, it is highly useful to study the distribution of internal local strains because they sensitively affect the rates of adsorption and diffusion of guest molecules within zeolites. Here, we report the observation of an unusual triangular deformation field distribution in ZSM-5 zeolites by coherent X-ray diffraction imaging, showing the presence of a strain within the crystal arising from the heterogeneous core-shell structure, which is supported by finite element model calculation and confirmed by fluorescence measurement. The shell is composed of H-ZSM-5 with intrinsic negative thermal expansion whereas the core exhibits a different thermal expansion behaviour due to the presence of organic template residues, which usually remain when the starting materials are insufficiently calcined. Engineering such strain effects could have a major impact on the design of future catalysts. PMID:23832126

  12. Structural Analysis of Determinants of Histo-Blood Group Antigen Binding Specificity in Genogroup I Noroviruses

    PubMed Central

    Shanker, Sreejesh; Czako, Rita; Sankaran, Banumathi; Atmar, Robert L.; Estes, Mary K.

    2014-01-01

    ABSTRACT Human noroviruses (NoVs) cause acute epidemic gastroenteritis. Susceptibility to the majority of NoV infections is determined by genetically controlled secretor-dependent expression of histo-blood group antigens (HBGAs), which are also critical for NoV attachment to host cells. Human NoVs are classified into two major genogroups (genogroup I [GI] and GII), with each genogroup further divided into several genotypes. GII NoVs are more prevalent and exhibit periodic emergence of new variants, suggested to be driven by altered HBGA binding specificities and antigenic drift. Recent epidemiological studies show increased activity among GI NoVs, with some members showing the ability to bind nonsecretor HBGAs. NoVs bind HBGAs through the protruding (P) domain of the major capsid protein VP1. GI NoVs, similar to GII, exhibit significant sequence variations in the P domain; it is unclear how these variations affect HBGA binding specificities. To understand the determinants of possible strain-specific HBGA binding among GI NoVs, we determined the structure of the P domain of a GI.7 clinical isolate and compared it to the previously determined P domain structures of GI.1 and GI.2 strains. Our crystallographic studies revealed significant structural differences, particularly in the loop regions of the GI.7 P domain, altering its surface topography and electrostatic landscape and potentially indicating antigenic variation. The GI.7 strain bound to H- and A-type, Lewis secretor, and Lewis nonsecretor families of HBGAs, allowing us to further elucidate the structural determinants of nonsecretor HBGA binding among GI NoVs and to infer several contrasting and generalizable features of HBGA binding in the GI NoVs. IMPORTANCE Human noroviruses (NoVs) cause acute epidemic gastroenteritis. Recent epidemiological studies have shown increased prevalence of genogroup I (GI) NoVs. Although secretor-positive status is strongly correlated with NoV infection, cases of NoV infection

  13. 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

  14. 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

  15. 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

  16. Lipopolysaccharide variation in Coxiella burnetti: intrastrain heterogeneity in structure and antigenicity.

    PubMed Central

    Hackstadt, T; Peacock, M G; Hitchcock, P J; Cole, R L

    1985-01-01

    We isolated lipopolysaccharides (LPSs) from phase variants of Coxiella burnetii Nine Mile and compared the isolated LPS and C. burnetii cells by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. The LPSs were found to be the predominant component which varied structurally and antigenically between virulent phase I and avirulent phase II. A comparison of techniques historically used to extract the phase I antigenic component revealed that the aqueous phase of phenol-water, trichloroacetic acid, and dimethyl sulfoxide extractions of phase I C. burnettii cells all contained phase I LPS, although the efficiency and specificity of extraction varied. Our studies provide additional evidence that phase variation in C. burnetii is analogous to the smooth-to-rough LPS variation of gram-negative enteric bacteria, with phase I LPS being equivalent to smooth LPS and phase II being equivalent to rough LPS. In addition, we identified a variant with a third LPS chemotype with appears to have a structural complexity intermediate to phase I and II LPSs. All three C. burnetii LPS contain a 2-keto-3-deoxyoctulosonic acid-like substance, heptose, and gel Limulus amoebocyte lysates in subnanogram amounts. The C. burnetii LPSs were nontoxic to chicken embryos at doses of over 80 micrograms per embryo, in contrast to Salmonella typhimurium smooth- and rough-type LPSs, which were toxic in nanogram amounts. Images PMID:3988339

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. MRC OX-2 antigen: a lymphoid/neuronal membrane glycoprotein with a structure like a single immunoglobulin light chain.

    PubMed Central

    Clark, M J; Gagnon, J; Williams, A F; Barclay, A N

    1985-01-01

    The MRC OX-2 antigen is a rat cell surface glycoprotein of mol. wt. 41 000-47 000 found on neurones, thymocytes, B cells, follicular dendritic cells and endothelium. We now report the amino sequence for this antigen as deduced from the nucleotide sequence of cDNA clones detected by use of an oligonucleotide probe. The sequence contains 248 amino acid residues of which 202 residues are likely to be outside the cell with two domains that show homology with immunoglobulins. The N-terminal domain fits best with Ig V domains and Thy-1 antigen while the C-terminal part is like an Ig C domain. Thus the structure overall is similar to an Ig light chain or the T cell receptor beta chain. Three glycosylation sites are identified on each of the MRC OX-2 antigen domains. Images Fig. 1. Fig. 2. PMID:2862025

  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. Reactivity of IgE antibodies with crustacea and oyster allergens: evidence for common antigenic structures.

    PubMed

    Lehrer, S B; McCants, M L

    1987-08-01

    IgE-antibody reactivity to oysters and crustacea of sera from six oyster-sensitive, seven oyster- and crustacea-sensitive, and 12 crustacea-sensitive subjects was investigated. All six subjects with a history of only oyster sensitivity had minimal RAST reactivity (ratios 2 to 5) to extracts of raw or boiled oysters. Three of the seven oyster- and crustacea-sensitive subjects and six of the 12 crustacea-sensitive, oyster-tolerant or unexposed subjects had elevated RAST ratios to oyster (14 to 41). Generally, elevated oyster RAST correlated with skin prick test reactivity to oyster but not with total serum IgE levels. The oyster RAST values of the 19 crustacea-sensitive subjects (with or without oyster sensitivity) correlated with crustacea RAST reactivity (crab RAST, most significant; shrimp RAST, least significant). Rabbit antisera to crustacea extracts detected precipitating antigens present in extracts of raw or boiled oysters. Significant inhibition of the oyster RAST was obtained with oyster or crustacea extracts. These studies suggest that in the diagnosis of oyster sensitivity the RAST may not be useful and that oyster and crustacea contain common antigenic structures.

  5. The prediction of T- and B-combined epitope and tertiary structure of the Eg95 antigen of Echinococcus granulosus

    PubMed Central

    MA, XIUMIN; ZHOU, XIAOTAO; ZHU, YUEJIE; LI, YANHUA; WANG, HONGYING; MAMUTI, WULAMU; LI, YUJIAO; WEN, HAO; DING, JIANBING

    2013-01-01

    Echinococcosis, also known as hydatid disease, is a type of zoonotic parasitic disease caused by the Echinococcus larvae infection. The disease is severely harmful to both humans and animals. Research and development of an epitope vaccine is crucial. To determine the dominant epitopes of the Eg95 antigen, the tertiary structure and the T- and B-combined epitope of the Eg95 protein for Echinococcus granulosus were predicted and analyzed in the present study. The tertiary structure of the Eg95 protein was predicted using the 3DLigandsite server and RasMol software. The T- and B-combined epitope of the Eg95 antigen was analyzed using the DNAStar (V5.0), IEDB, SYFPEITHI and BIMAS. Tertiary structure prediction results showed that there were potential epitopes in Eg95 antigen. Bioinformatics analysis revealed the T- and B-combined epitopes of Eg95 antigen. Four and six T- and B-combined epitopes induced immune responses in humans and mice. Additionally, four T- and B-combined epitopes induced immune responses in both humans and mice. The tertiary structure and T- and B-combined epitopes of the Eg95 protein were also determined. The results obtained in the present study may be beneficial in the investigation of Eg95 antigenicity and the development of dominant epitope vaccines. PMID:24137242

  6. Characterization of CD8+ cytotoxic T-lymphocyte responses after genetic immunization with retrovirus vectors expressing different forms of the hepatitis B virus core and e antigens.

    PubMed Central

    Townsend, K; Sällberg, M; O'Dea, J; Banks, T; Driver, D; Sauter, S; Chang, S M; Jolly, D J; Mento, S J; Milich, D R; Lee, W T

    1997-01-01

    Cytotoxic T-lymphocyte (CTL) activity appears to play an important role in resolving hepatitis B virus (HBV) infection, and the ability to induce such responses remains an important goal for developing effective immunotherapeutics. A panel of recombinant retrovirus vectors expressing different forms of the HBV core antigen (HBcAg) or e antigen (eAg) were found to induce antigen-specific major histocompatibility complex-restricted CTL responses in both mice and macaques. In addition, a novel retrovirus vector expressing an HBcAg-neomycin phosphotransferase II (HBc-Neo) fusion protein [LHBc-NEO(6A3)], which allows the measurement of the anti-Neo antibody response as a means of directly tracking biological activity of the vector, was generated. Doses greater than 10(7) CFU were necessary to induce CTL responses in H-2(k) mice. Intramuscular injections with 10(8) CFU of the LHBc-NEO(6A3) retrovirus vector into rhesus monkeys induced HBc/eAg-specific antibody production and CD8+ CTLs. The CTL response from one of the two responder rhesus monkeys was directed against a 9-residue peptide, GELMTLATW, at positions 63 to 71 of the HBc/eAg sequence. The CTL response is long lived, being detectable as late as 16 weeks after immunization, and can be boosted upon reimmunization. The potent ability of recombinant retrovirus vectors to induce HBcAg- and eAg-specific CTL responses may prove beneficial as a therapeutic treatment for chronic hepatitis B infection. PMID:9094605

  7. A model of the dynamical structure of Earth's outer core

    NASA Astrophysics Data System (ADS)

    Loper, David E.

    2000-01-01

    The dynamical state of the outer core is quantified, assuming that the convective pattern consists of buoyant parcels which rise to the top, forcing a broad descending flow in the bulk of the outer core. This convective circulation is assumed sufficiently rapid that the outer core is close to a well-mixed adiabatic state. Small compositional deviations from this state, resulting from the secular evolution of composition as the solid inner core grows, make the descending portion of the outer core stably stratified. Thermal deviations result from the mismatch between effective volumetric heating and the divergence of conducted heat. Effective volumetric heating is the sum of secular cooling, compressional heating and Ohmic heating. Divergence of heat is negative and larger in magnitude than effective volumetric heating throughout the core, resulting in a stabilizing thermal gradient in the descending fluid which reinforces the compositional gradient. The compositional and thermal contributions to the stable stratification are of comparable magnitudes. The strength of stratification depends on the strength of the convective circulation, which is unquantified. This stratification, coupled with Coriolis and Lorentz forces, has the potential to inhibit turbulence in the descending portions of the outer core. The thermal and compositional perturbations arising from processes at the inner-core boundary and core-mantle boundary are quantified and the dynamic behavior of the rising parcels is discussed and quantified. Depending on the sign and magnitude of exchanges of heat and composition, convective motions may be inhibited or suppressed near the top of the outer core.

  8. Selection of peptide inhibitors of interactions involved in complex protein assemblies: association of the core and surface antigens of hepatitis B virus.

    PubMed Central

    Dyson, M R; Murray, K

    1995-01-01

    As an example for studies of contacts involved in complex biological systems, peptide ligands that bind to the core antigen of hepatitis B virus (HBcAg) have been selected from a random hexapeptide library displayed on filamentous phage. Affinity-purified phage bearing aa sequence LLGRMK, or some related sequences, bound full-length or truncated HBcAg but did not bind denatured HBcAg. The long (L), but not the short (S), hepatitis B virus envelope polypeptide, when synthesized in an in vitro system, bound firmly to HBcAg, indicating that interaction between HBcAg and the pre-S region of the L polypeptide is critical for virus morphogenesis. This interaction was inhibited by peptide ALLGRMKG, suggesting that this and related small molecules may inhibit viral assembly. Images Fig. 2 PMID:7892246

  9. High titre of antibody to hepatitis B core antigen detected by immune adherence haemagglutination in HBsAg-positive acute hepatitis.

    PubMed

    Ikegami, F; Takasu, S; Jo, K; Miyakawa, Y; Tsuda, F; Mayumi, M

    1982-08-01

    Nine patients with HBsAg-positive acute hepatitis were tested for antibody to hepatitis B core antigen (anti-HBc) by the immune adherence haemagglutination method. A high anti-HBc titre (2(15) or more) was found in three, while anti-HBc was not detectable in the remaining six. All of them recovered from hepatitis with the return of hepatic function tests to normal, but HBsAg persisted in the three patients whose acute-phase serum had revealed high anti-HBc titres. On the basis of these observations, the three patients were thought to be persistent HBsAg carriers who had contracted opportunistic acute hepatitis of non-B aetiology. Titration of anti-HBc may be indicated in patients with HBsAg-positive acute hepatitis, because it helps distinguish persistent HBsAg carriers with non-B hepatitis from patients with hepatitis B at the outset, during the episode of acute hepatitis.

  10. 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

  11. Vaccination of ducks with a whole-cell vaccine expressing duck hepatitis B virus core antigen elicits antiviral immune responses that enable rapid resolution of de novo infection.

    PubMed

    Miller, Darren S; Halpern, Michael; Kotlarski, Ieva; Jilbert, Allison R

    2006-05-10

    As a first step in developing immuno-therapeutic vaccines for patients with chronic hepatitis B virus infection, we examined the ability of a whole-cell vaccine, expressing the duck hepatitis B virus (DHBV) core antigen (DHBcAg), to target infected cells leading to the resolution of de novo DHBV infections. Three separate experiments were performed. In each experiment, ducks were vaccinated at 7 and 14 days of age with primary duck embryonic fibroblasts (PDEF) that had been transfected 48 h earlier with plasmid DNA expressing DHBcAg with and without the addition of anti-DHBcAg (anti-DHBc) antibodies. Control ducks were injected with either 0.7% NaCl or non-transfected PDEF. The ducks were then challenged at 18 days of age by intravenous inoculation with DHBV (5 x 10(8) viral genome equivalents). Liver biopsies obtained on day 4 post-challenge demonstrated that vaccination did not prevent infection of the liver as similar numbers of infected hepatocytes were detected in all vaccinated and control ducks. However, analysis of liver tissue obtained 9 or more days post-challenge revealed that 9 out of 11 of the PDEF-DHBcAg vaccinated ducks and 8 out of 11 ducks vaccinated with PDEF-DHBcAg plus anti-DHBc antibodies had rapidly resolved the DHBV infection with clearance of infected cells. In contrast, 10 out of 11 of the control unvaccinated ducks developed chronic DHBV infection. In conclusion, vaccination of ducks with a whole-cell PDEF vaccine expressing DHBcAg elicited immune responses that induced a rapid resolution of DHBV infection. The results establish that chronic infection can be prevented via the vaccine-mediated induction of a core-antigen-specific immune response.

  12. Structural studies of the antigen III cell wall polysaccharide of Trichosporon domesticum.

    PubMed

    Ichikawa, T; Nishikawa, A; Wada, H; Ikeda, R; Shinoda, T

    2001-02-28

    Cell wall and soluble polysaccharides that reacted with Trichosporon domesticum factor III serum were isolated from the type strain of T. domesticum. The fractions contained O-acetyl groups, which contributed to the serological reactivity. The antigenic structure was characterized by chromatographic and spectroscopic methods. The polysaccharide has an alpha-(1-->3)-D-mannan backbone with hetero-oligosaccharide side chains consisting of a 2-O-substituted beta-D-glucuronic acid residue bound to O-2 of the mannose residue, beta-D-xylopyranosyl residues located in the middle of the side chain, and a nonreducing terminal alpha-L-arabinopyranosyl residue bound to 0-4 of xylose. The mannan backbone is O-acetylated at O-6 of the mannose residues.

  13. Immunohistochemical detection of papillomavirus structural antigens in animal hyperplastic and neoplastic epithelial lesions.

    PubMed

    Sironi, G; Caniatti, M; Scanziani, E

    1990-12-01

    One hundred and seventy-two hyperplastic and neoplastic epithelial lesions from 8 different mammalian and 1 avian species have been tested with an immunohistochemical technique to detect papillomavirus structural antigens. Selected lesions were diagnosed histologically as papilloma, fibropapilloma, equine sarcoid, squamous cell carcinoma, basalioma, epulis, keratoacanthoma, trichoepithelioma, pilomatrixoma, epidermal inclusion cyst, and hyperkeratotic or acanthotic epidermal lesions. Positive nuclear staining was detected in 14 out of 23 papillomas, 8 out of 32 fibropapillomas and in 1 out of 3 hyperplastic epidermal lesions. Positive samples were found in 5 of 8 mammalian species. Selected samples were also examined by transmission electron microscopy. In 4 samples papillomavirus was seen. In two other samples, negative with immunoperoxidase technique, papovavirus-like particles were observed.

  14. Crystal structures of two active proliferating cell nuclear antigens (PCNAs) encoded by Thermococcus kodakaraensis

    PubMed Central

    Ladner, Jane E.; Pan, Miao; Hurwitz, Jerard; Kelman, Zvi

    2011-01-01

    Proliferating cell nuclear antigen (PCNA) is a ring-shaped protein that encircles duplex DNA and plays an essential role in many DNA metabolic processes in archaea and eukarya. The eukaryotic and euryarchaea genomes contain a single gene encoding for PCNA. Interestingly, the genome of the euryarchaeon Thermococcus kodakaraensis contains two PCNA-encoding genes (TK0535 and TK0582), making it unique among the euryarchaea kingdom. It is shown here that the two T. kodakaraensis PCNA proteins support processive DNA synthesis by the polymerase. Both proteins form trimeric structures with characteristics similar to those of other archaeal and eukaryal PCNA proteins. One of the notable differences between the TK0535 and TK0582 rings is that the interfaces are different, resulting in different stabilities for the two trimers. The possible implications of these observations for PCNA functions are discussed. PMID:21270332

  15. 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

  16. 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

  17. 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.

  18. Generic eukaryotic core promoter prediction using structural features of DNA.

    PubMed

    Abeel, Thomas; Saeys, Yvan; Bonnet, Eric; Rouzé, Pierre; Van de Peer, Yves

    2008-02-01

    Despite many recent efforts, in silico identification of promoter regions is still in its infancy. However, the accurate identification and delineation of promoter regions is important for several reasons, such as improving genome annotation and devising experiments to study and understand transcriptional regulation. Current methods to identify the core region of promoters require large amounts of high-quality training data and often behave like black box models that output predictions that are difficult to interpret. Here, we present a novel approach for predicting promoters in whole-genome sequences by using large-scale structural properties of DNA. Our technique requires no training, is applicable to many eukaryotic genomes, and performs extremely well in comparison with the best available promoter prediction programs. Moreover, it is fast, simple in design, and has no size constraints, and the results are easily interpretable. We compared our approach with 14 current state-of-the-art implementations using human gene and transcription start site data and analyzed the ENCODE region in more detail. We also validated our method on 12 additional eukaryotic genomes, including vertebrates, invertebrates, plants, fungi, and protists.

  19. Similarity of "core" structures in two different glycans of tyrosine-linked eubacterial S-layer glycoproteins.

    PubMed Central

    Messner, P; Christian, R; Neuninger, C; Schulz, G

    1995-01-01

    Previously, the repeating-unit structure of the S-layer glycoprotein from the eubacterium Bacillus alvei CCM 2051 has been determined to be [-->3)-beta-D-Galp-(1-->4)-[alpha-D-Glcp-(1-->6)-]-beta-D-ManpNAc- (1-->]n (E. Altman, J.-R. Brisson, P. Messner, and U. B. Sleytr, Biochem. Cell Biol. 69:72-78, 1991). Nuclear magnetic resonance spectroscopic reexamination of this glycan reveals that the O-antigen-like domain of the polysaccharide is [see text] connected with the S-layer polypeptide through the "core" structure -->3)-alpha-L-Rhap-(1-->3)-alpha-L-Rhap-(1-->3)-alpha-L-R hap-(1-->3)-beta-D-Galp-(1-->O)-Tyr. Except for the substitution in position 4 of the nonreducing rhamnose with the modified glyceric acid phosphate residue GroA-2-->OPO2-->4-beta-D-ManpNAc-(1-->, this core is identical to the core of the tyrosine-linked glycan from the S-layer glycoprotein of Thermoanaerobacter thermohydrosulfuricus L111-69 (K. Bock, J. Schuster-Kolbe, E. Altman, G. Allmaier, B. Stahl, R. Christian, U. B. Sleytr, and P. Messner, J. Biol. Chem. 269:7137-7144, 1994). PMID:7721708

  20. 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

  1. 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

  2. Antigenic and Cryo-Electron Microscopy Structure Analysis of a Chimeric Sapovirus Capsid

    PubMed Central

    Miyazaki, Naoyuki; Taylor, David W.

    2015-01-01

    ABSTRACT The capsid protein (VP1) of all caliciviruses forms an icosahedral particle with two principal domains, shell (S) and protruding (P) domains, which are connected via a flexible hinge region. The S domain forms a scaffold surrounding the nucleic acid, while the P domains form a homodimer that interacts with receptors. The P domain is further subdivided into two subdomains, termed P1 and P2. The P2 subdomain is likely an insertion in the P1 subdomain; consequently, the P domain is divided into the P1-1, P2, and P1-2 subdomains. In order to investigate capsid antigenicity, N-terminal (N-term)/S/P1-1 and P2/P1-2 were switched between two sapovirus genotypes GI.1 and GI.5. The chimeric VP1 constructs were expressed in insect cells and were shown to self-assemble into virus-like particles (VLPs) morphologically similar to the parental VLPs. Interestingly, the chimeric VLPs had higher levels of cross-reactivities to heterogeneous antisera than the parental VLPs. In order to better understand the antigenicity from a structural perspective, we determined an intermediate-resolution (8.5-Å) cryo-electron microscopy (cryo-EM) structure of a chimeric VLP and developed a VP1 homology model. The cryo-EM structure revealed that the P domain dimers were raised slightly (∼5 Å) above the S domain. The VP1 homology model allowed us predict the S domain (67–229) and P1-1 (229–280), P2 (281–447), and P1-2 (448–567) subdomains. Our results suggested that the raised P dimers might expose immunoreactive S/P1-1 subdomain epitopes. Consequently, the higher levels of cross-reactivities with the chimeric VLPs resulted from a combination of GI.1 and GI.5 epitopes. IMPORTANCE We developed sapovirus chimeric VP1 constructs and produced the chimeric VLPs in insect cells. We found that both chimeric VLPs had a higher level of cross-reactivity against heterogeneous VLP antisera than the parental VLPs. The cryo-EM structure of one chimeric VLP (Yokote/Mc114) was solved to 8.5-

  3. Structure and gene cluster organization of the O-antigen of Providencia alcalifaciens O45:H25.

    PubMed

    Ovchinnikova, Olga G; Shashkov, Alexander S; Moryl, Magdalena; Liu, Bin; Rozalski, Antoni; Knirel, Yuriy A

    2014-10-29

    O-Polysaccharide was obtained by mild acid degradation of the lipopolysaccharide of Providencia alcalifaciens O45:H25 and studied by sugar analysis, Smith degradation, and (1)H and (13)C NMR spectroscopy. The following structure of the pentasaccharide repeat of the O-polysaccharide was established: [structure: see text]. The O-antigen gene cluster of P. alcalifaciens O45 was sequenced and found to be in full agreement with the O-polysaccharide structure established.

  4. Secondary structure and 3D homology modeling of swine leukocyte antigen class 2 (SLA-2) molecules.

    PubMed

    Gao, Feng-Shan; Xu, Chong-bo; Long, Yi-hou; Xia, Chun

    2009-01-01

    No information to date is available to elucidate the structure of swine leukocyte antigen class I (SLA-I) molecule which is comprised by a heavy chain of SLA-I non-covalently associated with a light chain, beta(2)-microglobulin (beta(2)m) proteins. Presently, one of SLA-I gene SLA-2 and beta(2)m gene were expressed as soluble maltose binding proteins (MBP-proteins) in a pMAL-p2X/Escherichia coli TB1 system and identified by western blotting with anti-MBP polyclonal antibodies. The expressed proteins MBP-SLA-2 and MBP-beta(2)m were purified on amylose affinity columns followed by DEAE-Sepharose. The purified products were cleaved by Factor Xa, respectively, and the interest of proteins SLA-2 and beta(2)m were purified on amylose affinity columns followed by separation from MBP on DEAE-Sepharose. The secondary structures of SLA-2 and beta(2)m were analyzed by circular dichroism (CD) spectrophotometry. The three-dimensional (3D) structure of their peptide-binding domain (PBD) was modeled-based sequence homology. The content of the alpha-helix, beta-sheet, turn, and random coil in the SLA-2 protein were 76, 95, 36, and 67aa, respectively. In the 98aa of beta(2)m, the contents of the alpha-helix, beta-sheet, turn, and random coil were 0, 45, 8, and 45aa, respectively. The SLA-2 protein displayed a typical alpha-helix structure while beta(2)m protein displayed a typical beta-sheet structure. Homology modeling of the SLA-2 and beta(2)m proteins demonstrated similarities with the structure of human and mouse MHC (major histocompatibility complex) class I proteins.

  5. Crystal structure of human prostate-specific antigen in a sandwich antibody complex.

    PubMed

    Stura, Enrico A; Muller, Bruno H; Bossus, Marc; Michel, Sandrine; Jolivet-Reynaud, Colette; Ducancel, Frédéric

    2011-12-01

    Human prostate-specific antigen (PSA or human kallikrein-related peptidase 3) present in small quantities in the sera of healthy men becomes elevated in prostate cancer (PCa) and other prostate disorders. The ability to identify the free PSA fraction associated with PCa could increase the reliability of the PSA diagnostic test. Here we present the crystal structure of human PSA from seminal fluid in a sandwich complex with two monoclonal antibodies (mAbs). MAb 5D5A5 captures total PSA with exceptionally high affinity, and mAb 5D3D11 selectively discriminates between free PSA subforms that are more abundant in sera from patients with PCa. Although the antigen is not of seric origin, several insights into cancer diagnosis can be discerned from this complex. MAb 5D3D11 recognizes a PSA conformation different from that previously reported. Interacting with the kallikrein loop, the PSA N-linked glycan attached to asparagine 61 is an uncommonly complex sialated triantennary chain. O-linked glycosylation is observed at threonine 125. The description of how PSA subforms in prostatic fluid can be discriminated using pairs of antibodies is a first step in the design of new strategies that are capable of real discrimination among PSA subforms, which will lead to the formulation of more reliable diagnostic tests. In a companion article [Muller, B. H., Savatier, A., L'Hostis, G., Costa, N., Bossus, M., Michel, S., et al. (2011). In vitro affinity maturation of an anti-PSA antibody for prostate cancer diagnostic assay. J. Mol. Biol.], we describe engineering efforts to improve the affinity of mAb 5D3D11, a first step towards such goal. PMID:22037582

  6. 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

  7. Identification of a Novel Lipopolysaccharide Core Biosynthesis Gene Cluster in Bordetella pertussis, and Influence of Core Structure and Lipid A Glucosamine Substitution on Endotoxic Activity▿

    PubMed Central

    Geurtsen, Jeroen; Dzieciatkowska, Monika; Steeghs, Liana; Hamstra, Hendrik-Jan; Boleij, Johanna; Broen, Kelly; Akkerman, Grietsje; el Hassan, Hassan; Li, Jianjun; Richards, James C.; Tommassen, Jan; van der Ley, Peter

    2009-01-01

    Lipopolysaccharide (LPS), also known as endotoxin, is one of the main constituents of the gram-negative bacterial outer membrane. Whereas the lipid A portion of LPS is generally considered the main determinant for endotoxic activity, the oligosaccharide moiety plays an important role in immune evasion and the interaction with professional antigen-presenting cells. Here we describe a novel four-gene cluster involved in the biosynthesis of the Bordetella pertussis core oligosaccharide. By insertionally inactivating these genes and studying the resulting LPS structures, we show that at least two of the genes encode active glycosyltransferases, while a third gene encodes a deacetylase also required for biosynthesis of full-length oligosaccharide. In addition, we demonstrate that mutations in the locus differentially affect LPS and whole-cell endotoxic activities. Furthermore, while analyzing the mutant LPS structures, we confirmed a novel modification of the lipid A phosphate with glucosamine and found that inactivation of the responsible glycosyltransferase reduces the endotoxic activity of the LPS. PMID:19364841

  8. Structure of a metal-independent bacterial glycosyltransferase that catalyzes the synthesis of histo-blood group A antigen

    PubMed Central

    Thiyagarajan, Nethaji; Pham, Tram T. K.; Stinson, Brittany; Sundriyal, Amit; Tumbale, Percy; Lizotte-Waniewski, Michelle; Brew, Keith; Acharya, K. Ravi

    2012-01-01

    Histo-blood group antigens (HBGAs) are a source of antigenic variation between individuals that modulates resistance and susceptibility to pathogens and is a barrier to the spread of enveloped viruses. HBGAs are also produced by a few prokaryotes where they are synthesized by glycosyltransferases (GTs) related to human HBGA synthases. Here we report the first structure of a bacterial GT of this family, from an intestinal resident, Bacteroides ovatus. Unlike its mammalian homologues and other GTs with similar folds, this protein lacks a metal-binding Asp-X-Asp motif and is fully active in the absence of divalent metal ions, yet is strikingly similar in structure and in its interactions with substrates to structurally characterized mammalian metal-dependent mammalian homologues. This shows how an apparently major divergence in catalytic properties can be accommodated by minor structural adjustments and illustrates the structural underpinnings of horizontal transfer of a functional gene from prokaryotes to vertebrates. PMID:23230506

  9. Polymeric hepatitis C virus non-structural protein 5A nanocapsules induce intrahepatic antigen-specific immune responses.

    PubMed

    Fichter, Michael; Piradashvili, Keti; Pietrzak-Nguyen, Anette; Pretsch, Leah; Kuhn, Gabor; Strand, Susanne; Knuf, Markus; Zepp, Fred; Wurm, Frederik R; Mailänder, Volker; Landfester, Katharina; Gehring, Stephan

    2016-11-01

    Targeting antigen combined with adjuvants to hepatic antigen-presenting cells (APCs) is essential for the induction of intrahepatic T cellular immunity controlling and resolving viral infections of the liver. Intravenous injection of antigen-loaded nanoparticles is a promising approach for the delivery of antigens to liver APCs. Accordingly, polymeric nanocapsules (NCs) synthesized exclusively of hepatitis C virus non-structural protein 5A (NS5A) and the adjuvant monophosphoryl lipid A (MPLA) adsorbed to the nanocapsule surface were developed. Aim of the present study was the evaluation of the in vitro and in vivo behavior of MPLA-functionalized NS5A-NCs regarding the interaction with liver dendritic cells (DCs) and the potential to induce intrahepatic immune responses in a mouse model. Maturation of DCs was significantly increased by application of NS5A+MPLA-NCs compared to non-functionalized NS5A-NCs promoting a vigorous expression of CD40, CD80, CD86 and a strong secretion of the Th1-related cytokine IL-12. NS5A-NCs were preferentially deposited in DCs and Kupffer cells residing in the liver after intravenous administration. Immunization with NS5A-NCs induced intrahepatic antigen-specific CD4(+) T cellular immune responses determined by the secretion of IFNγ and IL-2. Furthermore, supplementation with MPLA induced significant levels of NS5A-specific antibodies. The application of polymeric nanocapsules synthesized exclusively out of antigen avoids the risk of unintended side effects caused by additional carrier substances. Functionalization with adjuvants like MPLA and the efficient targeting to liver-resident APCs inherits the potential for application of antigen nanocapsules in further vaccination approaches against pathogens affecting the liver. PMID:27614817

  10. 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.

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

    PubMed

    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

    2014-12-01

    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.

  12. 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

  13. 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

  14. 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

  15. 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

  16. Total Hepatitis B Core Antigen Antibody, a Quantitative Non-Invasive Marker of Hepatitis B Virus Induced Liver Disease.

    PubMed

    Yuan, Quan; Song, Liu-Wei; Cavallone, Daniela; Moriconi, Francesco; Cherubini, Beatrice; Colombatto, Piero; Oliveri, Filippo; Coco, Barbara Agata; Ricco, Gabriele; Bonino, Ferruccio; Shih, James Wai Kuo; Xia, Ning-Shao; Brunetto, Maurizia Rossana

    2015-01-01

    Non invasive immunologic markers of virus-induced liver disease are unmet needs. We tested the clinical significance of quantitative total and IgM-anti-HBc in well characterized chronic-HBsAg-carriers. Sera (212) were obtained from 111 HBsAg-carriers followed-up for 52 months (28-216) during different phases of chronic-HBV-genotype-D-infection: 10 HBeAg-positive, 25 inactive-carriers (HBV-DNA≤2000IU/ml, ALT<30U/L), 66 HBeAg-negative-CHB-patients and 10 with HDV-super-infection. In 35 patients treated with Peg-IFN±nucleos(t)ide-analogues (NUCs) sera were obtained at baseline, end-of-therapy and week-24-off-therapy and in 22 treated with NUCs (for 60 months, 42-134m) at baseline and end-of-follow-up. HBsAg and IgM-anti-HBc were measured by Architect-assays (Abbott, USA); total-anti-HBc by double-antigen-sandwich-immune-assay (Wantai, China); HBV-DNA by COBAS-TaqMan (Roche, Germany). Total-anti-HBc were detectable in all sera with lower levels in HBsAg-carriers without CHB (immune-tolerant, inactive and HDV-superinfected, median 3.26, range 2.26-4.49 Log10 IU/ml) versus untreated-CHB (median 4.68, range 2.76-5.54 Log10 IU/ml), p<0.0001. IgM-anti-HBc positive using the chronic-hepatitis-cut-off" (0.130-S/CO) were positive in 102 of 212 sera (48.1%). Overall total-anti-HBc and IgM-anti-HBc correlated significantly (p<0.001, r=0.417). Total-anti-HBc declined significantly in CHB patients with response to Peg-IFN (p<0.001) and in NUC-treated patients (p<0.001); the lowest levels (median 2.68, range 2.12-3.08 Log10 IU/ml) were found in long-term responders who cleared HBsAg subsequently. During spontaneous and therapy-induced fluctuations of CHB (remissions and reactivations) total- and IgM-anti-HBc correlated with ALT (p<0.001, r=0.351 and p=0.008, r=0.185 respectively). Total-anti-HBc qualifies as a useful marker of HBV-induced-liver-disease that might help to discriminate major phases of chronic HBV infection and to predict sustained response to antivirals.

  17. Total Hepatitis B Core Antigen Antibody, a Quantitative Non-Invasive Marker of Hepatitis B Virus Induced Liver Disease

    PubMed Central

    Cavallone, Daniela; Moriconi, Francesco; Cherubini, Beatrice; Colombatto, Piero; Oliveri, Filippo; Coco, Barbara Agata; Ricco, Gabriele; Bonino, Ferruccio; Shih, James Wai Kuo; Xia, Ning-Shao; Brunetto, Maurizia Rossana

    2015-01-01

    Non invasive immunologic markers of virus-induced liver disease are unmet needs. We tested the clinical significance of quantitative total and IgM-anti-HBc in well characterized chronic-HBsAg-carriers. Sera (212) were obtained from 111 HBsAg-carriers followed-up for 52 months (28-216) during different phases of chronic-HBV-genotype-D-infection: 10 HBeAg-positive, 25 inactive-carriers (HBV-DNA≤2000IU/ml, ALT<30U/L), 66 HBeAg-negative-CHB-patients and 10 with HDV-super-infection. In 35 patients treated with Peg-IFN±nucleos(t)ide-analogues (NUCs) sera were obtained at baseline, end-of-therapy and week-24-off-therapy and in 22 treated with NUCs (for 60 months, 42-134m) at baseline and end-of-follow-up. HBsAg and IgM-anti-HBc were measured by Architect-assays (Abbott, USA); total-anti-HBc by double-antigen-sandwich-immune-assay (Wantai, China); HBV-DNA by COBAS-TaqMan (Roche, Germany). Total-anti-HBc were detectable in all sera with lower levels in HBsAg-carriers without CHB (immune-tolerant, inactive and HDV-superinfected, median 3.26, range 2.26-4.49 Log10 IU/ml) versus untreated-CHB (median 4.68, range 2.76-5.54 Log10 IU/ml), p<0.0001. IgM-anti-HBc positive using the chronic-hepatitis-cut-off" (0.130-S/CO) were positive in 102 of 212 sera (48.1%). Overall total-anti-HBc and IgM-anti-HBc correlated significantly (p<0.001, r=0.417). Total-anti-HBc declined significantly in CHB patients with response to Peg-IFN (p<0.001) and in NUC-treated patients (p<0.001); the lowest levels (median 2.68, range 2.12-3.08 Log10 IU/ml) were found in long-term responders who cleared HBsAg subsequently. During spontaneous and therapy-induced fluctuations of CHB (remissions and reactivations) total- and IgM-anti-HBc correlated with ALT (p<0.001, r=0.351 and p=0.008, r=0.185 respectively). Total-anti-HBc qualifies as a useful marker of HBV-induced-liver-disease that might help to discriminate major phases of chronic HBV infection and to predict sustained response to antivirals. PMID

  18. Structural characterization and MHCII-dependent immunological properties of the zwitterionic O-chain antigen of Morganella morganii.

    PubMed

    Young, N Martin; Kreisman, Lori S C; Stupak, Jacek; MacLean, Leann L; Cobb, Brian A; Richards, James C

    2011-10-01

    Morganella morganii is a commensal Gram-negative bacterium that has long been known to produce an antigen bearing phosphocholine groups. We determined the structure of this O-chain antigen and found that its repeating unit also contains a free amino group and a second phosphate: This alternating charge character places the M. morganii O-chain polysaccharide into a small family of zwitterionic polysaccharides (ZPSs) known to induce T-cell-dependent immune responses via presentation by class II major histocompatibility complex (MHCII) molecules. In vitro binding assays demonstrate that this O-chain interacts with MHCII in a manner that competes with binding of the prototypical ZPS antigen PSA from Bacteroides fragilis, despite its lack of a helical structure. Cellular studies also showed that the M. morganii polysaccharide induces activation of CD4(+) T-cells. Antibody binding experiments using acid hydrolyzed fragments representing the monomer and higher oligomers of the repeating unit showed that the phosphocholine group was the dominant element of the epitope with an overall affinity (K(D)) of about 5 × 10(-5) M, a typical value for an IgM anti-carbohydrate antibody but much lower than the affinity for phosphocholine itself. These data show that the structure of the M. morganii polysaccharide contains a unique zwitterionic repeating unit which allows for immune recognition by T-cells, making it the first identified T-cell-dependent O-chain antigen.

  19. Silver stained core-like structures in chinese hamster metaphase Chromosomes.

    PubMed

    Kaiserman, M Z; Burkholder, G D

    1980-01-01

    Chinese hamster metaphase chromosomes, subjected to prolonged hypotonic pretreatment and subsequently stained with ammoniacal silver, contained a darkly-stained core-like structure in each chromatid, surrounded by a halo of dispersed chromatin which was pale yellow to brown in color. The core was variable in its appearance, ranging from a continuous linear configuration to a spiral structure or a discontinuous, particulate structure. Within the centromeric regions, the cores frequently appeared more intensely stained than elsewhere in the chromosome. The nucleolus organizers also stained darkly and appeared to be attached to the core-like structures. It remains to be determined whether the cores represent a real component of metaphase chromosome structure, or whether they are artifacts resulting from abnormal chromatin aggregation arising at the time of chromosome preparation. PMID:6165446

  20. Vortex-core structure in neutral fermion superfluids with population imbalance.

    PubMed

    Takahashi, M; Mizushima, T; Ichioka, M; Machida, K

    2006-11-01

    Quantized vortex-core structure is theoretically investigated in fermion superfluids with population imbalance for two atom species of neutral atom clouds near a Feshbach resonance. In contrast with the vortex core in balance case where the quantum depletion makes a vortex visible through the density profile measurement, the vortex core is filled in and becomes less visible because the quantized discrete bound states are occupied exclusively by the majority species. Yet it is shown that the core can be visible through the minority density profile experiment using phase contrast imaging, revealing an interesting opportunity to examine low-lying fermionic core bound states unexplored so far.

  1. Topology of Type II REases revisited; structural classes and the common conserved core.

    PubMed

    Niv, Masha Y; Ripoll, Daniel R; Vila, Jorge A; Liwo, Adam; Vanamee, Eva S; Aggarwal, Aneel K; Weinstein, Harel; Scheraga, Harold A

    2007-01-01

    Type II restriction endonucleases (REases) are deoxyribonucleases that cleave DNA sequences with remarkable specificity. Type II REases are highly divergent in sequence as well as in topology, i.e. the connectivity of secondary structure elements. A widely held assumption is that a structural core of five beta-strands flanked by two alpha-helices is common to these enzymes. We introduce a systematic procedure to enumerate secondary structure elements in an unambiguous and reproducible way, and use it to analyze the currently available X-ray structures of Type II REases. Based on this analysis, we propose an alternative definition of the core, which we term the alphabetaalpha-core. The alphabetaalpha-core includes the most frequently observed secondary structure elements and is not a sandwich, as it consists of a five-strand beta-sheet and two alpha-helices on the same face of the beta-sheet. We use the alphabetaalpha-core connectivity as a basis for grouping the Type II REases into distinct structural classes. In these new structural classes, the connectivity correlates with the angles between the secondary structure elements and with the cleavage patterns of the REases. We show that there exists a substructure of the alphabetaalpha-core, namely a common conserved core, ccc, defined here as one alpha-helix and four beta-strands common to all Type II REase of known structure.

  2. Structural and antigenic characteristics of Campylobacter coli FlaA flagellin.

    PubMed Central

    Power, M E; Guerry, P; McCubbin, W D; Kay, C M; Trust, T J

    1994-01-01

    The polar flagellar filament of Campylobacter coli VC167 is composed of two highly related (98%) flagellin subunit proteins, FlaA and FlaB, whose antigenic specificities result from posttranslational modification. FlaA is the predominant flagellin species, and mutants expressing only FlaA form a full-length flagellar filament. Although the deduced M(r) of type 2 (T2) FlaA is 58,884 and the apparent M(r) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis is 59,500, the solution weight-average M(r) by sedimentation analysis was 63,000. Circular dichroism studies in the presence or absence of 0.1% sodium dodecyl sulfate or 50% trifluorethanol showed that the secondary structure of T2 FlaA flagellin was altered, with alpha-helix structure being increased to 25% in the nonpolar environment. The molecule also contained 35 to 48% beta-sheet and 11 to 29% beta-turn structure. Mimeotope analysis of octapeptides representing the sequence of FlaA together with immunoelectron microscopy and enzyme-linked immunosorbent assay with a panel of antisera indicated that many residues in presumed linear epitopes were inaccessible or nonepitopic in the assembled filament, with the majority being in the N-terminal 337 residues of the 572-residue flagellin. Residues at the carboxy-terminal end of the T2 FlaA subunit also become inaccessible upon assembly. Digestion with trypsin, chymotrypsin, and endoproteinase Glu-C revealed a protease-resistant domain with an approximate M(r) of 18,700 between residues 193 and 375. Digestion with endoproteinase Arg-C and endoproteinase Lys-C allowed the mapping of a segment of surface-exposed FlaA sequence which contributes serospecificity to the VC167 T2 flagellar filament at residues between 421 and 480. Images PMID:7515043

  3. 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...

  4. 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.

  5. Correlation between serum hepatitis B virus core-related antigen and intrahepatic covalently closed circular DNA in chronic hepatitis B patients.

    PubMed

    Suzuki, Fumitaka; Miyakoshi, Hideo; Kobayashi, Mariko; Kumada, Hiromitsu

    2009-01-01

    Nucleos(t)ide analogues are utilized for the treatment of chronic HBV infection, and HBe seroconversion and HBV DNA levels are commonly used as markers of viral status and as primary treatment endpoints. Recently, a new assay was prepared for the detection of serum HBV core-related antigen (HBcrAg), consisting of HBcAg, HBeAg, and p22cr, which is a precore protein from amino acid -28 to at least amino acid 150, by coding the precore/core region. In this study, we examined the correlation between serum HBcrAg concentration and viral status by the analysis of serum HBeAg, HBsAg, peripheral HBV DNA, and intrahepatic covalently closed circular DNA (cccDNA) in 57 chronic hepatitis B patients. Intrahepatic cccDNA was detected in all 57 patients, 42 patients were HBcrAg-positive, and serum HBcrAg concentration level was closely correlated with cccDNA. Additionally, positive HBcrAg concentration level results were observed in 6 out of 13 HBsAg seroclearance patients and 20 out of 31 HBV DNA-negative patients. Moreover, the correlation between HBcrAg and cccDNA in these 31 HBV DNA-negative patients was statistically significant (r = 0.482, P = 0.006). These data suggest that serum HBcrAg concentration is well correlated with intrahepatic cccDNA level, and that the measurement of serum HBcrAg may be clinically useful for monitoring intrahepatic HBV viral status, especially in patients under treatment with nucleos(t)ide analogues.

  6. Genetic and Structural Characterization of the Core Region of the Lipopolysaccharide from Serratia marcescens N28b (Serovar O4)

    PubMed Central

    Coderch, Núria; Piqué, Núria; Lindner, Buko; Abitiu, Nihal; Merino, Susana; Izquierdo, Luis; Jimenez, Natalia; Tomás, Juan M.; Holst, Otto; Regué, Miguel

    2004-01-01

    The gene cluster (waa) involved in Serratia marcescens N28b core lipopolysaccharide (LPS) biosynthesis was identified, cloned, and sequenced. Complementation analysis of known waa mutants from Escherichia coli K-12, Salmonella enterica, and Klebsiella pneumoniae led to the identification of five genes coding for products involved in the biosynthesis of a shared inner core structure: [l,d-HeppIIIα(1→7)-l,d-HeppIIα(1→3)-l,d-HeppIα(1→5)-KdopI(4←2)αKdopII] (l,d-Hepp, l-glycero-d-manno-heptopyranose; Kdo, 3-deoxy-d-manno-oct-2-ulosonic acid). Complementation and/or chemical analysis of several nonpolar mutants within the S. marcescens waa gene cluster suggested that in addition, three waa genes were shared by S. marcescens and K. pneumoniae, indicating that the core region of the LPS of S. marcescens and K. pneumoniae possesses additional common features. Chemical and structural analysis of the major oligosaccharide from the core region of LPS of an O-antigen-deficient mutant of S. marcescens N28b as well as complementation analysis led to the following proposed structure: β-Glc-(1→6)-α-Glc-(1→4))-α-d-GlcN-(1→4)-α-d-GalA-[(2←1)-α-d,d-Hep-(2←1)-α-Hep]-(1→3)-α-l,d-Hep[(7←1)-α-l,d-Hep]-(1→3)-α-l,d-Hep-[(4←1)-β-d-Glc]-(1→5)-Kdo. The D configuration of the β-Glc, α-GclN, and α-GalA residues was deduced from genetic data and thus is tentative. Furthermore, other oligosaccharides were identified by ion cyclotron resonance-Fourier-transformed electrospray ionization mass spectrometry, which presumably contained in addition one residue of d-glycero-d-talo-oct-2-ulosonic acid (Ko) or of a hexuronic acid. Several ions were identified that differed from others by a mass of +80 Da, suggesting a nonstoichiometric substitution by a monophosphate residue. However, none of these molecular species could be isolated in substantial amounts and structurally analyzed. On the basis of the structure shown above and the analysis of nonpolar mutants

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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.

  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. Polymeric structure and host Toll-like receptor 4 dictate immunogenicity of NY-ESO-1 antigen in vivo.

    PubMed

    Liu, Yanan; Tian, Xiaoli; Leitner, Wolfgang W; Aldridge, Michael E; Zheng, Junying; Yu, Zhiya; Restifo, Nicholas P; Weiss, Richard; Scheiblhofer, Sandra; Xie, Chong; Sun, Ren; Cheng, Genhong; Zeng, Gang

    2011-10-28

    In search of intrinsic factors that contribute to the distinctively strong immunogenicity of a non-mutated cancer/testis antigen, we found that NY-ESO-1 forms polymeric structures through disulfide bonds. NY-ESO-1 binding to immature dendritic cells was dependent on its polymeric structure and involved Toll-like receptor-4 (TLR4) on the surface of immature dendritic cells in mouse and human. Gene gun-delivered plasmid encoding the wild-type NY-ESO-1 readily induced T cell-dependent antibody (Ab) responses in wild-type C57BL/10 mice but not TLR4-knock-out C57BL/10ScNJ mice. Disrupting polymeric structures of NY-ESO-1 by cysteine-to-serine (Cys-to-Ser) substitutions lead to diminished immunogenicity and altered TLR4-dependence in the induced Ab response. To demonstrate its adjuvant effect, NY-ESO-1 was fused with a major mugwort pollen allergen Art v 1 and a tumor-associated antigen, carbonic anhydrase 9. Plasmid DNA vaccines encoding the fusion genes generated robust immune responses against otherwise non-immunogenic targets in mice. Polymeric structure and TLR4 may play important roles in rendering NY-ESO-1 immunogenic and thus serve as a potent molecular adjuvant. NY-ESO-1 thus represents the first example of a cancer/testis antigen that is a also damage-associated molecular pattern.

  20. The core structure of basal dislocations in deformed sapphire (alpha-Al₂O₃).

    PubMed

    Heuer, A H; Jia, C L; Lagerlöf, K P D

    2010-11-26

    The atomic structure of dislocation cores is decisive for the understanding of plasticity in crystalline solids. The core structure of dislocations in sapphire introduced by high-temperature plastic deformation has been investigated with the use of the negative spherical-aberration imaging technique. The ability of this technique to discriminate oxygen columns from aluminum (Al) columns, combined with reproduction of subtle contrast features by image simulation, leads to a markedly detailed atomic model of the dislocation cores. The partial dislocations are Al-terminated, with electrical neutrality being achieved because half of the Al columns are missing. These partials also undergo core spreading, which results in random occupancy of both tetrahedrally and octahedrally coordinated sites, though Al in tetrahedral coordination never occurs in a perfect crystal. Unusual dislocation core structures may be present in other technologically important nonmetallic solids. PMID:21109669

  1. 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.

  2. Effects of valence-valence, core-valence and core-core correlations on the fine-structure energy levels in Zn-like ions

    NASA Astrophysics Data System (ADS)

    Hu, F.; Jiang, G.; Yang, J. M.; Wang, C. K.; Zhao, X. F.; Hao, L. H.

    2011-01-01

    We report on large ab initio calculation for the 4s^2- 4s4p transitions in the Zinc-like sequence, using the multi-configuration Dirac-Hartree-Fock method. Results for fine-structure energy levels, the wavelengths, transition rates and lifetimes between Z = 70 (Yb) and Z= 92 (U) are presented and compared with other theories and experiments. The calculated values including core-valence correlation are found to be similar and to compare very well with other theories and experiments values. We believe that our extensive calculated values can guide experimentalists in identifying the fine-structure levels in their future work.

  3. Prevalence, Risk Factors, and Impact of Isolated Antibody to Hepatitis B Core Antigen and Occult Hepatitis B Virus Infection in HIV-1–Infected Pregnant Women

    PubMed Central

    Khamduang, Woottichai; Ngo-Giang-Huong, Nicole; Gaudy-Graffin, Catherine; Jourdain, Gonzague; Suwankornsakul, Weerapong; Jarupanich, Tapnarong; Chalermpolprapa, Veeradate; Nanta, Sirisak; Puarattana-aroonkorn, Noossara; Tonmat, Sakchai; Lallemant, Marc; Goudeau, Alain; Sirirungsi, Wasna

    2013-01-01

    Background. Prevalence and risk factors for isolated antibody to hepatitis B core antigen (anti-HBc) and occult hepatitis B virus (HBV) infection are not well known in human immunodeficiency virus type 1 (HIV-1)–infected pregnant women. It is unclear if women with occult infections are at risk of transmitting HBV to their infants. Methods. HIV-1–infected and HBV surface antigen (HBsAg)–negative pregnant women were tested for antibody to HBsAg (anti-HBs) and anti-HBc using enzyme immunoassay. Women with isolated anti-HBc were assessed for occult HBV infection, defined as HBV DNA levels >15 IU/mL, using the Abbott RealTime HBV DNA assay. Infants born to women with isolated anti-HBc and detectable HBV DNA were tested at 4 months of age for HBV DNA. Logistic regression analysis was used to identify factors associated with isolated anti-HBc and occult HBV infection. Results. Among 1812 HIV-infected pregnant women, 1682 were HBsAg negative. Fourteen percent (95% confidence interval [CI], 12%–15%) of HBsAg-negative women had an isolated anti-HBc that was independently associated with low CD4 count, age >35 years, birth in northern Thailand, and positive anti–hepatitis C virus serology. Occult HBV infection was identified in 24% (95% CI, 18%–30%) of women with isolated anti-HBc, representing 2.6% (95% CI, 1.9%–3.5%) of HIV-1–infected pregnant women, and was inversely associated with HIV RNA levels. None of the women with isolated anti-HBc and occult HBV infection transmitted HBV to their infants. Conclusions. HIV-1–infected pregnant women with isolated anti-HBc and occult HBV infection have very low HBV DNA levels and are thus at very low risk to transmit HBV to their infants. PMID:23487379

  4. Structural and antigenic preservation of plant samples by microwave-enhanced fixation, using dedicated hardware, minimizing heat-related effects.

    PubMed

    Lería, Francisca; Marco, Roberto; Medina, Francisco Javier

    2004-09-01

    We explored the use of microwave technology in fixation with the objective of achieving quicker fixation regimes, lower concentrations of toxic and volatile reagents, and enhanced antigen detection. We used a modified domestic microwave oven (900 W) and a low-power (5 W) microwave bench. The work was done on plant materials. The oven was supplemented with a cooling device, a stirring system, and a record of the sample temperature and the time of effective irradiation. The sample, immersed in a fixative solution of 1% paraformaldehyde (PFA) in PBS, was irradiated for only 10 minutes. The sample temperature did not exceed 37 degrees C. In these mild conditions, the quality of the (ultra)structural preservation of the samples, morphometrically assessed, was at the same level as obtained with the same fixative, using conventional methods. On the contrary, samples fixed in the same conditions without irradiation showed a poor structural preservation. The antigenic preservation of the irradiated samples was excellent, since the labeling levels of two nucleolar proteins, detected by immunogold, were three times higher than in conventionally fixed samples. In the so-called microwave bench, the pathway of microwaves is guided, so that low-power microwaves directly hit the sample and there is no dispersion of energy. Temperature of fixative did not increase after microwave irradiation. Fixation in the bench with either 4% PFA, or 1% PFA, for 20 minutes resulted in structural preservation of samples similar in quality as obtained with conventional fixation and in a similar or better level of antigen preservation. Therefore, controlling temperature and effective irradiation is crucial in order to obtain optimal structural and antigen preservation with microwave-enhanced fixation. The dramatic differences observed between microwave-irradiated samples and samples fixed in the same conditions without irradiation, strongly support the existence of specific effects of microwaves on

  5. Structural studies of the O-antigenic polysaccharide of the bovine mastitis isolate Escherichia coli serotype O174.

    PubMed

    Duda, Katarzyna A; Fruth, Angelika; Holst, Otto

    2013-05-24

    Escherichia coli is one of the major causative agents of bovine mastitis, a disease affecting dairy herds. The lipopolysaccharide (LPS) of E. coli was plays a prominent role during infection. Here, we report on the O-antigen chemical structure of the LPS from Escherichia coli strain 2188 (serotype O174:H28) isolated from a mastitis-diseased cow. The structure of the OPS was analyzed by 1 and 2D NMR spectroscopy, and methylation analysis, which identified the branched repeating tetrasaccharide biological unit. [structure: see text].

  6. Metallothionein: structure/antigenicity and detection/quantitation in normal physiological fluids.

    PubMed Central

    Garvey, J S

    1984-01-01

    Recent experiments in the application of radioimmunoassay (RIA) in the detection and quantitation of metallothionein (MT) in human sera and urines demonstrate that it is possible to extend the lower limit of practical quantitation from the previous limit of 50-100 pg to 1 pg.RIA of normal sera indicates that the typical range of concentrations of MT is from less than 0.01 ng/mL to about 1 ng/mL, and that concentrations above 2 ng/mL should be considered abnormal. The typical range for normal urines is from less than 1 ng/mL to 10 ng/mL; concentrations above 10 ng/mL should be considered abnormal. A complementary assay, the enzyme-linked immunosorbent assay (ELISA), is under development. The ELISA is a competitive binding assay, detection and quantitation of MT being either by colorimetric or fluorimetric methods. The present useful range for MT quantitation in the ELISA is from about 50-50000 pg (fluorimetric) or 500-5000 pg (colorimetric). Recent experiments using the RIA have identified the principal antigenic determinants of vertebrate MTs as involving the immediate amino terminal residues (-MDPNC-) and the segment including residues 20-25 (-KCKECK- in human MT). Theoretical predictions of secondary structure based on hydrophilicity and sequence analysis indicate that the conformational profile is dominated by tetrapeptide candidates for beta turns (reverse turns) with 2-3 hexapeptide sequences being candidates for helical conformation and 4-5 short sequences (3-5 residues) being candidates for beta chain conformation. The helical candidates are predicted to be unstable and the analysis favors reverse turns for both determinants of vertebrate MT and a sequestered location for the joining region between clusters A and B. PMID:6203731

  7. 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.

  8. Structural heterogeneity in HLA-B70, a high-frequency antigen of black populations.

    PubMed

    Domena, J D; Little, A M; Madrigal, A J; Hildebrand, W H; Johnston-Dow, L; du Toit, E; Bias, W B; Parham, P

    1993-11-01

    Although the B70 antigen exhibits allele frequencies of 8-23% in African and American black populations, it remains poorly defined. Cloning and sequencing of cDNA encoding B70 antigens from six cell lines has identified a group of three closely related alleles: B*1503, B*1509 and B*1510, that form a subgroup of the B15 family. The sequences of these alleles and, in particular, B*1503, are close to that of the HLA-B consensus consistent with the difficulty in their serological definition. The products of the three alleles correspond to three electrophoretically detected variants of the B70 antigen and some correlation with the B71 and B72 subspecificities of the B70 antigen can be made. A fourth allele, B*7901, previously described by Choo et al. (J. Immunol. 147: 174-180, 1991) that was not serologically typed as B70, differs by a single nucleotide substitution from B*1510. The sensitivity of alloantibodies to single differences in peptide binding residues suggest a role for bound peptides in the HLA-B70 alloantigenic specificities. The heavy chains encoded by the four alleles differ at four peptide binding residues of the antigen recognition site, the evolutionary modification of which can be explained in terms of interallelic recombination events.

  9. Hepatitis B core-related antigen (HBcrAg) levels in the natural history of hepatitis B virus infection in a large European cohort predominantly infected with genotypes A and D.

    PubMed

    Maasoumy, B; Wiegand, S B; Jaroszewicz, J; Bremer, B; Lehmann, P; Deterding, K; Taranta, A; Manns, M P; Wedemeyer, H; Glebe, D; Cornberg, M

    2015-06-01

    Hepatitis B core-related antigen (HBcrAg) has been suggested as an additional marker of hepatitis B virus (HBV) infection. HBcrAg combines the antigenic reactivity resulting from denatured hepatitis B e antigen (HBeAg), HBV core antigen and an artificial core-related protein (p22cr). In Asian patients, high levels of HBcrAg have been suggested to be an independent risk factor for hepatocellular carcinoma, while low levels could guide safe cessation of treatment with nucleos(t)ide analogues. We here studied HBcrAg levels in different phases of HBV infection in a large European cohort predominantly infected with genotypes A and D: HBeAg-positive immune tolerance (n = 30), HBeAg-positive immune clearance (IC) (n = 60), HBeAg-negative hepatitis (ENH) (n = 50), HBeAg-negative inactive/quiescent carrier phase (c) (n = 109) and acute hepatitis B (n = 8). Median HBcrAg levels were high in the immune tolerance and immune clearance phases (8.41 and 8.11 log U/mL, respectively), lower in ENH subjects (4.82 log U/mL) but only 2.00 log U/mL in ENQ subjects. Correlation between HBcrAg and HBV DNA varied among the different phases of HBV infection, while HBcrAg moderately correlated with hepatitis B surface antigen in all phases. ENQ patients had HBcrAg levels <3 log U/mL in 79%, in contrast to only 12% in the ENH group. HBcrAg levels vary significantly during the different phases of HBV infection. HBcrAg may serve as valuable marker for virus replication and reflect the transcriptional activity of intrahepatic cccDNA. In HBeAg-negative patients, HBcrAg may help to distinguish between inactive carriers (ENQ) and those with active disease (ENH).

  10. Structural details of HIV-1 recognition by the broadly neutralizing monoclonal antibody 2F5: epitope conformation, antigen-recognition loop mobility, and anion-binding site.

    PubMed

    Julien, Jean-Philippe; Bryson, Steve; Nieva, Jose L; Pai, Emil F

    2008-12-12

    2F5 is a monoclonal antibody with potent and broadly neutralizing activity against HIV-1. It targets the membrane-proximal external region (MPER) of the gp41 subunit of the envelope glycoprotein and interferes with the process of fusion between viral and host cell membranes. This study presents eight 2F5 F(ab)' crystal structures in complex with various gp41 peptide epitopes. These structures reveal several key features of this antibody-antigen interaction. (1) Whenever free of contacts caused by crystal artifacts, the extended complementarity-determining region H3 loop is mobile; this is true for ligand-free and epitope-bound forms. (2) The interaction between the antibody and the gp41 ELDKWA epitope core is absolutely critical, and there are also close and specific contacts with residues located N-terminal to the epitope core. (3) Residues located at the C-terminus of the gp41 ELDKWA core do not interact as tightly with the antibody. However, in the presence of a larger peptide containing the gp41 fusion peptide segment, these residues adopt a conformation consistent with the start of an alpha-helix. (4) At high sulfate concentrations, the electron density maps of 2F5 F(ab)'-peptide complexes contain a peak that may mark a binding site for phosphate groups of negatively charged lipid headgroups. The refined atomic-level details of 2F5 paratope-epitope interactions revealed here should contribute to a better understanding of the mechanism of 2F5-based virus neutralization, in general, and prove important for the design of potential vaccine candidates intended to elicit 2F5-like antibody production.

  11. 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.

  12. 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.

  13. 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

  14. Structure of a human IgA1 Fab fragment at 1.55 Å resolution: potential effect of the constant domains on antigen-affinity modulation.

    PubMed

    Correa, Agustin; Trajtenberg, Felipe; Obal, Gonzalo; Pritsch, Otto; Dighiero, Guillermo; Oppezzo, Pablo; Buschiazzo, Alejandro

    2013-03-01

    Despite being the most abundant class of immunoglobulins in humans and playing central roles in the adaptive immune response, high-resolution structural data are still lacking for the antigen-binding region of human isotype A antibodies (IgAs). The crystal structures of a human Fab fragment of IgA1 in three different crystal forms are now reported. The three-dimensional organization is similar to those of other Fab classes, but FabA1 seems to be more rigid, being constrained by a hydrophobic core in the interface between the variable and constant domains of the heavy chain (VH-CH1) as well as by a disulfide bridge that connects the light and heavy chains, influencing the relative heavy/light-chain orientation. The crystal structure of the same antibody but with a G-isotype CH1 which is reported to display different antigen affinity has also been solved. The differential structural features reveal plausible mechanisms for constant/variable-domain long-distance effects whereby antibody class switching could alter antigen affinity.

  15. 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.

  16. Liquid-crystalline hybrid materials based on [60]fullerene and bent-core structures.

    PubMed

    Vergara, Jorge; Barberá, Joaquín; Serrano, José Luis; Ros, M Blanca; Sebastián, Nerea; de la Fuente, Rosario; López, David O; Fernández, Gustavo; Sánchez, Luis; Martín, Nazario

    2011-12-23

    What a core-ker! By the appropriate combination of promesogenic bent-core structures and the C(60)  unit, lamellar polar liquid-crystal phases were induced. The supramolecular organization of the functional fullerene-based assemblies, the temperature range of the soft phase, the stabilization of the mesophase-like order at room temperature, and the molecular switching under an electric field can be tuned, depending on the molecular structure.

  17. Three-dimensional structure of inner core anisotropy from PKP differential travel times and waveforms

    NASA Astrophysics Data System (ADS)

    Song, X.

    2003-12-01

    Discussion with Prof. Don Anderson was one of the most inspiring and stimulating experiences in my science career when we were searching for evidence for inner core anisotropy a little over ten years ago. At the time, the hypothesis of inner core anisotropy was not fully accepted. Now models of 3D inner core anisotropy have been proposed. Recent studies suggest that the uppermost inner core is nearly isotropic and western and eastern hemispheres of the inner core are different in both velocity and anisotropy. Yet differential PKP travel times at near antipodal distances show convincingly that significant anisotropy exists in the bulk of the inner core at both hemispheres. Recently Xinlei Sun and I assemble differential PKP travel-time measurements at distances of 145 to 180o, obtained by us and others over the years, to investigate the 3-D structure of the inner core anisotropy. These differential times reduces the biases from earthquake mislocations and heterogeneous upper mantle. We invert for 3D inner core anisotropy by dividing the inner core into four layers in radius and six sectors in longitudes. The top 100 km of the inner core is assumed to be isotropic. Our inversion suggests that at depth of 100-500 km below the inner core boundary, the quasi-eastern hemisphere (40 to 160oE) is nearly isotropic (less than 1% of anisotropy) while the western hemisphere is strongly anisotropic (3 to 5% anisotropy). However, at depth of 500-900 km, both hemispheres are anisotropic (about 3% anisotropy). At the innermost 300 km of the inner core, the form of anisotropy seems distinctly different. One of the most dramatic manifestations of changes in anisotropy is the observation of seismic triplication of inner core waves; a type of multipathing effect due to heterogeneity that Don challenged to think about even in the early days. The best example is the seismic triplication observed from South Sandwich Islands earthquakes recorded at stations in Canada and Alaska.

  18. Measurement of the hepatitis B core-related antigen is valuable for predicting the pathological status of liver tissues in chronic hepatitis B patients.

    PubMed

    Zhang, Zhan-Qing; Lu, Wei; Wang, Yan-Bing; Weng, Qi-Cheng; Zhang, Zhi-Yong; Yang, Zhi-Qiang; Feng, Yan-Ling

    2016-09-01

    The objective of this study was to evaluate the validities of serum hepatitis B core-related antigen (HBcrAg) for predicting the pathological status of liver tissues of chronic hepatitis B (CHB). A total of 205 Chinese patients with CHB, including 121 HBeAg-positive and 84 HBeAg-negative patients, were enrolled in this study. In HBeAg-positive patients, AUCs of serum HBcrAg for predicting severe necro-inflammation and advanced fibrosis were greater than 0.70; using serum HBcrAg<=4.81×10(4)kUmL(-1) and <=2.45×10(4)kUmL(-1) as cutoffs, the sensitivities, specificities, accuracies for predicting severe necro-inflammation and advanced fbrosis were 0.697, 0.716, 0.711 and 0.818, 0.778, 0.785, respectively. In HBeAg-negative patients, the AUCs of serum HBcrAg for predicting significant necro-inflammation and significant fibrosis were greater than 0.70; using serum HBcrAg>=1.70×10(2)kUmL(-1) and >=4.02kUmL(-1) as cutoffs, the sensitivities, specificities, accuracies for predicting significant necro-inflammation and significant fibrosis were 0.929, 0.964, 0.952 and 1.000, 1.000, 1.000, respectively. These results indicated favorable performances of serum HBcrAg for predicting severe necro-inflammation and advanced fibrosis in HBeAg-positive patients and significant necro-inflammation and significant fibrosis in negative patients.

  19. New Enzyme Immunoassay for Detection of Hepatitis B Virus Core Antigen (HBcAg) and Relation between Levels of HBcAg and HBV DNA

    PubMed Central

    Kimura, Tatsuji; Rokuhara, Akinori; Matsumoto, Akihiro; Yagi, Shintaro; Tanaka, Eiji; Kiyosawa, Kendo; Maki, Noboru

    2003-01-01

    A new enzyme immunoassay specific for hepatitis B virus (HBV) core antigen (HBcAg) was developed. In order to detect HBcAg, specimens were pretreated with detergents to release HBcAg from the HBV virion and disassemble it to dimers, and simultaneously, the treatment inactivated anti-HBc antibodies. HBcAg detected by the assay peaked with HBV DNA in density gradient fractions of HBV-positive sera. The assay showed a wide detection range from 2 to 100,000 pg/ml. We observed no interference from anti-HBc antibody or blood components, but the assay was inhibited by very high concentrations (>1 μg/ml; corresponding to 80 signal/cutoff) of HBeAg. When the cutoff value was tentatively set at 4 pg/ml, all healthy control (HBsAg and HBV DNA negative, n = 160) and anti-hepatitis C virus-positive (n = 55) sera were identified as negative. HBcAg concentrations correlated very closely with HBV DNA (r = 0.946, n = 145) in 216 samples from 72 hepatitis B patients. In seroconversion panels, HBcAg concentrations changed in parallel with HBV DNA levels. The assay, therefore, offers a simple method for monitoring hepatitis B patients. With a series of sera during lamivudine therapy, HBV DNA levels fell sharply and the HBcAg concentration also decreased, but the change in HBcAg was smaller and more gradual. The supposed mechanism of these changes and their clinical significance are discussed. PMID:12734224

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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.

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

    PubMed

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

    1986-05-01

    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.

  10. 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.

  11. 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

  12. Variable domain-linked oligosaccharides of a human monoclonal IgG: structure and influence on antigen binding.

    PubMed Central

    Leibiger, H; Wüstner, D; Stigler, R D; Marx, U

    1999-01-01

    The variable-domain-attached oligosaccharide side chains of a human IgG produced by a human-human-mouse heterohybridoma were analysed. In addition to the conserved N-glycosylation site at Asn-297, an N-glycosylation consensus sequence (Asn-Asn-Ser) is located at position 75 in the variable region of its heavy chain. The antibody was cleaved into its antigen-binding (Fab) and crystallizing fragments. The oligosaccharides of the Fab fragment were released by digestion with various endo- and exoglycosidases and analysed by anion-exchange chromatography and fluorophore-assisted carbohydrate electrophoresis. The predominant components were disialyl- bi-antennary and tetra-sialyl tetra-antennary complex carbohydrates. Of note is the presence in this human IgG of oligosaccharides containing N-glycolylneuraminic acid and N-acetylneuraminic acid in the ratio of 94:6. Furthermore, we determined N-acetylgalactosamine in the Fab fragment of this antibody, suggesting the presence of O-linked carbohydrates. A three-dimensional structure of the glycosylated variable (Fv) fragment was suggested using computer-assisted modelling. In addition, the influence of the Fv-associated oligosaccharides of the CBGA1 antibody on antigen binding was tested in several ELISA systems. Deglycosylation resulted in a decreased antigen-binding activity. PMID:10024532

  13. 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.

  14. 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

  15. Second harmonic generation in composites of ellipsoidal particles with core-shell structure

    NASA Astrophysics Data System (ADS)

    Zhang, Wen; Liu, De-Hua

    2009-01-01

    We study the enhancement of the second-harmonic generation (SHG) coefficient in a random composite consisting of ellipsoidal particles with a core-shell structure in a linear dielectric host. The material making up the ellipsoidal core is assumed to be dielectric, but with a nonlinear susceptibility for SHG. The coating material is assumed to be metallic with a linear susceptibility. The effective SHG coefficient is derived and its expression is related to various local field factors. The numerical calculations of the effective SHG response per unit volume of nonlinear material can be greatly enhanced at certain frequencies. For coated ellipsoidal particles, the core-shell structure and the particle shape allow for tuning of the resonance through the choice of material parameters and/or the ratio of the core to shell volume fraction and the depolarization factor of the particles.

  16. Second harmonic generation in random composites of particles with core-shell structure

    NASA Astrophysics Data System (ADS)

    Xu, C.; Hui, P. M.

    2006-08-01

    We study the effective second harmonic generation (SHG) coefficient in a random composite consisting of particles with a core-shell structure embedded in a linear dielectric host. The material making up the core of the particles is assumed to be nonconducting, but with a nonlinear susceptibility for SHG. The coating material is assumed to be linear and metallic. An expression for the effective SHG coefficient is obtained, in terms of various local field factors. The effective SHG response per unit volume of nonlinear material is found to be greatly enhanced at certain frequencies. For coated particles, the core-shell structure allows for tuning of the resonance through the choice of material parameters and/or the ratio of the core to shell volume fraction.

  17. Establishing the Structural Integrity of Core-Shell Nanoparticles against Elemental Migration using Luminescent Lanthanide Probes.

    PubMed

    Chen, Bing; Peng, Dengfeng; Chen, Xian; Qiao, Xvsheng; Fan, Xianping; Wang, Feng

    2015-10-19

    Core-shell structured nanoparticles are increasingly used to host luminescent lanthanide ions but the structural integrity of these nanoparticles still lacks sufficient understanding. Herein, we present a new approach to detect the diffusion of dopant ions in core-shell nanostructures using luminescent lanthanide probes whose emission profile and luminescence lifetime are sensitive to the chemical environment. We show that dopant ions in solution-synthesized core-shell nanoparticles are firmly confined in the designed locations. However, annealing at certain temperatures (greater than circa 350 °C) promotes diffusion of the dopant ions and leads to degradation of the integrity of the nanoparticles. These insights into core-shell nanostructures should enhance our ability to understand and use lanthanide-doped luminescent nanoparticles.

  18. Comparative structural analysis of HLA-A2 antigens distinguishable by cytotoxic T lymphocytes: variants M7 and DR1.

    PubMed

    Krangel, M S; Taketani, S; Biddison, W E; Strong, D M; Strominger, J L

    1982-11-23

    Comparative primary structural analyses have begun to elucidate polymorphic residues and segments of the class I antigens of the major histocompatibility complex, at least some of which presumably contribute to determinants important in immune recognition events. HLA-A2 structural variants have been described which are serologically indistinguishable from other HLA-A2 antigens, yet which can be recognized neither by HLA-A2 specific alloimmune nor by HLA-A2 restricted, virus immune cytotoxic T lymphocytes. This study utilizes double-label tryptic peptide comparisons in combination with both conventional and microsequence analyses to investigate the structure of two such variants, M7 and DR1. We find that these variants are identical with each other and differ from the predominant HLA-A2 heavy chain species by a glutamine to arginine substitution at residue 43, by an unidentified substitution in the tryptic peptide spanning residues 147-157, and by an as yet poorly defined alteration in glycosylation. Structural information from these and other variants should be useful in precisely defining functionally important determinants on the molecule. PMID:6983890

  19. 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.

  20. Genetic, structural, and antigenic analyses of glycan diversity in the O-linked protein glycosylation systems of human Neisseria species.

    PubMed

    Børud, Bente; Aas, Finn Erik; Vik, Ashild; Winther-Larsen, Hanne C; Egge-Jacobsen, Wolfgang; Koomey, Michael

    2010-06-01

    Bacterial capsular polysaccharides and lipopolysaccharides are well-established ligands of innate and adaptive immune effectors and often exhibit structural and antigenic variability. Although many surface-localized glycoproteins have been identified in bacterial pathogens and symbionts, it not clear if and how selection impacts associated glycoform structure. Here, a systematic approach was devised to correlate gene repertoire with protein-associated glycoform structure in Neisseria species important to human health and disease. By manipulating the protein glycosylation (pgl) gene content and assessing the glycan structure by mass spectrometry and reactivity with monoclonal antibodies, it was established that protein-associated glycans are antigenically variable and that at least nine distinct glycoforms can be expressed in vitro. These studies also revealed that in addition to Neisseria gonorrhoeae strain N400, one other gonococcal strain and isolates of Neisseria meningitidis and Neisseria lactamica exhibit broad-spectrum O-linked protein glycosylation. Although a strong correlation between pgl gene content, glycoform expression, and serological profile was observed, there were significant exceptions, particularly with regard to levels of microheterogeneity. This work provides a technological platform for molecular serotyping of neisserial protein glycans and for elucidating pgl gene evolution.

  1. 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.

  2. 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

  3. 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.

  4. Effect of the parameters of a sandwich structure with a honeycomb core on its soundproofing capacity

    NASA Astrophysics Data System (ADS)

    Tkachev, A. A.

    Expressions for estimating the soundproofing capacity of sandwich structures with a honeycomb core are obtained by using equations of transverse vibrations of a plate with allowance for the flexural and shear waves. The expressions provide an adequate description of the experimentally observed effects and make it possible to predict the effect of the parameters of a structure on its soundproofing efficiency.

  5. The structure of the Morganella morganii lipopolysaccharide core region and identification of its genomic loci.

    PubMed

    Vinogradov, Evgeny; Nash, John H E; Foote, Simon; Young, N Martin

    2015-01-30

    The core region of the lipopolysaccharide of Morganella morganii serotype O:1ab was obtained by hydrolysis of the LPS and studied by 2D NMR, ESI MS, and chemical methods. Its structure was highly homologous to those from the two major members of the same Proteeae tribe, Proteus mirabilis and Providencia alcalifaciens, and analysis of the M. morganii genome disclosed that the loci for its outer core, lipid A and Ara4N moieties are similarly conserved.

  6. Molecular structures that influence the immunomodulatory properties of the lipid A and inner core region oligosaccharides of bacterial lipopolysaccharides.

    PubMed Central

    Baker, P J; Hraba, T; Taylor, C E; Stashak, P W; Fauntleroy, M B; Zähringer, U; Takayama, K; Sievert, T R; Hronowski, X; Cotter, R J

    1994-01-01

    The relationship between chain length as well as the position of fatty acyl groups to the ability of lipid A to abolish the expression of suppressor T-cell (Ts) activity was examined. Fatty acyl chain lengths of C12 to C14, as in the lipid A of Escherichia coli and Salmonella minnesota, appear to be optimal for this bioactivity, since lipid A preparations with fatty acyl groups of relatively short chain length (C10 to C12 for Pseudomonas aeruginosa and Chromobacterium violaceum) or predominantly long chain length (C18 for Helicobacter pylori) are without effect. The presence of an acyloxyacyl group of appropriate chain length at the 3' position of the glucosamine disaccharide backbone of lipid A also plays a decisive role. By contrast, the lipid A proximal inner core region oligosaccharides of some bacterial lipopolysaccharides increase the expression of Ts activity; this is due mainly to the capacity of such oligosaccharides, which are relatively conserved in structure among gram-negative bacteria, to enlarge or expand upon the population of CD8+ Ts generated during the course of a normal antibody response to unrelated microbial antigens. The minimal structure required for the expression of the added immunosuppression observed appears to be a hexasaccharide containing one 2-keto-3-deoxyoctonate residue, two glucose residues, and three heptose residues to which are attached two pyrophosphorylethanolamine groups. The relevance of these findings to virulence and to the pathogenesis of gram-negative infections is discussed. PMID:8188347

  7. 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.

  8. Noise control for a ChamberCore cylindrical structure using long T-shaped acoustic resonators

    NASA Astrophysics Data System (ADS)

    Li, Deyu; Vipperman, Jeffrey S.

    2003-10-01

    The Air Force Research Laboratory, Space Vehicles Directorate has developed a new advanced composite launch vehicle fairing (referred to as ``ChamberCore''). The ChamberCore is sandwich-type structure fabricated from multi-layered composite face sheets separated by channels that form passive acoustic chambers. These acoustic chambers have a potential to create an acoustic resonator network that can be used to attenuate noise inside the closed ChamberCore cylindrical structure. In this study, first, the feasibility of using cylindrical Helmholtz resonators to control noise in a mock-scale ChamberCore composite cylinder is investigated. The targeted frequencies for noise control are the first four acoustic cavity resonances of the ChamberCore cylinder. The optimal position of the Helmholtz resonators for controlling each targeted cavity mode is discussed, and the effects of resonator spacing on noise attenuation are also experimentally evaluated. Next, six long T-shaped acoustic resonators are designed and constructed within the acoustic chambers of the structure and investigated. Several tests are conducted to evaluate the noise control ability of the resonators in the ChamberCore cylinder. Reductions ranging from 3.2 to 6.0 dB were observed in the overall mean-square noise reduction spectrum at the targeted inner cavity resonance frequencies. [Work supported by AFRL/DV.

  9. 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.

  10. 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.

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

    PubMed

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

    2016-02-01

    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

  12. 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.

  13. 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

  14. 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

  15. Electronic structure and intersubband magnetoabsorption spectra of CdSe/CdS core-shell nanowires

    NASA Astrophysics Data System (ADS)

    Xiong, Wen

    2016-10-01

    The electronic structures of CdSe/CdS core-shell nanowires are calculated based on the effective-mass theory, and it is found that the hole states in CdSe/CdS core-shell nanowires are strongly mixed, which are very different from the hole states in CdSe or CdS nanowires. In addition, we find the three highest hole states at the Γ point are almost localized in the CdSe core and the energies of the hole states in CdSe/CdS core-shell nanowires can be enhanced greatly when the core radius Rc increases and the total radius R is fixed. The degenerate hole states are split by the magnetic field, and the split energies will increase when |Jh | increases from 1/2 to 7/2, while they are almost not influenced by the change of the core radius Rc. The absorption spectra of CdSe/CdS core-shell nanowires at the Γ point are also studied in the magnetic field when the temperature T is considered, and we find there are only two peaks will arise if the core radius Rc and the temperature T increase. The intensity of each optical absorption can be considerably enhanced by increasing the core radius Rc when the temperature T is fixed, it is due to the increase of their optical transition matrix element. Meanwhile, the intensity of each optical absorption can be decreased when the temperature T increases and the core radius Rc is fixed, and this is because the Fermi-Dirac distribution function of the corresponding hole states will increase as the increase of the temperature T.

  16. 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

  17. 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

  18. Photoelectrochemical behavior of hierarchically structured Si/WO3 core-shell tandem photoanodes.

    PubMed

    Coridan, Robert H; Arpin, Kevin A; Brunschwig, Bruce S; Braun, Paul V; Lewis, Nathan S

    2014-05-14

    WO3 thin films have been deposited in a hierarchically structured core-shell morphology, with the cores consisting of an array of Si microwires and the shells consisting of a controlled morphology WO3 layer. Porosity was introduced into the WO3 outer shell by using a self-assembled microsphere colloidal crystal as a mask during the deposition of the WO3 shell. Compared to conformal, unstructured WO3 shells on Si microwires, the hierarchically structured core-shell photoanodes exhibited enhanced near-visible spectral response behavior, due to increased light absorption and reduced distances over which photogenerated carriers were collected. The use of structured substrates also improved the growth rate of microsphere-based colloidal crystals and suggests strategies for the use of colloidal materials in large-scale applications.

  19. Design and optimization of 3-mode×12-core dual-ring structured few-mode multi-core fiber

    NASA Astrophysics Data System (ADS)

    Tu, Jiajing; Long, Keping; Saitoh, Kunimasa

    2016-12-01

    We adopt dual-ring structure (DRS) for the core arrangement of 3-mode (LP01, LP11a and LP11b)×12-core few-mode multi-core fiber (FM-MCF) and then introduce the design method for this DRS-FM-MCF. After investigating the characteristics such as differential mode delay (DMD), inter-core crosstalk (XT), threshold value of bending radius (Rpk), relative core multiplicity factor (RCMF) and cable cutoff wavelength (λcc), we present an optimized scheme for this DRS-FM-MCF. For the optimized DRS-FM-MCF, | DMD | is ≤ 100 ps / km over C+L band, the maximum XT at wavelength (λ) of 1625 nm achieves -33 dB/100 km, maximum Rpk is 11.03 cm, RCMF (LP01, LP11a and LP11b) reaches 25.49 and maximum λcc is ≤ 1530 nm. Compared with one-ring structure (ORS), DRS has much more space to enlarge core pitch (Λ) so that lower XT can be achieved. Furthermore, DRS has less confinement degree on mode than square-lattice structure (SLS) if Λ and cladding diameter (Dcl) are set at similar values. It means that it is easier for DRS to make sure λcc would not be larger than the lower limit of C+L bands. In this paper, DRS is proved as a suitable core arrangement for 3-mode×12-core FM-MCF.

  20. 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

  1. 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.

  2. Core-Cone Structured Monodispersed Mesoporous Silica Nanoparticles with Ultra-large Cavity for Protein Delivery.

    PubMed

    Xu, Chun; Yu, Meihua; Noonan, Owen; Zhang, Jun; Song, Hao; Zhang, Hongwei; Lei, Chang; Niu, Yuting; Huang, Xiaodan; Yang, Yannan; Yu, Chengzhong

    2015-11-25

    A new type of monodispersed mesoporous silica nanoparticles with a core-cone structure (MSN-CC) has been synthesized. The large cone-shaped pores are formed by silica lamellae closely packed encircling a spherical core, showing a structure similar to the flower dahlia. MSN-CC has a large pore size of 45 nm and a high pore volume of 2.59 cm(3) g(-1). MSN-CC demonstrates a high loading capacity of large proteins and successfully delivers active β-galactosidase into cells, showing their potential as efficient nanocarriers for the cellular delivery of proteins with large molecular weights. PMID:26426420

  3. 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.

  4. 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

  5. Antigenic relationships among homologous structural polypeptides of porcine, feline, and canine coronaviruses.

    PubMed Central

    Horzinek, M C; Lutz, H; Pedersen, N C

    1982-01-01

    Transmissible gastroenteritis virus of swine (TGEV), feline infectious peritonitis virus (FIPV), and canine coronavirus were studied with respect to their serological cross-reactivity in homologous and heterologous virus neutralization, immune precipitation of radiolabeled TGEV, electroblotting, and enzyme-linked immunosorbent assay using individual virion polypeptides prepared by polyacrylamide gel electrophoresis. TGEV was neutralized by feline anti-FIPV serum, and the reaction was potentiated by complement; heterologous neutralization involved antibody reacting with the peplomer protein (P), the envelope protein (E), and cellular (glycolipid) components incorporated into the TGEV membrane. Electrophoretic analysis of immune precipitates containing [35S]methionine-labeled disrupted TGEV and feline anti-FIPV antibody confirmed the reaction with the P and E polypeptides and showed the nucleocapsid protein (N) in addition. Electroblotting, followed by incubation with antibody, 125I-labeled protein A, and fluorography, disclosed cross-reactions between the three viruses at the N and E levels and revealed differences in the apparent molecular weights of the latter. Enzyme immunoassays performed with standard amounts of immobilized P, N, and E polypeptides of the three viruses showed recognition of the antigens by homologous and heterologous antibody to comparable degrees. These results indicate a close antigenic relationship between TGEV, FIPV, and canine coronavirus due to common determinants on the three major virion proteins. The taxonomic implications of these findings are discussed. Images PMID:6182101

  6. Delta hepatitis agent: structural and antigenic properties of the delta-associated particle.

    PubMed Central

    Bonino, F; Hoyer, B; Shih, J W; Rizzetto, M; Purcell, R H; Gerin, J L

    1984-01-01

    Delta agent (delta) was serially passaged to a second and third hepatitis B surface antigen (HBsAg) carrier chimpanzee, using as inoculum the peak delta antigen (delta Ag) serum of an animal previously infected with human serum. The characteristics of serially transmitted delta Ag were similar to those described in first-passage animals. It was consistently detected before the development of anti-delta, in association with a 35- to 37-nm subpopulation of HBsAg particles and a unique low-molecular-weight (5.5 X 10(5)) RNA. RNase susceptibility of the delta-associated RNA and release of delta Ag activity upon treatment of delta-associated particles with detergent revealed that this particle is organized into a virion-like form with the RNA and delta Ag as internal components within a coat of HBsAg. Surface determinants of the delta-associated particle other than HBsAg were not detected by radioimmunoprecipitation experiments, using sera of humans and chimpanzees convalescent from delta hepatitis. The HBsAg-associated particle is the "candidate agent" of delta hepatitis. Images PMID:6698598

  7. 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.

  8. The Structure and Dark Halo Core Properties of Dwarf Spheroidal Galaxies

    NASA Astrophysics Data System (ADS)

    Burkert, A.

    2015-08-01

    The structure and dark matter halo core properties of dwarf spheroidal galaxies (dSphs) are investigated. A double-isothermal (DIS) model of an isothermal, non-self-gravitating stellar system embedded in an isothermal dark halo core provides an excellent fit to the various observed stellar surface density distributions. The stellar core scale length a* is sensitive to the central dark matter density ρ0,d. The maximum stellar radius traces the dark halo core radius {r}c,d. The concentration c* of the stellar system, determined by a King profile fit, depends on the ratio of the stellar-to-dark-matter velocity dispersion {σ }*/{σ }d. Simple empirical relationships are derived that allow us to calculate the dark halo core parameters ρ0,d, {r}c,d, and σd given the observable stellar quantities σ*, a*, and c*. The DIS model is applied to the Milky Way’s dSphs. All dSphs closely follow the same universal dark halo scaling relations {ρ }0,d× {r}c,d={75}-45+85 M⊙ pc‑2 that characterize the cores of more massive galaxies over a large range in masses. The dark halo core mass is a strong function of core radius, {M}c,d∼ {r}c,d2. Inside a fixed radius of ∼400 pc the total dark matter mass is, however, roughly constant with {M}d=2.6+/- 1.4× {10}7 M⊙, although outliers are expected. The dark halo core densities of the Galaxy’s dSphs are very high, with {ρ }0,d ≈ 0.2 M⊙ pc‑3. dSphs should therefore be tidally undisturbed. Evidence for tidal effects might then provide a serious challenge for the CDM scenario.

  9. Purified thick filaments from the nematode Caenorhabditis elegans: evidence for multiple proteins associated with core structures

    PubMed Central

    1988-01-01

    The thick filaments of the nematode, Caenorhabditis elegans, arising predominantly from the body-wall muscles, contain two myosin isoforms and paramyosin as their major proteins. The two myosins are located in distinct regions of the surfaces, while paramyosin is located within the backbones of the filaments. Tubular structures constitute the cores of the polar regions, and electron-dense material is present in the cores of the central regions (Epstein, H.F., D.M. Miller, I. Ortiz, and G.C. Berliner. 1985. J. Cell Biol. 100:904-915). Biochemical, genetic, and immunological experiments indicate that the two myosins and paramyosin are not necessary core components (Epstein, H.F., I. Ortiz, and L.A. Traeger Mackinnon. 1986. J. Cell Biol. 103:985-993). The existence of the core structures suggests, therefore, that additional proteins may be associated with thick filaments in C. elegans. To biochemically detect minor associated proteins, a new procedure for the isolation of thick filaments of high purity and structural preservation has been developed. The final step, glycerol gradient centrifugation, yielded fractions that are contaminated by, at most, 1-2% with actin, tropomyosin, or ribosome-associated proteins on the basis of Coomassie Blue staining and electron microscopy. Silver staining and radioautography of gel electrophoretograms of unlabeled and 35S-labeled proteins, respectively, revealed at least 10 additional bands that cosedimented with thick filaments in glycerol gradients. Core structures prepared from wild-type thick filaments contained at least six of these thick filament-associated protein bands. The six proteins also cosedimented with thick filaments purified by gradient centrifugation from CB190 mutants lacking myosin heavy chain B and from CB1214 mutants lacking paramyosin. For these reasons, we propose that the six associated proteins are potential candidates for putative components of core structures in the thick filaments of body-wall muscles of

  10. 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.

  11. 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

  12. 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

  13. 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

  14. Consideration of the three-dimensional structure of core shells (capsids) in spherical retroviruses.

    PubMed

    Nermut, Milan V; Mulloy, Barbara

    2007-01-01

    The problem of three-dimensional organization of retroviral cores has been a matter of interest for the past 30 years. The general opinion in favor of icosahedral symmetry based on electron microscopy observations was questioned when cryo-electron microscopy failed to provide convincing evidence in its favor. More recent studies by cryo-electron microscopy, X-ray crystallography and in vitro assembly of the CA domain of Human immuno deficiency virus (HIV), Murine leukemia virus (MuLV) and Rous sarcoma virus (RSV) threw new light on the organization of retroviral cores. In this communication we report how we produced a three-dimensional (3D) model of MuLV core using data from CA assembly on a lipid film [Ganser, B.K., Cheng, A., Sundquist, W.I., Yeager, M., 2003. Three-dimensional structure of the M-MuLV CA protein on a lipid monolayer: a general model for retroviral capsid assembly. EMBO J. 22, 2886-2892]. The resulting structure revealed that the molecular organization of the core shell is specific and the presence of a 5,3,2 rotational symmetry of the 3D model provides support for icosahedral shape of MuLV cores. The model made it possible to determine the diameter of the cores and calculate the number of CA copies as well as the molecular mass of a core of specific diameter. Thus MuLV cores 68 (or 81.6) nm in diameter consist of 1500 (or 2160) copies of CA. About 12% of molecules from fullerene-like Gag shells versus 71% of molecules of closely packed (core-like). Gag shells were not incorporated into the core shells (capsids). Our 3D models received support from X-ray data of MuLV CA NTD domain published by Mortuza et al. [Mortuza, G., Haire, L.F., Stevens, A., Smerdon, S.J., Stoye, J.P., Taylor, I.A., 2004. High resolution structure of a retroviral capsid hexameric amino-terminal domain. Nature 431, 481-485].

  15. 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

  16. Synthesis of Cu(core) Pt(shell) nanoparticles as model structures for core-shell electrocatalysts by direct platinum electrodeposition on copper.

    PubMed

    Kulp, Christian; Gillmeister, Konrad; Widdra, Wolf; Bron, Michael

    2013-04-15

    The synthesis of Cu(core)Pt(shell) model catalysts by the direct electrochemical deposition of Pt on Cu particles is presented. Cu particles with an average diameter of 200 nm have been deposited on glassy-carbon electrodes by double pulse electrodeposition from a copper sulfate solution. Subsequent deposition from a platinum nitrate solution under potential control allows for a high selectivity of the Pt deposition towards Cu. Using a combination of cyclic voltammetry, XPS and sputtering, the structure of the generated particles has been analyzed and their core-shell configuration proven. It is shown that the electrocatalytic activity for the oxygen reduction is similar to that of other PtCu catalyst systems. The synthesized structures could allow for the analysis of structure-activity relations of core-shell catalysts on the way to the simple and controlled synthesis of supported Cu(core)Pt(shell) nanoparticles as oxygen reduction catalysts.

  17. Structures of synthetic O-antigen fragments from serotype 2a Shigella flexneri in complex with a protective monoclonal antibody.

    PubMed

    Vulliez-Le Normand, B; Saul, F A; Phalipon, A; Bélot, F; Guerreiro, C; Mulard, L A; Bentley, G A

    2008-07-22

    The anti-LPS IgG mAb F22-4, raised against Shigella flexneri serotype 2a bacteria, protects against homologous, but not heterologous, challenge in an experimental animal model. We report the crystal structures of complexes formed between Fab F22-4 and two synthetic oligosaccharides, a decasaccharide and a pentadecasaccharide that were previously shown to be both immunogenic and antigenic mimics of the S. flexneri serotype 2a O-antigen. F22-4 binds to an epitope contained within two consecutive 2a serotype pentasaccharide repeat units (RU). Six sugar residues from a contiguous nine-residue segment make direct contacts with the antibody, including the nonreducing rhamnose and both branching glucosyl residues from the two RUs. The glucosyl residue, whose position of attachment to the tetrasaccharide backbone of the RU defines the serotype 2a O-antigen, is critical for recognition by F22-4. Although the complete decasaccharide is visible in the electron density maps, the last four pentadecasaccharide residues from the reducing end, which do not contact the antibody, could not be traced. Although considerable mobility in the free oligosaccharides can thus be expected, the conformational similarity between the individual RUs, both within and between the two complexes, suggests that short-range transient ordering to a helical conformation might occur in solution. Although the observed epitope includes the terminal nonreducing residue, binding to internal epitopes within the polysaccharide chain is not precluded. Our results have implications for vaccine development because they suggest that a minimum of two RUs of synthetic serotype 2a oligosaccharide is required for optimal mimicry of O-Ag epitopes.

  18. 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

  19. 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 +.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. An ISOCAM absorption survey of the structure of pre-stellar cloud cores

    NASA Astrophysics Data System (ADS)

    Bacmann, A.; André, P.; Puget, J.-L.; Abergel, A.; Bontemps, S.; Ward-Thompson, D.

    2000-09-01

    We present the results of a mid-infrared (lambda =~ 7 mu m) imaging survey of a sample of 24 starless dense cores carried out at an angular resolution of 6arcsec with the ISOCAM camera aboard the Infrared Space Observatory (ISO). The targeted cores are believed to be pre-stellar in nature and to represent the initial conditions of low-mass, isolated star formation. In previous submillimeter dust continuum studies of such pre-stellar cores, it was found that the derived column density profiles did not follow a single power-law such as NH2 ~ bar r-1 throughout their full extent but flattened out near their centre. These submillimeter observations however could not constrain the density profiles at radii greater than ~ 10000 AU. The present absorption study uses ISOCAM's sensitivity to map these pre-stellar cores in absorption against the diffuse mid-infrared background. The goal was to determine their structure at radii that extend beyond the limits of sensitivity of the submillimeter continuum maps and at twice as good an angular resolution. Among the 24 cores observed in our survey, a majority of them show deep absorption features. The starless cores studied here all show a column density profile that flattens in the centre, which confirms the submillimeter emission results. Moreover, beyond a radius of ~ 5000-10000 AU, the typical column density profile steepens with distance from core centre and gets steeper than NH2 ~ bar r-1, until it eventually merges with the low-density ambient molecular cloud. At least three of the cores present sharp edges at R ~ 15000-30000 AU and appear to be decoupled from their parent clouds, providing finite reservoirs of mass for subsequent star formation. Based on observations with ISO, an ESA project with instruments funded by ESA Member States (especially the PI countries: France, Germany, the Netherlands and the United Kingdom) and with the participation of ISAS and NASA.

  6. Structural evaluation of a mimicry-recognizing paratope: plasticity in antigen-antibody interactions manifests in molecular mimicry.

    PubMed

    Tapryal, Suman; Gaur, Vineet; Kaur, Kanwal J; Salunke, Dinakar M

    2013-07-01

    Molecular mimicry manifests antagonistically with respect to the specificity of immune recognition. However, it often occurs because different Ags share surface topologies in terms of shape or chemical nature. It also occurs when a flexible paratope accommodates dissimilar Ags by adjusting structural features according to the antigenic epitopes or differential positioning in the Ag combining site. Toward deciphering the structural basis of molecular mimicry, mAb 2D10 was isolated from a maturing immune response elicited against methyl α-d-mannopyranoside and also bound equivalently to a dodecapeptide. The physicochemical evidence of this carbohydrate-peptide mimicry in the case of mAb 2D10 had been established earlier. These studies had strongly suggested direct involvement of a flexible paratope in the observed mimicry. Surprisingly, comparison of the Ag-free structure of single-chain variable fragment 2D10 with those bound to sugar and peptide Ags revealed a conformationally invariant state of the Ab while binding to chemically and structurally disparate Ags. This equivalent binding of the two dissimilar Ags was through mutually independent interactions, demonstrating functional equivalence in the absence of structural correlation. Thus, existence of a multispecific, mature Ab in the secondary immune response was evident, as was the plasticity in the interactions while accommodating topologically diverse Ags. Although our data highlight the structural basis of receptor multispecificity, they also illustrate mechanisms adopted by the immune system to neutralize the escape mutants generated during pathogenic insult.

  7. Hierarchical Structure of Lattices in Film Formation of Core-Shell Type Polymer Microspheres

    PubMed

    Saito; Sugita; Ishizu

    1997-03-15

    By adding polystyrene homopolymer in the solid state, super-lattice structures of poly(4-vinyl pyridine) core-polystyrene shell type polymer microspheres were hierarchically changed from a disordered state to a face-centered cubic via a body-centered cubic. The transition of the lattice structures was investigated from the view point of the excluded volume of the microsphere, which was controlled by a changing of the molecular weights and blend tarios of polystyrene homopolymers.

  8. The Role of Hepatitis C Virus Core Antigen Testing in the Era of Direct Acting Antiviral Therapies: What We Can Learn from the Protease Inhibitors

    PubMed Central

    Nguyen, Linh Thuy; Gray, Emma; O'Leary, Aisling; Carr, Michael; De Gascun, Cillian F.

    2016-01-01

    Direct-acting antiviral (DAA) therapies have revolutionised the treatment of hepatitis C virus (HCV). The financial cost of DAAs however is significant, and first generation protease inhibitors (PIs) also require frequent monitoring of viral RNA levels to guide treatment. In this context, we examined the relevance of HCV antigen testing to evaluate the potential role in monitoring virological response to HCV antiviral treatment with the PI-based triple therapies, telaprevir (TVR) and boceprevir (BOC). Chronic HCV-infected individuals (n = 152) enrolled in the Irish Hepatitis C Outcomes Research Network (ICORN) study were prospectively analysed for baseline markers and the early viral kinetics associated with SVR. The sustained virological response (SVR) rates in the cohort receiving TVR and BOC were 87.3% and 73.8%, respectively. Baseline factors associated with successful outcome in TVR therapy were age (P = 0.0098), IFNL3 genotype (P = 0.0330) and viral load (P = 0.0456). RNA level at week 4 (P = 0.0068) and viral antigen negativity at week 2 (P = 0.0359) were predictive of SVR for TVR-based therapy. In BOC therapy, prior interferon treatment (P = 0.0209) and IFNL3 genotype (P = 0.0410) were baseline predictors of SVR. Evidence of viraemia based either on viral RNA or antigen at week 4 predicted SVR in these patients. Our data showed that rapid decline of HCV antigen to negative level at week 2 in TVR treatment and <0.96 log fmol/l in BOC treatment after commencement of PI triple therapy were associated with SVR. HCV antigen measurement should be considered as a potential alternative for monitoring treatment response during DAA-based regimens. PMID:27711230

  9. 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

  10. 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

  11. 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.

  12. Vertically aligned P(VDF-TrFE) core-shell structures on flexible pillar arrays

    DOE PAGES

    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

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Supplemental materials for the ICDP-USGS Eyreville A, B, and C core holes, Chesapeake Bay impact structure: Core-box photographs, coring-run tables, and depth-conversion files

    USGS Publications Warehouse

    Durand, C.T.; Edwards, L.E.; Malinconico, M.L.; Powars, D.S.

    2009-01-01

    During 2005-2006, the International Continental Scientific Drilling Program and the U.S. Geological Survey drilled three continuous core holes into the Chesapeake Bay impact structure to a total depth of 1766.3 m. A collection of supplemental materials that presents a record of the core recovery and measurement data for the Eyreville cores is available on CD-ROM at the end of this volume and in the GSA Data Repository. The supplemental materials on the CD-ROM include digital photographs of each core box from the three core holes, tables of the three coring-run logs, as recorded on site, and a set of depth-conversion programs. In this chapter, the contents, purposes, and basic applications of the supplemental materials are briefly described. With this information, users can quickly decide if the materials will apply to their specific research needs. ?? 2009 The Geological Society of America.

  20. Tuning upconversion through a sensitizer/activator-isolated NaYF4 core/shell structure

    NASA Astrophysics Data System (ADS)

    Ye, Shuai; Chen, Guanying; Shao, Wei; Qu, Junle; Prasad, Paras N.

    2015-02-01

    The ability to tune the emission color of upconversion nanoparticles (UCNPs) will greatly enhance the scope of their applications, ranging from infrared solar cells to volumetric multiplexed bioimaging. Conventional methods to tune upconversion are to vary the type and/or the concentration of doped rare-earth ions in these nanoparticle formulations. Here, we introduce a different approach to vary the emission colors of the frequently used sensitizer/activator pairs of Yb3+/RE3+ (RE = Ho, Er, Tm) via utilization of a sensitizer/activator-isolated NaYF4 core-shell structure. We show that the typical green, yellow, and blue luminescent colors from Yb3+/Ho3+-, Yb3+/Er3+-, and Yb3+/Tm3+-co-doped NaYF4 UCNPs can be converted into the quasi-white, green, and pink blue, when corresponding core-shell structures of NaYF4:Yb3+ @NaYF4:Ho3+, NaYF4:Yb3+ @NaYF4:Er3+ and NaYF4:Yb3+ @NaYF4:Tm3+ are built. Time-resolved spectra indicate that decay lifetimes of the emission bands from the sensitizer/activator-isolated core-shell structure significantly vary from that of the sensitizer/activator-codoped NaYF4 UCNPs, verifying the strain-induced modulation of emission channels in the core-shell structure. These sensitizer-activator-isolated core-shell UCNPs have implications for a range of biophotonic or photonic applications.The ability to tune the emission color of upconversion nanoparticles (UCNPs) will greatly enhance the scope of their applications, ranging from infrared solar cells to volumetric multiplexed bioimaging. Conventional methods to tune upconversion are to vary the type and/or the concentration of doped rare-earth ions in these nanoparticle formulations. Here, we introduce a different approach to vary the emission colors of the frequently used sensitizer/activator pairs of Yb3+/RE3+ (RE = Ho, Er, Tm) via utilization of a sensitizer/activator-isolated NaYF4 core-shell structure. We show that the typical green, yellow, and blue luminescent colors from Yb3+/Ho3+-, Yb3+/Er

  1. Tuning upconversion through a sensitizer/activator-isolated NaYF₄ core/shell structure.

    PubMed

    Ye, Shuai; Chen, Guanying; Shao, Wei; Qu, Junle; Prasad, Paras N

    2015-03-01

    The ability to tune the emission color of upconversion nanoparticles (UCNPs) will greatly enhance the scope of their applications, ranging from infrared solar cells to volumetric multiplexed bioimaging. Conventional methods to tune upconversion are to vary the type and/or the concentration of doped rare-earth ions in these nanoparticle formulations. Here, we introduce a different approach to vary the emission colors of the frequently used sensitizer/activator pairs of Yb(3+)/RE(3+) (RE = Ho, Er, Tm) via utilization of a sensitizer/activator-isolated NaYF4 core-shell structure. We show that the typical green, yellow, and blue luminescent colors from Yb(3+)/Ho(3+)-, Yb(3+)/Er(3+)-, and Yb(3+)/Tm(3+)-co-doped NaYF4 UCNPs can be converted into the quasi-white, green, and pink blue, when corresponding core-shell structures of NaYF4:Yb(3+) @NaYF4:Ho(3+), NaYF4:Yb(3+) @NaYF4:Er(3+) and NaYF4:Yb(3+) @NaYF4:Tm(3+) are built. Time-resolved spectra indicate that decay lifetimes of the emission bands from the sensitizer/activator-isolated core-shell structure significantly vary from that of the sensitizer/activator-codoped NaYF4 UCNPs, verifying the strain-induced modulation of emission channels in the core-shell structure. These sensitizer-activator-isolated core-shell UCNPs have implications for a range of biophotonic or photonic applications.

  2. 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.

  3. Hub-Filament Systems and Spiral Structures from Cloud to Core Scales

    NASA Astrophysics Data System (ADS)

    Galvan-Madrid, Roberto; Liu, Hauyu Baobab; Immer, Katharina; Juarez, Carmen; Palau, Aina

    2015-08-01

    We present evidence, from several separate observational studies, that molecular clouds and the clumps and cores within are (sometimes) arranged in a hub-filament morphology with spiral-like features. This arrangementoccurs at multiple scales: from the < 0.05 pc scales of low-mass star-forming cores, to the ~0.5 pc scales of clumps in massive star formation regions, to Giant Molecular Clouds. These structures have appeared in data of well known sources because of the increased sensitivy of new instruments like ALMA or the CSO SHARC-II, or after a detailed combination of single-dish and interferometer data. Reports of such structures may become more common in the near future. Presumably, these structures appear in systems that are dense enough to be prone to gravitational instabilities, and that have a non-negligible angularmomentum.

  4. Systematic mining of analog series with related core structures in multi-target activity space.

    PubMed

    Gupta-Ostermann, Disha; Hu, Ye; Bajorath, Jürgen

    2013-08-01

    We have aimed to systematically extract analog series with related core structures from multi-target activity space to explore target promiscuity of closely related analogous. Therefore, a previously introduced SAR matrix structure was adapted and further extended for large-scale data mining. These matrices organize analog series with related yet distinct core structures in a consistent manner. High-confidence compound activity data yielded more than 2,300 non-redundant matrices capturing 5,821 analog series that included 4,288 series with multi-target and 735 series with multi-family activities. Many matrices captured more than three analog series with activity against more than five targets. The matrices revealed a variety of promiscuity patterns. Compound series matrices also contain virtual compounds, which provide suggestions for compound design focusing on desired activity profiles.

  5. 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.

  6. 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

  7. The stability and catalytic activity of W13@Pt42 core-shell structure

    PubMed Central

    Huo, Jin-Rong; Wang, Xiao-Xu; Li, Lu; Cheng, Hai-Xia; Su, Yan-Jing; Qian, Ping

    2016-01-01

    This paper reports a study of the electronic properties, structural stability and catalytic activity of the W13@Pt42 core-shell structure using the First-principles calculations. The degree of corrosion of W13@Pt42 core-shell structure is simulated in acid solutions and through molecular absorption. The absorption energy of OH for this structure is lower than that for Pt55, which inhibits the poison effect of O containing intermediate. Furthermore we present the optimal path of oxygen reduction reaction catalyzed by W13@Pt42. Corresponding to the process of O molecular decomposition, the rate-limiting step of oxygen reduction reaction catalyzed by W13@Pt42 is 0.386 eV, which is lower than that for Pt55 of 0.5 eV. In addition by alloying with W, the core-shell structure reduces the consumption of Pt and enhances the catalytic efficiency, so W13@Pt42 has a promising perspective of industrial application. PMID:27759038

  8. 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.

  9. 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.

  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. 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.

  12. The influence of inertial waves on the structure of vortex cores

    NASA Astrophysics Data System (ADS)

    Kozel, Vladimir; Vatistas, Georgios H.; Wang, Jian

    1992-01-01

    The paper reports on numerical results concerning the influence of waves in the hollow core of a liquid vortex produced inside a cylindrical container with a disk rotating at the bottom. The numerical algorithm used was based on the Los Alamos SOLA-VOF algorithm. The computations produced free-surface elevation profiles that agree closely with the experiments. The computed secondary toroidal vortex structures, taking place in the radial-azimuthal plane, and the vortex core wandering during the spin-up process correspond to experimental visualizations. Under prevailing conditions the numerical solutions show that the core surface is modulated by a single or the superposition of waves. In the future, the developed scheme might enable one to construct the state manifold.

  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. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. Switching of the core structures of glycosphingolipids from globo- and lacto- to ganglio-series upon human embryonic stem cell differentiation.

    PubMed

    Liang, Yuh-Jin; Kuo, Huan-Hsien; Lin, Chi-Hung; Chen, Yen-Ying; Yang, Bei-Chia; Cheng, Yuan-Yuan; Yu, Alice L; Khoo, Kay-Hooi; Yu, John

    2010-12-28

    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 Gb(4)Cer, Lc(4)Cer, fucosyl Lc(4)Cer, Globo H, and disialyl Gb(5)Cer. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. High-pressure core structures of Si nanoparticles for solar energy conversion.

    PubMed

    Wippermann, S; Vörös, M; Rocca, D; Gali, A; Zimanyi, G; Galli, G

    2013-01-25

    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.

  10. Yolk–Shell‐Structured Aluminum Phenylphosphonate Microspheres with Anionic Core and Cationic Shell

    PubMed Central

    Zhang, Liqiu; Qian, Kun; Wang, Xupeng; Zhang, Fan; Jiang, Yijiao; Liu, Shaomin; Jaroniec, Mietek

    2016-01-01

    Spherical materials with yolk‐shell structure have great potential for a wide range of applications. The main advantage of the yolk‐shell geometry is the possibility of introducing different chemical or physical properties within a single particle. Here, a one‐step hydrothermal synthesis route for fabricating amphoteric yolk‐shell structured aluminum phenylphosphonate microspheres using urea as the precipitant is proposed. The resulting microspheres display 3D sphere‐in‐sphere architecture with anionic core and cationic shell. The controllable synthesis of aluminum phosphates with various morphologies is also demonstrated. The anionic core and cationic shell of the aluminum phenylphosphonate microspheres provide docking sites for selective adsorption of both cationic methylene blue and anionic binuclear cobalt phthalocyanine ammonium sulphonate. These new adsorbents can be used for simultaneous capture of both cations and anions from a solution, which make them very attractive for various applications such as environmental remediation of contaminated water. PMID:27812467

  11. High-pressure core structures of Si nanoparticles for solar energy conversion.

    PubMed

    Wippermann, S; Vörös, M; Rocca, D; Gali, A; Zimanyi, G; Galli, G

    2013-01-25

    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. PMID:25166189

  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. 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).

  14. 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.

  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. 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.

  17. Structural evidence for the role of polar core residue Arg175 in arrestin activation

    PubMed Central

    Granzin, Joachim; Stadler, Andreas; Cousin, Anneliese; Schlesinger, Ramona; Batra-Safferling, Renu

    2015-01-01

    Binding mechanism of arrestin requires photoactivation and phosphorylation of the receptor protein rhodopsin, where the receptor bound phosphate groups cause displacement of the long C-tail ‘activating’ arrestin. Mutation of arginine 175 to glutamic acid (R175E), a central residue in the polar core and previously predicted as the ‘phosphosensor’ leads to a pre-active arrestin that is able to terminate phototransduction by binding to non-phosphorylated, light-activated rhodopsin. Here, we report the first crystal structure of a R175E mutant arrestin at 2.7 Å resolution that reveals significant differences compared to the basal state reported in full-length arrestin structures. These differences comprise disruption of hydrogen bond network in the polar core, and three-element interaction including disordering of several residues in the receptor-binding finger loop and the C-terminus (residues 361–404). Additionally, R175E structure shows a 7.5° rotation of the amino and carboxy-terminal domains relative to each other. Consistent to the biochemical data, our structure suggests an important role of R29 in the initial activation step of C-tail release. Comparison of the crystal structures of basal arrestin and R175E mutant provide insights into the mechanism of arrestin activation, where binding of the receptor likely induces structural changes mimicked as in R175E. PMID:26510463

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. Structural mimicry of O-antigen by a peptide revealed in a complex with an antibody raised against Shigella flexneri serotype 2a.

    PubMed

    Theillet, François-Xavier; Saul, Frederick A; Vulliez-Le Normand, Brigitte; Hoos, Sylviane; Felici, Franco; Weintraub, Andrej; Mulard, Laurence A; Phalipon, Armelle; Delepierre, Muriel; Bentley, Graham A

    2009-05-15

    The use of carbohydrate-mimicking peptides to induce immune responses against surface polysaccharides of pathogenic bacteria offers a novel approach to vaccine development. Factors governing antigenic and immunogenic mimicry, however, are complex and poorly understood. We have addressed this question using the anti-lipopolysaccharide monoclonal antibody F22-4, which was raised against Shigella flexneri serotype 2a and shown to protect against homologous infection in a mouse model. In a previous crystallographic study, we described F22-4 in complex with two synthetic fragments of the O-antigen, the serotype-specific saccharide moiety of lipopolysaccharide. Here, we present a crystallographic and NMR study of the interaction of F22-4 with a dodecapeptide selected by phage display using the monoclonal antibody. Like the synthetic decasaccharide, the peptide binds to F22-4 with micromolar affinity. Although the peptide and decasaccharide use very similar regions of the antigen-binding site, indicating good antigenic mimicry, immunogenic mimicry by the peptide was not observed. The F22-4-antigen interaction is significantly more hydrophobic with the peptide than with oligosaccharides; nonetheless, all hydrogen bonds formed between the peptide and F22-4 have equivalents in the oligosaccharide complex. Two bridging water molecules are also in common, adding to partial structural mimicry. Whereas the bound peptide is entirely helical, its structure in solution, as shown by NMR, is helical in the central region only. Moreover, docking the NMR structure into the antigen-binding site shows that steric hindrance would occur, revealing poor complementarity between the major solution conformation and the antibody that could contribute to the absence of immunogenic mimicry.

  4. Structure and heterogeneity of the O-antigen chain of Salmonella Agona lipopolysaccharide.

    PubMed

    Szafranek, Janusz; Kumirska, Jolanta; Czerwicka, Małgorzata; Kunikowska, Danuta; Dziadziuszko, Halina; Głośnicka, Renata

    2006-11-01

    Lipopolysaccharide of Salmonella Agona smooth-type cells was obtained from bacteria by a hot phenol-water extraction procedure. Mild acid hydrolysis of lipopolysaccharide, followed by gel filtration, yielded the pure O-polysaccharide. Abequose, rhamnose, mannose, galactose and glucose in the molar ratio 0.8 : 1.0 : 1.0 : 1.1 : 0.5 were detected, and their linkages were established. Sugar configurations were determined by gas chromatography. Two repeating units, namely -->2)-[alpha-Abep-(1-->3)-]-alpha-d-Manp-(1-->4)-alpha-l-Rhap-(1-->3)-alpha-d-Galp-(1-->and -->2)-[alpha-Abep-(1-->3)-]-alpha-d-Manp-(1-->4)-alpha-l-Rhap-(1-->3)-[alpha-d-Glcp-(1-->4)-]-alpha-d-Galp-(1-->, were deduced from nuclear magnetic resonance studies. The effort to separate them was unsuccessful. An immunochemical test performed by means of Western blotting with anti O12 serum demonstrated that glucose was present in the longer lipopolysaccharide chains, at some distance from the core region.

  5. Immune recognition of protein antigens

    SciTech Connect

    Laver, W.G.; Air, G.M.

    1985-01-01

    This book contains 33 papers. Some of the titles are: Antigenic Structure of Influenze Virus Hemagglutinin; Germ-line and Somatic Diversity in the Antibody Response to the Influenza Virus A/PR/8/34 Hemagglutinin; Recognition of Cloned Influenza A Virus Gene Products by Cytotoxic T Lymphocytes; Antigenic Structure of the Influenza Virus N2 Neuraminidase; and The Molecular and Genetic Basis of Antigenic Variation in Gonococcal Pillin.

  6. 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.

  7. 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; 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.

  8. 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

  9. Structure-Dependent Photophysics of First-Generation; Phenyl-Cored Thiophene Dendrimers

    SciTech Connect

    Mitchell, W. J.; Ferguson, A. J.; Kose, M. E.; Rupert, B. L.; Ginley, D. S.; Rumbles, G.; Shaheen, S. E.; Kopidakis, N.

    2009-01-01

    We have prepared two series of first-generation thiophene-bridge dendrimers, with either three (3G1) or four (4G1) arms attached to a phenyl core, to elucidate their structure-property relationships. Optical properties were investigated with a combination of steady-state and time-resolved spectroscopic techniques. Steady-state spectroscopic data for the 3-arm dendrimers suggests that the exciton is delocalized over the {alpha}-conjugated thiophene segment and the phenyl core, but that the meta-linking of the dendrons prevents their electronic communication. In contrast, conjugation through the core to dendrons in the ortho and para positions is permitted in the 4-arm dendrimers, although the data suggest that the conjugation length does not extend over the full length of the {alpha}-conjugated sections of two coupled dendrons. This observation is due to steric interactions between neighboring arms, which forces the arms to twist and bend out of the plane of the phenyl core, and is particularly prevalent in disrupting the conjugation through the ortho positions. As expected, our results show that an increase in the bridge length results in an increase in the conjugation length for both dendrimers, and a subsequent red-shift of the absorption and emission. In addition, an increase in the dendron length results in an increase in the photoluminescence quantum yield and lifetime, suggesting that the ground and excited-state geometries are very similar and that the electronic transition is coupled to fewer vibrational modes.

  10. Fully Zwitterionic Nanoparticle Antimicrobial Agents through Tuning of Core Size and Ligand Structure.

    PubMed

    Huo, Shuaidong; Jiang, Ying; Gupta, Akash; Jiang, Ziwen; Landis, Ryan F; Hou, Singyuk; Liang, Xing-Jie; Rotello, Vincent M

    2016-09-27

    Zwitterionic nanoparticles are generally considered nontoxic and noninteracting. Here, we report effective and selective antimicrobial activity of zwitterionic gold nanoparticles (AuNP) through modulation NP size and surface charge orientation. Using a set of 2, 4, and 6 nm core AuNPs, increasing particle size increased antimicrobial efficiency through bacterial membrane disruption. Further improvement was observed through control of the ligand structure, generating antimicrobial particles with low hemolytic activity and demonstrating the importance of size and surface structure in dictating the bioactivity properties of nanomaterials. PMID:27622756

  11. 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.

  12. Structure of Smectic Defect Cores: X-Ray Study of 8CB Liquid Crystal Ultrathin Films

    SciTech Connect

    Michel, Jean-Philippe; Lacaze, Emmanuelle; Goldmann, Michel; Gailhanou, Marc; Boissieu, Marc de; Alba, Michel

    2006-01-20

    We study the structure of very thin liquid crystal films frustrated by antagonistic anchorings in the smectic phase. In a cylindrical geometry, the structure is dominated by the defects for film thicknesses smaller than 150 nm and the detailed topology of the defects' cores can be revealed by x-ray diffraction. They appear to be split in half tube-shaped rotating grain boundaries (RGB). We determine the RGB spatial extension and evaluate its energy per unit length. Both are significantly larger than the ones usually proposed in the literature.

  13. Crystal structure of core streptavidin determined from multiwavelength anomalous diffraction of synchrotron radiation.

    PubMed Central

    Hendrickson, W A; Pähler, A; Smith, J L; Satow, Y; Merritt, E A; Phizackerley, R P

    1989-01-01

    A three-dimensional crystal structure of the biotin-binding core of streptavidin has been determined at 3.1-A resolution. The structure was analyzed from diffraction data measured at three wavelengths from a single crystal of the selenobiotinyl complex with streptavidin. Streptavidin is a tetramer with subunits arrayed in D2 symmetry. Each protomer is an 8-stranded beta-barrel with simple up-down topology. Biotin molecules are bound at one end of each barrel. This study demonstrates the effectiveness of multiwavelength anomalous diffraction (MAD) procedures for macromolecular crystallography and provides a basis for detailed study of biotin-avidin interactions. PMID:2928324

  14. 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.

  15. Characterization of antigenic structures in auto-immune atrophic gastritis with pernicious anaemia. The parietal cell H,K-ATPase and the chief cell pepsinogen are the two major antigens.

    PubMed

    Mårdh, S; Song, Y H

    1989-08-01

    Using isolated cells and subcellular fractions from pig gastric mucosa, antigenic structures with specific binding of IgG from sera of patients with auto-immune atrophic gastritis were characterized by means of immunoblotting and enzyme-linked immunosorbent assay. In immunoblotting experiments using mucosal cells as the antigen source, two dominating bands of 94 and 41 kDa were found. The two major antigens were identified as the H,K-ATPase (94 kDa), which constitutes the parietal cell acid pump, and pepsinogen (41 kDa) located in the chief cells. There was also a small but significant binding of antibodies to a preparation of Na,K-ATPase, an enzyme which is about 60% homologous to H,K-ATPase. Commercial preparations of hog gastric pepsinogen and pepsin bound pernicious anaemia IgG with equal efficacy. When sera from seven patients with the diagnosis pernicious anaemia were tested, all were found to contain auto-antibodies against H,K-ATPase as well as pepsinogen. In intact, isolated H,K-ATPase-containing vesicles the cytosolic part of the ATPase molecule is facing the outside of the vesicles. Both intact and trypsinized vesicles were incubated with patient sera and with a monoclonal antibody against H,K-ATPase. Pernicious anaemia IgG was found to bind to a cytosolic, trypsin-resistant structure, but the binding of the monoclonal antibody was lost upon trypsinization. The present results indicate that intracellular structures of the gastric mucosa, due to cell damage, may be exposed to immune-competent cells, which do not recognize these structures as 'self'.

  16. Two-stage selection of sequences from a random phage display library delineates both core residues and permitted structural range within an epitope.

    PubMed

    Miceli, R M; DeGraaf, M E; Fischer, H D

    1994-01-01

    Libraries of random peptides can be screened to identify species which interact with antibodies or receptors. Similarly, maps of native molecular interactions can frequently be deduced by screening a limited set of peptide fragments derived from sequences within a native antigen or ligand. However, the existence of cross-reactive sequences that mimic original epitopes and the limited replaceability of amino acid residues suggest that the sequence space accessible by a receptor can be much broader. Definition of this space is of particular importance where structural information is required for peptidomimetic or drug design. We have used a two-stage selection scheme to expand the sequence space accessible by a phage display library and to define peptide epitopes of the anti-FLAG octapeptide monoclonal M2 antibody. Affinity selection of a primary library of 2 x 10(6) random decapeptides identified a non-contiguous core of three residues in the binding motif Tyr-Lys-Xaa-Xaa-Asp. A second stage library with 2 x 10(7) individual clones bearing the core motif but with the remaining flanking and internal residues re-randomized permitted access to a broader sequence space represented in a library equivalent to several orders of magnitude larger. Data here demonstrate that extended access to binding sequence space permitted by multi-stage screening of phage display libraries can reveal not only essential residues required for ligand binding, but also the ligand structural range permitted within the receptor binding pocket.

  17. 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

  18. 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

  19. 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.

  20. Structures of large T antigen at the origin of SV40 DNA replication by atomic force microscopy.

    PubMed Central

    Mastrangelo, I A; Bezanilla, M; Hansma, P K; Hough, P V; Hansma, H G

    1994-01-01

    For inorganic crystals such as calcite (CaCO3), Atomic Force Microscopy (AFM) has provided surface structure at atomic resolution (Ohnesorge and Binnig, 1993). As part of a broad effort to obtain high resolution for an individual protein or protein assembly (Binnig et al., 1986; Rugar and Hansma, 1990; Radmacher et al., 1992), we applied AFM to study the ATP-dependent double hexamer of SV40 large T antigen, which assembles around the viral origin of DNA replication. Multimeric mass has been determined in two-dimensional projected images by Scanning Transmission Electron Microscopy (STEM) (Mastrangelo et al., 1989). By AFM, if the DNA-protein preparation has been stained positively by uranyl acetate, the contour at the junction between hexamers is visible as a cleft, 2-4 nm deep. The cleft, whether determined as a fraction of height by AFM or as a fraction of mass thickness by STEM, is of comparable magnitude. On either side of the cleft, hexamers attain a maximum height of 13-16 nm. Monomers found in the absence of ATP show heights of 5-7 nm. Taken together, the z coordinates provide a surface profile of complete and partial replication assemblies consistent with the spatial distribution of recognition pentanucleotides on the DNA, and they contribute direct geometrical evidence for a ring-like hexamer structure. Images FIGURE 1 FIGURE 2 FIGURE 3 PMID:8161681

  1. The antigen 43 structure reveals a molecular Velcro-like mechanism of autotransporter-mediated bacterial clumping

    PubMed Central

    Heras, Begoña; Totsika, Makrina; Peters, Kate M.; Paxman, Jason J.; Gee, Christine L.; Jarrott, Russell J.; Perugini, Matthew A.; Whitten, Andrew E.; Schembri, Mark A.

    2014-01-01

    Aggregation and biofilm formation are critical mechanisms for bacterial resistance to host immune factors and antibiotics. Autotransporter (AT) proteins, which represent the largest group of outer-membrane and secreted proteins in Gram-negative bacteria, contribute significantly to these phenotypes. Despite their abundance and role in bacterial pathogenesis, most AT proteins have not been structurally characterized, and there is a paucity of detailed information with regard to their mode of action. Here we report the structure–function relationships of Antigen 43 (Ag43a), a prototypic self-associating AT protein from uropathogenic Escherichia coli. The functional domain of Ag43a displays a twisted L-shaped β-helical structure firmly stabilized by a 3D hydrogen-bonded scaffold. Notably, the distinctive Ag43a L shape facilitates self-association and cell aggregation. Combining all our data, we define a molecular “Velcro-like” mechanism of AT-mediated bacterial clumping, which can be tailored to fit different bacterial lifestyles such as the formation of biofilms. PMID:24335802

  2. 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.

  3. 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

  4. 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

  5. Potassium dependent rescue of a myopathy with core-like structures in mouse.

    PubMed

    Hanson, M Gartz; Wilde, Jonathan J; Moreno, Rosa L; Minic, Angela D; Niswander, Lee

    2015-01-07

    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.

  6. Sequences flanking the core-binding site modulate glucocorticoid receptor structure and activity.

    PubMed

    Schöne, Stefanie; Jurk, Marcel; Helabad, Mahdi Bagherpoor; Dror, Iris; Lebars, Isabelle; Kieffer, Bruno; Imhof, Petra; Rohs, Remo; Vingron, Martin; Thomas-Chollier, Morgane; Meijsing, Sebastiaan H

    2016-09-01

    The glucocorticoid receptor (GR) binds as a homodimer to genomic response elements, which have particular sequence and shape characteristics. Here we show that the nucleotides directly flanking the core-binding site, differ depending on the strength of GR-dependent activation of nearby genes. Our study indicates that these flanking nucleotides change the three-dimensional structure of the DNA-binding site, the DNA-binding domain of GR and the quaternary structure of the dimeric complex. Functional studies in a defined genomic context show that sequence-induced changes in GR activity cannot be explained by differences in GR occupancy. Rather, mutating the dimerization interface mitigates DNA-induced changes in both activity and structure, arguing for a role of DNA-induced structural changes in modulating GR activity. Together, our study shows that DNA sequence identity of genomic binding sites modulates GR activity downstream of binding, which may play a role in achieving regulatory specificity towards individual target genes.

  7. Hydrophobic core/hydrophilic shell structured mesoporous silica nanospheres: enhanced adsorption of organic compounds from water.

    PubMed

    Li, Shuru; Jiao, Xuan; Yang, Hengquan

    2013-01-29

    Inspired by the structure features of micelle, we attempt to synthesize a novel functionalized mesoporous silica nanosphere consisting of a hydrophobic core and a hydrophilic shell. The obtained solid materials were structurally confirmed by N(2) sorption, X-ray diffraction (XRD), and transmission electron microscopy (TEM). Their compositions were characterized by Fourier transfer infrared spectroscopy (FT-IR), solid state NMR, X-ray photoelectron spectroscopy (XPS), and elemental analysis. Its fundamental properties such as dispersibility in water or organic phase, wettability, and adsorption ability toward hydrophobic organics in water were investigated. It was revealed that these important properties could be facilely adjusted through varying structure and composition. In particular, these materials showed much better adsorption ability toward hydrophobic organic molecules in water than conventional monofunctionalized mesoporous materials, owing to possessing the hydrophobic/hydrophilic domain-segregated and hierarchically functionalized mesoporous structures. The intriguing properties would make mesoporous materials more accessible to many important applications, especially in aqueous systems.

  8. Structure-based design of a B cell antigen from B. pseudomallei.

    PubMed

    Gaudesi, Davide; Peri, Claudio; Quilici, Giacomo; Gori, Alessandro; Ferrer-Navarro, Mario; Conchillo-Solé, Oscar; Thomas, Rachael; Nithichanon, Arnone; Lertmemongkolchai, Ganjana; Titball, Richard; Daura, Xavier; Colombo, Giorgio; Musco, Giovanna

    2015-03-20

    Burkholderia pseudomallei is the etiological agent of melioidosis, a severe endemic disease in South-East Asia, causing septicemia and organ failure with high mortality rates. Current treatments and diagnostic approaches are largely ineffective. The development of new diagnostic tools and vaccines toward effective therapeutic opportunities against B. pseudomallei is therefore an urgent priority. In the framework of a multidisciplinary project tackling melioidosis through reverse and structural vaccinology, BPSL1050 was identified as a candidate for immunodiagnostic and vaccine development based on its reactivity against the sera of melioidosis patients. We determined its NMR solution structure and dynamics, and by novel computational methods we predicted immunogenic epitopes that once synthesized were able to elicit the production of antibodies inducing the agglutination of the bacterium and recognizing both BPSL1050 and B. pseudomallei crude extracts. Overall, these results hold promise for novel chemical biology approaches in the discovery of new diagnostic and prophylactic tools against melioidosis.

  9. Molecular and Structural Basis of Inner Core Lipopolysaccharide Alterations in Escherichia coli

    PubMed Central

    Klein, Gracjana; Müller-Loennies, Sven; Lindner, Buko; Kobylak, Natalia; Brade, Helmut; Raina, Satish

    2013-01-01

    It is well established that lipopolysaccharide (LPS) often carries nonstoichiometric substitutions in lipid A and in the inner core. In this work, the molecular basis of inner core alterations and their physiological significance are addressed. A new inner core modification of LPS is described, which arises due to the addition of glucuronic acid on the third heptose with a concomitant loss of phosphate on the second heptose. This was shown by chemical and structural analyses. Furthermore, the gene whose product is responsible for the addition of this sugar was identified in all Escherichia coli core types and in Salmonella and was designated waaH. Its deduced amino acid sequence exhibits homology to glycosyltransferase family 2. The transcription of the waaH gene is positively regulated by the PhoB/R two-component system in a growth phase-dependent manner, which is coordinated with the transcription of the ugd gene explaining the genetic basis of this modification. Glucuronic acid modification was observed in E. coli B, K12, R2, and R4 core types and in Salmonella. We also show that the phosphoethanolamine (P-EtN) addition on heptose I in E. coli K12 requires the product of the ORF yijP, a new gene designated as eptC. Incorporation of P-EtN is also positively regulated by PhoB/R, although it can occur at a basal level without a requirement for any regulatory inducible systems. This P-EtN modification is essential for resistance to a variety of factors, which destabilize the outer membrane like the addition of SDS or challenge to sublethal concentrations of Zn2+. PMID:23372159

  10. Structure and magnetic properties of irradiated Fe/Fe oxide core-shell nanoclusters

    SciTech Connect

    McCloy, John S.; Jiang, Weilin; Sundararajan, Jennifer A.; Qiang, You; Burks, Edward; Liu, Kai

    2013-04-25

    A cluster deposition method was used to produce a film of loosely aggregated particles of Fe-Fe3O4 core-shell nanoclusters with an 8 nm iron core size and 2 nm oxide shell thickness. The film of particles on a silicon substrate was irradiated with 5.5 MeV Si2+ ions to a fluence of 1016 cm-2 near room temperature, and computer simulations based on the SRIM (Stopping and Range of Ions in Matter) code show that the implanted Si species stops near the film-substrate interface. The ion irradiation creates a structural change in the film with corresponding chemical and magnetic changes. X-ray diffraction shows that the core size and chemistry stay the same but the shell becomes FeO that grows to a thickness of 17 nm. Helium ion microscopy shows that the previously separate particles have densified into a nearly continuous film. Major loop magnetic hysteresis measurements show a decrease in saturation magnetization that we attribute to the presence of the antiferromagnetic (AFM) FeO shell. First-order reversal curve measurements on the irradiated film performed with a vibrating sample magnetometer show that the AFM shell prevents the particles from interacting magnetically, leading to low coercivity from the iron core and little bias field from the core interactions. These results, and others reported previously on different compositions (Fe3O4 or FeO+Fe3N nanoclusters), show that the ion irradiation behavior of nanocluster films such as these depends strongly on the initial nanostructure and chemistry.

  11. 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

  12. 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.

  13. Linear structures in the core of the Coma cluster of galaxies.

    PubMed

    Sanders, J S; Fabian, A C; Churazov, E; Schekochihin, A A; Simionescu, A; Walker, S A; Werner, N

    2013-09-20

    The hot x-ray-emitting plasma in galaxy clusters is predicted to have turbulent motion, which can contribute around 10% of the cluster's central energy density. We report deep Chandra X-ray Observatory observations of the Coma cluster core, showing the presence of quasi-linear high-density arms spanning 150 kiloparsecs, consisting of low-entropy material that was probably stripped from merging subclusters. Two appear to be connected with a subgroup of galaxies at a 650-kiloparsec radius that is merging into the cluster, implying coherence over several hundred million years. Such a long lifetime implies that strong isotropic turbulence and conduction are suppressed in the core, despite the unrelaxed state of the cluster. Magnetic fields are presumably responsible. The structures seen in Coma present insight into the past billion years of subcluster merger activity.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Observation of self-assembled core-shell structures in epitaxially embedded TbErAs nanoparticles.

    PubMed

    Dongmo, Pernell; Hartshorne, Matthew; Cristiani, Thomas; Jablonski, Michael L; Bomberger, Cory; Isheim, Dieter; Seidman, David N; Taheri, Mitra L; Zide, Joshua

    2014-12-10

    Self-assembled core-shell structured rare-earth nanoparticles (TbErAs) are observed in a III-V semiconductor host matrix (In0.53Ga0.47As) nominally lattice-matched to InP, grown via molecular beam epitaxy. Atom probe tomography demonstrates that the TbErAs nanoparticles have a core-shell structure, as seen both in the tomographic atom-by-atom reconstruction and concentration profiles. A simple thermodynamic model is created to determine when it is energetically favorable to have core-shell structures; the results strongly agree with the observations.

  3. Methane gas-related structures in the Gulf of Cádiz: evidence from gravity cores

    NASA Astrophysics Data System (ADS)

    Fernández-Puga, M. C.; Martín Puertas, C.; Vázquez, J. T.; Mata, P.; Somoza, L.; Hernández-Molina, F. J.; Díaz del Río, V.

    2003-04-01

    The Gulf of Cádiz is located at the SW margin of the Iberian Peninsula, on the eastern Atlantic part of the plate boundary between Eurasia and Africa. This area has been extensively surveyed previously with different geophysical methods and there have been identified several methane gas-related seafloor structures, as mud volcanoes, carbonate chimneys, pipes and mounds. Gravity cores were collected during ANASTASYA/01 cruise on numerous seafloor structures, mainly mud volcanoes. A detailed study of cores and a mineralogical analysis have been performed in order to show the relation of the mud volcanoes to methane fluid seepage. The sediments are mainly constituted by mud and mud breccia. Characteristic colors are green to dark grey. A strong smell to H_2S and anomalous cold temperatures could be observed when sampled. Liquefaction features, probable due to a fast sublimation of little hydrates crystals, and the occurrence of chemosynthetic fauna (Pogonophora tubeworms), have been also documented. Mineralogical analysis, X ray-powder diffraction (XRD), was made on a selection of samples of the cores from mud volcano structures and pelagic sediments. The mineralogical assemblage is made of phyllosilicates, carbonates (calcite, dolomite and aragonite), quartz and minor amounts of oxides and feldspars. Phyllosilicate content in mud volcano samples is high, up to 80% in "Faro" mud volcano. Dolomite and calcite are frequent, while aragonite is scarce. The clay mineral assemblage related to mud volcano structures is dominated by expanding clay minerals (smectite). The bulk and clay mineral composition of the sediments suggests a probable detrital origin, nevertheless, more data is necessary in order to determine the provenance of these sediments and the interaction of clay minerals with the methane related fluids. The presence of carbonate crust, pipes and chimneys and values of δ13C of authigenic carbonates, fully demonstrate the relation with methane seeps. However

  4. Structures of a pan-specific antagonist antibody complexed to different isoforms of TGFβ reveal structural plasticity of antibody-antigen interactions.

    PubMed

    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

    2014-12-01

    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.

  5. 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

  6. Structural identity between HLA-A2 antigens differentially recognized by alloreactive cytotoxic T lymphocytes.

    PubMed

    Castaño, A R; Lauzurica, P; Domenech, N; López de Castro, J A

    1991-05-01

    Alloreactive CTL raised against HLA-A2 Ag often display heterogeneous recognition of HLA-A2+ target cells. This heterogeneity has been found to reflect structural polymorphism among the corresponding target Ag, thus defining HLA-A2 subtypes. A previous study (van der Poel et al. 1986. Human Immunol. 16:247) established the existence of a new HLA-A2.4 variant, A2-SCHU, that was distinguished from A*0206 (A2.4a) by HLA-A2-specific alloreactive CTL. The same CTL subdivided HLA-A2.1 Ag into two subgroups. In the present study, the molecular basis of this heterogeneity has been examined by double-label comparative peptide mapping analysis of differentially recognized A2.1 and A2.4 Ag. In addition, we have determined the complete sequence of polymerase chain reaction-amplified full length cDNA from A2-SCHU. The results show that: 1) A2-SCHU is indistinguishable from A*0206 by peptide mapping; 2) the cDNA sequence of A2-SCHU is identical to that of A*0206; and 3) two differentially recognized A2.1 Ag are both indistinguishable from A*0201 by comparative peptide mapping. These results indicate that differential recognition by alloreactive CTL can occur among structurally identical class I HLA Ag and suggest that allorecognition by such CTL may involve corecognition of endogenous peptides, presumably derived from polymorphic proteins. PMID:2016531

  7. 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.

  8. 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.

  9. Immunohistological demonstration of serum proteins and structural and viral antigens in paraffin sections of nervous tissues.

    PubMed

    Budka, H

    1983-01-01

    A brief outline is given of applications of immunohistological techniques to the study of normal and diseased nervous tissue. Protease treatment of paraffin sections usually enhances sensitivity and reliability both of IF and PAP techniques. Sensitivity of immunohistological examination of paraffin sections is comparable to that of virus detection by normal virological techniques in animal rabies and slightly superior to EM search for virions in SSPE and PML. Immunostaining for MBP appears to be the most sensitive method for myelin, especially for demonstration of very thin myelin sheaths, which are important in studies of myelogenesis and cortical myeloarchitecture. Prolonged fixation in formalin clearly diminishes or abolishes immunoreactivity. Compacted myelin stains less well for MBP than preparative myelin artefacts and the surface of myelinated fibers. GFAP production is enhanced when glioma cells invade surrounding mesenchymal structures. The chance finding of GFAP-like immunoreactivity in a cancer metastasis casts doubt on the astroglial specificity of GFAP.

  10. 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.

  11. 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

  12. Structural insights into the adaptation of proliferating cell nuclear antigen (PCNA) from Haloferax volcanii to a high-salt environment

    PubMed Central

    Morgunova, Ekaterina; Gray, Fiona C.; MacNeill, Stuart A.; Ladenstein, Rudolf

    2009-01-01

    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 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. PMID:19770505

  13. 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.

  14. 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

  15. 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.

  16. Molecular cloning, expression and first antigenic characterization of human astrovirus VP26 structural protein and a C-terminal deleted form.

    PubMed

    Royuela, Enrique; Sánchez-Fauquier, Alicia

    2010-01-01

    The open reading frame 2 (ORF2) of human astrovirus (HAstV) encodes the structural VP26 protein that seems to be the main antigenic viral protein. However, its functional role remains unclear. Bioinformatic predictions revealed that VP29 and VP26 proteins could be involved in virus-cell interaction. In this study, we describe for the first time the cloning and expression in Escherichia coli (E. coli) of a recombinant VP26 (rVP26) protein and a VP26 C-terminal truncated form (VP26 Delta C), followed by purification by NTA-Ni(2+) agarose affinity chromatography. Protein expression and purification were evaluated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot (WB). Then, the purified proteins were evaluated for antigenic properties in enzyme linked immunosorbent assay (ELISA) using a polyclonal antibody (PAb) and a neutralizing monoclonal antibody (nMAb) named PL2, both of them directed to HAstV. The results presented herein indicate that the C-terminal end of the VP26 protein is essential to maintain the neutralizing epitope recognized by nMAb PL2 and that the N-terminus of VP26 protein may contain antigenic lineal-epitopes recognized by PAb. Thus, these recombinant proteins can be ideal tools for further antigenic, biochemical, structural and functional VP26 protein characterization, in order to evaluate its potential role in immunodiagnosis and vaccine studies.

  17. 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.

  18. 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.

  19. 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.

  20. Repacking protein cores with backbone freedom: structure prediction for coiled coils.

    PubMed

    Harbury, P B; Tidor, B; Kim, P S

    1995-08-29

    Progress in homology modeling and protein design has generated considerable interest in methods for predicting side-chain packing in the hydrophobic cores of proteins. Present techniques are not practically useful, however, because they are unable to model protein main-chain flexibility. Parameterization of backbone motions may represent a general and efficient method to incorporate backbone relaxation into such fixed main-chain models. To test this notion, we introduce a method for treating explicitly the backbone motions of alpha-helical bundles based on an algebraic parameterization proposed by Francis Crick in 1953 [Crick, F. H. C. (1953) Acta Crystallogr. 6, 685-689]. Given only the core amino acid sequence, a simple calculation can rapidly reproduce the crystallographic main-chain and core side-chain structures of three coiled coils (one dimer, one trimer, and one tetramer) to within 0.6-A root-mean-square deviations. The speed of the predictive method [approximately 3 min per rotamer choice on a Silicon Graphics (Mountain View, CA) 4D/35 computer] permits it to be used as a design tool.

  1. 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.

  2. 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.

  3. A facile asymmetric approach to the multicyclic core structure of mangicol A.

    PubMed

    Ying, Jun; Pu, Lin

    2014-12-01

    Chiral propargylic ether-based triene-ynes are synthesized with high enantiomeric purity by employing an asymmetric enyne addition to aldehydes catalyzed by 1,1'-bi-2-naphthol in combination with ZnEt2 , Ti(OiPr)4 and dicyclohexylamine at room temperature. These substrates are found to undergo a one-pot domino Pauson-Khand and Diels-Alder cycloaddition catalyzed by [RhCl(CO)2 ]2 under CO to generate a series of multicyclic products with high chemoselectivity and stereoselectivity. These products contain the multicyclic core structure of mangicol A which could facilitate the synthesis and study of this class of natural products.

  4. Performance of truss panels with kagome cores and design of a high authority shape morphing structure

    NASA Astrophysics Data System (ADS)

    Wang, Ju

    This dissertation includes two parts: First, the performance of a light weight truss panels with Kagome cores; Second, design of a high authority morphing structure for hinging and twisting. The performance characteristics of a truss core sandwich panel design based on the 3D Kagome are measured and compared with earlier numerical simulations and the consistency is demonstrated. Panels are fabricated by investment casting and tested in compression, shear and 3-point bending. The isotropic nature of this core design is confirmed. The superior performance relative to truss designs based on the tetrahedron is demonstrated and attributed to the greater resistance to plastic buckling at the equivalent core density. The failed samples are examined in the scanning electron microscope and imperfections are identified to have caused the premature failures. A concept for a high authority shape morphing plate is described. The design incorporates an active Kagome back-plane capable of changing the shape of a solid face by transmitting loads through a tetrahedral core. The two shape deformations to be achieved and demonstrated consist of hinging and twisting. The design is performed by a combination of analytic estimation and numerical simulation, guided by previous assessments of the Kagome configuration. The objective is to ascertain designs that provide the maximum edge displacement subjected to specified passive load. An optimization is used to ascertain the largest displacement achievable within the force capacity of the actuators. These displacements have been demonstrated and shown to correspond with values predicted by numerical simulation. Non-linear effects, such as face wrinkling, are probed by using a finite element method and the fidelity of the results assessed through comparison with measurements. The numerical results are used to validate a dimensional analysis of trends in the actuation resistance of the structure with geometry, as well as the passive load

  5. 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

    2014-11-14

    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.

  6. 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

  7. Analysis of core-periphery organization in protein contact networks reveals groups of structurally and functionally critical residues.

    PubMed

    Isaac, Arnold Emerson; Sinha, Sitabhra

    2015-10-01

    The representation of proteins as networks of interacting amino acids, referred to as protein contact networks (PCN), and their subsequent analyses using graph theoretic tools, can provide novel insights into the key functional roles of specific groups of residues. We have characterized the networks corresponding to the native states of 66 proteins (belonging to different families) in terms of their core-periphery organization. The resulting hierarchical classification of the amino acid constituents of a protein arranges the residues into successive layers - having higher core order - with increasing connection density, ranging from a sparsely linked periphery to a densely intra-connected core (distinct from the earlier concept of protein core defined in terms of the three-dimensional geometry of the native state, which has least solvent accessibility). Our results show that residues in the inner cores are more conserved than those at the periphery. Underlining the functional importance of the network core, we see that the receptor sites for known ligand molecules of most proteins occur in the innermost core. Furthermore, the association of residues with structural pockets and cavities in binding or active sites increases with the core order. From mutation sensitivity analysis, we show that the probability of deleterious or intolerant mutations also increases with the core order. We also show that stabilization centre residues are in the innermost cores, suggesting that the network core is critically important in maintaining the structural stability of the protein. A publicly available Web resource for performing core-periphery analysis of any protein whose native state is known has been made available by us at http://www.imsc.res.in/ ~sitabhra/proteinKcore/index.html.

  8. 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.

  9. Antigenic regions within the hepatitis C virus envelope 1 and non-structural proteins: identification of an IgG3-restricted recognition site with the envelope 1 protein.

    PubMed Central

    Sällberg, M; Rudén, U; Wahren, B; Magnius, L O

    1993-01-01

    Antibody binding to antigenic regions of hepatitis C virus (HCV) envelope 1 (E1; residues 183-380, E2/non-structural (NS) 1 (residues 380-437), NS1 (residues 643-690), and NS4 (1684-1751) proteins were assayed for 50 sera with antibodies to HCV (anti-HCV) and for 46 sera without anti-HCV. Thirty-four peptides, 18 residues long with an eight-amino acid overlap within each HCV region, were synthesized and tested with all 96 sera. Within the E region 183-380, the major binding site was located to residues 203-220, and was recognized by eight sera. Within the E2/NS1 region 380-437, the peptide covering residues 410-427 was recognized by two sera, and within the NS1 region 643-690, peptides covering residues 663-690 were recognized by four sera. Within the NS4 region 1684-1751, 27 sera were reactive to one or more of the NS4 peptides, and 21 out of these were reactive with peptide 1694-1711. One part of the major binding site could be located to residues 1701-1704, with the sequence Leu-Tyr-Arg-Glu. The IgG1, IgG3 and IgG4 subclasses were reactive with the five antigenic regions of HCV core, residues 1-18, 11-28, 21-38, 51-68 and 101-118. Reactivity to the major envelope site consisted almost exclusively of IgG3, and reactivity to the major site of NS4 consisted only of IgG1. Thus, a non-restricted IgG response to linear HCV-encoded binding sites was found to the core protein, whereas IgG subclass-restricted linear binding sites were found within the E1 protein, and within the NS4 protein. PMID:7680297

  10. Core structure of a dissociated edge dislocation and pipe diffusion in copper investigated by molecular dynamics

    NASA Astrophysics Data System (ADS)

    Huang, J.; Meyer, M.; Pontikis, V.

    1991-06-01

    The atomic core structure of two Schockley partial dislocations in copper has been investigated as a function of temperature using molecular dynamics. We employed a resonant model pseudopotential adapted to copper. Our results show that at increasing temperature, the core of the partials becomes increasingly extended and invades entirely the fault ribbon, yet, the separation distance between the partials remains unchanged. At high temperatures vibrational amplitudes of atoms are much larger in the core of the partials than in the bulk of the perfect crystal and the local atomic structure becomes highly disordered. Although disordered, the core structure remains solid-like up to temperatures close to the melting point. Pipe diffusion along this dissociated dislocation has also been investigated. The formation energies of a vacancy and an interstitial are obtained by quasi-dynamics relaxation at T = 0 K while the migration energies for pipe diffusion are calculated at high temperature. Contrary to current assumptions in favour of a vacancy mechanism, we found that in our model the two types of defects may contribute comparably to pipe diffusion since their activation energies are very close. The trajectories of the migrating defects involve not only the partials' cores but also the stacking fault ribbon extending between them, thus explaining why pipe diffusion is slower when the dislocations are dissociated. La structure de coeur de deux dislocations partielles de Schockley a été étudiée, par dynamique moléculaire, en fonction de la température. Nous avons utilisé un pseudopotentiel calculé pour le cuivre à l'aide d'un modèle de résonance. Nos résultats montrent que le coeur des partielles s'étend de plus en plus à mesure que la température augmente et qu'il recouvre complètement le ruban de faute. Cependant la distance de dissociation entre les partielles ne change pas. A haute température, les amplitudes de vibration atomique sont nettement plus

  11. 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

  12. 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.

  13. Interface effect of magnetic properties in Ni nanoparticles with a hcp core and fcc shell structure.

    PubMed

    Choo, Seongmin; Lee, Kyujoon; Jo, Younghun; Yoon, Seon-Mi; Choi, Jae-Young; Kim, Jea-Young; Park, Jea-Hoon; Lee, Kyung-Jin; Lee, Jong-Heun; Jung, Myung-Hwa

    2011-07-01

    We have fabricated hexagonal close-packed (hcp) Ni nanoparticles covered by a face-centered cubic (fcc) Ni surface layer by polyol method. The magnetic properties have been investigated as a function of temperature and applied magnetic field. The magnetic behavior reveals that the system should be divided magnetically into three distinct phases with different origins. The fcc Ni phase on the shell contributes to the superparamagnetism through a wide temperature range up to 360 K. The hcp Ni phase at the core is associated with antiferromagnetic nature below 12 K. These observations are in good agreement with the X-ray absorption spectroscopy and magnetic circular dichroism measurements. In our particular case, the unique hcp core and fcc shell structure gives rise to an additional anomaly at 20 K in the zero-field-cooled magnetization curve. Its position is barely affected by the magnetic field but its structure disappears above 30 kOe, showing a metamagnetic transition in the magnetization versus magnetic field curve. This new phase originates from the magnetic exchange at the interface between the hcp and fcc Ni sublattices.

  14. 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

  15. 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

  16. 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.

  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.

  18. 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.

  19. Novel structural features of the immunocompetent ceramide phospho-inositol glycan core from Trichomonas vaginalis.

    PubMed

    Heiss, Christian; Wang, Zhirui; Black, Ian; Azadi, Parastoo; Fichorova, Raina N; Singh, Bibhuti N

    2016-01-01

    The ceramide phosphoinositol glycan core (CPI-GC) of the lipophosphoglycan of Trichomonas vaginalis is a major virulent factor of this common genitourinary parasite. While its carbohydrate composition has been reported before, its structure has remained largely unknown. We isolated the glycan portions of CPI-GC by nitrous acid deamination and hydrofluoric acid treatment and investigated their structures by methylation analysis and 1- and 2-D NMR. We found that the α-anomer of galactose is a major constituent of CPI-GC. The β-anomer was found exclusively at the non-reducing end of CPI-GC side chains. Furthermore the data showed that the rhamnan backbone is more complex than previously thought and that the inositol residue at the reducing end is linked to a 4-linked α-glucuronic acid (GlcA) residue. This appears to be the most striking and novel feature of this GPI-anchor type molecule.

  20. Comparative structural analysis of HLA-A2 antigens distinguishable by cytotoxic T lymphocytes. II. Variant DK1: evidence for a discrete CTL recognition region.

    PubMed

    Krangel, M S; Biddison, W E; Strominger, J L

    1983-04-01

    Multiple amino acid sequence differences distinguish individual HLA antigens. Those residues important in immune recognition events have not been defined. Recent studies have identified HLA-A2 structural variants that, although serologically indistinguishable from other HLA-A2 antigens, are recognized poorly, if at all, by HLA-A2-restricted, influenza virus-immune, or HLA-A2-specific alloimmune CTL. In this study we utilize double-label tryptic peptide comparisons performed by both reverse-phase HPLC and cation exchange chromatography, in conjunction with conventional and microsequence analysis, to characterize the HLA-A2 heavy chains derived from variant DK1. We detect a single tryptic peptide that distinguishes DK1 HLA-A2 from the predominant HLA-A2 heavy chain species. This peptide spans residues 147 to 157 in the second heavy chain domain, and carries substitutions at positions 149, 152, and 156. Residues in this segment of the polypeptide are also altered in another HLA-A2 variant, as well as one H-2Kb mutant. Thus, this segment appears to be critical in forming determinants important in CTL recognition of class I antigens in general. On the basis of these and other results, we suggest that in contrast to recognition by alloantibodies, a discrete region of class I antigens may be crucial for CTL recognition. PMID:6601143

  1. Facilitation of cell adhesion by immobilized dengue viral nonstructural protein 1 (NS1): arginine-glycine-aspartic acid structural mimicry within the dengue viral NS1 antigen.

    PubMed

    Chang, Hsin-Hou; Shyu, Huey-Fen; Wang, Yo-Ming; Sun, Der-Shan; Shyu, Rong-Hwa; Tang, Shiao-Shek; Huang, Yao-Shine

    2002-09-15

    Dengue virus infection causes life-threatening hemorrhagic fever. Increasing evidence implies that dengue viral nonstructural protein 1 (NS1) exhibits a tendency to elicit potentially hazardous autoantibodies, which show a wide spectrum of specificity against extracellular matrix and platelet antigens. How NS1 elicits autoantibodies remains unclear. To address the hypothesis that NS1 and matrix proteins may have structural and functional similarity, cell-matrix and cell-NS1 interactions were evaluated using a cell-adhesion assay. The present study showed that dengue NS1 immobilized on coverslips resulted in more cell adhesion than did the control proteins. This cell adhesion was inhibited by peptides containing arginine-glycine-aspartic acid (RGD), a motif important for integrin-mediated cell adhesion. In addition, anti-NS1 antibodies blocked RGD-mediated cell adhesion. Although there is no RGD motif in the NS1 protein sequence, these data indicate that RGD structural mimicry exists within the NS1 antigen.

  2. 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, good dynamic properties and high bending stiffness-to-weight ratio. This can be found well such structures in the nature (for example, internal structure of bones, plants, etc.). New trend which prefers eco-friendly products and energy efficiency is emerging in industries recently. Demand for materials with high strength and light weight is also increasing. In line with these trends, researches about manufacturing methods of sandwich material have been actively conducted. In this study, a sandwich structure named as “Shaped Pyramidal Truss Structure” is proposed to improve mechanical strength and to apply a manufacturing process suitable for massive production. The new sandwich structure was designed to enhance compressive strength by changing the cross-sectional shape at the central portion of the core. As the next step, optimization of the shape was required. Optimization technique used here was the SZGA(Successive Zooming Genetic Algorithm), which is one of GA(Genetic Algorithm) methods gradually reducing the area of design variable. The objective function was defined as moment of inertia of the cross-sectional shape of the strut. The control points of cubic Bezier curve, which was assumed to be the shape of the cross section, were used as design variables. By using FEM simulation, it was found that the structure exhibited superior mechanical properties compared to the simple design of the prior art.

  3. Isostructural solid-solid phase transition in monolayers of soft core-shell particles at fluid interfaces: structure and mechanics.

    PubMed

    Rey, Marcel; Fernández-Rodríguez, Miguel Ángel; Steinacher, Mathias; Scheidegger, Laura; Geisel, Karen; Richtering, Walter; Squires, Todd M; Isa, Lucio

    2016-04-21

    We have studied the complete two-dimensional phase diagram of a core-shell microgel-laden fluid interface by synchronizing its compression with the deposition of the interfacial monolayer. Applying a new protocol, different positions on the substrate correspond to different values of the monolayer surface pressure and specific area. Analyzing the microstructure of the deposited monolayers, we discovered an isostructural solid-solid phase transition between two crystalline phases with the same hexagonal symmetry, but with two different lattice constants. The two phases corresponded to shell-shell and core-core inter-particle contacts, respectively; with increasing surface pressure the former mechanically failed enabling the particle cores to come into contact. In the phase-transition region, clusters of particles in core-core contacts nucleate, melting the surrounding shell-shell crystal, until the whole monolayer moves into the second phase. We furthermore measured the interfacial rheology of the monolayers as a function of the surface pressure using an interfacial microdisk rheometer. The interfaces always showed a strong elastic response, with a dip in the shear elastic modulus in correspondence with the melting of the shell-shell phase, followed by a steep increase upon the formation of a percolating network of the core-core contacts. These results demonstrate that the core-shell nature of the particles leads to a rich mechanical and structural behavior that can be externally tuned by compressing the interface, indicating new routes for applications, e.g. in surface patterning or emulsion stabilization.

  4. Interspecies antigenic determinants of structural proteins of mammalian type-C viruses as detected by a competitive sepharose bead immunofluorescence assay.

    PubMed

    Micheel, B; Fiebach, H; Wunderlich, V

    1979-01-01

    The present paper describes a competitive immunoassay using antiserum to FeLV p 27 and SSV-conjugated Sepharose beads. The assay is applied to compare the interspecies-specific antigenic determinants of the major structural proteins of type-C viruses of different mammalian species. The test proves to be highly sensitive and specific and may be used for the demonstration of viral proteins in crude cellular extracts.

  5. Seismic investigations of core-mantle boundary structure and source properties of deep-focus earthquakes

    NASA Astrophysics Data System (ADS)

    Persh, Steven Eric

    This dissertation investigates geophysical problems concerning the structure of the Earth's interior and the physics of the earthquake source by stacking seismograms recorded at global and regional networks. The core-mantle boundary (CMB) region contains thermal and compositional heterogeneities at different length-scales, including thin layers at the base of the mantle with large P-wave velocity reductions (ULVZs). Core-reflected seismic phases PcP and ScP are sensitive to velocity and density changes within ULVZs, discontinuity sharpness, and CMB variability on short length-scales. Amplitudes of globally-recorded PcP and ScP reveal a sharp average CMB with no more than 10% velocity reductions in the mantle for P- and S-waves. The amplitudes do not support proposed 30% S-wave velocity reductions or core-mantle transition zones. No precursor arrivals to PcP and ScP are visible on regional network stacks at times and amplitudes predicted for ULVZ properties. This suggests ULUZs transition gradually from the lower mantle. Diminished core-grazing P-waves sampling the CNM in a localized region of the mid-Pacific provide evidence for short length-scale variation, possibly reflecting dynamical processes. Time histories of moment release provide insight into rupture processes of deep earthquakes, whose physical mechanism remains unknown. We compare source time functions computed from stacks of teleseismic P-waves of 111 deep earthquakes with MW ≥ 6.4 and depth ≥ 100 km. An abrupt change in character occurs at 550 km. Earthquakes deeper than 550 km have shorter durations and simpler time functions. Shallow events have longer durations, and the 350--550 km range averages more subevents. Radiated energy-to-moment ratios are lower than for large shallow earthquakes and maximum seismic efficiency decreases slightly with depth. Initiations and terminations are consistent with self-similar rupture, although large events tend to begin more rapidly. Aftershock productivity

  6. 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

  7. Structure-based non-canonical amino acid design to covalently crosslink an antibody–antigen complex

    PubMed Central

    Xu, Jianqing; Tack, Drew; Hughes, Randall A.; Ellington, Andrew D.; Gray, Jeffrey J.

    2014-01-01

    Engineering antibodies to utilize non-canonical amino acids (NCAA) should greatly expand the utility of an already important biological reagent. In particular, introducing crosslinking reagents into antibody complementarity determining regions (CDRs) should provide a means to covalently crosslink residues at the antibody–antigen interface. Unfortunately, finding the optimum position for crosslinking two proteins is often a matter of iterative guessing, even when the interface is known in atomic detail. Computer-aided antibody design can potentially greatly restrict the number of variants that must be explored in order to identify successful crosslinking sites. We have therefore used Rosetta to guide the introduction of an oxidizable crosslinking NCAA, l-3,4-dihydroxyphenylalanine (l-DOPA), into the CDRs of the anti-protective antigen scFv antibody M18, and have measured crosslinking to its cognate antigen, domain 4 of the anthrax protective antigen. Computed crosslinking distance, solvent accessibility, and interface energetics were three factors considered that could impact the efficiency of l-DOPA-mediated crosslinking. In the end, 10 variants were synthesized, and crosslinking efficiencies were generally 10% or higher, with the best variant crosslinking to 52% of the available antigen. The results suggest that computational analysis can be used in a pipeline for engineering crosslinking antibodies. The rules learned from l-DOPA crosslinking of antibodies may also be generalizable to the formation of other crosslinked interfaces and complexes. PMID:23680795

  8. Differentiation antigens in lymphohemopoietic tissues

    SciTech Connect

    Miyasaka, M.; Trnka, Z.

    1988-01-01

    This book contains 15 chapters. Some of the chapter titles are: In Situ Characterization of Human Lymphoid Cells Using Monoclonal Antibodies; Structural and Functional Aspects of HLA Clas II Genes; Cell-Surface Differentiation Antigens Expressed on Thymocytes and T Cells of the Mouse; and Differentiation Antigens on Lymphoid Cells of the Guinea Pig.

  9. Studies on the O-antigen of Hafnia alvei PCM 1224 structurally and serologically related to the O-antigen of H. alvei 481-L.

    PubMed

    Katzenellenbogen, Ewa; Kocharova, Nina A; Pietkiewicz, Jadwiga; Gamian, Andrzej; Shashkov, Alexander S; Knirel, Yuriy A

    2013-02-15

    Mild hydrolysis of the lipopolysaccharide of Hafnia alvei PCM 1224 at pH 4.2 cleaved partially the O-polysaccharide chain by the glycosyl phosphate linkages to yield a phosphorylated hexasaccharide representing the repeating unit of the O-polysaccharide and higher oligosaccharides consisting of two or more repeating units. Studies of the degradation products before and after dephosphorylation by sugar and methylation analyses along with 1D and 2D (1)H and (13)C NMR spectroscopy, including 2D (1)H,(1)H COSY, TOCSY, ROESY, (1)H,(13)C HSQC, HSQC-TOCSY, and (1)H,(31)P HMBC experiments, enabled elucidation of the following structure of the O-polysaccharide: [formula - see text]. This structure is similar to that of the O-polysaccharide of H. alvei 481-L established earlier (Kubler-Kielb, J.; Vinogradov, E.; Garcia Fernandez, J. M.; Szostko, B.; Zwiefka, A.; Gamian, A. Carbohydr. Res.2006, 341, 2980-2985), which has the same sugar composition and the same main chain structure and differs in the site of attachment of α-d-Glcp only. A two-way serological cross-reactivity of the lipopolysaccharides of H. alvei PCM 1224 and 481-L with polyclonal rabbit antisera indicated the expediency of classification of both strains to the same O-serogroup. PMID:23276652

  10. Common Structural Core of Three-Dozen Residues Reveals Intersuperfamily Relationships.

    PubMed

    Mönttinen, Heli A M; Ravantti, Janne J; Poranen, Minna M

    2016-07-01

    Identification of relationships among protein families or superfamilies is a challenge. However, functionally essential protein regions typically retain structural integrity, even when the corresponding protein sequences evolve. Consequently, comparison of protein structures enables deeper phylogenetic analyses than achievable through the use of sequence information only. Here, we focus on a group of distantly related viral and cellular enzymes involved in nucleic acid or nucleotide processing and synthesis. All these enzymes share an apparently similar protein fold at their active site, which resembles the palm subdomain of the right-hand-shaped polymerases. Using a structure-based hierarchical clustering method, we identified a common structural core of 36 equivalent residues for this functionally diverse group of enzymes, representing five protein superfamilies. Based on the properties of these 36 residues, we deduced a structural distance-based tree in which the proteins were accurately clustered according to the established family classification. Within this tree, the enzymes catalyzing genomic nucleic acid replication or transcription were separated from those performing supplementary nucleic acid or nucleotide processing functions. In addition, we found that the family Y DNA polymerases are structurally more closely related to the nucleotide cyclase superfamily members than to the other members of the DNA/RNA polymerase superfamily, and these enzymes share 88 equivalent residues comprising a Β: 1- Α: 1- Α: 2- Β: 2- Β: 3- Α: 3- Β: 4- Α: 4- Β: 5 fold. The results highlight the power of structure-based hierarchical clustering in identifying remote evolutionary relationships. Furthermore, our study implies that a protein substructure of only three-dozen residues can contain a substantial amount of information on the evolutionary history of proteins.

  11. Sequences flanking the core-binding site modulate glucocorticoid receptor structure and activity

    PubMed Central

    Schöne, Stefanie; Jurk, Marcel; Helabad, Mahdi Bagherpoor; Dror, Iris; Lebars, Isabelle; Kieffer, Bruno; Imhof, Petra; Rohs, Remo; Vingron, Martin; Thomas-Chollier, Morgane; Meijsing, Sebastiaan H.

    2016-01-01

    The glucocorticoid receptor (GR) binds as a homodimer to genomic response elements, which have particular sequence and shape characteristics. Here we show that the nucleotides directly flanking the core-binding site, differ depending on the strength of GR-dependent activation of nearby genes. Our study indicates that these flanking nucleotides change the three-dimensional structure of the DNA-binding site, the DNA-binding domain of GR and the quaternary structure of the dimeric complex. Functional studies in a defined genomic context show that sequence-induced changes in GR activity cannot be explained by differences in GR occupancy. Rather, mutating the dimerization interface mitigates DNA-induced changes in both activity and structure, arguing for a role of DNA-induced structural changes in modulating GR activity. Together, our study shows that DNA sequence identity of genomic binding sites modulates GR activity downstream of binding, which may play a role in achieving regulatory specificity towards individual target genes. PMID:27581526

  12. Internal transcribed spacer 1 secondary structure analysis reveals a common core throughout the anaerobic fungi (Neocallimastigomycota).

    PubMed

    Koetschan, Christian; Kittelmann, Sandra; Lu, Jingli; Al-Halbouni, Djamila; Jarvis, Graeme N; Müller, Tobias; Wolf, Matthias; Janssen, Peter H

    2014-01-01

    The internal transcribed spacer (ITS) is a popular barcode marker for fungi and in particular the ITS1 has been widely used for the anaerobic fungi (phylum Neocallimastigomycota). A good number of validated reference sequences of isolates as well as a large number of environmental sequences are available in public databases. Its highly variable nature predisposes the ITS1 for low level phylogenetics; however, it complicates the establishment of reproducible alignments and the reconstruction of stable phylogenetic trees at higher taxonomic levels (genus and above). Here, we overcame these problems by proposing a common core secondary structure of the ITS1 of the anaerobic fungi employing a Hidden Markov Model-based ITS1 sequence annotation and a helix-wise folding approach. We integrated the additional structural information into phylogenetic analyses and present for the first time an automated sequence-structure-based taxonomy of the ITS1 of the anaerobic fungi. The methodology developed is transferable to the ITS1 of other fungal groups, and the robust taxonomy will facilitate and improve high-throughput anaerobic fungal community structure analysis of samples from various environments.

  13. Biogenesis and structure of a type VI secretion membrane core complex.

    PubMed

    Durand, Eric; Nguyen, Van Son; Zoued, Abdelrahim; Logger, Laureen; Péhau-Arnaudet, Gérard; Aschtgen, Marie-Stéphanie; Spinelli, Silvia; Desmyter, Aline; Bardiaux, Benjamin; Dujeancourt, Annick; Roussel, Alain; Cambillau, Christian; Cascales, Eric; Fronzes, Rémi

    2015-07-30

    Bacteria share their ecological niches with other microbes. The bacterial type VI secretion system is one of the key players in microbial competition, as well as being an important virulence determinant during bacterial infections. It assembles a nano-crossbow-like structure in the cytoplasm of the attacker cell that propels an arrow made of a haemolysin co-regulated protein (Hcp) tube and a valine-glycine repeat protein G (VgrG) spike and punctures the prey's cell wall. The nano-crossbow is stably anchored to the cell envelope of the attacker by a membrane core complex. Here we show that this complex is assembled by the sequential addition of three type VI subunits (Tss)-TssJ, TssM and TssL-and present a structure of the fully assembled complex at 11.6 Å resolution, determined by negative-stain electron microscopy. With overall C5 symmetry, this 1.7-megadalton complex comprises a large base in the cytoplasm. It extends in the periplasm via ten arches to form a double-ring structure containing the carboxy-terminal domain of TssM (TssMct) and TssJ that is anchored in the outer membrane. The crystal structure of the TssMct-TssJ complex coupled to whole-cell accessibility studies suggest that large conformational changes induce transient pore formation in the outer membrane, allowing passage of the attacking Hcp tube/VgrG spike.

  14. Sequences flanking the core-binding site modulate glucocorticoid receptor structure and activity.

    PubMed

    Schöne, Stefanie; Jurk, Marcel; Helabad, Mahdi Bagherpoor; Dror, Iris; Lebars, Isabelle; Kieffer, Bruno; Imhof, Petra; Rohs, Remo; Vingron, Martin; Thomas-Chollier, Morgane; Meijsing, Sebastiaan H

    2016-01-01

    The glucocorticoid receptor (GR) binds as a homodimer to genomic response elements, which have particular sequence and shape characteristics. Here we show that the nucleotides directly flanking the core-binding site, differ depending on the strength of GR-dependent activation of nearby genes. Our study indicates that these flanking nucleotides change the three-dimensional structure of the DNA-binding site, the DNA-binding domain of GR and the quaternary structure of the dimeric complex. Functional studies in a defined genomic context show that sequence-induced changes in GR activity cannot be explained by differences in GR occupancy. Rather, mutating the dimerization interface mitigates DNA-induced changes in both activity and structure, arguing for a role of DNA-induced structural changes in modulating GR activity. Together, our study shows that DNA sequence identity of genomic binding sites modulates GR activity downstream of binding, which may play a role in achieving regulatory specificity towards individual target genes. PMID:27581526

  15. Thermal and Chemical Structures at the Core-Mantle Boundary: Implications for the Mantle Dynamics

    NASA Astrophysics Data System (ADS)

    Stein, C.; Mertens, M.; Hansen, U.

    2013-12-01

    The core-mantle boundary (CMB) represents the lower boundary layer of the actively convecting Earth's mantle and is structurally very complex. For example, large low shear wave velocity provinces (LLSVPs) but also small-scale ultra-low velocity zones (ULVZs) have been detected seismically. Thermal and chemical structures such as thermal plumes and thermochemical piles have been considered to explain the complexities. Both affect the dynamics of the Earth's mantle and its temporal evolution. But also the surface plates are an essential aspect of mantle convection that strongly influence the dynamics of the interior. Cold subducting slabs penetrating the lower boundary layer will also affect the CMB topography. To study the structure and dynamics of the lower mantle we use numerical thermochemical models of mantle convection with a complex rheological approach, including a strong temperature-, stress- and pressure-dependent viscosity. This allows for the investigation of thermal plumes and thermochemical piles in combination with plate-like surface motion and deep subduction. In thermochemical convection dense material is viscously trapped by the flow and piled beneath plumes. The presence of the dense layer reduces the mobility of the surface plates but during plate evolution we find a variety of plume classes (plumes, thermals, line-plumes) leaving a complex structure in the CMB topography.

  16. Structure of evolving Accretion Discs and their Implications to the Formation of Planetary Cores

    NASA Astrophysics Data System (ADS)

    Bitsch, Bertram; Morbidelli, A.; Crida, A.; Lega, E.

    2013-10-01

    Two features in a protoplanetary disc can have profound effects on planet formation. The first feature is "pressure bumps", i.e. local maxima in the gas surface density distribution that can arise e.g. at the inner edge of the dead zone. Pressure bumps stop the inward migration of small bodies undergoing gas drag (Brauer et al., 2008), promote the onset of the streaming instability (Johansen and Youdin, 2007), help the accretion of planetary embryos by the pebble-accretion process (Lambrechts and Johansen, 2012) and stop inward type-I migration by the planet-trap mechanism (Masset et al., 2006). The second feature is "scale height bumps", that originate from opacity transitions. The regions of the disc that are shadowed, where H/r decreases with r, allow planetary cores to migrate outwards due to entropy gradient effects (Paardekooper and Mellema (2006), Baruteau and Masset (2008)), until they reach the local minimum of the H/r profile (Bitsch et al. 2013). Thus, it is important to model the existence and the location of these structures in realistic protoplanetary discs. The structure of the disc is dependent on the mass-flux (accretion rate) through the disc, which determines the evolution of the density profile. This mass-flux changes in time, as the whole disc gets accreted onto the central star. We will show using 2D hydrodynamical models how the change of the accretion rate affects the disc structure and how this will change the sweet-spots for saving planetary cores from too rapid inward migration. We will focus here on "scale height bumps" in the disc that will change the alpha-viscosity and consequently the gas surface density (as the mass-flux is constant through the disc). Therefore the formation of pressure bumps is possible, whose prominence and effects on migration will be investigated in detail. This will give important indications of where and when in the disc the cores of giant planets and thus giant planets can form.

  17. 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

  18. 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.

  19. Structural properties of fluids interacting via piece-wise constant potentials with a hard core

    NASA Astrophysics Data System (ADS)

    Santos, Andrés; Yuste, Santos B.; de Haro, Mariano López; Bárcenas, Mariana; Orea, Pedro

    2013-08-01

    The structural properties of fluids whose molecules interact via potentials with a hard core plus two piece-wise constant sections of different widths and heights are presented. These follow from the more general development previously introduced for potentials with a hard core plus n piece-wise constant sections [A. Santos, S. B. Yuste, and M. Lopez de Haro, Condens. Matter Phys. 15, 23602 (2012)], 10.5488/CMP.15.23602 in which use was made of a semi-analytic rational-function approximation method. The results of illustrative cases comprising eight different combinations of wells and shoulders are compared both with simulation data and with those that follow from the numerical solution of the Percus-Yevick and hypernetted-chain integral equations. It is found that the rational-function approximation generally predicts a more accurate radial distribution function than the Percus-Yevick theory and is comparable or even superior to the hypernetted-chain theory. This superiority over both integral equation theories is lost, however, at high densities, especially as the widths of the wells and/or the barriers increase.

  20. 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 technical publication 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. Following an examination of previously developed tests and a recent evaluation of a selection of these methods, a single cantilever beam (SCB) specimen was identified as being a promising candidate for establishing such a standardized test procedure. The objective of the work described here was to begin development of a protocol for conducting a SCB test that will render the procedure suitable for standardization. To this end, a sizing methodology was developed to ensure appropriate SCB specimen dimensions are selected for a given sandwich system. Application of this method to actual sandwich systems yielded SCB specimen dimensions that would be practical for use. This study resulted in the development of a practical SCB specimen sizing method, which should be well-suited for incorporation into a standardized testing protocol.

  1. Core level excitations—A fingerprint of structural and electronic properties of epitaxial silicene

    SciTech Connect

    Friedlein, R. Fleurence, A.; Aoyagi, K.; Yamada-Takamura, Y.; Jong, M. P. de; Van Bui, H.; Wiggers, F. B.; Yoshimoto, S.; Koitaya, T.; Shimizu, S.; Noritake, H.; Mukai, K.; Yoshinobu, J.

    2014-05-14

    From the analysis of high-resolution Si 2p photoelectron and near-edge x-ray absorption fine structure (NEXAFS) spectra, we show that core level excitations of epitaxial silicene on ZrB{sub 2}(0001) thin films are characteristically different from those of sp{sup 3}-hybridized silicon. In particular, it is revealed that the lower Si 2p binding energies and the low onset in the NEXAFS spectra as well as the occurrence of satellite features in the core level spectra are attributed to the screening by low-energy valence electrons and interband transitions between π bands, respectively. The analysis of observed Si 2p intensities related to chemically distinct Si atoms indicates the presence of at least one previously unidentified component. The presence of this component suggests that the observation of stress-related stripe domains in scanning tunnelling microscopy images is intrinsically linked to the relaxation of Si atoms away from energetically unfavourable positions.

  2. Alloy Cu3Pt nanoframes through the structure evolution in Cu-Pt nanoparticles with a core-shell construction

    PubMed Central

    Han, Lin; Liu, Hui; Cui, Penglei; Peng, Zhijian; Zhang, Suojiang; Yang, Jun

    2014-01-01

    Noble metal nanoparticles with hollow interiors and customizable shell compositions have immense potential for catalysis. Herein, we present an unique structure transformation phenomenon for the fabrication of alloy Cu3Pt nanoframes with polyhedral morphology. This strategy starts with the preparation of polyhedral Cu-Pt nanoparticles with a core-shell construction upon the anisotropic growth of Pt on multiply twinned Cu seed particles, which are subsequently transformed into alloy Cu3Pt nanoframes due to the Kirkendall effect between the Cu core and Pt shell. The as-prepared alloy Cu3Pt nanoframes possess the rhombic dodecahedral morphology of their core-shell parents after the structural evolution. In particular, the resulting alloy Cu3Pt nanoframes are more effective for oxygen reduction reaction but ineffective for methanol oxidation reaction in comparison with their original Cu-Pt core-shell precursors. PMID:25231376

  3. Alloy Cu3Pt nanoframes through the structure evolution in Cu-Pt nanoparticles with a core-shell construction

    NASA Astrophysics Data System (ADS)

    Han, Lin; Liu, Hui; Cui, Penglei; Peng, Zhijian; Zhang, Suojiang; Yang, Jun

    2014-09-01

    Noble metal nanoparticles with hollow interiors and customizable shell compositions have immense potential for catalysis. Herein, we present an unique structure transformation phenomenon for the fabrication of alloy Cu3Pt nanoframes with polyhedral morphology. This strategy starts with the preparation of polyhedral Cu-Pt nanoparticles with a core-shell construction upon the anisotropic growth of Pt on multiply twinned Cu seed particles, which are subsequently transformed into alloy Cu3Pt nanoframes due to the Kirkendall effect between the Cu core and Pt shell. The as-prepared alloy Cu3Pt nanoframes possess the rhombic dodecahedral morphology of their core-shell parents after the structural evolution. In particular, the resulting alloy Cu3Pt nanoframes are more effective for oxygen reduction reaction but ineffective for methanol oxidation reaction in comparison with their original Cu-Pt core-shell precursors.

  4. Polystyrene-ZnO core-shell microspheres and hollow ZnO structures synthesized with the sulfonated polystyrene templates

    SciTech Connect

    Yang Yang; Chu Ying . E-mail: chuying@nenu.edu.cn; Zhang Yanping; Yang Fuyong; Liu Jinglin

    2006-02-15

    Mono-sized sulfonated polystyrene (PS) microspheres were used as templates to prepare PS-zinc oxide (ZnO) core-shell microspheres. Two different hollow ZnO structures were obtained after removing the PS cores by solvent extraction or calcinations. However, we obtained rod-like ZnO by either using unsulfonated PS microspheres as templates or without any templates. Transmission electron microscope (TEM) and scanning electron microscope (SEM) images were used to characterize the structures and morphologies of all the samples. X-ray diffraction (XRD), electron diffraction (ED) and infrared (IR) spectra were, respectively, used to study the crystal structure and composition of samples, respectively.

  5. Electronic structure of ZnO/MgxZn1-xO core-shell nanowires in the magnetic field

    NASA Astrophysics Data System (ADS)

    Xiong, Wen; Zhang, Ying

    2013-12-01

    The conduction band and valence band offset of ZnO/MgxZn1-xO core-shell nanowires are determined numerically for the first time, then the six-band k · p effective-mass theory for calculating the electronic structure of the free-standing nanowires is extended to calculate the electronic structure of ZnO/MgxZn1-xO core-shell nanowires. It is found that the degenerate hole states with positive Jh and negative Jh are split by the applied magnetic field, the split energies are affected slightly by changing the radius of ZnO core and the content of magnesium in MgxZn1-xO shell. The order of the hole states will reverse if the radius of ZnO core varies, even so, the optical circularly polarized property of the lowest transition does not change when the radius of ZnO core increases. In addition, the radiative intensity of the lowest transition increases slowly with the increase of the wave vector when the magnetic field, the radius of ZnO core and the content of magnesium are fixed, while the radiative intensity of the lowest transition increases at first, then decreases with the increase of the radius of ZnO core when the wave vector is fixed.

  6. The core and O-polysaccharide structure of the Caulobacter crescentus lipopolysaccharide.

    PubMed

    Jones, Michael D; Vinogradov, Evgeny; Nomellini, John F; Smit, John

    2015-01-30

    Here we describe the analysis of the structure of the lipopolysaccharide (LPS) from Caulobacter crescentus strain JS1025, a derivative of C. crescentus CB15 NA1000 with an engineered amber mutation in rsaA, leading to the loss of the protein S-layer and gene CCNA_00471 encoding a putative GDP-L-fucose synthase. LPS was isolated using an aqueous membrane disruption method. Polysaccharide and core oligosaccharide were produced by mild acid hydrolysis and analyzed by nuclear magnetic resonance spectroscopy and chemical methods. Spectra revealed the presence of two polysaccharides, one of them, a rhamnan, could be removed using periodate oxidation. Another polymer, built from 4-amino-4-deoxy-D-rhamnose (perosamine), mannose, and 3-O-methyl-glucose, should be the O-chain of the LPS according to genetic data. The attribution of the rhamnan as a part of LPS or a separate polymer was not possible.

  7. Using Powder Cored Tubular Wire Technology to Enhance Electron Beam Freeform Fabricated Structures

    NASA Technical Reports Server (NTRS)

    Gonzales, Devon; Liu, Stephen; Domack, Marcia; Hafley, Robert

    2016-01-01

    Electron Beam Freeform Fabrication (EBF3) is an additive manufacturing technique, developed at NASA Langley Research Center, capable of fabricating large scale aerospace parts. Advantages of using EBF3 as opposed to conventional manufacturing methods include, decreased design-to-product time, decreased wasted material, and the ability to adapt controls to produce geometrically complex parts with properties comparable to wrought products. However, to fully exploit the potential of the EBF3 process development of materials tailored for the process is required. Powder cored tubular wire (PCTW) technology was used to modify Ti-6Al-4V and Al 6061 feedstock to enhance alloy content, refine grain size, and create a metal matrix composite in the as-solidified structures, respectively.

  8. Crystal structure of the RC-LH1 core complex from Rhodopseudomonas palustris.

    PubMed

    Roszak, Aleksander W; Howard, Tina D; Southall, June; Gardiner, Alastair T; Law, Christopher J; Isaacs, Neil W; Cogdell, Richard J

    2003-12-12

    The crystal structure at 4.8 angstrom resolution of the reaction center-light harvesting 1 (RC-LH1) core complex from Rhodopseudomonas palustris shows the reaction center surrounded by an oval LH1 complex that consists of 15 pairs of transmembrane helical alpha- and beta-apoproteins and their coordinated bacteriochlorophylls. Complete closure of the RC by the LH1 is prevented by a single transmembrane helix, out of register with the array of inner LH1 alpha-apoproteins. This break, located next to the binding site in the reaction center for the secondary electron acceptor ubiquinone (UQB), may provide a portal through which UQB can transfer electrons to cytochrome b/c1.

  9. "Amorphous nickel sulfide" is hydrated nanocrystalline nis with a core-shell structure.

    PubMed

    Huang, Shanshan; Harris, Kenneth D M; Lopez-Capel, Elisa; Manning, David A C; Rickard, David

    2009-12-21

    The application of a range of experimental techniques shows that "amorphous nickel sulfide" (the material precipitated from aqueous solutions of Ni(II) salts and S(II-) under ambient conditions) is actually a hydrated nanoparticulate material with an approximate formula NiS.1.5H(2)O. The particles comprise a crystalline, anhydrous core (diameter ca. 1-3 nm) with the millerite (NiS) structure, surrounded by a hydrated shell phase. The materials prepared under acidic conditions (pH = 3 and 5) transform with age to form polydymite (Ni(3)S(4)) and heazlewoodite (Ni(3)S(2)), while materials prepared at pH = 7 and 9 do not undergo this transformation. At pH = 12, the preparation procedure yields NiAs-type NiS as a metastable phase.

  10. A facile asymmetric approach to the multicyclic core structure of mangicol A.

    PubMed

    Ying, Jun; Pu, Lin

    2014-12-01

    Chiral propargylic ether-based triene-ynes are synthesized with high enantiomeric purity by employing an asymmetric enyne addition to aldehydes catalyzed by 1,1'-bi-2-naphthol in combination with ZnEt2 , Ti(OiPr)4 and dicyclohexylamine at room temperature. These substrates are found to undergo a one-pot domino Pauson-Khand and Diels-Alder cycloaddition catalyzed by [RhCl(CO)2 ]2 under CO to generate a series of multicyclic products with high chemoselectivity and stereoselectivity. These products contain the multicyclic core structure of mangicol A which could facilitate the synthesis and study of this class of natural products. PMID:25302742

  11. Dislocation Core Structure and Peierls Stress of B2-Based AlSc in {110} Plane

    NASA Astrophysics Data System (ADS)

    Li, S. R.; Wu, X. Z.; Zhang, T.; Tian, Y. X.; Yan, Z. X.; Zhu, H. Z.

    2016-10-01

    The core structure and Peierls stress of <100>, <110>, and <111> dislocations in {110} plane of B2-based AlSc (B2-AlSc) have been investigated using improved dislocation equations combined with the generalized stacking fault (GSF) energy. The truncated approximation method is utilized to construct the dissociated and undissociated dislocations in AlSc, then the effects of dislocation angles on the elastic strain energy and misfit energy are presented. Specifically, with increasing dislocation angle, the misfit energy, elastic strain energy, and total energy, and their corresponding stresses, decrease on the <100>{110} and <110>{110} slip systems. However, for <111>{110} dislocation, all energies and corresponding stresses exhibit the relationship 0° > 54.7° > 35.3° > 90°. The misfit energy is always smaller than the elastic strain energy, even by one or two orders of magnitude, and their phases are always opposite.

  12. Domain structures as optical gratings controlled by electric field in a bent-core nematic.

    PubMed

    Xu, Ming-Ya; Zhou, Meng-jie; Xiang, Ying; Salamon, Péter; Éber, Nándor; Buka, Ágnes

    2015-06-15

    A regular domain structure consisting of parallel stripes - flexodomains - have been induced by low frequency (subHz) electric voltage in a bent core nematic liquid crystal. The wavelength of the pattern is in the range of 1-10 micrometers and thus can conveniently be observed in a polarizing microscope. It also serves as an optical grating and produces a regular system of laser diffraction spots. The pattern was found to emerge and disappear consecutively in each half period of the driving, with the wavelength of the flexodomains changing periodically as the ac voltage oscillates. Analyzing the polarization characteristics of the diffracted light, the polarization of the first order spot was found perpendicular to that of the incident light, in accordance with a recent theoretical calculation. PMID:26193504

  13. Structure-based design of a disulfide-linked oligomeric form of the simian virus 40 (SV40) large T antigen DNA-binding domain

    SciTech Connect

    Meinke, Gretchen; Phelan, Paul; Fradet-Turcotte, Amélie; Archambault, Jacques; Bullock, Peter A.

    2011-06-01

    With the aim of forming the ‘lock-washer’ conformation of the origin-binding domain of SV40 large T antigen in solution, using structure-based analysis an intermolecular disulfide bridge was engineered into the origin-binding domain to generate higher order oligomers in solution. The 1.7 Å resolution structure shows that the mutant forms a spiral in the crystal and has the de novo disulfide bond at the protein interface, although structural rearrangements at the interface are observed relative to the wild type. The modular multifunctional protein large T antigen (T-ag) from simian virus 40 orchestrates many of the events needed for replication of the viral double-stranded DNA genome. This protein assembles into single and double hexamers on specific DNA sequences located at the origin of replication. This complicated process begins when the origin-binding domain of large T antigen (T-ag ODB) binds the GAGGC sequences in the central region (site II) of the viral origin of replication. While many of the functions of purified T-ag OBD can be studied in isolation, it is primarily monomeric in solution and cannot assemble into hexamers. To overcome this limitation, the possibility of engineering intermolecular disulfide bonds in the origin-binding domain which could oligomerize in solution was investigated. A recent crystal structure of the wild-type T-ag OBD showed that this domain forms a left-handed spiral in the crystal with six subunits per turn. Therefore, we analyzed the protein interface of this structure and identified two residues that could potentially support an intermolecular disulfide bond if changed to cysteines. SDS–PAGE analysis established that the mutant T-ag OBD formed higher oligomeric products in a redox-dependent manner. In addition, the 1.7 Å resolution crystal structure of the engineered disulfide-linked T-ag OBD is reported, which establishes that oligomerization took place in the expected manner.

  14. Molecular and Structural Analysis of the Helicobacter pylori cag Type IV Secretion System Core Complex

    PubMed Central

    Frick-Cheng, Arwen E.; Pyburn, Tasia M.; Voss, Bradley J.; McDonald, W. Hayes

    2016-01-01

    ABSTRACT Bacterial type IV secretion systems (T4SSs) can function to export or import DNA, and can deliver effector proteins into a wide range of target cells. Relatively little is known about the structural organization of T4SSs that secrete effector proteins. In this report, we describe the isolation and analysis of a membrane-spanning core complex from the Helicobacter pylori cag T4SS, which has an important role in the pathogenesis of gastric cancer. We show that this complex contains five H. pylori proteins, CagM, CagT, Cag3, CagX, and CagY, each of which is required for cag T4SS activity. CagX and CagY are orthologous to the VirB9 and VirB10 components of T4SSs in other bacterial species, and the other three Cag proteins are unique to H. pylori. Negative stain single-particle electron microscopy revealed complexes 41 nm in diameter, characterized by a 19-nm-diameter central ring linked to an outer ring by spoke-like linkers. Incomplete complexes formed by Δcag3 or ΔcagT mutants retain the 19-nm-diameter ring but lack an organized outer ring. Immunogold labeling studies confirm that Cag3 is a peripheral component of the complex. The cag T4SS core complex has an overall diameter and structural organization that differ considerably from the corresponding features of conjugative T4SSs. These results highlight specialized features of the H. pylori cag T4SS that are optimized for function in the human gastric mucosal environment. PMID:26758182

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

    PubMed

    Neller, Michelle A; Ladell, Kristin; McLaren, James E; Matthews, Katherine K; Gostick, Emma; Pentier, Johanne M; Dolton, Garry; Schauenburg, Andrea J A; Koning, Dan; Fontaine Costa, Ana Isabel C A; 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

    2015-08-01

    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.

  16. Synthesis, structural characterization and magnetic properties of Fe/Pt core-shell nanoparticles

    SciTech Connect

    Pisane, K. L.; Singh, Sobhit; Seehra, M. S.

    2015-05-07

    Structural and magnetic properties of Fe/Pt core-shell nanostructure prepared by a sequential reduction process are reported. Transmission electron microscopy shows