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Sample records for anti-igg c3d polyspecific

  1. Heterogeneous antigen recognition behavior of induced polyspecific antibodies.

    Science.gov (United States)

    Dimitrov, Jordan D; Planchais, Cyril; Kang, Jonghoon; Pashov, Anastas; Vassilev, Tchavdar L; Kaveri, Srinivas V; Lacroix-Desmazes, Sebastien

    2010-07-23

    Polyspecific antibodies represent a significant fraction of the antibody repertoires in healthy animals and humans. Interestingly, certain antibodies only acquire a polyspecific antigen-binding behavior after exposure to protein-modifying conditions, such as those found at inflammation sites, or used in small- and large-scale immunoglobulin purification. This phenomenon is referred to as "criptic polyspecificity". In the present study, we compare the potential of different chemical agents to induce IgG polyspecificity. Depending on the treatment used, quantitative and qualitative differences in the recognition of individual antigens from a standard panel were observed. Antibodies with cryptic polyspecificity utilized common mechanisms for the recognition of structurally unrelated antigens when exposed to a particular inductor of polyspecificity. Our study contributes to the understanding of the mechanisms underlying the cryptic polyspecificity.

  2. Interstellar detection of c-C3D2

    CERN Document Server

    Spezzano, S; Schilke, P; Caselli, P; Menten, K M; McCarthy, M C; Bizzocchi, L; Trevino-Morales, S P; Aikawa, Y; Schlemmer, S

    2013-01-01

    We report the first interstellar detection of c-C3D2. The doubly deuterated cyclopropenylidene, a carbene, has been detected toward the starless cores TMC- 1C and L1544 using the IRAM 30m telescope. The J(Ka,Kc) = 3(0,3)-2(1,2), 3(1,3)-2(0,2), and 2(2,1)-1(1,0) transitions of this species have been observed at 3 mm in both sources. The expected 1:2 intensity ratio has been found in the 3(0,3)-2(1,2) and 3(1,3)-2(0,2) lines, belonging to the para and ortho species respectively. We also observed lines of the main species, c-C3H2, the singly deuterated c-C3HD, and the species with one 13C off of the principal axis of the molecule, c-H13CC2H. The lines of c-C3D2 have been observed with high signal to noise ratio, better than 7.5 sigma in TMC-1C and 9 sigma in L1544. The abundance of doubly deuterated cyclopropenylidene with respect to the normal species is found to be (0.4 - 0.8)% in TMC-1C and (1.2 - 2.1)% in L1544. The deuteration of this small hydrocarbon ring is analysed with a comprehensive gas-grain model, ...

  3. Disaster Prevention Coastal Map Production by MMS & C3D

    Science.gov (United States)

    Hatake, Shuhei; Kohori, Yuki; Watanabe, Yasushi

    2016-06-01

    In March 2011, Eastern Japan suffered serious damage of Tsunami caused by a massive earthquake. In 2012, Ministry of Land, Infrastructure and Transport published "Guideline of setting assumed areas of inundation by Tsunami" to establish the conditions of topography data used for simulation of Tsunami. In this guideline, the elevation data prepared by Geographical Survey Institute of Japan and 2m/5m/10m mesh data of NSDI are adopted for land area, while 500m mesh data of Hydrographic and Oceanographic Department of Japan Coast Guard and sea charts are adopted for water area. These data, however, do not have continuity between land area and water area. Therefore, in order to study the possibility of providing information for coastal disaster prevention, we have developed an efficient method to acquire continuous topography over land and water including tidal zone. Land area data are collected by Mobile Mapping System (MMS) and water area depth data are collected by interferometry echo sounder (C3D), and both data are simultaneously acquired on a same boat. Elaborate point cloud data of 1m or smaller are expected to be used for realistic simulation of Tsunami waves going upstream around shoreline. Tests were made in Tokyo Bay (in 2014) and Osaka Bay (in 2015). The purpose the test in Osaka Bay is to make coastal map for disaster prevention as a countermeasure for predicted Nankai massive earthquake. In addition to Tsunami simulation, the continuous data covering land and marine areas are expected to be used effectively for maintenance and repair of aged port and river facilities, maintenance and investigation of dykes, and ecosystem preservation.

  4. Discovery of Small Molecules for Fluorescent Detection of Complement Activation Product C3d.

    Science.gov (United States)

    Gorham, Ronald D; Nuñez, Vicente; Lin, Jung-Hsin; Rooijakkers, Suzan H M; Vullev, Valentine I; Morikis, Dimitrios

    2015-12-24

    Complement activation plays a major role in many acute and chronic inflammatory conditions. C3d, a terminal product of complement activation, remains covalently attached to cells and is an excellent biomarker of complement-mediated inflammation. We employed a virtual high-throughput screening protocol to identify molecules with predicted binding to complement C3d and with intrinsic fluorescence properties to enable detection. Pharmacophore models were developed based on known C3d-ligand interactions and information from computational analysis of structural and molecular dynamics data. Iterative pharmacophore-based virtual screening was performed to identify druglike molecules with physicochemical similarity to the natural C3d ligand CR2. Hits from the pharmacophore screens were docked to C3d and ranked based on predicted binding free energies. Top-ranked molecules were selected for experimental validation of binding affinity to C3d, using microscale thermophoresis, and for their suitability to become molecular imaging agents, using fluorescence spectroscopy. This work serves as a foundation for identifying additional fluorescent molecules with high-affinity for C3d that will subsequently be explored as noninvasive in vivo diagnostics of complement-mediated inflammation, for spatiotemporal monitoring of disease progression, and for targeting therapeutics to sites of inflammation.

  5. Mutational analysis of the complement receptor type 2 (CR2/CD21)-C3d interaction reveals a putative charged SCR1 binding site for C3d.

    Science.gov (United States)

    Hannan, Jonathan P; Young, Kendra A; Guthridge, Joel M; Asokan, Rengasamy; Szakonyi, Gerda; Chen, Xiaojiang S; Holers, V Michael

    2005-02-25

    We have characterized the interaction between the first two short consensus repeats (SCR1-2) of complement receptor type 2 (CR2, CD21) and C3d in solution, by utilising the available crystal structures of free and C3d-bound forms of CR2 to create a series of informative mutations targeting specific areas of the CR2-C3d complex. Wild-type and mutant forms of CR2 were expressed on the surface of K562 erythroleukemia cells and their binding ability assessed using C3dg-biotin tetramers complexed to fluorochrome conjugated streptavidin and measured by flow cytometry. Mutations directed at the SCR2-C3d interface (R83A, R83E, G84Y) were found to strongly disrupt C3dg binding, supporting the conclusion that the SCR2 interface reflected in the crystal structure is correct. Previous epitope and peptide mapping studies have also indicated that the PILN11GR13IS sequence of the first inter-cysteine region of SCR1 is essential for the binding of iC3b. Mutations targeting residues within or in close spatial proximity to this area (N11A, N11E, R13A, R13E, Y16A, S32A, S32E), and a number of other positively charged residues located primarily on a contiguous face of SCR1 (R28A, R28E, R36A, R36E, K41A, K41E, K50A, K50E, K57A, K57E, K67A, K67E), have allowed us to reassess those regions on SCR1 that are essential for CR2-C3d binding. The nature of this interaction and the possibility of a direct SCR1-C3d association are discussed extensively. Finally, a D52N mutant was constructed introducing an N-glycosylation sequence at an area central to the CR2 dimer interface. This mutation was designed to disrupt the CR2-C3d interaction, either directly through steric inhibition, or indirectly through disruption of a physiological dimer. However, no difference in C3dg binding relative to wild-type CR2 could be observed for this mutant, suggesting that the dimer may only be found in the crystal form of CR2.

  6. Capillary Deposition of Complement C4d and C3d in Chinese Renal Allograft Biopsies

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    Rong Lv

    2015-01-01

    Full Text Available Background. C3d is a product of both the classic and the alternative complement cascades; however, few studies have addressed the role of C3d in renal biopsies and its relationship with long-term graft survival rate is not very clear. Methods. 94 patients with biopsy-proven acute rejection episodes were included in the study. We investigated the associations between histological findings, clinical examinations, and outcome. Results. The overall prevalence for C4dPTC and C3dPTC was 42.6% and 29.8%. There was a significant association between C3dPTC and C4dPTC (P<0.001. C3dPTC and C4dPTC were related with histological types (P=0.024 and P<0.001, resp.. The long-term survival rate for C4dPTC positive transplants was lower than that of C4dPTC negative transplants, but it was not statistic significant in our study (P=0.150. The survival rate of C3dPTC positive group was much lower than the negative group (P=0.014. Patients with double positives for C4dPTC and C3dPTC exhibited the lowest survival rate significantly different from those of the C3dPTC only and C4dPTC only groups (P=0.01 and P=0.0037. Conclusions. This longitudinal cohort study has demonstrated that C3d deposition in the PTC was closely related to renal dysfunction and pathological changes.

  7. Glomerular C3d as a novel prognostic marker for renal vasculitis.

    Science.gov (United States)

    Villacorta, Javier; Diaz-Crespo, Francisco; Acevedo, Mercedes; Guerrero, Carmen; Campos-Martin, Yolanda; García-Díaz, Eugenio; Mollejo, Manuela; Fernandez-Juarez, Gema

    2016-10-01

    Pauci-immune necrotizing crescentic glomerulonephritis is the histologic substrate of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Several studies in animal models have demonstrated the crucial role of complement activation in the pathogenesis of ANCA-associated vasculitis, but only small series have analyzed the prognostic implications of complement glomerular deposits. This study aimed to assess the clinical and prognostic implications of C3d- and C4d-positive glomerular staining in renal vasculitis. Eighty-five patients with a diagnosis of pauci-immune necrotizing crescentic glomerulonephritis were included in the study. C3d and C4d were analyzed by immunohistochemical staining using a polyclonal antibody. The primary predictors were glomerular C3d- and C4d-positive staining. The primary end point was the cumulative percentage of patients who developed end-stage renal disease. Glomerular staining for C3d and C4d was observed in 42 (49.4%) of 85 biopsies and 38 (44.7%) of 85 biopsies, respectively. C3d-positive staining was associated with the severity of renal impairment and with a lower response rate to treatment (P=.003 and P=.04, respectively). Renal survival at 2 and 5 years was 60.9% and 51.8% in C3d-positive patients compared with 87.7% and 78.9% in C3d-negative patients (P=.04). C4d-positive staining did not show any impact in renal outcome. When adjusted by renal function and other histologic parameters, C3d staining remained as an independent predictor for renal survival (hazard ratio, 2.5; 95% confidence interval, 1.1-5.7; P=.03). Therefore, this study demonstrates that C3d-positive glomerular staining is an independent risk factor for the development of end-stage renal disease in ANCA-associated renal vasculitis.

  8. Human germline antibody gene segments encode polyspecific antibodies.

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    Willis, Jordan R; Briney, Bryan S; DeLuca, Samuel L; Crowe, James E; Meiler, Jens

    2013-04-01

    Structural flexibility in germline gene-encoded antibodies allows promiscuous binding to diverse antigens. The binding affinity and specificity for a particular epitope typically increase as antibody genes acquire somatic mutations in antigen-stimulated B cells. In this work, we investigated whether germline gene-encoded antibodies are optimal for polyspecificity by determining the basis for recognition of diverse antigens by antibodies encoded by three VH gene segments. Panels of somatically mutated antibodies encoded by a common VH gene, but each binding to a different antigen, were computationally redesigned to predict antibodies that could engage multiple antigens at once. The Rosetta multi-state design process predicted antibody sequences for the entire heavy chain variable region, including framework, CDR1, and CDR2 mutations. The predicted sequences matched the germline gene sequences to a remarkable degree, revealing by computational design the residues that are predicted to enable polyspecificity, i.e., binding of many unrelated antigens with a common sequence. The process thereby reverses antibody maturation in silico. In contrast, when designing antibodies to bind a single antigen, a sequence similar to that of the mature antibody sequence was returned, mimicking natural antibody maturation in silico. We demonstrated that the Rosetta computational design algorithm captures important aspects of antibody/antigen recognition. While the hypervariable region CDR3 often mediates much of the specificity of mature antibodies, we identified key positions in the VH gene encoding CDR1, CDR2, and the immunoglobulin framework that are critical contributors for polyspecificity in germline antibodies. Computational design of antibodies capable of binding multiple antigens may allow the rational design of antibodies that retain polyspecificity for diverse epitope binding.

  9. Effect of Ductile Agents on the Dynamic Behavior of SiC3D Network Composites

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    Zhu, Jingbo; Wang, Yangwei; Wang, Fuchi; Fan, Qunbo

    2016-10-01

    Co-continuous SiC ceramic composites using pure aluminum, epoxy, and polyurethane (PU) as ductile agents were developed. The dynamic mechanical behavior and failure mechanisms were investigated experimentally using the split Hopkinson pressure bar (SHPB) method and computationally by finite element (FE) simulations. The results show that the SiC3D/Al composite has the best overall performance in comparison with SiC3D/epoxy and SiC3D/PU composites. FE simulations are generally consistent with experimental data. These simulations provide valuable help in predicting mechanical strength and in interpreting the experimental results and failure mechanisms. They may be combined with micrographs for fracture characterizations of the composites. We found that interactions between the SiC phase and ductile agents under dynamic compression in the SHPB method are complex, and that interfacial condition is an important parameter that determines the mechanical response of SiC3D composites with a characteristic interlocking structure during dynamic compression. However, the effect of the mechanical properties of ductile agents on dynamic behavior of the composites is a second consideration in the production of the composites.

  10. Delineation of the complement receptor type 2-C3d complex by site-directed mutagenesis and molecular docking.

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    Shaw, Craig D; Storek, Michael J; Young, Kendra A; Kovacs, James M; Thurman, Joshua M; Holers, V Michael; Hannan, Jonathan P

    2010-12-10

    The interactions between the complement receptor type 2 (CR2) and the C3 complement fragments C3d, C3dg, and iC3b are essential for the initiation of a normal immune response. A crystal-derived structure of the two N-terminal short consensus repeat (SCR1-2) domains of CR2 in complex with C3d has previously been elucidated. However, a number of biochemical and biophysical studies targeting both CR2 and C3d appear to be in conflict with these structural data. Previous mutagenesis and heteronuclear NMR spectroscopy studies directed toward the C3d-binding site on CR2 have indicated that the CR2-C3d cocrystal structure may represent an encounter/intermediate or nonphysiological complex. With regard to the CR2-binding site on C3d, mutagenesis studies by Isenman and coworkers [Isenman, D. E., Leung, E., Mackay, J. D., Bagby, S. & van den Elsen, J. M. H. (2010). Mutational analyses reveal that the staphylococcal immune evasion molecule Sbi and complement receptor 2 (CR2) share overlapping contact residues on C3d: Implications for the controversy regarding the CR2/C3d cocrystal structure. J. Immunol. 184, 1946-1955] have implicated an electronegative "concave" surface on C3d in the binding process. This surface is discrete from the CR2-C3d interface identified in the crystal structure. We generated a total of 18 mutations targeting the two (X-ray crystallographic- and mutagenesis-based) proposed CR2 SCR1-2 binding sites on C3d. Using ELISA analyses, we were able to assess binding of mutant forms of C3d to CR2. Mutations directed toward the concave surface of C3d result in substantially compromised CR2 binding. By contrast, targeting the CR2-C3d interface identified in the cocrystal structure and the surrounding area results in significantly lower levels of disruption in binding. Molecular modeling approaches used to investigate disparities between the biochemical data and the X-ray structure of the CR2-C3d cocrystal result in highest-scoring solutions in which CR2 SCR1-2 is

  11. Polyspecific pyrrolysyl-tRNA synthetases from directed evolution.

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    Guo, Li-Tao; Wang, Yane-Shih; Nakamura, Akiyoshi; Eiler, Daniel; Kavran, Jennifer M; Wong, Margaret; Kiessling, Laura L; Steitz, Thomas A; O'Donoghue, Patrick; Söll, Dieter

    2014-11-25

    Pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNA(Pyl) have emerged as ideal translation components for genetic code innovation. Variants of the enzyme facilitate the incorporation >100 noncanonical amino acids (ncAAs) into proteins. PylRS variants were previously selected to acylate N(ε)-acetyl-Lys (AcK) onto tRNA(Pyl). Here, we examine an N(ε)-acetyl-lysyl-tRNA synthetase (AcKRS), which is polyspecific (i.e., active with a broad range of ncAAs) and 30-fold more efficient with Phe derivatives than it is with AcK. Structural and biochemical data reveal the molecular basis of polyspecificity in AcKRS and in a PylRS variant [iodo-phenylalanyl-tRNA synthetase (IFRS)] that displays both enhanced activity and substrate promiscuity over a chemical library of 313 ncAAs. IFRS, a product of directed evolution, has distinct binding modes for different ncAAs. These data indicate that in vivo selections do not produce optimally specific tRNA synthetases and suggest that translation fidelity will become an increasingly dominant factor in expanding the genetic code far beyond 20 amino acids.

  12. Polyspecific pyrrolysyl-tRNA synthetases from directed evolution

    Science.gov (United States)

    Guo, Li-Tao; Wang, Yane-Shih; Nakamura, Akiyoshi; Eiler, Daniel; Kavran, Jennifer M.; Wong, Margaret; Kiessling, Laura L.; Steitz, Thomas A.; O’Donoghue, Patrick; Söll, Dieter

    2014-01-01

    Pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNAPyl have emerged as ideal translation components for genetic code innovation. Variants of the enzyme facilitate the incorporation >100 noncanonical amino acids (ncAAs) into proteins. PylRS variants were previously selected to acylate Nε-acetyl-Lys (AcK) onto tRNAPyl. Here, we examine an Nε-acetyl-lysyl-tRNA synthetase (AcKRS), which is polyspecific (i.e., active with a broad range of ncAAs) and 30-fold more efficient with Phe derivatives than it is with AcK. Structural and biochemical data reveal the molecular basis of polyspecificity in AcKRS and in a PylRS variant [iodo-phenylalanyl-tRNA synthetase (IFRS)] that displays both enhanced activity and substrate promiscuity over a chemical library of 313 ncAAs. IFRS, a product of directed evolution, has distinct binding modes for different ncAAs. These data indicate that in vivo selections do not produce optimally specific tRNA synthetases and suggest that translation fidelity will become an increasingly dominant factor in expanding the genetic code far beyond 20 amino acids. PMID:25385624

  13. Anomalous absorption in c-C_3H and c-C_3D radicals

    Science.gov (United States)

    Chandra, S.; Shinde, S. V.; Kegel, W. H.; Sedlmayr, E.

    Yamamoto et al. (1987) reported the first detection of the c-C_3H radical in TMC-1 through its transition 2_1 2 rightarrow 1_1 1 at 91.5 GHz. The column density of c-C_3H in TMC-1 was estimated to be 6 times 10^12 cm^-2, which is about one order of magnitude lower than that of the c-C_3H_2 which is ubiquitous in galactic objects. Mangum & Wootten (1990) detected c-C_3H through the transition 1_1 0 rightarrow 1_1 1 at 14.8 GHz in 12 additional galactic objects. The most probable production mechanism of both the c-C_3H and c-C_3H_2 in dark clouds is a common dissociation reaction of the C_3H_3^+ ion (Adams & Smith 1987). Although the c-C_3H is 0.8 eV less stable than its isomer l-C_3H, finding of comparable column densities of both the isomers in TMC-1 suggests that the formation rate for both, c-C_3H and l-C_3H, are of about the same order in the cosmic objects. The existence of a metastable isomer under interstellar conditions is a well known phenomenon in astronomy. The aim of this investigation is a quantitative estimate of relative line intensities under NLTE conditions. For wide ranges of physical parameters, where these molecules may be found, we have solved a set of statistical equilibrium equations coupled with the equations of radiative transfer in an on-the-spot approximation. For c-C_3H, we accounted for 51 energy levels connected by 207 radiative transitions and for c-C_3D, we accounted for 51 energy levels connected by 205 radiative transitions. Our results show that the 3_3 1 rightarrow 3_3 0 transition of c-C_3H and c-C_3D may be found in absorption against the cosmic microwave background (CMB). Furthermore, we found population inversion for the 1_1 0 rightarrow 1_1 1 transition. These findings may be useful in identifying these molecules in other cosmic objects, as well as for the determination of physical parameters in these objects.

  14. The two sides of complement C3d: evolution of electrostatics in a link between innate and adaptive immunity.

    Directory of Open Access Journals (Sweden)

    Chris A Kieslich

    Full Text Available The interaction between complement fragment C3d and complement receptor 2 (CR2 is a key aspect of complement immune system activation, and is a component in a link between innate and adaptive immunities. The complement immune system is an ancient mechanism for defense, and can be found in species that have been on Earth for the last 600 million years. However, the link between the complement system and adaptive immunity, which is formed through the association of the B-cell co-receptor complex, including the C3d-CR2 interaction, is a much more recent adaptation. Human C3d and CR2 have net charges of -1 and +7 respectively, and are believed to have evolved favoring the role of electrostatics in their functions. To investigate the role of electrostatics in the function and evolution of human C3d and CR2, we have applied electrostatic similarity methods to identify regions of evolutionarily conserved electrostatic potential based on 24 homologues of complement C3d and 4 homologues of CR2. We also examine the effects of structural perturbation, as introduced through molecular dynamics and mutations, on spatial distributions of electrostatic potential to identify perturbation resistant regions, generated by so-called electrostatic "hot-spots". Distributions of electrostatic similarity based on families of perturbed structures illustrate the presence of electrostatic "hot-spots" at the two functional sites of C3d, while the surface of CR2 lacks electrostatic "hot-spots" despite its excessively positive nature. We propose that the electrostatic "hot-spots" of C3d have evolved to optimize its dual-functionality (covalently attaching to pathogen surfaces and interaction with CR2, which are both necessary for the formation B-cell co-receptor complexes. Comparison of the perturbation resistance of the electrostatic character of the homologues of C3d suggests that there was an emergence of a new role of electrostatics, and a transition in the function of C3

  15. The two sides of complement C3d: evolution of electrostatics in a link between innate and adaptive immunity.

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    Kieslich, Chris A; Morikis, Dimitrios

    2012-01-01

    The interaction between complement fragment C3d and complement receptor 2 (CR2) is a key aspect of complement immune system activation, and is a component in a link between innate and adaptive immunities. The complement immune system is an ancient mechanism for defense, and can be found in species that have been on Earth for the last 600 million years. However, the link between the complement system and adaptive immunity, which is formed through the association of the B-cell co-receptor complex, including the C3d-CR2 interaction, is a much more recent adaptation. Human C3d and CR2 have net charges of -1 and +7 respectively, and are believed to have evolved favoring the role of electrostatics in their functions. To investigate the role of electrostatics in the function and evolution of human C3d and CR2, we have applied electrostatic similarity methods to identify regions of evolutionarily conserved electrostatic potential based on 24 homologues of complement C3d and 4 homologues of CR2. We also examine the effects of structural perturbation, as introduced through molecular dynamics and mutations, on spatial distributions of electrostatic potential to identify perturbation resistant regions, generated by so-called electrostatic "hot-spots". Distributions of electrostatic similarity based on families of perturbed structures illustrate the presence of electrostatic "hot-spots" at the two functional sites of C3d, while the surface of CR2 lacks electrostatic "hot-spots" despite its excessively positive nature. We propose that the electrostatic "hot-spots" of C3d have evolved to optimize its dual-functionality (covalently attaching to pathogen surfaces and interaction with CR2), which are both necessary for the formation B-cell co-receptor complexes. Comparison of the perturbation resistance of the electrostatic character of the homologues of C3d suggests that there was an emergence of a new role of electrostatics, and a transition in the function of C3d, after the

  16. Electrostatic Contributions Drive the Interaction Between Staphylococcus aureus Protein Efb-C and its Complement Target C3d

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    Haspel, N.; Ricklin, D.; Geisbrecht, B.V.; Kavraki, L.E.; Lambris, J.D. (UPENN); (UMKC); (Rice)

    2008-11-13

    The C3-inhibitory domain of Staphylococcus aureus extracellular fibrinogen-binding protein (Efb-C) defines a novel three-helix bundle motif that regulates complement activation. Previous crystallographic studies of Efb-C bound to its cognate subdomain of human C3 (C3d) identified Arg-131 and Asn-138 of Efb-C as key residues for its activity. In order to characterize more completely the physical and chemical driving forces behind this important interaction, we employed in this study a combination of structural, biophysical, and computational methods to analyze the interaction of C3d with Efb-C and the single-point mutants R131A and N138A. Our results show that while these mutations do not drastically affect the structure of the Efb-C/C3d recognition complex, they have significant adverse effects on both the thermodynamic and kinetic profiles of the resulting complexes. We also characterized other key interactions along the Efb-C/C3d binding interface and found an intricate network of salt bridges and hydrogen bonds that anchor Efb-C to C3d, resulting in its potent complement inhibitory properties.

  17. Towards 3C-3D digital holographic fluid velocity vector field measurement—tomographic digital holographic PIV (Tomo-HPIV)

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    Soria, J.; Atkinson, C.

    2008-07-01

    Most unsteady and/or turbulent flows of geophysical and engineering interest have a highly three-dimensional (3D) complex topology and their experimental investigation is in pressing need of quantitative velocity measurement methods that are robust and can provide instantaneous 3C-3D velocity field data over a significant volumetric domain of the flow. This paper introduces and demonstrates a new method that uses multiple digital CCD array cameras to record in-line digital holograms of the same volume of seed particles from multiple orientations. This technique uses the same basic equipment as Tomo-PIV minus the camera lenses, it overcomes the depth-of-field problem of digital in-line holography and does not require the complex optical calibration of Tomo-PIV. The digital sensors can be oriented in an optimal manner to overcome the depth-of-field limitation of in-line holograms recorded using digital CCD or CMOS array cameras, resulting in a 3D reconstruction of the seed particles within the volume of interest, which can subsequently be analysed using 3D cross-correlation PIV analysis to yield a 3C-3D velocity field. A demonstration experiment of Tomo-HPIV using uniform translation with nominally 11 µm diameter seed particles shows that the 3D displacement derived from 3D cross-correlation Tomo-HPIV analysis can be measured within 5% of the imposed uniform translation, where the imposed uniform translation has an estimated standard uncertainty of 4.3%. So this paper proposes a multi-camera digital holographic imaging 3C-3D PIV method, which is identified as tomographic digital holographic PIV or Tomo-HPIV.

  18. Intravenous Immunoglobulin with Enhanced Polyspecificity Improves Survival in Experimental Sepsis and Aseptic Systemic Inflammatory Response Syndromes

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    Djoumerska-Alexieva, Iglika; Roumenina, Lubka; Pashov, Anastas; Dimitrov, Jordan; Hadzhieva, Maya; Lindig, Sandro; Voynova, Elisaveta; Dimitrova, Petya; Ivanovska, Nina; Bockmeyer, Clemens; Stefanova, Zvetanka; Fitting, Catherine; Bläss, Markus; Claus, Ralf; von Gunten, Stephan; Kaveri, Srini; Cavaillon, Jean-Marc; Bauer, Michael; Vassilev, Tchavdar

    2015-01-01

    Sepsis is a major cause for death worldwide. Numerous interventional trials with agents neutralizing single proinflammatory mediators have failed to improve survival in sepsis and aseptic systemic inflammatory response syndromes. This failure could be explained by the widespread gene expression dysregulation known as “genomic storm” in these patients. A multifunctional polyspecific therapeutic agent might be needed to thwart the effects of this storm. Licensed pooled intravenous immunoglobulin preparations seemed to be a promising candidate, but they have also failed in their present form to prevent sepsis-related death. We report here the protective effect of a single dose of intravenous immunoglobulin preparations with additionally enhanced polyspecificity in three models of sepsis and aseptic systemic inflammation. The modification of the pooled immunoglobulin G molecules by exposure to ferrous ions resulted in their newly acquired ability to bind some proinflammatory molecules, complement components and endogenous “danger” signals. The improved survival in endotoxemia was associated with serum levels of proinflammatory cytokines, diminished complement consumption and normalization of the coagulation time. We suggest that intravenous immunoglobulin preparations with additionally enhanced polyspecificity have a clinical potential in sepsis and related systemic inflammatory syndromes. PMID:26701312

  19. Clinical Accuracy of Three-Dimensional Fluoroscopy (IsoC-3D-Assisted Upper Thoracic Pedicle Screw Insertion

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    Sugimoto,Yoshihisa

    2010-06-01

    Full Text Available Correct screw placement is especially difficult in the upper thoracic vertebrae. At the cervicothoracic junction (C7-T2, problems can arise because of the narrowness of the pedicle and the difficulty of using a lateral image intensifier there. Other upper thoracic vertebrae (T3-6 pose a problem for screw insertion also because of the narrower pedicle. We inserted 154 pedicle screws into 78 vertebrae (C7 to T6 in 38 patients. Screws were placed using intraoperative data acquisition by an isocentric C-arm fluoroscope (Siremobile Iso-C3D and computer navigation. Out of 90 pedicle screws inserted into 45 vertebrae between C7 and T2, 87 of the 90 (96.7% screws were classified as grade 1 (no perforation. Of 64 pedicle screws inserted into 33 vertebrae between T3 and T6, 61 of 64 (95.3% screws were classified as grade 1. In this study, we reduced pedicle screw misplacement at the level of the C7 and upper thoracic (T1-6 vertebrae using the three-dimensional fluoroscopy navigation system.

  20. Solution structure of the complex between CR2 SCR 1-2 and C3d of human complement: an X-ray scattering and sedimentation modelling study.

    Science.gov (United States)

    Gilbert, Hannah E; Eaton, Julian T; Hannan, Jonathan P; Holers, V Michael; Perkins, Stephen J

    2005-02-25

    Complement receptor type 2 (CR2, CD21) forms a tight complex with C3d, a fragment of C3, the major complement component. Previous crystal structures of the C3d-CR2 SCR 1-2 complex and free CR2 SCR 1-2 showed that the two SCR domains of CR2 form contact with each other in a closed V-shaped structure. SCR 1 and SCR 2 are connected by an unusually long eight-residue linker peptide. Medium-resolution solution structures for CR2 SCR 1-2, C3d, and their complex were determined by X-ray scattering and analytical ultracentrifugation. CR2 SCR 1-2 is monomeric. For CR2 SCR 1-2, its radius of gyration R(G) of 2.12(+/-0.05) nm, its maximum length of 10nm and its sedimentation coefficient s20,w(o) of 1.40(+/-0.03) S do not agree with those calculated from the crystal structures, and instead suggest an open structure. Computer modelling of the CR2 SCR1-2 solution structure was based on the structural randomisation of the eight-residue linker peptide joining SCR 1 and SCR 2 to give 9950 trial models. Comparisons with the X-ray scattering curve indicated that the most favoured arrangements for the two SCR domains corresponded to an open V-shaped structure with no contacts between the SCR domains. For C3d, X-ray scattering and sedimentation velocity experiments showed that it exists as a monomer-dimer equilibrium with a dissociation constant of 40 microM. The X-ray scattering curve for monomeric C3d gave an R(G) value of 1.95 nm, and this together with its s20,w(o) value of 3.17 S gave good agreement with the monomeric C3d crystal structure. Modelling of the C3d dimer gave good agreements with its scattering and ultracentrifugation parameters. For the complex, scattering and ultracentrifugation experiments showed that there was no dimerisation, indicating that the C3d dimerisation site was located close to the CR2 SCR 1-2 binding site. The R(G) value of 2.44(+/-0.1) nm, its length of 9 nm and its s20,w(o) value of 3.45(+/-0.01) S showed that its structure was not much more

  1. C3d-defined complement receptor-binding peptide p28 conjugated to circumsporozoite protein provides protection against Plasmodium berghei.

    Science.gov (United States)

    Bergmann-Leitner, Elke S; Duncan, Elizabeth H; Leitner, Wolfgang W; Neutzner, Albert; Savranskaya, Tatyana; Angov, Evelina; Tsokos, George C

    2007-11-01

    Immune response against circumsporozoite protein (CSP) of Plasmodium berghei, a major surface protein on the sporozoite, confers protection in various murine malaria models. Engineered DNA vaccine encoding CSP and 3 copies of C3d caused an unexpected loss in protection attributed to the binding of C3d to the C-terminal region of CSP. Because the C3d region known as p28 represents the complement receptor (CR) 2-binding motif, we developed a CSP-3 copies of p28 DNA construct (CSP-3p28). CSP-3p28-immunized mice were better protected against P. berghei sporozoites than CSP-immunized mice 6 weeks after the 2nd boost, produced sufficient IgG1 anti-CSP and CSP C-terminus antibody and failed to produce IgG2a. CSP-3C3d-immunized mice were not protected, failed to produce IgG1 and produced high amounts of IgG2a. We conclude that use of the CR2-binding motif of C3d as molecular adjuvant to CSP results in anti-malaria protective immune response probably by targeting the chimeric protein to CR2.

  2. Detection of C3d-Binding Donor-Specific Anti-HLA Antibodies at Diagnosis of Humoral Rejection Predicts Renal Graft Loss

    Science.gov (United States)

    Sicard, Antoine; Ducreux, Stéphanie; Rabeyrin, Maud; Couzi, Lionel; McGregor, Brigitte; Badet, Lionel; Scoazec, Jean Yves; Bachelet, Thomas; Lepreux, Sébastien; Visentin, Jonathan; Merville, Pierre; Fremeaux-Bacchi, Véronique; Morelon, Emmanuel; Taupin, Jean-Luc; Dubois, Valérie

    2015-01-01

    Antibody-mediated rejection (AMR) is a major cause of kidney graft loss, yet assessment of individual risk at diagnosis is impeded by the lack of a reliable prognosis assay. Here, we tested whether the capacity of anti-HLA antibodies to bind complement components allows accurate risk stratification at the time of AMR diagnosis. Among 938 kidney transplant recipients for whom a graft biopsy was performed between 2004 and 2012 at the Lyon University Hospitals, 69 fulfilled the diagnosis criteria for AMR and were enrolled. Sera banked at the time of the biopsy were screened for the presence of donor-specific anti-HLA antibodies (DSAs) and their ability to bind C1q and C3d using flow bead assays. In contrast with C4d graft deposition, the presence of C3d-binding DSA was associated with a higher risk of graft loss (P<0.001). Despite similar trend, the difference did not reach significance with a C1q-binding assay (P=0.06). The prognostic value of a C3d-binding assay was further confirmed in an independent cohort of 39 patients with AMR (P=0.04). Patients with C3d-binding antibodies had worse eGFR and higher DSA mean fluorescence intensity. In a multivariate analysis, only eGFR<30 ml/min per 1.73 m2 (hazard ratio [HR], 3.56; 95% confidence interval [CI], 1.46 to 8.70; P=0.005) and the presence of circulating C3d-binding DSA (HR, 2.80; 95% CI, 1.12 to 6.95; P=0.03) were independent predictors for allograft loss at AMR diagnosis. We conclude that assessment of the C3d-binding capacity of DSA at the time of AMR diagnosis allows for identification of patients at risk for allograft loss. PMID:25125383

  3. Effective equine immunization protocol for production of potent poly-specific antisera against Calloselasma rhodostoma, Cryptelytrops albolabris and Daboia siamensis.

    Directory of Open Access Journals (Sweden)

    Sompong Sapsutthipas

    2015-03-01

    Full Text Available Snake envenomation has been estimated to affect 1.8 million people annually with about 94,000 deaths mostly in poor tropical countries. Specific antivenoms are the only rational and effective therapy for these cases. Efforts are being made to produce effective, affordable and sufficient antivenoms for these victims. The immunization process, which has rarely been described in detail, is one step that needs to be rigorously studied and improved especially with regard to the production of polyspecific antisera. The polyspecific nature of therapeutic antivenom could obviate the need to identify the culprit snake species. The aim of this study was to produce potent polyspecific antisera against 3 medically important vipers of Thailand and its neighboring countries, namely Cryptelytrops albolabris "White lipped pit viper" (CA, Calleoselasma rhodostoma "Malayan pit viper" (CR, and Daboia siamensis "Russell's viper" (DS. Four horses were immunized with a mixture of the 3 viper venoms using the 'low dose, low volume multi-site' immunization protocol. The antisera showed rapid rise in ELISA titers against the 3 venoms and reached plateau at about the 8th week post-immunization. The in vivo neutralization potency (P of the antisera against CA, CR and DS venoms was 10.40, 2.42 and 0.76 mg/ml, respectively and was much higher than the minimal potency limits set by Queen Soavabha Memorial Institute (QSMI. The corresponding potency values for the QSMI monospecific antisera against CA, CR and DS venoms were 7.28, 3.12 and 1.50 mg/ml, respectively. The polyspecific antisera also effectively neutralized the procoagulant, hemorrhagic, necrotic and nephrotoxic activities of the viper venoms. This effective immunization protocol should be useful in the production of potent polyspecific antisera against snake venoms, and equine antisera against tetanus, diphtheria or rabies.

  4. Structures of the Multidrug Transporter P-glycoprotein Reveal Asymmetric ATP Binding and the Mechanism of Polyspecificity.

    Science.gov (United States)

    Esser, Lothar; Zhou, Fei; Pluchino, Kristen M; Shiloach, Joseph; Ma, Jichun; Tang, Wai-Kwan; Gutierrez, Camilo; Zhang, Alex; Shukla, Suneet; Madigan, James P; Zhou, Tongqing; Kwong, Peter D; Ambudkar, Suresh V; Gottesman, Michael M; Xia, Di

    2017-01-13

    P-glycoprotein (P-gp) is a polyspecific ATP-dependent transporter linked to multidrug resistance in cancer; it plays important roles in determining the pharmacokinetics of many drugs. Understanding the structural basis of P-gp, substrate polyspecificity has been hampered by its intrinsic flexibility, which is facilitated by a 75-residue linker that connects the two halves of P-gp. Here we constructed a mutant murine P-gp with a shortened linker to facilitate structural determination. Despite dramatic reduction in rhodamine 123 and calcein-AM transport, the linker-shortened mutant P-gp possesses basal ATPase activity and binds ATP only in its N-terminal nucleotide-binding domain. Nine independently determined structures of wild type, the linker mutant, and a methylated P-gp at up to 3.3 Å resolution display significant movements of individual transmembrane domain helices, which correlated with the opening and closing motion of the two halves of P-gp. The open-and-close motion alters the surface topology of P-gp within the drug-binding pocket, providing a mechanistic explanation for the polyspecificity of P-gp in substrate interactions.

  5. Structures of the Multidrug Transporter P-glycoprotein Reveal Asymmetric ATP Binding and the Mechanism of Polyspecificity*♦

    Science.gov (United States)

    Esser, Lothar; Zhou, Fei; Pluchino, Kristen M.; Shiloach, Joseph; Ma, Jichun; Tang, Wai-kwan; Gutierrez, Camilo; Zhang, Alex; Shukla, Suneet; Madigan, James P.; Zhou, Tongqing; Kwong, Peter D.; Ambudkar, Suresh V.; Gottesman, Michael M.; Xia, Di

    2017-01-01

    P-glycoprotein (P-gp) is a polyspecific ATP-dependent transporter linked to multidrug resistance in cancer; it plays important roles in determining the pharmacokinetics of many drugs. Understanding the structural basis of P-gp, substrate polyspecificity has been hampered by its intrinsic flexibility, which is facilitated by a 75-residue linker that connects the two halves of P-gp. Here we constructed a mutant murine P-gp with a shortened linker to facilitate structural determination. Despite dramatic reduction in rhodamine 123 and calcein-AM transport, the linker-shortened mutant P-gp possesses basal ATPase activity and binds ATP only in its N-terminal nucleotide-binding domain. Nine independently determined structures of wild type, the linker mutant, and a methylated P-gp at up to 3.3 Å resolution display significant movements of individual transmembrane domain helices, which correlated with the opening and closing motion of the two halves of P-gp. The open-and-close motion alters the surface topology of P-gp within the drug-binding pocket, providing a mechanistic explanation for the polyspecificity of P-gp in substrate interactions. PMID:27864369

  6. Incorporation of the purified epstein barr virus/C3d receptor (CR2) into liposomes and demonstration of its dual ligand binding functions

    Energy Technology Data Exchange (ETDEWEB)

    Mold, C.; Cooper, N.R.; Nemerow, G.R.

    1986-06-01

    The 145-kDA molecule that has been identified as the C3d receptor CR2 was isolated from lysates of Raji cells by affinity chromatography by using the monoclonal antibody (MoAb)HB-5. The purified protein was incorporated into /sup 14/C-phosphatidylcholine liposomes by deoxycholate dialysis followed by flotation on discontinuous sucrose gradients. Incorporation of the receptor was verified by testing the gradient fractions for CR2 by an enzyme-linked immunosorbent assay. Liposomes were shown to be unilamellar vesicles ranging in diameter from 25 to 100 nm by electron microscopy. The external orientation of CR2 in the membranes was demonstrated by immunoelectron microscopy. The functional activities of liposomes containing CR2 and liposomes without protein were compared. CR2 liposomes bound to EC3d, but not to E, and this binding was inhibited by the anti-CR2 MoAb OKB7 and by a MoAb specific for C3d. Control liposomes failed to bind to either E or EC3D. The ability of CR2 to function as a receptor for Epstein Barr virus (EBV) was tested in two ways. First, CR2 liposomes bound to B95-8, a cell line expressing EBV membrane antigens, but not to B95-8 cells treated with the viral DNA polymerase inhibitor phosphonoformic acid. Second, liposomes containing CR2 were shown by ultracentrifugal analyses to bind directly to purified EBV, and this binding was also inhibited by OKB7. Control liposomes did not bind to B95-8 cells or to EBV. These findings show that CR2 purified from detergent extracts of Raji cells can be reconstituted into lipid membranes with maintenance of its dual functions as a receptor for C3d and EBV.

  7. Complement-activated oligodendroglia: a new pathogenic entity identified by immunostaining with antibodies to human complement proteins C3d and C4d.

    Science.gov (United States)

    Yamada, T; Akiyama, H; McGeer, P L

    1990-05-04

    Clusters of oligodendroglial fibers were identified immunohistochemically in human brain tissue with antibodies to the complement proteins C3d and C4d in several neurological disorders. These included Pick's, Huntington's, Parkinson's and Alzheimer's disease, amyotrophic lateral sclerosis, progressive supranuclear palsy and Shy-Drager syndrome. These complement-activated oligodendroglia occurred in selected areas of gray and white matter. They were rarely observed in control tissue. Immunogold electron microscopy established that the C4d antibody was attached to degenerating myelin sheaths. These data indicate attachment of classical complement pathway proteins to selective oligodendroglia in several neurological disorders.

  8. Role of a Hydrophobic Pocket in Polyamine Interactions with the Polyspecific Organic Cation Transporter OCT3.

    Science.gov (United States)

    Li, Dan C; Nichols, Colin G; Sala-Rabanal, Monica

    2015-11-13

    Organic cation transporter 3 (OCT3, SLC22A3) is a polyspecific, facilitative transporter expressed in astrocytes and in placental, intestinal, and blood-brain barrier epithelia, and thus elucidating the molecular mechanisms underlying OCT3 substrate recognition is critical for the rational design of drugs targeting these tissues. The pharmacology of OCT3 is distinct from that of other OCTs, and here we investigated the role of a hydrophobic cavity tucked within the translocation pathway in OCT3 transport properties. Replacement of an absolutely conserved Asp by charge reversal (D478E), neutralization (D478N), or even exchange (D478E) abolished MPP(+) uptake, demonstrating this residue to be obligatory for OCT3-mediated transport. Mutations at non-conserved residues lining the putative binding pocket of OCT3 to the corresponding residue in OCT1 (L166F, F450L, and E451Q) reduced the rate of MPP(+) transport, but recapitulated the higher sensitivity pharmacological profile of OCT1. Thus, interactions of natural polyamines (putrescine, spermidine, spermine) and polyamine-like potent OCT1 blockers (1,10-diaminodecane, decamethonium, bistriethylaminodecane, and 1,10-bisquinuclidinedecane) with wild-type OCT3 were weak, but were significantly potentiated in the mutant OCT3s. Conversely, a reciprocal mutation in OCT1 (F161L) shifted the polyamine-sensitivity phenotype toward that of OCT3. Further analysis indicated that OCT1 and OCT3 can recognize essentially the same substrates, but the strength of substrate-transporter interactions is weaker in OCT3, as informed by the distinct makeup of the hydrophobic cleft. The residues identified here are key contributors to both the observed differences between OCT3 and OCT1 and to the mechanisms of substrate recognition by OCTs in general.

  9. Study of the Invariants of the Velocity-Gradient Tensor in Homogeneous Isotropic Turbulence by means of 3C-3D Tomographic PIV

    Science.gov (United States)

    Buchmann, Nicolas; Rouvier, Sylvain; Soria, Julio

    2010-11-01

    The study of coherent structures (CS) in turbulent flows is essential for understanding turbulence mechanisms in technological and theoretical relevant flows. The recent advent of instantaneous three-component and three-dimensional (3C-3D) measurement techniques now permits detailed experimental investigation into the dynamics and topology of CSs by for example analysis of the invariants of the velocity gradient tensor. For this purpose, the present work presents instantaneous, high-resolution 3C-3D Tomographic Particle Image Velocimetry (TPIV) measurements in a grid-generated, homogeneous isotropic turbulent flow (Reλ 140). The experiments are conducted in a larger water tunnel facility using a passive grid, four high-resolution digital cameras and a pulsed Nd:YAG laser for volume illumination. The invariants of the velocity gradient, rate of strain and rate of rotation tensor are used to characterize the dynamics and topology of the turbulent flow field and in particular its dissipation and vortex structure. Preliminary results are in agreement with previous literature and DNS simulations. The objective of this work is to measure these quantities experimentally and directly without additional assumptions pertaining to the structure and dynamics of the turbulent flow field.

  10. 重组乳酸杆菌Lb.hCGβ-C3d3经鼻腔免疫BALB/c小鼠的抗生育潜能%The anti-fertility potential of inoculation via nose with recombinant live Lactobacilli of Lb.hCGβ-C3d3

    Institute of Scientific and Technical Information of China (English)

    王健理; 姚晓英; 李大金

    2011-01-01

    目的:探讨表达hCGβ-C3d3融合蛋白的重组乳酸杆菌避孕疫苗经鼻腔黏膜接种BALB/c小鼠及其抗生育潜能.方法:用野生型乳酸杆菌Lb.及重组乳酸杆菌Lb.hCGβ和Lb.hCGβ-C3d3 以两种剂量(109个和1010个)经鼻腔滴注接种6~8周龄雌性BALB/c小鼠.3周后用相同剂量加强免疫一次.于初次免疫后的第6、7、8周收集血清,分别培养MLTC-1、BeWo细胞;化学发光法检测培养上清中孕酮或hCGβ水平;免疫荧光观察抗血清处理后BeWo细胞的融合情况.结果:用1010个Lb.hCGβ-C3d3滴鼻免疫BALB/c小鼠产生的抗血清能显著抑制hCG刺激MLTC-1分泌孕酮,明显抑制BeWo细胞分泌hCGβ及细胞融合.结论:重组乳酸杆菌活疫苗Lb.hCGβ-C3d3经鼻腔接种诱导的hCGβ抗体可拮抗hCGβ生物学功能,并干扰滋养细胞功能,因此具有抗生育潜能.%0bjective :To evaluate the anti-fertility of potential by inoculation via nose with the recom binant live Lactobacilli expressing hCGβ-C3d3 fusion protein.Methods :Female BALB/cmie were inmunized with 1010,109 Lb,Lb.hCGβor Lb .hCGβ-C3d3,respectively,via nose .The antrserum was collected respectively in the 6-8th week after the primary inmunization M LTC-1and BeW o cell line were respectively treated with the anti-serum ,and then the supematant was recovered ,respective]y .Progesterone and hCGβ in the supematent were detemined by Chem olum inescence assay .Fusion of the BeW o cells was investigated by inmunofluorescence microscopy. Results :The anti-serum induced by the Lb. hCGβ-C3d3 inoculation with the dose of 1010 could significantly inhibit the progesterone production in MLTC-1 cells via neuttalizng hCG bioactivity ,and suppress the hCGβ secretion and fusion in vitro of BeW o cell line .Conclusion :Lb.hCGβ-C3d3 live Lactobacilli are effective in blocking hCG bioactivity,which appears anti-fertilily potential.

  11. Advanced Reservoir Characterization and Development through High-Resolution 3C3D Seismic and Horizontal Drilling: Eva South Marrow Sand Unit, Texas County, Oklahoma

    Energy Technology Data Exchange (ETDEWEB)

    Wheeler,David M.; Miller, William A.; Wilson, Travis C.

    2002-03-11

    The Eva South Morrow Sand Unit is located in western Texas County, Oklahoma. The field produces from an upper Morrow sandstone, termed the Eva sandstone, deposited in a transgressive valley-fill sequence. The field is defined as a combination structural stratigraphic trap; the reservoir lies in a convex up -dip bend in the valley and is truncated on the west side by the Teepee Creek fault. Although the field has been a successful waterflood since 1993, reservoir heterogeneity and compartmentalization has impeded overall sweep efficiency. A 4.25 square mile high-resolution, three component three-dimensional (3C3D) seismic survey was acquired in order to improve reservoir characterization and pinpoint the optimal location of a new horizontal producing well, the ESU 13-H.

  12. Contribution of C3d-P28 repeats to enhancement of immune responses against HBV-preS2/S induced by gene immunization

    Institute of Scientific and Technical Information of China (English)

    Li-Xin Wang; Wei Xu; Qing-Dong Guan; Yi-Wei Chu; Ying Wang; Si-Dong Xiong

    2004-01-01

    AIM: To investigate whether P28 derived from C3d can enhance the immune response to HBV-preS2/S induced by directly injection of naked plasmids containing variable repeats of P28 and HBV-preS2/S in fusion form.METHODS: One to four copies of C3d-P28 coding gene,amplified by PCR and modified by restriction endonucleases digestion, were subcloned into a eukaryotic expression vector pVAON33 to construct pVAON33-P28, pVAON33-P28.2, pVAON33-P28.3 and pVAON33-P28.4 (pVAON33-P28.[1-4]). HBV-preS2/S coding sequence was then introduced into the pVAON33-P28.[1-4] and identified by both PCR and DNA sequencing. BALB/c mice were primed by intramuscular gene immunization with 100 μg different recombinant plasmids on day 0 and were boosted by subcutaneous inoculation with HBsAg protein (1 μg) 12wk post-priming. The levels and avidity of specific IgG in sera collected at the indicated times from each group were determined by ELISA and NaSCN-displacement ELISA,respectively.RESULTS: HBsAg specific antibody response was elicited in groups primed with plasmids pVAON33-S2/S-P28.[1-4]and pVAON33-S2/S. However, the response against HBsAg in the groups primed with pVAON33-S2/S-P28.[1-4] was significantly higher than that in pVAON33-S2/S group, the highest level of the specific antibody response was observed in the groups primed with pVAON33-S2/S-P28.4 (P<0.01).After secondary immunization with specific antigen, the acceleration of antibody levels was significantly higher and faster in the mice primed with DNA expressing preS2/S-P28 fusions than that with DNA expressing preS2/S only (P<0.05).Interestingly, mice primed with DNA expressing preS2/SP28.4 fusions maintained the highest levels of anti-HBs antibodies in all animals. The avidity assay showed that the avidity index (AI) collected at 18 wk from mice primed with pVAON33-S2/S-P28.3 and pVAON33-S2/S-P28.4 were significantly higher than that from preS2/S-DNA vaccinated mice (P<0.01).CONCLUSION: Different repeats of C3d-P28 can

  13. Detection of tibial condylar fractures using 3D imaging with a mobile image amplifier (Siemens ISO-C-3D): Comparison with plain films and spiral CT; Frakturdiagnostik am Kniegelenk mit einem neuen mobilen CT-System (ISO-C-3D): Vergleich mit konventionellem Roentgen und Spiral-CT

    Energy Technology Data Exchange (ETDEWEB)

    Kotsianos, D.; Rock, C.; Wirth, S.; Linsenmaier, U.; Brandl, R.; Fischer, T.; Pfeifer, K.J.; Reiser, M. [Klinikum der Universitaet Muenchen-Innenstadt, Muenchen (Germany). Inst. fuer Klinische Radiologie; Euler, E.; Mutschler, W. [Klinikum der Universitaet Muenchen-Innenstadt, Muenchen (Germany). Chirurgische Klinik und Poliklinik

    2002-01-01

    Purpose: To analyze a prototype mobile C-arm 3D image amplifier in the detection and classification of experimental tibial condylar fractures with multiplanar reconstructions (MPR). Method: Human knee specimens (n=22) with tibial condylar fractures were examined with a prototype C-arm (ISO-C-3D, Siemens AG), plain films (CR) and spiral CT (CT). The motorized C-arm provides fluoroscopic images during a 190 orbital rotation computing a 119 mm data cube. From these 3D data sets MP reconstructions were obtained. All images were evaluated by four independent readers for the detection and assessment of fracture lines. All fractures were classified according to the Mueller AO classification. To confirm the results, the specimens were finally surgically dissected. Results: 97% of the tibial condylar fractures were easily seen and correctly classified according to the Mueller AO classification on MP reconstruction of the ISO-C-3D. There is no significant difference between ISO-C and CT in detection and correct classification of fractures, but ISO-CD-3D is significant by better than CR. (orig.) [German] Zielsetzung: Ziel der vorliegenden Studie war es, die diagnostischen Moeglichkeiten und Grenzen der Erkennbarkeit und Klassifizierung von Frakturen mit multiplanaren Rekonstruktionen (MPR) aus 3D-Datensaetzen eines fahrbaren C-Bogengeraetes an Kniegelenken zu pruefen. Methodik: Kniegelenke von Verstorbenen (n=22) mit Tibiakopffrakturen wurden an einem Prototyp eines mobilen C-Bogen Schnittbild-/Durchleuchtungsgeraets (ISO-C-3D, Siemens AG Erlangen) untersucht. Das Geraet erzeugt waehrend einer einmaligen 190-Grad-Rotation 100 Projektionsaufnahmen, aus denen ein 3D-Volumendatensatz gewonnen wird. Aus diesem werden Hochkontrastschnittbilder als MP-Rekonstruktionen in allen drei Raumebenen errechnet und visualisiert. Die Kniegelenke wurden von 4 unabhaengigen Befundern hinsichtlich Frakturerkennbarkeit, Frakturart und -ausmass unter Verwendung der MP

  14. Pharmacological and physiological functions of the polyspecific organic cation transporters : OCT1, 2, and 3 (SLC22A1-3)

    NARCIS (Netherlands)

    Jonker, JW; Schinkel, AH

    2004-01-01

    For the elimination of environmental toxins and metabolic waste products, the body is equipped with a range of broad-specificity transporters that are generally present in the liver, kidney, and intestine. The polyspecific organic cation transporters OCT1, 2, and 3 (SLC22A1-3) mediate the facilitate

  15. A Newly Cloned ClC-3 Isoform, ClC-3d, as well as ClC-3a Mediates Cd2+-Sensitive Outwardly Rectifying Anion Currents

    Directory of Open Access Journals (Sweden)

    Toshiaki Okada

    2014-02-01

    Full Text Available Background: ClC-3, a member of the ClC family, is predicted to have six isoforms, ClC-3a to -3f, with distinct N- and C-terminal amino acid sequences. There have been conflicting reports on the properties of ClC-3a (also known as the N-terminal short form of ClC-3 and ClC-3b (the N-terminal long form of ClC-3 as plasmalemmal Cl- channels. Meanwhile, little is known about other isoforms. The amino acid sequence of ClC-3d (a C-terminal variant of the short form listed in the NCBI database was derived from the genomic sequence, but there has been no experimental evidence for the mRNA. Methods: PCR-cloning was made to obtain the full coding region of ClC-3d from mouse liver. Its molecular expression on the plasma membrane was microscopically examined in HEK293T cells transfected with GFP-tagged ClC-3d. Its functional plasmalemmal expression and the properties of currents were studies by whole-cell recordings in the cells transfected with ClC-3d. Results: The cloned ClC-3d was found to be the only isoform which has an N-terminal amino acid sequence identical to ClC-3a. When introduced into HEK293T cells, a minor fraction of exogenous ClC-3d proteins was detected at the plasma membrane, and activation of anion currents was observed at neutral pH under normotonic conditions. The properties of ClC-3d currents were found to be shared by ClC-3a-mediated currents. Also, both ClC-3d and -3a currents were found to be sensitive to Cd2+. ClC-3d overexpression never affected the endogenous activity of acid- or swelling-activated anion channels. Conclusion: We thus conclude that plasmalemmal ClC-3d, like ClC-3a, mediates Cd2+-sensitive outwardly rectifying anion currents and that ClC-3d is distinct from the molecular entities of acid- and volume-sensitive anion channels.

  16. Monoclonal antibody OKB7, which identifies the 14OKd complement receptor type 2 (CR/sub 2/), also identifies a 72Kd secreted fragment of CR/sub 2/ that contains the C3d-binding site

    Energy Technology Data Exchange (ETDEWEB)

    Myones, B.L.; Ross, G.D.

    1986-03-05

    CR/sub 2/ is a 140-145Kd glycoprotein expressed on B lymphocytes which binds both C3d and Epstein-Barr virus (EBV). OKB7, an IgG/sub 2a/ monoclonal antibody to CR/sub 2/, blocks C3d and EBV binding, while HB-5, another monoclonal IgG/sub 2a/ anti-CR/sub 2/, does not. A 72Kd C3d-binding glycoprotein (gp72), isolated from Raji cell media, was previously thought to be CR/sub 2/ because a polyclonal rabbit anti-gp72 inhibited EC3d rosettes. ELISA assay demonstrated that OKB7, but not HB-5, bound to purified gp72 fixed to microtiter wells. Insoluble and soluble gp72 blocked Raji cell uptake of /sup 125/I-labeled OKB7, but not labeled anti-B2 or HB-5. Rabbit anti-gp72 immunoprecipitated bands at 140Kd and 72Kd from /sup 125/I-labelled and solubilized B cell membranes. Culture media from Raji cells grown in the presence /sup 3/H-labeled amino acids was sequentially immunoprecipitated by irrelevant antibody, OKB7, and HB-5. A single 72Kd radiolabeled band was demonstrated only with OKB7, and this was identical to that produced by the immunoprecipitation of /sup 125/I-labeled gp72 with rabbit anti-gp72. Thus, OKB7, which identifies the 140Kd CR/sub 2/ molecule, also identifies a 72Kd shed fragment of CR/sub 2/ isolated from Raji cell media, which contains the C3d-binding site.

  17. VH and VL Domains of Polyspecific IgM and Monospecific IgG Antibodies Contribute Differentially to Antigen Recognition and Virus Neutralization Functions.

    Science.gov (United States)

    Pasman, Y; Kaushik, A K

    2016-07-01

    We analysed contributions of variable heavy (FdVH ) and variable light (FdVL ) domains in comparison to scFv (FdVH +FdVL ) of naturally occurring polyspecific bovine IgM with an exceptionally long CDR3H and an induced monospecific bovine herpes virus-1 (BoHV-1) neutralizing IgG1 antibody in the context of to antigen-binding site and antibody function. Various recombinant FdVH , FdVL and scFv were constructed and expressed in Pichia pastoris from the bovine IgM and IgG1 antibody encoding cDNA. The scFv1H12 showed polyspecific antigen binding similar to parent IgM antibody, though subtle differences, for example, higher thyroglobulin recognition. Such differences reflect influence of the constant region on the antigen-binding site configuration. Unlike, variable light domain FdVL 1H12, the variable heavy domain FdVH 1H12 alone recognized multiple antigens that differed from the recognition pattern of scFv1H12 (FdVH +FdVL ) and the parent IgM antibody. Nonetheless, role of FdVL 1H12 in providing structural support to FdVH in antigen recognition is noted, apart from its intrinsic antigen recognition ability. Surface plasmon resonance analysis revealed low to moderate affinity of scFv1H12 to IgG antigen. By contrast, the individual FdVH 073 and FdVL 074, originating from induced BoHV-1 neutralizing IgG1 antibody, recognized target epitope on BoHV-1 weakly when compared to FdVH +FdVL (scFv3-18L). Interestingly, both the FdVH and FdVL domains of induced IgG antibody are required to achieve BoHV-1 neutralization. To conclude, there exist subtle functional differences in the contribution of FdVH and FdVL to antigen-binding site generation of polyspecific IgM and monospecific IgG antibodies relevant to antigen recognition and virus neutralization functions.

  18. Toxicity of Bothrops sp snake venoms from Ecuador and preclinical assessment of the neutralizing efficacy of a polyspecific antivenom from Costa Rica.

    Science.gov (United States)

    Laines, Johana; Segura, Álvaro; Villalta, Mauren; Herrera, María; Vargas, Mariángela; Alvarez, Gladys; Gutiérrez, José María; León, Guillermo

    2014-09-01

    The toxicological profile of the venoms of the snakes Bothrops asper and Bothrops atrox from Ecuador was investigated, together with the venom of a population of B. asper formerly classified as 'Bothrops xanthogrammus'. The three venoms exerted lethal, hemorrhagic, myotoxic, coagulant and defibrinogenating effects, in agreement with the characteristic toxicological profile of Bothrops sp venoms. A polyspecific antivenom (bothropic-crotalic-lachesic) manufactured in Costa Rica was assessed for its preclinical efficacy against the toxic activities of these Ecuadorian venoms. Antivenom was effective in the neutralization of the five activities tested in the three venoms. These observations are in agreement with previous reports on the extensive cross-reactivity and paraspecific neutralization of antivenoms manufactured in Latin America against the venoms of Bothrops sp snakes.

  19. Design and development of TT30, a novel C3d-targeted C3/C5 convertase inhibitor for treatment of human complement alternative pathway-mediated diseases.

    Science.gov (United States)

    Fridkis-Hareli, Masha; Storek, Michael; Mazsaroff, Istvan; Risitano, Antonio M; Lundberg, Ante S; Horvath, Christopher J; Holers, V Michael

    2011-10-27

    To selectively modulate human complement alternative pathway (CAP) activity implicated in a wide range of acute and chronic inflammatory conditions and to provide local cell surface and tissue-based inhibition of complement-induced damage, we developed TT30, a novel therapeutic fusion protein linking the human complement receptor type 2 (CR2/CD21) C3 fragment (C3frag = iC3b, C3dg, C3d)-binding domain with the CAP inhibitory domain of human factor H (fH). TT30 efficiently blocks ex vivo CAP-dependent C3frag accumulation on activated surfaces, membrane attack complex (MAC) formation and hemolysis of RBCs in a CR2-dependent manner, and with a ∼ 150-fold potency gain over fH, without interference of C3 activation or MAC formation through the classic and lectin pathways. TT30 protects RBCs from hemolysis and remains bound and detectable for at least 24 hours. TT30 selectively inhibits CAP in cynomolgus monkeys and is bioavailable after subcutaneous injection. Using a unique combination of targeting and effector domains, TT30 controls cell surface CAP activation and has substantial potential utility for the treatment of human CAP-mediated diseases.

  20. New structure–activity relationships of chalcone inhibitors of breast cancer resistance protein: polyspecificity toward inhibition and critical substitutions against cytotoxicity

    Directory of Open Access Journals (Sweden)

    Rangel LP

    2013-09-01

    Full Text Available Luciana Pereira Rangel,1,2,* Evelyn Winter,1,3,* Charlotte Gauthier,1 Raphaël Terreux,4 Louise D Chiaradia-Delatorre,5 Alessandra Mascarello,5 Ricardo J Nunes,5 Rosendo A Yunes,5 Tania B Creczynski-Pasa,3 Sira Macalou,1 Doriane Lorendeau,1 Hélène Baubichon-Cortay,1 Antonio Ferreira-Pereira,2 Attilio Di Pietro11Equipe Labellisée Ligue 2013, BMSSI UMR 5086 CNRS/Université Lyon 1, Institut de Biologie et Chimie des Protéines, Lyon, France; 2Department of General Microbiology, Institute of Microbiology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 3Department of Pharmaceutical Sciences, PPGFAR, Federal University of Santa Catarina, Florianopolis, Santa Catarina, Brazil; 4Equipe BISI, BMSSI UMR 5086 CNRS/Université Lyon 1, Institut de Biologie et Chimie des Protéines, Lyon, France; 5Department of Chemistry, Federal University of Santa Catarina, Florianopolis, Santa Catarina, Brazil*These authors contributed equally to this workAbstract: Adenosine triphosphate-binding cassette subfamily G member 2 (ABCG2 plays a major role in cancer cell multidrug resistance, which contributes to low efficacy of chemotherapy. Chalcones were recently found to be potent and specific inhibitors, but unfortunately display a significant cytotoxicity. A cellular screening against ABCG2-mediated mitoxantrone efflux was performed here by flow cytometry on 54 chalcone derivatives from three different series with a wide panel of substituents. The identified leads, with submicromolar IC50 (half maximal inhibitory concentration values, showed that the previously identified 2'-OH-4',6'-dimethoxyphenyl, as A-ring, could be efficiently replaced by a 2'-naphthyl group, or a 3',4'-methylenedioxyphenyl with lower affinity. Such a structural variability indicates polyspecificity of the multidrug transporter for inhibitors. At least two methoxyl groups were necessary on B-ring for optimal inhibition, but substitution at positions 3, 4, and 5 induced cytotoxicity

  1. Minimally invasive percutaneous fixation based on ISO-C3D computerized navigational system for fracture of the acetabulum%ISO-C3D计算机辅助导航技术经皮微创内固定治疗髋臼骨折

    Institute of Scientific and Technical Information of China (English)

    马玉鹏; 周东生; 李连欣; 穆卫东; 何吉亮; 李庆虎

    2013-01-01

    BACKGROUND:Percutaneous hol ow screw under X-Ray fluoroscopy has been shown to treat fracture of acetabulum of the pelvis, but the time of internal fixation was long, and the amount of radiation exposure to the patients and physicians was large. OBJECTIVE:To test the application of the ISO-C3D METHODS:Thirty-one patients with fracture of the acetabulum were treated with percutaneous hol ow screw under a fluoroscopy-based ISO-C computerized navigational system for fracture of acetabulum. 3D computerized navigational system. The interval from injury to operation was 4 to 13 days. Al patients were fol owed up for one year. RESULTS AND CONCLUSION:The average bleeding volume during operation was only 18 mL, except that the bleeding volume of only one patient, who suffered from the sacroiliacjoint injury and received open reduction and internal fixation, was up to 300 mL. The total number of screws used in the operation was 42, among which 24 were screws for acetabular anterior column fracture and 18 for posterior column fracture. Al screws were implanted once precisely. The average time of internal fixation was 59 minutes, and the mean time for fluoroscopy was 39 seconds. The 31 patients were pain-free one week after the operation and no complication (infection, vascular nerve injury or implant breakage) was noted post-operatively. When the fol ow-up ended, radiography revealed fracture union with satisfactory screw fixation (no screw breakage or loosening). According to Matta functional scoring, results were excellent in 23 cases, good in 8 cases, with an excellent and good rate of 100%. According to Majeed functional scoring, the results were excellent in 22 cases, good in 6 cases and average in 3 cases, with an excellent and good rate of 90%. These results indicated that ISO-C3D computerized navigational system can supply stable internal fixation without an increase of complication.%背景:文献报道采用X射线透视下经皮空心螺钉治疗骨盆髋臼骨

  2. SHEAR WAVE SEISMIC STUDY COMPARING 9C3D SV AND SH IMAGES WITH 3C3D C-WAVE IMAGES

    Energy Technology Data Exchange (ETDEWEB)

    John Beecherl; Bob A. Hardage

    2004-07-01

    The objective of this study was to compare the relative merits of shear-wave (S-wave) seismic data acquired with nine-component (9-C) technology and with three-component (3-C) technology. The original proposal was written as if the investigation would be restricted to a single 9-C seismic survey in southwest Kansas (the Ashland survey), on the basis of the assumption that both 9-C and 3-C S-wave images could be created from that one data set. The Ashland survey was designed as a 9-C seismic program. We found that although the acquisition geometry was adequate for 9-C data analysis, the source-receiver geometry did not allow 3-C data to be extracted on an equitable and competitive basis with 9-C data. To do a fair assessment of the relative value of 9-C and 3-C seismic S-wave data, we expanded the study beyond the Ashland survey and included multicomponent seismic data from surveys done in a variety of basins. These additional data were made available through the Bureau of Economic Geology, our research subcontractor. Bureau scientists have added theoretical analyses to this report that provide valuable insights into several key distinctions between 9-C and 3-C seismic data. These theoretical considerations about distinctions between 3-C and 9-C S-wave data are presented first, followed by a discussion of differences between processing 9-C common-midpoint data and 3-C common-conversion-point data. Examples of 9-C and 3-C data are illustrated and discussed in the last part of the report. The key findings of this study are that each S-wave mode (SH-SH, SV-SV, or PSV) involves a different subsurface illumination pattern and a different reflectivity behavior and that each mode senses a different Earth fabric along its propagation path because of the unique orientation of its particle-displacement vector. As a result of the distinct orientation of each mode's particle-displacement vector, one mode may react to a critical geologic condition in a more optimal way than do the other modes. A conclusion of the study is that 9-C seismic data contain more rock and fluid information and more sequence and facies information than do 3-C seismic data; 9-C data should therefore be acquired in multicomponent seismic programs whenever possible.

  3. Photodissociation of the Propargyl (C3D3) Radicals at 248 nm and 193 nm

    Energy Technology Data Exchange (ETDEWEB)

    Neumark., D.M.; Crider, P.E.; Castiglioni, L.; Kautzman, K.K.

    2009-01-21

    The photodissociation of perdeuterated propargyl (D{sub 2}CCCD) and propynyl (D{sub 3}CCC) radicals was investigated using fast beam photofragment translational spectroscopy. Radicals were produced from their respective anions by photodetachment at 540 nm and 450 nm (below and above the electron affinity of propynyl). The radicals were then photodissociated by 248 nm or 193 nm light. The recoiling photofragments were detected in coincidence with a time- and position-sensitive detector. Three channels were observed: D{sub 2} loss, CD + C{sub 2}D{sub 2}, and CD{sub 3} + C{sub 2}. Obervation of the D loss channel was incompatible with this experiment and was not attempted. Our translational energy distributions for D{sub 2} loss peaked at nonzero translational energy, consistent with ground state dissociation over small (< 1 eV) exit barriers with respect to separated products. Translational energy distributions for the two heavy channels peaked near zero kinetic energy, indicating dissociation on the ground state in the absence of exit barriers.

  4. Biological Fixation of N2 in Mono and Polyspecific Legume Pasture in the Humid Mediterranean Zone of Chile Fijación Biológica de N2 en Praderas Mono y Poliespecíficas de Leguminosas en la Zona Mediterránea Húmeda de Chile

    Directory of Open Access Journals (Sweden)

    Soledad Espinoza

    2011-03-01

    Full Text Available Despite annual legume pasture are of great importance for dryland agricultural systems in Mediterranean environments, there are few studies of N2 biological fixation (NBF reported in Chile. In this study the NBF of four annual legume species: subterranean clover (Trifolium subterraneum L., yellow serradella (Ornithopus compressus L., arrow-leaf clover (T. vesiculosum L., and crimson clover (T. incarnatum L. (Experiment 1, as well as seven mixtures of these species (Experiment 2 were assessed. The NBF was measured by the 15N natural abundance technique. The objective was to determine NBF in the legume species and in distinct mixtures used. The study was carried out in an Andisol of the Andean Precordillera located in the humid Mediterranean zone of Chile. Pasture was evaluated for biomass; and total N and natural abundance of 15N were analyzed in plant material samples. In Experiment 1 (monospecific legume species pasture, N derived from fixation ranged between 43 and 147 kg N ha-1 and where T. vesiculosum and T. subterraneum presented statistical differences (P ≤ 0.05 in connection with the other species. In the legume mixtures (Experiment 2, N derived by fixation varied between 97 and 214 kg N ha-1 where the 50-50 mixtures (T. subterraneum and O. compressus, or T. subterraneum and T. vesiculosum, respectively had the highest N fixation. Fixed N ranged between 12 and 25 kg N t-1 DM, showing significant differences among mono and polyspecific legume species.A pesar de la gran importancia que las praderas de leguminosas tienen en los sistemas agrícolas de secano en ambientes mediterráneos, existe muy poca información sobre la fijación biológica de N2 (FBN reportada en Chile. En este estudio se evaluó la FBN en cuatro leguminosas forrajeras anuales: trébol subterráneo (Trifolium subterraneum L., serradela amarilla (Ornithopus compressus L., trébol vesiculoso (T. vesiculosum L. y trébol encarnado (T. incarnatum L. (Experimento 1, adem

  5. Targeted complement inhibition by C3d recognition ameliorates tissue injury without apparent increase in susceptibility to infection.

    Science.gov (United States)

    Atkinson, Carl; Song, Hongbin; Lu, Bo; Qiao, Fei; Burns, Tara A; Holers, V Michael; Tsokos, George C; Tomlinson, Stephen

    2005-09-01

    Previous studies indicate a pivotal role for complement in mediating both local and remote injury following ischemia and reperfusion of the intestine. Here, we report on the use of a mouse model of intestinal ischemia/reperfusion injury to investigate the strategy of targeting complement inhibition to sites of complement activation by linking an iC3b/C3dg-binding fragment of mouse complement receptor 2 (CR2) to a mouse complement-inhibitory protein, Crry. We show that the novel CR2-Crry fusion protein targets sites of local and remote (lung) complement activation following intestinal ischemia and reperfusion injury and that CR2-Crry requires a 10-fold lower dose than its systemic counterpart, Crry-Ig, to provide equivalent protection from both local and remote injury. CR2-Crry has a significantly shorter serum half-life than Crry-Ig and, unlike Crry-Ig, had no significant effect on serum complement activity at minimum effective therapeutic doses. Furthermore, the minimum effective dose of Crry-Ig significantly enhanced susceptibility to infection in a mouse model of acute septic peritonitis, whereas the effect of CR2-Crry on susceptibility to infection was indistinguishable from that of PBS control. Thus, compared with systemic inhibition, CR2-mediated targeting of a complement inhibitor of activation improved bioavailability, significantly enhanced efficacy, and maintained host resistance to infection.

  6. C3D及其与传统侧扫声纳的比较%Comparison Between C3D and Traditional Side-scan Sonar

    Institute of Scientific and Technical Information of China (English)

    张济博; 潘国富; 苟诤慷; 丁维凤; 蒋维杰

    2013-01-01

    C3D是Benthos公司近年来推出的基于CAATI技术的一种新型测深侧扫声纳系统.从工作原理、技术参数、数据采集与后处理平台以及实测数据等方面将C3D和传统侧扫声纳进行了对比.对比表明两者的工作原理不同,C3D的采集数据密度更高,对采集和处理软件要求比传统声纳高,最后对两者采集的数据进行了分析.通过对比,为侧扫声纳系统的选用和引进提供了依据.

  7. Molecular Cloning and Characteristics of Sheep C3d Gene%绵羊C3d基因克隆及分子特征

    Institute of Scientific and Technical Information of China (English)

    岳耀敬; 焦硕; 郭宪; 冯瑞林

    2008-01-01

    从绵羊(Ovis aries)肝脏组织克隆到了补体C3d基因并对其核苷酸序列和推导的氨基酸序列以及蛋白结构进行了分析.绵羊补体C3d基因的编码区含有909个核苷酸,编码303个氨基酸残基(GenBank No.EF681138).绵羊C3d与人(Homo sapiens)、牛(Bos taurus)、山羊(Capra hircus)、野猪(Sus scrofa)、金仓鼠(Mesocricetus auratus)、小鼠(Mus musculus)、褐鼠(Rattus norvegicus)、大袋鼠(Macropus eugenii)、兔(Oryctolagus cuniculus)和原鸡(Gallus gallus)推导出的C3d氨基酸序列的一致性分别为80.4%,94.7%,96.9%,82.8%,81.1%,80.6%,80.2%,71.0%,75.2%和60.3%.绵羊与原鸡C3d的一致性最低为60.3%,而与其它动物C3d之间的一致性则较高为71.0%~96.9%.生物学软件分析发现,绵羊C3d蛋白有2个蛋白激酶C磷酸化位点,1个氨基葡聚糖附着位点,1个酪蛋白激酶Ⅱ磷酸化位点,1个酪氨酸激酶磷酸化位点,1个十四(烷)酰化位点.绵羊C3d二级结构中螺旋和转角交替出现,其中α螺旋占55.12%,β折叠为2.31%,转角区域为42.57%,这样的结构有利于其桶状结构的形成.ESyPred3D同源建模预测可知绵羊C3d三级结构与人C3d一样也形成由核心和外层构成的桶状分子结构.

  8. Programs Lucky and Lucky{sub C} - 3D parallel transport codes for the multi-group transport equation solution for XYZ geometry by Pm Sn method

    Energy Technology Data Exchange (ETDEWEB)

    Moriakov, A. [Russian Research Centre, Kurchatov Institute, Moscow (Russian Federation); Vasyukhno, V.; Netecha, M.; Khacheresov, G. [Research and Development Institute of Power Engineering, Moscow (Russian Federation)

    2003-07-01

    Powerful supercomputers are available today. MBC-1000M is one of Russian supercomputers that may be used by distant way access. Programs LUCKY and LUCKY{sub C} were created to work for multi-processors systems. These programs have algorithms created especially for these computers and used MPI (message passing interface) service for exchanges between processors. LUCKY may resolved shielding tasks by multigroup discreet ordinate method. LUCKY{sub C} may resolve critical tasks by same method. Only XYZ orthogonal geometry is available. Under little space steps to approximate discreet operator this geometry may be used as universal one to describe complex geometrical structures. Cross section libraries are used up to P8 approximation by Legendre polynomials for nuclear data in GIT format. Programming language is Fortran-90. 'Vector' processors may be used that lets get a time profit up to 30 times. But unfortunately MBC-1000M has not these processors. Nevertheless sufficient value for efficiency of parallel calculations was obtained under 'space' (LUCKY) and 'space and energy' (LUCKY{sub C}) paralleling. AUTOCAD program is used to control geometry after a treatment of input data. Programs have powerful geometry module, it is a beautiful tool to achieve any geometry. Output results may be processed by graphic programs on personal computer. (authors)

  9. Circadian and diurnal variation of circulating immune complexes, complement-mediated solubilization, and the complement split product C3d in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Petersen, Ivan; Baatrup, Gunnar; Brandslund, I;

    1986-01-01

    Nine patients with active classical rheumatoid arthritis (ARA criteria) were studied with reference to circadian variation of immunological and clinical parameters. Complement-mediated solubilization (CMS) of immune complexes (IC) and the level of circulating IC were found to be inversely related...

  10. C3D测深侧扫声呐系统在人工鱼礁建设中的应用%The application of C3D bathymetry side scan sonar system in artificial reef construction

    Institute of Scientific and Technical Information of China (English)

    沈蔚; 章守宇; 李勇攀; 张进; 沈天跃; 沈赟; 张翔

    2013-01-01

    长期以来将多波束测深数据和侧扫声呐图像进行融合叠加,一直是水下测绘领域的研究难题,而美国Benthos公司近年推出的C3D测深侧扫声呐系统,采用了多阵列换能器,CAATI专利算法,可同步获得高分辨率的侧扫图像和高质量的测深数据.本文着重研究:(1)在鱼礁区的设计阶段,C3D系统提供三维的水下地形、等深线等数据,进行三维可视化的鱼礁礁址的选择和布设方案设计;提供高分辨率的水下地貌图像,进行海底地质的分类,也可直观判断水下的各种地貌和障碍物等.(2)在鱼礁施工阶段,利用C3D水下图像对鱼礁的位置和状态进行评估,改进投放方法和工艺,确保设计方案的实施到位.(3)在鱼礁竣工后的监测阶段,利用不同时期的C3D高分辨率图像及水深数据进行比对,以判断鱼礁区的地形地貌变化,鱼礁的稳定性、掩埋损坏等情况.实验表明,C3D是一款性能优越的水下声呐探测系统,可为人工鱼礁方案设计提供详细的海底地形和底质信息,可对人工鱼礁建设的过程和结果进行科学的评估,将为各地人工鱼礁工程的顺利实施和效果保障发挥重要作用.研究亮点:首次在国内将先进的C3D测深侧扫声呐系统应用于人工鱼礁的建设,并以东海区多个人工鱼礁项目为例,分析了C3D在鱼礁建设的设计阶段、施工阶段和监测阶段中发挥的重要作用,为人工鱼礁建设的过程保障和效果评估提供了很好的技术方案.

  11. IL-1beta-induced pro-apoptotic signalling is facilitated by NCAM/FGF receptor signalling and inhibited by the C3d ligand in the INS-1E rat beta cell line

    DEFF Research Database (Denmark)

    Petersen, L G; Størling, J; Heding, P

    2006-01-01

    AIMS/HYPOTHESIS: IL-1beta released from immune cells induces beta cell pro-apoptotic signalling via mitogen-activated protein kinases (MAPKs) and nuclear factor-kappaB (NF-kappaB). In neurons, the neural cell adhesion molecule (NCAM) signals to several elements involved in IL-1beta-induced pro-ap...

  12. A comparative study of venomics of Naja naja from India and Sri Lanka, clinical manifestations and antivenomics of an Indian polyspecific antivenom.

    Science.gov (United States)

    Sintiprungrat, Kitisak; Watcharatanyatip, Kamolwan; Senevirathne, W D S T; Chaisuriya, Papada; Chokchaichamnankit, Daranee; Srisomsap, Chantragan; Ratanabanangkoon, Kavi

    2016-01-30

    Naja naja (Indian cobra) from Sri Lanka and India is the WHO Category 1 medically important snakes in both countries. Some antivenom produced against Indian N. naja (NNi) were less effective against Sri Lankan N. naja (NNsl). Proteomes of NNi and NNsl venoms were studied by RP-HPLC, SDS-PAGE and LC/MS/MS. Six protein families were identified in both venoms with the most abundant were the 3 finger toxins (3FTs) where cytotoxins (CTX) subtype predominated, followed by phospholipase A2, cysteine-rich venom protein, snake venom metalloproteases, venom growth factors, and protease inhibitors. Qualitative and quantitative differences in the venomics profiles were observed. Some proteins were isolated from either NNi or NNsl venom. Postsynaptic neurotoxins (NTX) were identified for the first time in NNsl venom. Thus, there are geographic intra-specific variations of venom composition of the two N. naja. The relative abundance of CTX and NTX explained well the clinical manifestations of these venoms. Antivenomics study of an Indian antivenom (Vins) showed the antibodies effectively bound all venom toxins from both snakes but more avidly to the Indian venom proteins. The lower antibody affinity towards the 'heterologous' venom was the likely cause of poor efficacy of the Indian antivenom used to treat NNsl envenoming.

  13. Reduced hepatic uptake and intestinal excretion of organic cations in mice with a targeted disruption of the organic cation transporter 1 (Oct1 [Slc22a1]) gene

    NARCIS (Netherlands)

    Jonker, JW; Wagenaar, E; Mol, CAAM; Buitelaar, M; Koepsell, H; Smit, JW; Schinkel, AH

    2001-01-01

    The polyspecific organic cation transporter 1 (OCT1 [SLC22A1]) mediates facilitated transport of small (hydrophilic) organic cations. OCT1 is localized at the basolateral membrane of epithelial cells in the liver, kidney, and intestine and could therefore be involved in the elimination of endogenous

  14. Toxicovenomics and antivenom profiling of the Eastern green mamba snake (Dendroaspis angusticeps)

    DEFF Research Database (Denmark)

    Lauridsen, Line P.; Laustsen, Andreas Hougaard; Lomonte, Bruno;

    2016-01-01

    -neurotoxins were identified. Proteins of the Kunitz-type proteinase inhibitor family include dendrotoxins. Toxicological screening revealed a lack of lethal activity in all RP-HPLC fractions, except one, at the doses tested. Thus, the overall toxicity depends on the synergistic action of various types of proteins......, such as dendrotoxins, fasciculins, and probably other synergistically-acting toxins. Polyspecific antivenoms manufactured in South Africa and India were effective in the neutralization of venom-induced lethality. These antivenoms also showed a pattern of broad immunorecognition of the different HPLC fractions by ELISA...... mainly on mammals. It is therefore likely that the predominant clinical manifestations of human envenomings by these species also differ, although in both cases neurotoxic manifestations predominate. Polyspecific antivenoms manufactured in South Africa and India were effective in the neutralization...

  15. Coincidence of cellular and antibody mediated rejection in heart transplant recipients – preliminary report

    Science.gov (United States)

    Nożyński, Jerzy; Konecka-Mrówka, Dominika; Babińska, Agnieszka; Flak, Bożena; Hrapkowicz, Tomasz; Zembala, Marian

    2014-01-01

    Antibody mediated rejection (AMR) can significantly influence the results of orthotopic heart transplantation (OHT). However, AMR and cellular rejection (CR) coexistence is poorly described. Therefore we performed a prospective pilot study to assess AMR/CR concomitance in endomyocardial biopsies (EMBs) obtained electively in 27 OHT recipients (21 M/6 F, 45.4 ± 14.4 y/o). Biopsy samples were paraffin embedded and processed typically with hematoxylin/eosin staining to assess CR, and, if a sufficient amount of material remained, treated with immunohistochemical methods to localize particles C3d and C4d as markers of antibody dependent complement activation. With this approach 80 EMBs, including 41 (51%) harvested within the first month after OHT, were qualified for the study. Among them 14 (18%) were C3d+, 37 (46%) were C4d+, and 12 (15%) were both C3d and C4d positive. At least one C3d+, C4d+, and C3d/C4d+ EMB was found in 10 (37%), 17 (63%), and 8 (30%) patients, respectively. Among 37 CR0 EMBs C3d was observed in 4 (11%), C4d in 17 (46%), and both C3d/C4d in 3 (8%) cases. Among 28 CR1 EMBs C3d was observed in 3 (11%), C4d in 11 (39%), and C3d/C4d in 3 (11%) cases. Among 15 CR2 EMBs C3d was observed in 7 (47%), C4d in 9 (60%), and C3d/C4d in 6 (40%) cases. Differences in C3d and C3d/C4d occurrence between grouped CR0-1 EMBs and CR2 EMBs (7/65 – 11% vs. 7/15 – 47%; 6/65 – 9% vs. 6/15 – 40%) were significant (p = 0.0035 and p = 0.0091, respectively, χ2 test). In conclusion, apparently frequent CR and AMR coexistence demonstrated in this preliminary study warrants further investigation in this field. PMID:26336395

  16. Coincidence of cellular and antibody mediated rejection in heart transplant recipients - preliminary report.

    Science.gov (United States)

    Zakliczyński, Michał; Nożyński, Jerzy; Konecka-Mrówka, Dominika; Babińska, Agnieszka; Flak, Bożena; Hrapkowicz, Tomasz; Zembala, Marian

    2014-03-01

    Antibody mediated rejection (AMR) can significantly influence the results of orthotopic heart transplantation (OHT). However, AMR and cellular rejection (CR) coexistence is poorly described. Therefore we performed a prospective pilot study to assess AMR/CR concomitance in endomyocardial biopsies (EMBs) obtained electively in 27 OHT recipients (21 M/6 F, 45.4 ± 14.4 y/o). Biopsy samples were paraffin embedded and processed typically with hematoxylin/eosin staining to assess CR, and, if a sufficient amount of material remained, treated with immunohistochemical methods to localize particles C3d and C4d as markers of antibody dependent complement activation. With this approach 80 EMBs, including 41 (51%) harvested within the first month after OHT, were qualified for the study. Among them 14 (18%) were C3d+, 37 (46%) were C4d+, and 12 (15%) were both C3d and C4d positive. At least one C3d+, C4d+, and C3d/C4d+ EMB was found in 10 (37%), 17 (63%), and 8 (30%) patients, respectively. Among 37 CR0 EMBs C3d was observed in 4 (11%), C4d in 17 (46%), and both C3d/C4d in 3 (8%) cases. Among 28 CR1 EMBs C3d was observed in 3 (11%), C4d in 11 (39%), and C3d/C4d in 3 (11%) cases. Among 15 CR2 EMBs C3d was observed in 7 (47%), C4d in 9 (60%), and C3d/C4d in 6 (40%) cases. Differences in C3d and C3d/C4d occurrence between grouped CR0-1 EMBs and CR2 EMBs (7/65 - 11% vs. 7/15 - 47%; 6/65 - 9% vs. 6/15 - 40%) were significant (p = 0.0035 and p = 0.0091, respectively, χ(2) test). In conclusion, apparently frequent CR and AMR coexistence demonstrated in this preliminary study warrants further investigation in this field.

  17. An Experimental and Computational Investigation of Dynamic Ductile Fracture in Stainless Steel Welds

    Science.gov (United States)

    2002-05-01

    su- peralloy ......... ................................... 59 3.3 Model parameters for integration of user-material subroutine VUMAT . 84 4.1 Void...post-coalescence flow potential 4+ ........... .......................... 75 3.13 ABAQUS/ VUMAT integration of the material model for 1 C3D8R Finite...Element ........ ............................... 82 3.14 ABAQUS/ VUMAT integration for 1 C3D8R element: Macroscopic flow stress

  18. Domain Modeling: NP_001833.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_001833.1 chr9 Crystal structure of Interleukin-23 c3d85d_ chr9/NP_001833.1/NP_001833....1_apo_39-294.pdb c3d87d_ chr9/NP_001833.1/NP_001833.1_holo_39-294.pdb blast 245R,246Y,247R,248P,249L,250I,275E,276Y,293W MAN,PO4 1 ...

  19. Immunoglobulin for necrotising soft tissue infections (INSTINCT)

    DEFF Research Database (Denmark)

    Madsen, Martin Bruun; Lange, Theis; Hjortrup, Peter Buhl;

    2016-01-01

    INTRODUCTION: Necrotising soft tissue infections (NSTI) are aggressive infections that can result in severe disability or death. Intravenous polyspecific immunoglobulin G (IVIG) is used as supplementary treatment for patients with NSTIs. The level of evidence is very low, but suggests that IVIG may....... Secondary outcomes are: mortality; time to resolution of shock; bleeding; sequential organ failure assessment scores on days 1-7; use of renal-replacement therapy, mechanical ventilation and vasopressors; days alive and out of hospital; amputation; and severe adverse reactions. CONCLUSION: This study...

  20. A COMPLEX OF INTERMEDIATE FILAMENT PROTEIN-DNA: A TARGET FOR AUTOANTIBODIES IN SYSTEMIC LUPUS ERYTHEMATOSUS?

    Institute of Scientific and Technical Information of China (English)

    阎锡德; S.Kuhn; P.Traub

    1995-01-01

    Autoantibodies in systemic lupus erythematosus which cross-react with double stranded DNA and in-termediate filament proteins are frequently reported.However,little is Known about the origin and the target of these antibodies.In this paper,a polyspecific monoclonal antibody,XY12,produced by the im-munization of genetically non-autoimmune mice with a DNA-protein complex is detsiled.Its antigen bind-ing patterms are very similar to the autoantibodies.The data suggest that these autoantibodies may be trig-gered by a circulating nucleoprotein.

  1. Genus Calliophis of Asiatic coral snakes: A deficiency of venom cross-reactivity and neutralization against seven regional elapid antivenoms.

    Science.gov (United States)

    Tan, Choo Hock; Liew, Jia Lee; Tan, Kae Yi; Tan, Nget Hong

    2016-10-01

    Venoms of Calliophis bivirgata and Calliophis intestinalis exhibited moderate binding activities toward Neuro Bivalent Antivenom (Taiwan) but not the other six elapid monovalent or bivalent antivenoms available in the region. All antivenoms failed to neutralize C. bivirgata venom lethality in mice. The findings indicate the need to validate antivenom cross-reactivity with in vivo cross-neutralization, and imply that distinct antigens of Calliophis venoms should be incorporated in the production of a pan-regional poly-specific antivenom.

  2. Ontogeny of recognition specificity and functionality for the broadly neutralizing anti-HIV antibody 4E10.

    Directory of Open Access Journals (Sweden)

    Kathryn A K Finton

    2014-09-01

    Full Text Available The process of antibody ontogeny typically improves affinity, on-rate, and thermostability, narrows polyspecificity, and rigidifies the combining site to the conformer optimal for binding from the broader ensemble accessible to the precursor. However, many broadly-neutralizing anti-HIV antibodies incorporate unusual structural elements and recognition specificities or properties that often lead to autoreactivity. The ontogeny of 4E10, an autoreactive antibody with unexpected combining site flexibility, was delineated through structural and biophysical comparisons of the mature antibody with multiple potential precursors. 4E10 gained affinity primarily by off-rate enhancement through a small number of mutations to a highly conserved recognition surface. Controverting the conventional paradigm, the combining site gained flexibility and autoreactivity during ontogeny, while losing thermostability, though polyspecificity was unaffected. Details of the recognition mechanism, including inferred global effects due to 4E10 binding, suggest that neutralization by 4E10 may involve mechanisms beyond simply binding, also requiring the ability of the antibody to induce conformational changes distant from its binding site. 4E10 is, therefore, unlikely to be re-elicited by conventional vaccination strategies.

  3. Exquisite specificity and peptide epitope recognition promiscuity, properties shared by antibodies from sharks to humans.

    Science.gov (United States)

    Marchalonis, J J; Adelman, M K; Robey, I F; Schluter, S F; Edmundson, A B

    2001-01-01

    This review considers definitions of the specificity of antibodies including the development of recent concepts of recognition polyspecificity and epitope promiscuity. Using sets of homologous and unrelated peptides derived from the sequences of immunoglobulin and T cell receptor chains we offer operational definitions of cross-reactivity by investigating correlations of either identities in amino acid sequence, or in hydrophobicity/hydrophilicity profiles with degree of binding in enzyme-linked immunosorbent assays. Polyreactivity, or polyspecificity, are terms used to denote binding of a monoclonal antibody or purified antibody preparation to large complex molecules that are structurally unrelated, such as thyroglobulin and DNA. As a first approximation, there is a linear correlation between degree of sequence identity or hydrophobicity/hydrophilicity and antigenic cross-binding. However, catastrophic interchanges of amino acids can occur where changing of one amino acid out of 16 in a synthetic peptide essentially eliminates binding to certain antibodies. An operational definition of epitope promiscuity for peptides is the case where two peptides show little or no identity in amino acid sequence but bind strongly to the same antibody as shown by either direct binding or competitive inhibition. Analysis of antibodies of humans and sharks, the two most divergent species in evolution to express antibodies and the combinatorial immune response, indicates that the capacity for both exquisite specificity and epitope recognition promiscuity are essential conserved features of individual vertebrate antibodies.

  4. Synthesis of isotopically labeled versions of L-MTP-PE (mifamurtide) and MDP.

    Science.gov (United States)

    Li, Yuexian; Plesescu, Mihaela; Prakash, Shimoga R

    2013-01-01

    L-MTP-PE (1), an immunomodulator and its metabolite MDP (4) were synthesized from labeled l-alanine and its protected derivative, respectively. The key intermediate product for the labeled L-MTP-PE synthesis, [(13) C3 ,D4 ]-alanyl-cephalin (2A), was synthesized from [(13) C3 ,D4 ]-l-alanine (3A) in three steps. The key intermediate product for labeled MDP synthesis, amine 11, was prepared from [(13) C3 ,(15) N]-Boc-l-alanine (5A) in two steps.

  5. Highly sensitive detection of the group A Rotavirus using Apolipoprotein H-coated ELISA plates compared to quantitative real-time PCR

    Directory of Open Access Journals (Sweden)

    Veas Francisco

    2011-02-01

    Full Text Available Abstract Background The principle of a capture ELISA is binding of specific capture antibodies (polyclonal or monoclonal to the surface of a suitable 96 well plate. These immobilized antibodies are capable of specifically binding a virus present in a clinical sample. Subsequently, the captured virus is detected using a specific detection antibody. The drawback of this method is that a capture ELISA can only function for a single virus captured by the primary antibody. Human Apolipoprotein H (ApoH or β2-glycoprotein 1 is able to poly-specifically bind viral pathogens. Replacing specific capture antibodies by ApoH should allow poly-specific capture of different viruses that subsequently could be revealed using specific detection antibodies. Thus, using a single capture ELISA format different viruses could be analysed depending on the detection antibody that is applied. In order to demonstrate that this is a valid approach we show detection of group A rotaviruses from stool samples as a proof of principle for a new method of capture ELISA that should also be applicable to other viruses. Results Stool samples of different circulating common human and potentially zoonotic group A rotavirus strains, which were pretested in commercial EIAs and genotyped by PCR, were tested in parallel in an ApoH-ELISA set-up and by quantitative real-time PCR (qPCR. Several control samples were included in the analysis. The ApoH-ELISA was suitable for the capture of rotavirus-particles and the detection down to 1,000 infectious units (TCID50/ml. Subsets of diagnostic samples of different G- and P-types were tested positive in the ApoH-ELISA in different dilutions. Compared to the qPCR results, the analysis showed high sensitivity, specificity and low cross-reactivity for the ApoH-ELISA, which was confirmed in receiver operating characteristics (ROC analysis. Conclusions In this study the development of a highly sensitive and specific capture ELISA was demonstrated by

  6. 29 CFR Appendix D to Subpart R of... - Illustration of the Use of Control Lines To Demarcate Controlled Decking Zones (CDZs): Non...

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 8 2010-07-01 2010-07-01 false Illustration of the Use of Control Lines To Demarcate Controlled Decking Zones (CDZs): Non-mandatory Guidelines for Complying With § 1926.760(c)(3) D Appendix D... Steel Erection Pt. 1926, Subpt. R, App. D Appendix D to Subpart R of Part 1926—Illustration of the...

  7. Complement and Immunotheraphy of Breast Cancer

    Science.gov (United States)

    2007-10-01

    immunized with either MUC1/TR5 or MUC1/TR5-C3d recombinant fusion protein. The isolated splenocytes were used in an interferon gamma ELISPOT to...on day 78 by interferon gamma ELISPOT. Gamma irradiated vector or MUC1 transfected EO771 cells were used as targets. Results are representative of

  8. Immune haemolytic anaemia associated with ampicillin dependent warm antibodies and high titre cold agglutinins in a patient with Mycoplasma pneumonia

    DEFF Research Database (Denmark)

    Mickley, H; Sørensen, P G

    1984-01-01

    A case of severe immune haemolytic anaemia in a 54-year-old man suffering from Mycoplasma pneumonia is presented. A strongly positive direct Coombs test with erythrocyte bound IgG, C3d and C4 was demonstrated during the haemolytic process. Further, serologic investigations revealed ampicillin...

  9. Vibrational Spectroscopy of CH/CD Stretches in Propadiene: An Algebraic Approach

    Institute of Scientific and Technical Information of China (English)

    Joydeep Choudhury; Nirmal Kumar Sarkar; Srinivasa Rao Kaxumuri; Ramendu Bhattacharjee

    2009-01-01

    Using Hamiltonian based on Lie algebraic method, the stretching vibrational modes of C3H4 and C3D4 molecules are calculated up to higher overtones. The model appears to describe C-H and C-D stretching modes with less number of parameters. The locality parameter ξ confirms the highly local behaviour of the stretching modes of these molecules.

  10. Complement binding to erythrocytes is associated with macrophage activation and reduced haemoglobin in Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Goka, B Q; Kwarko, H; Kurtzhals, J A

    2001-01-01

    of 199 patients had a positive DAT. Of these, 45 samples reacted with anti-C3d antibodies, 2 with anti-IgG and 6 with both reagents. There were significantly lower haemoglobin (Hb)-levels and higher prevalence of spleen enlargement in DAT-positive than in DAT-negative patients. Hb-levels were...

  11. Domain Modeling: NP_003794.3 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_003794.3 chr18 Crystal structure of a prolactin receptor antagonist bound to the... extracellular domain of the prolactin receptor c3d48r_ chr18/NP_003794.3/NP_003794.3_holo_933-1136.pdb psi-blast 0 ...

  12. Disease: H00473 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available rome (LS) [DS:H01354]; Leber Hereditary Optic Neuropathy (LHON) [DS:H00068]; Leber Optic Atrophy and Dystoni...y, encephalopathy (including MELAS), cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber...l complex I deficiency (MT-C1D); Complex II deficiency (MT-C2D); Complex III deficiency (MT-C3D); Leigh synd

  13. Activation of human microglia by fibrillar prion protein-related peptides is enhanced by amyloid-associated factors SAP and C1q

    NARCIS (Netherlands)

    Veerhuis, R.; Boshuizen, R.S.; Morbin, M.; Mazzoleni, G.; Hoozemans, J.J.; Langedijk, J.P.; Tagliavini, F.; Langeveld, J.P.M.; Eikelenboom, P.

    2005-01-01

    Complement activation products C1q and C3d, serum amyloid P component (SAP) and activated glial cells accumulate in amyloid deposits of conformationally changed prion protein (PrPSc) in Creutzfeldt¿Jakob disease, Gerstmann¿Sträussler¿Scheinker disease and scrapie-infected mouse brain. Biological pro

  14. Comparison of Isocentric C-Arm 3-Dimensional Navigation and Conventional Fluoroscopy for Percutaneous Retrograde Screwing for Anterior Column Fracture of Acetabulum: An Observational Study.

    Science.gov (United States)

    He, Jiliang; Tan, Guoqing; Zhou, Dongsheng; Sun, Liang; Li, Qinghu; Yang, Yongliang; Liu, Ping

    2016-01-01

    Percutaneous screw insertion for minimally displaced or reducible acetabular fracture using x-ray fluoroscopy and computer-assisted navigation system has been advocated by some authors. The purpose of this study was to compare intraoperative conditions and clinical results between isocentric C-arm 3-dimensional (Iso-C 3D) fluoroscopy and conventional fluoroscopy for percutaneous retrograde screwing of acetabular anterior column fracture.A prospective cohort study was conducted. A total of 22 patients were assigned to 2 different groups: 10 patients in the Iso-C 3D navigation group and 12 patients in the conventional group. The operative time, fluoroscopic time, time of screw insertion, blood loss, and accuracy were analyzed between the 2 groups.There were significant differences in operative time, screw insertion time, fluoroscopy time, and mean blood loss between the 2 groups. Totally 2 of 12 (16.7%) screws were misplaced in the conventional fluoroscopy group, and all 10 screws were in safe zones in the navigation group. Percutaneous screw fixation using the Iso-C 3D computer-assisted navigation system significantly reduced the intraoperative fluoroscopy time and blood loss in percutaneous screwing for acetabular anterior column fracture.The Iso-C 3D computer-assisted navigation system provided a reliable and effective method for percutaneous screw insertion in acetabular anterior column fractures compared to conventional fluoroscopy.

  15. Hyperpolarized (13) C,(15) N2 -Urea MRI for assessment of the urea gradient in the porcine kidney

    DEFF Research Database (Denmark)

    Hansen, Esben S S; Stewart, Neil J; Wild, Jim M;

    2016-01-01

    function in healthy porcine kidneys resembling the human physiology. METHODS: Five healthy female Danish domestic pigs (weight 30 kg) were scanned at 3 Tesla (T) using a (13) C 3D balanced steady-state MR pulse sequence following injection of hyperpolarized (13) C,(15) N2 -urea via a femoral vein catheter...

  16. Utilization of stable isotopes for studying biological macromolecules by high-resolution NMR; Utilisation des isotopes stables pour l`etude de macromolecules biologiques par R.M.N. a haute resolution

    Energy Technology Data Exchange (ETDEWEB)

    Jamin, N.; Gilles, N.; Lirsac, P.N.; Menez, A.; Toma, F. [CEA Centre d`Etudes de Saclay, 91 - Gif-sur-Yvette (France). Direction des Sciences du Vivant; Bostadt, A.; Gabrielsen, O.S. [Oslo Univ. (Norway)

    1994-12-31

    Stable isotope labelling applications for nuclear magnetic resonance study of proteins are reviewed and several examples of utilization of these techniques are given. Resolution limitations for very large protein are discussed. Examples are also given for labelling other biomolecules such as ARN and ADN with {sup 2}H, {sup 15}N and {sup 13}C (3D structure of proteins). 2 figs., 39 refs.

  17. The Effect of Bovine IFN-α on the Immune Response in Guinea Pigs Vaccinated with DNA Vaccine of Foot-and-Mouth Disease Virus

    Institute of Scientific and Technical Information of China (English)

    Hui-Chen GUO; Zai-Xin LIU; Shi-Qi SUN; Qing-Wen LENG; Dong LI; Xiang-Tao LIU; Qing-Ge XIE

    2004-01-01

    In this study, we constructed recombinant plasmid pcDNA3.1/P 12X3C3D including P 1, 2A,3C, 3D and part of 2B gene of FMDV and pcDNA3.1/IFN containing the gene encoding bovine IFN-α. We inoculated the DNA vaccine pcDNA3.1/P 12X3C3D with or without pcDNA3.1/IFN to evaluate the efficiency of this DNA vaccine and the immunogenicity of DNA vaccine enhanced by the co-delivery with pcDNA3.1/IFN. After two times of vaccination with DNA vaccine, all of guinea pigs were challenged with 103 ID50 FMDV type O. Anti-FMDV antibody levels were detected by ELISA and T lymphocyte proliferation response was tested by MTT assay. The result shows that guinea pigs inoculated by pcDNA3. 1/P 12X3C3D alone or with pcDNA3.1/IFN generated specific antibodies and induced an FMDV-specific T lymphocyte proliferation response. FMDV challenge tests showed that one in four guinea pigs immunized by pcDNA3.1/P 12X3C3D with pcDNA3.1/IFN was protected from the FMDV serotype O infection. This result indicated that the efficiency of the DNA vaccine was enhanced by co-delivery with pcDNA3.1/IFN. However, the protection rate was considerably lower than that immunized with conventional FMD vaccine.

  18. The Structure-Function Relationships of Complement Receptor Type 2 (CR2; CD21).

    Science.gov (United States)

    Hannan, Jonathan Paul

    2016-01-01

    Human complement receptor type 2 (CR2; CD21) is a surface-associated glycoprotein which binds to a variety of endogenous ligands, including the complement component C3 fragments iC3b, C3dg and C3d, the low-affinity IgE receptor CD23, and the type I cytokine, interferon-alpha. CR2 links the innate complement-mediated immune response to pathogens and foreign antigens with the adaptive immune response by binding to C3d that is covalently attached to targets, and which results in a cell signalling phenomenon that lowers the threshold for B cell activation. Variations or deletions of the CR2 gene in humans, or the Cr2 gene in mice associate with a variety of autoimmune and inflammatory conditions. A number of infectious agents including Epstein-Barr virus (EBV), Human Immunodeficiency Virus (HIV) and prions also bind to CR2 either directly or indirectly by means of C3d-targeted immune complexes. In this review we discuss the interactions that CR2 undertakes with its best characterized ligands C3d, CD23 and the EBV gp350/220 envelope protein. To date only a single physiologically relevant complex of CR2 with one of its ligands, C3d, has been elucidated. By contrast, the interactions with CD23 and EBV gp350/220, while being important from physiologic and disease-associated standpoints, respectively, are only incompletely understood. A detailed knowledge of the structure-function relationships that CR2 undergoes with its ligands is necessary to understand the implications of using recombinant CR2 in therapeutic or imaging agents, or alternatively targeting CR2 to down-regulate the antibody mediated immune response in cases of autoimmunity.

  19. Cloning and expression of the Legionella micdadei "common antigen" in Escherichia coli

    DEFF Research Database (Denmark)

    Bangsborg, Jette Marie; Collins, M T; Høiby, N;

    1989-01-01

    To study individual Legionella antigens, a Legionella micdadei genomic library in Escherichia coli SC181 was established. Partially Sau3A digested L. micdadei DNA fragments (15-25 kilobase pairs (kb] were cloned into the tetracycline resistance gene of the cosmid vector pHC79. Four thousand...... ampicillin resistant recombinants were obtained; seven hundred were screened for expression of Legionella antigens in Western blot analysis with a polyspecific E. coli-absorbed anti-L. micdadei rabbit antibody. One of the positive clones expressed a 60 kilodalton (K) antigen, which reacted strongly...... will provide important information with respect to genetic vs. antigenic relatedness among Legionellae and other Gram-negative species, as well as to CA structure and possible function....

  20. [Hybridization of crucian carp, Carassius carassius (Linnaeus, 1758), in Ukrainian reservoirs and genetic structure of hybrids].

    Science.gov (United States)

    Mezhzheryn, S V; Kokodyĭĭ, S V; Kulysh, A V; Verlat'iĭĭ, D B; Fedorenko, L V

    2012-01-01

    Hybridization of crucian carps Carassius carassius in polyspecific crucian populations of reservoirs of Ukraine and genetic structure of the hybrids were investigated using biochemical gene marking and cytometric procedure. The fact of wide hybridization between C. auratus and C. carassius was proved to be true by large number of hybrids which can form populations consisting only from hybrid individuals. Hybrids C. auratus x C. carassius were diploid, tryploid and in exceptional cases tetraploid; females and males which most likely breed by hybridogenesis. Besides, some clonal hybrids C. carassius x C. gibelio-1 appearing as tetraploid females, and one triploid female C. carassius x Tinca tinca were revealed. It is supported that hybridization of alien C. auratus with endemic C. carassius became one of mechanisms of replacement and depressions of populations of the last.

  1. The choreography of multidrug export.

    Science.gov (United States)

    Doshi, Rupak; Gutmann, Daniel A P; Khoo, Yvonne S K; Fagg, Lisa A; van Veen, Hendrik W

    2011-06-01

    Multidrug transporters have a crucial role in causing the drug resistance that can arise in infectious micro-organisms and tumours. These integral membrane proteins mediate the export of a broad range of unrelated compounds from cells, including antibiotics and anticancer agents, thus reducing the concentration of these compounds to subtoxic levels in target cells. In spite of intensive research, it is not clear exactly how multidrug transporters work. The present review focuses on recent advancements in the biochemistry and structural biology of bacterial and human multidrug ABC (ATP-binding cassette) transporters. These advancements point to a common mechanism in which polyspecific drug-binding surfaces in the membrane domains are alternately exposed to the inside and outside surface of the membrane in response to the ATP-driven dimerization of nucleotide-binding domains and their dissociation following ATP hydrolysis.

  2. Characterisation of non-maternal serum proteins in amniotic fluid at weeks 16 to 18 of gestation

    DEFF Research Database (Denmark)

    Drøhse, H; Christensen, H; Myrhøj, Vibeke;

    1998-01-01

    Proteins found in amniotic fluid are mainly serum proteins, probably of maternal origin. About 5% of the total protein concentration has the potential of being fetal or decidual in origin. Only a few of these proteins have been isolated and characterised. In order to describe the foetal...... and decidual components in amniotic fluid more extensively, a polyspecific antiserum to amniotic fluid at weeks 16-18 of gestation was raised. Specificities in the antiserum to serum proteins were removed by adsorption. Several proteins of non-serum protein origin reacted with the antiserum. Three...... of these proteins were chosen for isolation and further characterisation. With the use of immunological methods, SDS-PAGE and N-terminal sequencing we identified two of the proteins as C-terminal propeptides of procollagen Type I and Type III, which have not hitherto been described in amniotic fluid. The third...

  3. Rheumatoid factors, B cells and immunoglobulin genes.

    Science.gov (United States)

    Jefferis, R

    1995-04-01

    The paradigm of self, non-self discrimination in the immune system is under review as autoreactive B or T cells are increasingly delineated within normal individuals. The products of autoreactive B cells are, mostly, polyspecific IgM antibodies of low affinity. These 'natural' antibodies include rheumatoid factors (RF) encoded by unmutated germline immunoglobulin genes. In rheumatoid arthritis (RA) the RF may be of the IgM, IgG or IgA isotype, show evidence of somatic mutation and have increased affinity; consistent with maturation of an antigen driven immune response. This response could be initiated or driven by an auto-immunogenic form of IgG or an exogenous cross-reactive antigen. Changes in galactosylation of IgG have been reported to be a valuable diagnostic and prognostic indicator in RA. Speculation that these changes may precipitate some of the disease processes is critically reviewed.

  4. The role played by drug efflux pumps in bacterial multidrug resistance.

    Science.gov (United States)

    Chitsaz, Mohsen; Brown, Melissa H

    2017-02-28

    Antimicrobial resistance is a current major challenge in chemotherapy and infection control. The ability of bacterial and eukaryotic cells to recognize and pump toxic compounds from within the cell to the environment before they reach their targets is one of the important mechanisms contributing to this phenomenon. Drug efflux pumps are membrane transport proteins that require energy to export substrates and can be selective for a specific drug or poly-specific that can export multiple structurally diverse drug compounds. These proteins can be classified into seven groups based on protein sequence homology, energy source and overall structure. Extensive studies on efflux proteins have resulted in a wealth of knowledge that has made possible in-depth understanding of the structures and mechanisms of action, substrate profiles, regulation and possible inhibition of many clinically important efflux pumps. This review focuses on describing known families of drug efflux pumps using examples that are well characterized structurally and/or biochemically.

  5. Welcome to Antibodies: A New Open Access, Multidisciplinary Journal

    Directory of Open Access Journals (Sweden)

    Tomohiro Kurosaki

    2011-12-01

    Full Text Available Secreted antibodies are a key player for exerting appropriate humoral immunity. For instance, in infectious diseases, poly-specific “natural” antibodies provide early protection, independent of T cell help. If this line of defense is crossed, T cell-dependent immune responses then generate a humoral memory provided by long-lived plasma cells secreting specific antibodies of adapted avidity and isotype. Secreted antibodies provide an efficient line of defense against re-infection and are backed up by specific memory B and T cells. In the field of humoral immunity, great discoveries including identification of a special T cell subset helping B cell activation (TFH, have been made in a last couple of years; however, important questions (such as mechanisms for affinity maturation of antibodies still remain. [...

  6. Antibody engineering and therapeutics, The Annual Meeting of the Antibody Society: December 8-12, 2013, Huntington Beach, CA.

    Science.gov (United States)

    Almagro, Juan Carlos; Gilliland, Gary L; Breden, Felix; Scott, Jamie K; Sok, Devin; Pauthner, Matthias; Reichert, Janice M; Helguera, Gustavo; Andrabi, Raiees; Mabry, Robert; Bléry, Mathieu; Voss, James E; Laurén, Juha; Abuqayyas, Lubna; Barghorn, Stefan; Ben-Jacob, Eshel; Crowe, James E; Huston, James S; Johnston, Stephen Albert; Krauland, Eric; Lund-Johansen, Fridtjof; Marasco, Wayne A; Parren, Paul W H I; Xu, Kai Y

    2014-01-01

    The 24th Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates.

  7. The protective effect of modified intravenous immunoglobulin in LPS sepsis model is associated with an increased IRA B cells response.

    Science.gov (United States)

    Djoumerska-Alexieva, Iglika; Pashova, Shina; Vassilev, Tchavdar; Pashov, Anastas

    2013-04-01

    Intravenous immunoglobulin preparations (IVIg) that have undergone a mild oxidizing treatment with ferrous ions have an increased polyspecificity, which is not associated with a higher propensity to form aggregates. Among other biological properties of the modified IVIg, a protective effect in LPS sepsis model stands out as the native preparation is totally devoid of it or even exacerbates sepsis. A recent finding identified an LPS induced subset of B1 lymphocytes that migrate from the peritoneal cavity to the spleen acquiring the expression of CD93, GM-CSF as well as the capacity to control sepsis. This report demonstrates that modified IVIg, but not the native preparation, causes a further increase in this population during LPS sepsis. Partial targeted suppression of the peritoneal B cell proliferation by an intracellular dye abrogates this effect and the clinical benefit of modified IVIg.

  8. [The bipolarity of the genetic structure of communities of the crucian carp (Carassius linnaeus, 1758) as a reflection of paradoxal reproductive relationships].

    Science.gov (United States)

    Mezhzherin, S V; Kokodiy, S V; Kulish, A V; Pukhtaevitch, P P

    2015-01-01

    An analysis of 133 populations of Carasiius spp. from water bodies in Ukraine showed their polyspecific structure: 62% of individuals of the studied 3453 specimens. turned out to be bisexual goldfishes C. auratus, 25%. were unisexual Prissian carps C. gibelio, 6% accounted for the aboriginal species crucian carp C. carassius, and 6% were hybrids C. auratus x C. carassius. In this case a clear trend has been revealed towards the formation of homogeneous alternative populations, specifically: either C. auratus, or C. gibelio. Individuals of C. carassius and the hybrids C. auratus x C. carassius typically comprise an admixture in various populations. The cause of the bipolar distribution of individuals of C. auratus and C. gibelio between various water bodies is the instability of mixed populations as far as individuals of C. auratus very quickly replace females of C. gibelio due to their low reproductive potential.

  9. The value of csf analysis for the differential diagnosis of HTLV-I associated myelopathy and multiple sclerosis Valor da análise do LCR para o diagnóstico diferencial de mielopatia associada ao HTLV-I e esclerose múltipla

    Directory of Open Access Journals (Sweden)

    Marzia Puccioni-Sohler

    1995-12-01

    Full Text Available Cerebrospinal fluid (CSF and serum of 17 patients with HAM/TSP (HTLV-I associated myelopathy/ tropical spastic paraparesis, six with multiple sclerosis and six with idiopathic epilepsy (non inflammatory control from Brazil were analysed for the presence of intrathecal synthesis of virus-specific antibodies against measles, rubella, varicella zoster virus and herpes simplex virus by enzyme-linked immunosorbent assay (ELISA. All HAM/TSP and multiple sclerosis cases had an intrathecal immune response (oligoclonal IgG. In HAM/TSP, only 1/17 case showed a polyspecific intrathecal immune response against measles and rubella virus. In multiple sclerosis, specific antibodies against measles and rubella (MRZ response were observed in all patients but not in the control with idiopathic epilepsy. The diagnostic and theoretical relevance of mono- and polyspecific immune responses is discussed for these chronic neurological diseases.Amostras de líquido cefalorraquidiano (LCR e soro de 17 pacientes brasileiros com HAM/TSP, seis com esclerose múltipla e seis com epilepsia idiopática (controle não-inflamatório foram analisadas para a presença de anticorpos para os vírus do sarampo, rubéola, varicela zoster e herpes simples pelo método de ELISA. Todos os casos de HAM/TSP e esclerose múltipla tinham resposta imune intratecal (IgG oligoclonal. Somente 1/17 casos de HAM/TSP apresentavam resposta imune poliespecifica intratecal para sarampo e rubéola. Anticorpos específicos para sarampo e rubeola (resposta MRZ foram observados em todos os pacientes com esclerose múltipla, mas não nos controles com epilepsia idiopática. A relevância das respostas poliespecifica e monoespecifica é discutida para essas doenças neurológicas crônicas.

  10. ZZAP和CDP放散DAT阳性红细胞的效果评价%Effect of ZZAP and CDP elution tests on DAT(+)red blood cells

    Institute of Scientific and Technical Information of China (English)

    何子毅; 刘赴平; 刘景春; 车嘉林; 师清莲; 刘仁强; 唐斯; 陈晨

    2009-01-01

    目的:比较ZZAP和CDP两种放散方法放散DAT(+)红细胞的效果及放散后红细胞吸收自身抗体的能力,为DAT(+)红细胞的抗体放散方法提供依据.方法:收集本站送检的DAT(+)交叉配血标本,选择抗-IgG型与抗-(IgG+C3d)复合型各20例作为研究对象,分别采用ZZAP和CDP两种放散方法进行抗体放散试验,对放散后红细胞分别进行DAT试验;用放散后的红细胞吸收患者血浆自身抗体后进行交叉配血试验,评价自身抗体的吸收效果.结果:抗-(IgG+C3d)复合型DAT(+)红细胞用ZZAP和CDP放散效果无差别,ZZAP放散抗-IgG型的效果好于抗-(IgG+C3d)复合型(P<0.05),CDP放散抗-IgG型与抗-(IgG+C3d)复合型的效果无差异;ZZAP放散抗-IgG型和抗-(IgG+C3d)复合型DAT(+)红细胞后的抗体吸收效果均好于CDP(P<0.05),ZZAP和CDP放散抗-IgG型DAT(+)红细胞后的吸收效果无明显差异,CDP放散抗-IgG型和抗-(IgG+C3d)复合型DAT(+)红细胞后的吸收效果无差别,ZZAP放散抗-IgG型DAT(+)红细胞后的吸收效果均好于抗-(IgG+C3d)复合型(P<0.05).结论:抗-(IgG+C3d)复合型DAT(+)红细胞用两种方法均不能很好的解离自身抗体,但对抗-IgG型自身抗体的解离用ZZAP好于CDP,提示临床交叉配血试验中对抗-(IgG+C3d)复合型自身抗体最好选择盲配原则的配血方案,对抗-IgG型自身抗体用ZZAP进行吸收放散效果较好.

  11. A novel trifunctional IgG-like bispecific antibody to inhibit HIV-1 infection and enhance lysis of HIV by targeting activation of complement

    Directory of Open Access Journals (Sweden)

    Tomlinson Stephen

    2010-06-01

    Full Text Available Abstract Background The complement system is not only a key component of innate immunity but also provides a first line of defense against invading pathogens, especially for viral pathogens. Human immunodeficiency virus (HIV, however, possesses several mechanisms to evade complement-mediated lysis (CoML and exploit the complement system to enhance viral infectivity. Responsible for this intrinsic resistance against complement-mediated virolysis are complement regulatory membrane proteins derived from the host cell that inherently downregulates complement activation at several stages of the cascade. In addition, HIV is protected from complement-mediated lysis by binding soluble factor H (fH through the viral envelope proteins, gp120 and gp41. Whereas inhibition of complement activity is the desired outcome in the vast majority of therapeutic approaches, there is a broader potential for complement-mediated inhibition of HIV by complement local stimulation. Presentation of the hypothesis Our previous studies have proven that the complement-mediated antibody-dependent enhancement of HIV infection is mediated by the association of complement receptor type 2 bound to the C3 fragment and deposited on the surface of HIV virions. Thus, we hypothesize that another new activator of complement, consisting of two dsFv (against gp120 and against C3d respectively linked to a complement-activating human IgG1 Fc domain ((anti-gp120 × anti-C3d-Fc, can not only target and amplify complement activation on HIV virions for enhancing the efficiency of HIV lysis, but also reduce the infectivity of HIV through blocking the gp120 and C3d on the surface of HIV. Testing the hypothesis Our hypothesis was tested using cell-free HIV-1 virions cultivated in vitro and assessment of virus opsonization was performed by incubating appropriate dilutions of virus with medium containing normal human serum and purified (anti-gp120 × anti-C3d-Fc proteins. As a control group, viruses

  12. The terminal complement complex is generated in chronic leg ulcers in the absence of protectin (CD59)

    DEFF Research Database (Denmark)

    Balslev, E; Thomsen, H K; Danielsen, L;

    1999-01-01

    hypertension leg ulcers. The deposition of complement, plasma complement regulators and expression of membrane regulators were detected by immunohistochemical methods, including immunofluorescence with antibodies against C3d, the terminal complement complex (TCC), vitronectin, clusterin, decay......-accelerating factor (CD55) and protectin (CD59). Eleven frozen biopsies from ischaemic leg ulcers, 10 biopsies from venous hypertension leg ulcers, and 10 biopsies from normal skin were studied. In 9 of 11 ischaemic and in 5 of 10 venous hypertension leg ulcers, marked staining for TCC was found around...... the capillaries, most often at the ulcer margin. No TCC staining was found in normal skin. Staining for TCC was always accompanied by staining for clusterin and vitronectin and C3d. In normal skin, CD59 was found on the elastic fibers in the dermis, on the muscle coat, the Schwann sheath and acinar cells...

  13. A Ballistic Material Model for Cross-Plied Unidirectional Ultra-High Molecular-Weight Polyethylene Fiber-Reinforced Armor-Grade Composites

    Science.gov (United States)

    2008-01-01

    user subroutine, VUMAT , of the commercial finite-element program ABAQUS/ Explicit [2]. This subroutine is compiled and linked with the finite-element...ABAQUS/Explicit designation C3D6R) are used. The essential features of the coupling between the ABAQUS/Explicit finite-element solver and the VUMAT ...state variable(s) at the end of the time increment are determined within the VUMAT and returned to the ABAQUS/Explicit finite- element solver. In

  14. Binding of peanut lectin to germinal-centre cells: a marker for B-cell subsets of follicular lymphoma?

    OpenAIRE

    De Rose, M L; Habeshaw, J A; R. Kennedy; Sloane, J.; Wiltshaw, E; Davies, A. J.

    1981-01-01

    The binding of horseradish-peroxidase-labelled peanut lectin (HRP-PNL) to cryostat sections of tonsil, lymphoma lymph nodes, reactive lymph nodes and miscellaneous tumours demonstrated that PNL binds selectively to lymphocytes in germinal centres. Lymph nodes from 21 patients with non-Hodgkin's lymphomas were phenotyped as cell suspensions for PNL binding, and the following surface markers: E rosetting, C3d, SIg, OK markers of T-cell subsets, Ig heavy-chain and light-chain classes. There was ...

  15. Canada in 3D - Toward a Sustainable 3D Model for Canadian Geology from Diverse Data Sources

    Science.gov (United States)

    Brodaric, B.; Pilkington, M.; Snyder, D. B.; St-Onge, M. R.; Russell, H.

    2015-12-01

    Many big science issues span large areas and require data from multiple heterogeneous sources, for example climate change, resource management, and hazard mitigation. Solutions to these issues can significantly benefit from access to a consistent and integrated geological model that would serve as a framework. However, such a model is absent for most large countries including Canada, due to the size of the landmass and the fragmentation of the source data into institutional and disciplinary silos. To overcome these barriers, the "Canada in 3D" (C3D) pilot project was recently launched by the Geological Survey of Canada. C3D is designed to be evergreen, multi-resolution, and inter-disciplinary: (a) it is to be updated regularly upon acquisition of new data; (b) portions vary in resolution and will initially consist of four layers (surficial, sedimentary, crystalline, and mantle) with intermediary patches of higher-resolution fill; and (c) a variety of independently managed data sources are providing inputs, such as geophysical, 3D and 2D geological models, drill logs, and others. Notably, scalability concerns dictate a decentralized and interoperable approach, such that only key control objects, denoting anchors for the modeling process, are imported into the C3D database while retaining provenance links to original sources. The resultant model is managed in the database, contains full modeling provenance as well as links to detailed information on rock units, and is to be visualized in desktop and online environments. It is anticipated that C3D will become the authoritative state of knowledge for the geology of Canada at a national scale.

  16. Thermal In-Pouch Microwave Sterilization

    Science.gov (United States)

    2011-06-30

    vari- ables (water activity, vitamin content, oxidative vulnerabilities, etc.) ’ Model primary oxidative and moisture dynamics within packag- ing...B> 2- ^_ — — • _ — — — — # 1- o- C, C2 C3 D, D2 Dj...I stopped woiklno durifio UW run. tempeiatuie hrstorv lor thft trieb was lost ■ TTI from Aug 2010 M\\V testing, max "PC for D3 was 131,2*C Old

  17. Domain Modeling: NP_783641.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_783641.1 chr1 CR2-C3D COMPLEX STRUCTURE c1w2sb_ chr1/NP_783641.1/NP_783641.1_apo..._154-288.pdb c1ghqb_ chr1/NP_783641.1/NP_783641.1_holo_154-288.pdb blast 239I,240L,243D,244N,245R,252E,253V _ZN 1 ...

  18. Biomechanical ToolKit: Open-source framework to visualize and process biomechanical data.

    Science.gov (United States)

    Barre, Arnaud; Armand, Stéphane

    2014-04-01

    C3D file format is widely used in the biomechanical field by companies and laboratories to store motion capture systems data. However, few software packages can visualize and modify the integrality of the data in the C3D file. Our objective was to develop an open-source and multi-platform framework to read, write, modify and visualize data from any motion analysis systems using standard (C3D) and proprietary file formats (used by many companies producing motion capture systems). The Biomechanical ToolKit (BTK) was developed to provide cost-effective and efficient tools for the biomechanical community to easily deal with motion analysis data. A large panel of operations is available to read, modify and process data through C++ API, bindings for high-level languages (Matlab, Octave, and Python), and standalone application (Mokka). All these tools are open-source and cross-platform and run on all major operating systems (Windows, Linux, MacOS X).

  19. Comparison of hexahedral and tetrahedral elements in finite element analysis of the foot and footwear.

    Science.gov (United States)

    Tadepalli, Srinivas C; Erdemir, Ahmet; Cavanagh, Peter R

    2011-08-11

    Finite element analysis has been widely used in the field of foot and footwear biomechanics to determine plantar pressures as well as stresses and strains within soft tissue and footwear materials. When dealing with anatomical structures such as the foot, hexahedral mesh generation accounts for most of the model development time due to geometric complexities imposed by branching and embedded structures. Tetrahedral meshing, which can be more easily automated, has been the approach of choice to date in foot and footwear biomechanics. Here we use the nonlinear finite element program Abaqus (Simulia, Providence, RI) to examine the advantages and disadvantages of tetrahedral and hexahedral elements under compression and shear loading, material incompressibility, and frictional contact conditions, which are commonly seen in foot and footwear biomechanics. This study demonstrated that for a range of simulation conditions, hybrid hexahedral elements (Abaqus C3D8H) consistently performed well while hybrid linear tetrahedral elements (Abaqus C3D4H) performed poorly. On the other hand, enhanced quadratic tetrahedral elements with improved stress visualization (Abaqus C3D10I) performed as well as the hybrid hexahedral elements in terms of contact pressure and contact shear stress predictions. Although the enhanced quadratic tetrahedral element simulations were computationally expensive compared to hexahedral element simulations in both barefoot and footwear conditions, the enhanced quadratic tetrahedral element formulation seems to be very promising for foot and footwear applications as a result of decreased labor and expedited model development, all related to facilitated mesh generation.

  20. TU-G-BRA-07: Characterization of Tumor Proliferation During Successive Cycles of Anti-Angiogenic Therapy Using [F-18]FLT PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Scarpelli, M; Perlman, S; Harmon, S; Perk, T; Scully, P; Bruce, J; Liu, G; Jeraj, R [University of Wisconsin, Madison, WI (United States)

    2015-06-15

    Purpose: Studies have shown cessation of anti-angiogenic treatment during the first cycle of therapy resulted in rebound of tumor proliferation (flare). This study characterized proliferation dynamics during the first and third cycle of anti-angiogenic treatment using [F-18]FLT PET. Methods: Thirteen patients with various solid cancers were treated with Axitinib (Pfizer, Inc) at a dose of 5mg orally, twice daily, on contiguous three-week cycles with intermittent dosing (two-weeks-on/one-week-off). All patients received three FLT PET/CT scans during cycle 1 (C1): at baseline (C1D0), peak Axitinib concentration (C1D14), and the end of washout (C1D21). Ten patients received up to an additional three scans at corresponding time points during cycle 3 (C3). Lesions were identified by a nuclear medicine physician and manually contoured. Tumor burden was quantified using standard SUV metrics. Correlations between imaging metrics across C1 and C3 were calculated using the Spearman correlation. Results: At C1 peak drug concentration 11/13 patients had decreases in SUVtotal, with median decrease of 50% (change from C1D0 to C1D14). At C3 peak drug concentration 7/7 patients had decreases in SUVtotal, with median decrease of 20% (C3D0 to C3D14). Proliferative flare during C1 washout (>20% increase from C1D14 to C1D21) occurred in 9/13 patients, with median SUVtotal increase of 190%. Flare was also seen in C3 for 5/5 patients, with median SUVtotal increase of 70% (change from C3D14 to C3D21). Correlations were found between changes in imaging metrics across C1 and C3, notably the change in SUVtotal from C1D0 to C1D21 and the change in SUVtotal from C1D0 to C3D0 (ρ = 0.80). Conclusion: Measurements of SUVtotal showed that both patient response to treatment and flare were evident in both cycles of treatment. Correlation between changes in SUVtotal across C1 and C3 suggest early time points could be used to characterize patient response in later cycles. Research funded in part by

  1. An Outdated Notion of Antibody Specificity is One of the Major Detrimental Assumptions of the Structure-Based Reverse Vaccinology Paradigm, Which Prevented It from Helping to Develop an Effective HIV-1 Vaccine.

    Science.gov (United States)

    Van Regenmortel, Marc H V

    2014-01-01

    The importance of paradigms for guiding scientific research is explained with reference to the seminal work of Karl Popper and Thomas Kuhn. A prevalent paradigm, followed for more than a decade in HIV-1 vaccine research, which gave rise to the strategy known as structure-based reverse vaccinology is described in detail. Several reasons why this paradigm did not allow the development of an effective HIV-1 vaccine are analyzed. A major reason is the belief shared by many vaccinologists that antibodies possess a narrow specificity for a single epitope and are not polyspecific for a diverse group of potential epitopes. When this belief is abandoned, it becomes obvious that the one particular epitope structure observed during the crystallographic analysis of a neutralizing antibody-antigen complex does not necessarily reveal, which immunogenic structure should be used to elicit the same type of neutralizing antibody. In the physical sciences, scientific explanations are usually presented as logical deductions derived from a relevant law of nature together with certain initial conditions. In immunology, causal explanations in terms of a single cause acting according to a law of nature are not possible because numerous factors always play a role in bringing about an effect. The implications of this state of affairs for the rational design of HIV vaccines are outlined. An alternative approach to obtain useful scientific understanding consists in intervening empirically in the immune system and it is suggested that manipulating the system experimentally is needed to learn to control it and achieve protective immunity by vaccination.

  2. Crystal structure of the antigen-binding fragment of a monoclonal antibody specific for the multidrug-resistance-linked ABC transporter human P-glycoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Esser, Lothar; Shukla, Suneet; Zhou, Fei; Ambudkar, Suresh V.; Xia, Di

    2016-07-27

    P-glycoprotein (P-gp) is a polyspecific ATP-dependent transporter linked to multidrug resistance in cancers that plays important roles in the pharmacokinetics of a large number of drugs. The drug-resistance phenotype of P-gp can be modulated by the monoclonal antibody UIC2, which specifically recognizes human P-gp in a conformation-dependent manner. Here, the purification, sequence determination and high-resolution structure of the Fab fragment of UIC2 (UIC2/Fab) are reported. Purified UIC2/Fab binds human P-gp with a 1:1 stoichiometry. Crystals of UIC2/Fab are triclinic (space groupP1), with unit-cell parametersa= 40.67,b= 44.91,c= 58.09 Å, α = 97.62, β = 99.10, γ = 94.09°, and diffracted X-rays to 1.6 Å resolution. The structure was determined by molecular replacement and refined to 1.65 Å resolution. The asymmetric unit contains one molecule of UIC2/Fab, which exhibits a positively charged antigen-binding surface, suggesting that it might recognize an oppositely charged extracellular epitope of P-gp.

  3. Rigidity Emerges during Antibody Evolution in Three Distinct Antibody Systems: Evidence from QSFR Analysis of Fab Fragments.

    Directory of Open Access Journals (Sweden)

    Tong Li

    2015-07-01

    Full Text Available The effects of somatic mutations that transform polyspecific germline (GL antibodies to affinity mature (AM antibodies with monospecificity are compared among three GL-AM Fab pairs. In particular, changes in conformational flexibility are assessed using a Distance Constraint Model (DCM. We have previously established that the DCM can be robustly applied across a series of antibody fragments (VL to Fab, and subsequently, the DCM was combined with molecular dynamics (MD simulations to similarly characterize five thermostabilizing scFv mutants. The DCM is an ensemble based statistical mechanical approach that accounts for enthalpy/entropy compensation due to network rigidity, which has been quite successful in elucidating conformational flexibility and Quantitative Stability/Flexibility Relationships (QSFR in proteins. Applied to three disparate antibody systems changes in QSFR quantities indicate that the VH domain is typically rigidified, whereas the VL domain and CDR L2 loop become more flexible during affinity maturation. The increase in CDR H3 loop rigidity is consistent with other studies in the literature. The redistribution of conformational flexibility is largely controlled by nonspecific changes in the H-bond network, although certain Arg to Asp salt bridges create highly localized rigidity increases. Taken together, these results reveal an intricate flexibility/rigidity response that accompanies affinity maturation.

  4. Machine learning-, rule- and pharmacophore-based classification on the inhibition of P-glycoprotein and NorA.

    Science.gov (United States)

    Ngo, T-D; Tran, T-D; Le, M-T; Thai, K-M

    2016-09-01

    The efflux pumps P-glycoprotein (P-gp) in humans and NorA in Staphylococcus aureus are of great interest for medicinal chemists because of their important roles in multidrug resistance (MDR). The high polyspecificity as well as the unavailability of high-resolution X-ray crystal structures of these transmembrane proteins lead us to combining ligand-based approaches, which in the case of this study were machine learning, perceptual mapping and pharmacophore modelling. For P-gp inhibitory activity, individual models were developed using different machine learning algorithms and subsequently combined into an ensemble model which showed a good discrimination between inhibitors and noninhibitors (acctrain-diverse = 84%; accinternal-test = 92% and accexternal-test = 100%). For ligand promiscuity between P-gp and NorA, perceptual maps and pharmacophore models were generated for the detection of rules and features. Based on these in silico tools, hit compounds for reversing MDR were discovered from the in-house and DrugBank databases through virtual screening in an attempt to restore drug sensitivity in cancer cells and bacteria.

  5. Phenotypic and functional characteristics of human newborns' B lymphocytes.

    Science.gov (United States)

    Durandy, A; Thuillier, L; Forveille, M; Fischer, A

    1990-01-01

    It has been demonstrated two major facts concerning human newborns' B lymphocytes: 1) they differentiate poorly into Ig-producing cells and 2) they express CD5 and CD1c membrane proteins. We have further analyzed human newborns' B cell characteristics and found that approximately half of them express activation Ag, i.e., 4F2 and IL-2R, both associated in significant proportions with CD23 and Bac-1. These membrane Ag were found both on CD5(+) and CD5(-) B cells. Newborns' B cells do not exhibit other activation markers because they express surface IgD, and because their size, RNA, and DNA contents do not differ from those of adults' B cells, indicating that they are in the G0/G1 cell cycle phase. Newborns' B cell proliferation can be induced by rIL-2, rIL-4, low m.w. B cell growth factor, and by Staphylococcus aureus protein A. It is presently difficult to build a hypothesis accounting for all the specific findings made on newborns' B cells. It is not known for instance whether CD5(+) and (-) B cells belong to distinct subsets as suggested by the fluorescence intensity curve obtained with an anti-CD5 antibody or to distinct stages in a unique pattern of B cell maturation during fetal and newborn life. This may indicate that partially activated B cells actually produce natural polyspecific autoantibodies of the IgM isotype found in newborns' human serum.

  6. A new Dendropsophus Fitzinger, 1843 (Anura: Hylidae) of the parviceps group from the lowlands of the Guiana Shield.

    Science.gov (United States)

    Fouquet, Antoine; Orrico, Victor Goyannes Dill; Ernst, Raffael; Blanc, Michel; Martinez, Quentin; Vacher, Jean-Pierre; Rodrigues, Miguel Trefaut; Ouboter, Paul; Jairam, Rawien; Ron, Santiago

    2015-12-01

    Many Amazonian frog species that are considered widely distributed may actually represent polyspecific complexes.. A minute tree frog from the Guiana Shield originally assigned to the allegedly widely distributed Dendropsophus brevifrons proved to be a yet undescribed species within the D. parviceps group. We herein describe this new species and present a phylogeny for the D. parviceps group. The new species is diagnosed from other Dendropsophus of the parviceps group by its small body size (19.6-21.7 mm in males, 22.1-24.5 mm in females), thighs dorsally dark grey with cream blotches without bright yellow patch, absence of dorsolateral and canthal stripe, and an advertisement call comprising trills (length 0.30-0.35 s) composed of notes emitted at a rate of 131-144 notes/s, generally followed by click series of 2-3 notes. Its tadpole is also singular by having fused lateral marginal papillae and absence of both labial teeth and submarginal papillae. Genetic distances (p-distance) are >5.3% on the 12S and >9.3% on the 16S from D. brevifrons, its closest relative. This species occurs from the Brazilian state of Amapá, across French Guiana and Suriname to central Guyana and is likely to also occur in adjacent Brazilian states and eastern Venezuela. This species is not rare but is difficult to collect because of its arboreal habits and seasonal activity peaks.

  7. Strongyloides stercoralis and other Enteroparasites in Children at Uberlândia City, State of Minas Gerais, Brazil

    Directory of Open Access Journals (Sweden)

    Rodrigues Machado Eleuza

    1998-01-01

    Full Text Available To evaluate the rate of infection by Strongyloides stercoralis and other enteroparasites a survey was conducted in the city of Uberlândia, State of Minas Gerais, Brazil. A total of 900 stool samples from 300 children aging from four months to seven years, randomly selected in ten nursery schools from September 1994 to December 1995, were examined, both by the Baermann-Moraes and Lutz methods. Thirty nine children (13% were found to be infected by S. stercoralis, 64.1% were boys and 35.9% were girls. Taking all the enteroparasites as a whole the results of the survey pointed out that 265 (88.4% of the 300 children were infected by the following: Giardia lamblia, 78.3%; Ascaris lumbricoides, 15.3%; S. stercoralis, 13%; Hymenolepis nana, 6.7%; hookworms, 6%; Enterobius vermicularis, 4%; Hymenole-pis diminuta, 4% and Trichuris trichiura, 0.7%. From 265 infected children 64.5% were mono-infected, 27.2% were infected by two parasites and 8.3% had a poly-specific parasite burden. It was concluded that strongyloidiasis is hyperendemic in this area

  8. Role of acetylcholine and muscarinic receptors in serotonin-induced bronchoconstriction in the mouse.

    Science.gov (United States)

    Kummer, Wolfgang; Wiegand, Silke; Akinci, Sibel; Schinkel, Alfred H; Wess, Jürgen; Koepsell, Hermann; Haberberger, Rainer Viktor; Lips, Katrin Susanne

    2006-01-01

    For the murine trachea, it has been reported that constriction evoked by serotonin (5-HT) is largely dependent on acetylcholine (ACh) released from the epithelium, owing to the sensitivity of the 5-HT response to epithelium removal, sensitivity to atropine, and insensitivity to tetrodotoxin (Moffatt et al., 2003). Consistent with this assumption, the respiratory epithelium contains ACh, its synthesizing enzyme, and the high-affinity choline transporter CHT1 (Reinheimer et al., 1996; Pfeil et al., 2003; Proskocil et al., 2004). Recently, we demonstrated that ACh can be released from non-neuronal cells by corticosteroid-sensitive polyspecific organic cation transporters (OCTs), which are also expressed by airway epithelial cells (Lips et al., 2005). Hence, we proposed that 5-HT evokes release of ACh from epithelial cells via OCTs and that this epithelial-derived ACh induces bronchoconstriction. We tested this hypothesis in a well-established model of videomorphometric analysis of bronchial diameter in precision-cut murine lung slices utilizing epithelium removal to assess the role of the epithelium, OCT mouse knockout (KO) strains to assess the role of OCT isoforms, and muscarinic receptor M2/M3 double-KO mice to assess the cholinergic component of 5-HT induced bronchoconstriction, as bronchi of this strain are entirely unresponsive to cholinergic stimulation(Struckmann et al., 2003).

  9. Use of the uteroglobin platform for the expression of a bivalent antibody against oncofetal fibronectin in Escherichia coli.

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    Elisa Ventura

    Full Text Available Escherichia coli is a robust, economic and rapid expression system for the production of recombinant therapeutic proteins. However, the expression in bacterial systems of complex molecules such as antibodies and fusion proteins is still affected by several drawbacks. We have previously described a procedure based on uteroglobin (UG for the engineering of very soluble and stable polyvalent and polyspecific fusion proteins in mammalian cells (Ventura et al. 2009. J. Biol. Chem. 284∶26646-26654. Here, we applied the UG platform to achieve the expression in E. coli of a bivalent human recombinant antibody (L19 toward the oncofetal fibronectin (B-FN, a pan-tumor target. Purified bacterial L19-UG was highly soluble, stable, and, in all molecules, the L19 moiety maintained its immunoreactivity. About 50-70% of the molecules were covalent homodimer, however after refolding with the redox couple reduced-glutathione/oxidized-glutathione (GSH/GSSG, 100% of molecules were covalent dimers. Mass spectrometry studies showed that the proteins produced by E. coli and mammalian cells have an identical molecular mass and that both proteins are not glycosylated. L19-UG from bacteria can be freeze-dried without any loss of protein and immunoreactivity. In vivo, in tumor-bearing mice, radio-iodinated L19-UG selectively accumulated in neoplastic tissues showing the same performance of L19-UG from mammalian cells. The UG-platform may represent a general procedure for production of various biological therapeutics in E. coli.

  10. Computational predictive models for P-glycoprotein inhibition of in-house chalcone derivatives and drug-bank compounds.

    Science.gov (United States)

    Ngo, Trieu-Du; Tran, Thanh-Dao; Le, Minh-Tri; Thai, Khac-Minh

    2016-11-01

    The human P-glycoprotein (P-gp) efflux pump is of great interest for medicinal chemists because of its important role in multidrug resistance (MDR). Because of the high polyspecificity as well as the unavailability of high-resolution X-ray crystal structures of this transmembrane protein, ligand-based, and structure-based approaches which were machine learning, homology modeling, and molecular docking were combined for this study. In ligand-based approach, individual two-dimensional quantitative structure-activity relationship models were developed using different machine learning algorithms and subsequently combined into the Ensemble model which showed good performance on both the diverse training set and the validation sets. The applicability domain and the prediction quality of the developed models were also judged using the state-of-the-art methods and tools. In our structure-based approach, the P-gp structure and its binding region were predicted for a docking study to determine possible interactions between the ligands and the receptor. Based on these in silico tools, hit compounds for reversing MDR were discovered from the in-house and DrugBank databases through virtual screening using prediction models and molecular docking in an attempt to restore cancer cell sensitivity to cytotoxic drugs.

  11. Development of Conformation Independent Computational Models for the Early Recognition of Breast Cancer Resistance Protein Substrates

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    Melisa Edith Gantner

    2013-01-01

    Full Text Available ABC efflux transporters are polyspecific members of the ABC superfamily that, acting as drug and metabolite carriers, provide a biochemical barrier against drug penetration and contribute to detoxification. Their overexpression is linked to multidrug resistance issues in a diversity of diseases. Breast cancer resistance protein (BCRP is the most expressed ABC efflux transporter throughout the intestine and the blood-brain barrier, limiting oral absorption and brain bioavailability of its substrates. Early recognition of BCRP substrates is thus essential to optimize oral drug absorption, design of novel therapeutics for central nervous system conditions, and overcome BCRP-mediated cross-resistance issues. We present the development of an ensemble of ligand-based machine learning algorithms for the early recognition of BCRP substrates, from a database of 262 substrates and nonsubstrates compiled from the literature. Such dataset was rationally partitioned into training and test sets by application of a 2-step clustering procedure. The models were developed through application of linear discriminant analysis to random subsamples of Dragon molecular descriptors. Simple data fusion and statistical comparison of partial areas under the curve of ROC curves were applied to obtain the best 2-model combination, which presented 82% and 74.5% of overall accuracy in the training and test set, respectively.

  12. Rigidity Emerges during Antibody Evolution in Three Distinct Antibody Systems: Evidence from QSFR Analysis of Fab Fragments.

    Science.gov (United States)

    Li, Tong; Tracka, Malgorzata B; Uddin, Shahid; Casas-Finet, Jose; Jacobs, Donald J; Livesay, Dennis R

    2015-07-01

    The effects of somatic mutations that transform polyspecific germline (GL) antibodies to affinity mature (AM) antibodies with monospecificity are compared among three GL-AM Fab pairs. In particular, changes in conformational flexibility are assessed using a Distance Constraint Model (DCM). We have previously established that the DCM can be robustly applied across a series of antibody fragments (VL to Fab), and subsequently, the DCM was combined with molecular dynamics (MD) simulations to similarly characterize five thermostabilizing scFv mutants. The DCM is an ensemble based statistical mechanical approach that accounts for enthalpy/entropy compensation due to network rigidity, which has been quite successful in elucidating conformational flexibility and Quantitative Stability/Flexibility Relationships (QSFR) in proteins. Applied to three disparate antibody systems changes in QSFR quantities indicate that the VH domain is typically rigidified, whereas the VL domain and CDR L2 loop become more flexible during affinity maturation. The increase in CDR H3 loop rigidity is consistent with other studies in the literature. The redistribution of conformational flexibility is largely controlled by nonspecific changes in the H-bond network, although certain Arg to Asp salt bridges create highly localized rigidity increases. Taken together, these results reveal an intricate flexibility/rigidity response that accompanies affinity maturation.

  13. Role of metalloproteases in vaccinia virus epitope processing for transporter associated with antigen processing (TAP)-independent human leukocyte antigen (HLA)-B7 class I antigen presentation.

    Science.gov (United States)

    Lorente, Elena; García, Ruth; Mir, Carmen; Barriga, Alejandro; Lemonnier, François A; Ramos, Manuel; López, Daniel

    2012-03-23

    The transporter associated with antigen processing (TAP) translocates the viral proteolytic peptides generated by the proteasome and other proteases in the cytosol to the endoplasmic reticulum lumen. There, they complex with nascent human leukocyte antigen (HLA) class I molecules, which are subsequently recognized by the CD8(+) lymphocyte cellular response. However, individuals with nonfunctional TAP complexes or tumor or infected cells with blocked TAP molecules are able to present HLA class I ligands generated by TAP-independent processing pathways. Herein, using a TAP-independent polyclonal vaccinia virus-polyspecific CD8(+) T cell line, two conserved vaccinia-derived TAP-independent HLA-B*0702 epitopes were identified. The presentation of these epitopes in normal cells occurs via complex antigen-processing pathways involving the proteasome and/or different subsets of metalloproteinases (amino-, carboxy-, and endoproteases), which were blocked in infected cells with specific chemical inhibitors. These data support the hypothesis that the abundant cellular proteolytic systems contribute to the supply of peptides recognized by the antiviral cellular immune response, thereby facilitating immunosurveillance. These data may explain why TAP-deficient individuals live normal life spans without any increased susceptibility to viral infections.

  14. The Potential Role of Solvation in Antibody Recognition of the Lewis Y Antigen

    Science.gov (United States)

    Saha, Somdutta; Murali, Ramachandran; Pashov, Anastas

    2015-01-01

    Solvents play an important role in protein folding, protein-protein associations, stability, and specificity of recognition as in the case of antibody-antigen interactions through hydrogen bonds. One of the underappreciated features of protein-associated waters is that it weakens inter- and intra-molecular interactions by modulating electrostatic interactions and influencing conformational changes. Such observations demonstrate the direct relationship between macroscopic solvent effects on protein-protein interactions and atom-scale solvent-protein interactions. Although crystallographic solvents do explain some aspects of solvent-mediated interactions, molecular simulation allows the study of the dynamic role of solvents. Thus, analysis of conformations from molecular simulations are employed to understand the role of solvent on the inherent polyspecificity of a Lewis Y reactive germline gene relative to its expanded hybridomas and a humanized anti-Lewis Y antibody. Our analysis reveals that solvent mediates critical contacts through charged residues to facilitate cross-reactivity to carbohydrate antigens, but also increases the flexibility of some anti-Lewis Y antibodies concomitant with mutations (amino acid substitutions) to the germline antibody. Such flexibility might better allow for recognition and binding of internal structures of extended carbohydrate structures on tumor cells. PMID:26492616

  15. Omics Meets Biology: Application to the Design and Preclinical Assessment of Antivenoms

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    Juan J. Calvete

    2014-12-01

    Full Text Available Snakebite envenoming represents a neglected tropical disease that has a heavy public health impact worldwide, mostly affecting poor people involved in agricultural activities in Africa, Asia, Latin America and Oceania. A key issue that complicates the treatment of snakebite envenomings is the poor availability of the only validated treatment for this disease, antivenoms. Antivenoms can be an efficacious treatment for snakebite envenoming, provided they are safe, effective, affordable, accessible and administered appropriately. The shortage of antivenoms in various regions, particularly in Sub-Saharan Africa and some parts of Asia, can be significantly alleviated by optimizing the use of current antivenoms and by the generation of novel polyspecific antivenoms having a wide spectrum of efficacy. Complementing preclinical testing of antivenom efficacy using in vivo and in vitro functional neutralization assays, developments in venomics and antivenomics are likely to revolutionize the design and preclinical assessment of antivenoms by being able to test new antivenom preparations and to predict their paraspecific neutralization to the level of species-specific toxins.

  16. Immunochemical analysis of Taenia taeniaeformis antigens expressed in Escherichia coli.

    Science.gov (United States)

    Bowtell, D D; Saint, R B; Rickard, M D; Mitchell, G F

    1986-12-01

    Previously we reported the isolation of several Escherichia coli clones expressing fragments of Taenia taeniaeformis antigens as beta-galactosidase fused proteins (Bowtell, Saint, Rickard & Mitchell, 1984). Here we describe the isolation of additional antigen-expressing clones from a larval cDNA library and the assignment of these clones to 7 antigen families. These were isolated with a polyspecific rabbit antiserum raised to the oncosphere. Since this serum was capable of reacting with a large number of antigens, it was important to develop techniques for rapidly determining the identity of the native T. taeniaeformis molecule corresponding to a cloned antigen gene. These included active immunization of rabbits with fused proteins and several techniques involving affinity purification on immobilized fused proteins. The reactivity of the antigen-positive clones with sera from humans infected with related parasites was also assessed. Finally, immunization of mice with several fused proteins failed to protect against subsequent infection, although antigens previously identified as candidate host-protective antigens (Bowtell, Mitchell, Anders, Lightowlers & Rickard, 1983) have yet to be identified in the expression library.

  17. Syndromic approach to treatment of snake bite in Sri Lanka based on results of a prospective national hospital-based survey of patients envenomed by identified snakes.

    Science.gov (United States)

    Ariaratnam, Christeine A; Sheriff, Mohamed H Rezvi; Arambepola, Carukshi; Theakston, R David G; Warrell, David A

    2009-10-01

    Of 860 snakes brought to 10 hospitals in Sri Lanka with the patients they had bitten, 762 (89%) were venomous. Russell's vipers (Daboia russelii) and hump-nosed pit vipers (Hypnale hypnale) were the most numerous and H. hypnale was the most widely distributed. Fifty-one (6%) were misidentified by hospital staff, causing inappropriate antivenom treatment of 13 patients. Distinctive clinical syndromes were identified to aid species diagnosis in most cases of snake bite in Sri Lanka where the biting species is unknown. Diagnostic sensitivities and specificities of these syndromes for envenoming were 78% and 96% by Naja naja, 66% and 100% by Bungarus caeruleus, 14% and 100% by Daboia russelii, and 10% and 97% by Hypnale hypnale, respectively. Although only polyspecific antivenoms are used in Sri Lanka, species diagnosis remains important to anticipate life-threatening complications such as local necrosis, hemorrhage and renal and respiratory failure and to identify likely victims of envenoming by H. hypnale who will not benefit from existing antivenoms. The technique of hospital-based collection, labeling and preservation of dead snakes brought by bitten patients is recommended for rapid assessment of a country's medically-important herpetofauna.

  18. Stress regulated members of the plant organic cation transporter family are localized to the vacuolar membrane

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    Koch Wolfgang

    2008-07-01

    Full Text Available Abstract Background In Arabidopsis six genes group into the gene family of the organic cation transporters (OCTs. In animals the members of the OCT-family are mostly characterized as polyspecific transporters involved in the homeostasis of solutes, the transport of monoamine neurotransmitters and the transport of choline and carnitine. In plants little is known about function, localisation and regulation of this gene family. Only one protein has been characterized as a carnitine transporter at the plasma membrane so far. Findings We localized the five uncharacterized members of the Arabidopsis OCT family, designated OCT2-OCT6, via GFP fusions and protoplast transformation to the tonoplast. Expression analysis with RNA Gel Blots showed a distinct, organ-specific expression pattern of the individual genes. With reporter gene fusion of four members we analyzed the tissue specific distribution of OCT2, 3, 4, and 6. In experiments with salt, drought and cold stress, we could show that AtOCT4, 5 and 6 are up-regulated during drought stress, AtOCT3 and 5 during cold stress and AtOCT 5 and 6 during salt stress treatments. Conclusion Localisation of the proteins at the tonoplast and regulation of the gene expression under stress conditions suggests a specific role for the transporters in plant adaptation to environmental stress.

  19. Intravenous administration of equine-derived whole IgG antivenom does not induce early adverse reactions in non-envenomed horses and cows.

    Science.gov (United States)

    Estrada, Ricardo; Herrera, María; Segura, Alvaro; Araya, Javier; Boschini, Carlos; Gutiérrez, José María; León, Guillermo

    2010-11-01

    Administration of antivenoms to treat snakebite envenomings has the potential risk of inducing early adverse reactions. The mechanisms involved in these reactions are unclear. In this study, polyspecific antivenom consisting of whole IgG purified from equine plasma by caprylic acid precipitation was administered intravenously to non-envenomed horses (n = 47) and cows (n = 20) at a dose of 0.4 mL/kg. It has been reported that, in humans, this formulation (administered at a dose of 0.4 mL/kg) induces mild noticeable early adverse reactions, such as fever, vomiting, diarrhea, urticaria, generalized rash, tachypnea or tachycardia, in about 15-20% of the patients. Unexpectedly, none of the animals receiving antivenom in our study showed any evidence of early adverse reaction. Moreover, no late adverse reactions, i.e. serum sickness, were observed during 40 days after antivenom administration. Unlike studies performed in envenomed humans, our present results were obtained in a group of non-envenomed individuals. It is concluded that, in addition to the physicochemical characteristics of the formulation, other unknown factors must determine the occurrence of adverse reactions in snakebite envenomed humans treated with equine-derived antivenoms.

  20. Antibodies of sharks: revolution and evolution.

    Science.gov (United States)

    Marchalonis, J J; Schluter, S F; Bernstein, R M; Hohman, V S

    1998-12-01

    The combinatorial immune response is restricted to jawed vertebrates with cartilaginous fishes being the lowest extant species to have the mechanism for diversification and an extensive panoply of immunoglobulins, T-cell receptors and MHC products. Here, we review the molecular events of the "big bang" or rapid evolutionary appearance of the functionally complete combinatorial immune system coincident with the appearance of ancestral jawed vertebrates, suggesting that this event was catalyzed by horizontal transfer of DNA processing systems. We analyze the nature and extent of variable and constant domain diversity among the distinct immunoglobulin sets of carcharhine sharks focusing upon the lambda-like light chains and the mu and omega heavy chains. The detection and isolation of natural antibodies from the blood of unimmunized sharks illustrates a surprising range of recognition specificities and the existence of polyspecificity suggests that the antibody-forming system of sharks offers unique opportunities for studies of immunological regulation. Although the homologies between shark and mammalian immunoglobulins are unequivocal, major differences in segmental gene organization present challenges to our understanding of basic immunological phenomena such as clonal restriction.

  1. Mapping of Lol p I allergenic epitopes by using murine monoclonal antibodies.

    Science.gov (United States)

    Mourad, W; Bernier, D; Jobin, M; Hébert, J

    1989-11-01

    Murine monoclonal antibodies (MAbs) against three non-overlapping epitopes of Lol p I allergen were previously produced and subsequently used for purification of the allergen. In the present study, these MAbs were further characterized, and the biological activity of the purified allergen assessed. The three MAbs were of the IgG isotype and carried a kappa light chain. Their affinity constants were in the range of 7.4-15.1 x 10(-9) mol/l. Purified Lol p I kept its biological activity, as shown by its ability to induce histamine release by basophils of Lol p I-sensitive patients. The profiles of histamine release induced by either Lol p I or crude Lolium perenne extracts were comparable. This observation suggests that human IgE bound to basophils are polyspecific which has been confirmed by immunoblot and inhibition assay. Our data indicated also that Lol p I possesses a major allergenic epitope recognized by all human serum IgE tested. This epitope seems to be partially shared by those recognized by the three MAbs. Finally, preincubation of Lol p I with either one of the Mabs did not affect significantly the basophil-histamine release induced by the purified allergen. This suggests that Lol p I possesses allergenic sites other than the one shared by MAbs and IgE Abs.

  2. The Optimization of Polyphenols Extraction Process of Prunus Humilis leaves%欧李叶片中多酚的提取工艺优化

    Institute of Scientific and Technical Information of China (English)

    唐洪梅; 李秀珍; 李学强

    2011-01-01

    [研究目的]以欧李叶片为试验材料,多酚提取率为评价指标,探讨欧李叶片多酚提取的工艺条件.[方法]以丙酮为提取剂,选定浸提时间、溶剂浓度、料液比、浸提温度为考察的4个因素,以L9(34)正交试验设计,采用常规提取法和微波提取法研究提取欧李叶片中多酚的最佳条件.[结果]利用常规法从欧李叶片中提取多酚各因素对多酚提取率影响的主次顺序为:浸提温度>浸提时间>固液比>提取剂浓度,得出最优方案为A1B3C3D3,与试验中最佳处理组合A1B3C3D3相一致;利用微波法从欧李叶片中提取多酚各因素对提取率影响的主次顺序为:提取剂浓度>固液比>辐射时间>辐射功率,得出最优方案为A1B2C3D2,与试验中最佳处理组合A1B2C2D2不一致.[结论]欧李叶片中多酚提取的最佳工艺为70%丙酮溶液,固液比1:450,浸提时间1.5 h,浸提温度70℃.%[OBJECTIVE] This paper used Prunus Humilis leaves as experimental materials, the rate of polyphenols extraction indicators as the evaluation standard to explore the extraction process conditions of polyphenols in Prunus Humilis leaves. [METHOD] This paper had chosen acetone as extraction agent, and selected the extraction time、 the solvent concentration、 the liquid-solid ratio and the extraction temperature as four investigation factors, and used the L9(34) orthogonal experiment design, and used regular extraction method and microwave extraction method to study the best conditions of the extraction process of polyphenols of Prunus Humilis leaves.[RESULTS]The primary and secondary effects of polyphenols extraction indicators by using regular extraction method from Prunus Humilis leaves was as follows: extraction temperature>extraction time>solid-liquid ratio>extraction concentration; the optimal scheme was A1B3C3D3, which corresponded with the best treatment combination A1B3C3D3. The primary and secondary effects of polyphenols extraction

  3. Expression and modulation of complement receptor 2 (CR2/CD21 in the pathophysiology of rheumatoid arthritis

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    Rozaleen Dash

    2016-08-01

    Full Text Available Background: The involvement of B cells, complement activation and subsequent immune complex deposition has been implicated in the pathogenesis of rheumatoid arthritis (RA. Although the reduced expression of complement receptor 2 (CR2, CD21 on the B cells of RA patients is known for long, we aimed at determining the modulation and expression of CR2 on PBMC of healthy individuals and RA patients. Methods: Sixty controls and 57 RA patients were enrolled. PBMC-CR2 transcript levels were correlated with the levels of C3, C3d and circulating immune complexes (CIC in controls and patients and with DAS28 in patients only. CIC levels were determined by PEG precipitation, C3 levels by nephlometry and C3d levels were determined by enzyme linked immunosorbent assay (ELISA. Sixteen patients were recruited for 6 months follow up studies of transcript levels of PBMC correlated with DAS28 score. Appropriate statistical methods were used for the analyses of data. Results: PBMC- CR2 transcript levels were declined in patients as compared to controls. PBMC-CR2 levels correlated negatively with DAS28 score. DAS28 correlated positively with levels of CIC, C3 and C3d. Levels of PBMC -CR2 increased in patients with decline in DAS28 scores in 6 months follow-up patients. Conclusions: Low level of CR2 expression in patients may, thus, contribute significantly to the pathological manifestation of RA. Cause-effect relationships of the up regulation of CR2 on improvement of health condition with the pathophysiology of RA and their importance as putative disease markers is being confirmed.

  4. Role of intraoperative Iso-C based navigation in challenging spine trauma

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    Jaiswal Ashish

    2007-01-01

    Full Text Available Background: Pedicle screw fixation is the most preferred method of stabilizing unstable spinal fractures. Pedicle screw placement may be difficult in presence of fractured posterior elements, deformed spine, gross instability and spinal pathology. Challenging spine-fracture fixation is defined as the presence of one or more of the following: 1 obscured topographical landmarks as in ankylosing spondylitis, 2 fractures in occipitocervical or cervicothoracic regions and 3 preexisting altered spinal alignment. We report a series of pedicle screw insertion with guidance of navigation in difficult fixation problems.. Materials and Methods: Fourteen patients [hangman′s fracture (n=3, odontoid fracture (n=4, C1C2 fracture (n=1 and spinal fracture with coexistent ankylosing spondylitis (n=6] underwent posterior stabilization. Intraoperatively after surgical exposure, images were acquired by Iso-C 3D C-arm and transferred to navigation system. Instrumentation was performed with navigational assistance. Postoperatively, placements of pedicle screws were evaluated with radiographs and CT scan. Results: Sixty-seven pedicle screws (cervical, n=33; thoracic, n=6; lumbar, n=26; sacral n=2 and 15 lateral mass screws were inserted with navigation guidance. The average time of image data acquisition by Iso-C 3D C-arm and its transfer to workstation was 4 minutes (range, 2-6 minutes. Postoperative CT scan revealed ideal placement of screws in 63 pedicles (94%, grade 1 cortical breaches (< 2 mm in 3 pedicles (4.5% and grade 2 cortical breach (2-4 mm in one pedicle (1.5%. There were no neurovascular complications. Deep infection was encountered in one case, which settled with debridement. Conclusions: Intraoperative Iso-C 3D C-arm based navigation is a useful adjunct while stabilizing challenging spinal trauma, rendering feasibility, accuracy and safety of pedicle screw placement even in difficult situations.

  5. Systemic complement activation in age-related macular degeneration.

    Science.gov (United States)

    Scholl, Hendrik P N; Charbel Issa, Peter; Walier, Maja; Janzer, Stefanie; Pollok-Kopp, Beatrix; Börncke, Florian; Fritsche, Lars G; Chong, Ngaihang V; Fimmers, Rolf; Wienker, Thomas; Holz, Frank G; Weber, Bernhard H F; Oppermann, Martin

    2008-07-02

    Dysregulation of the alternative pathway (AP) of complement cascade has been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of blindness in the elderly. To further test the hypothesis that defective control of complement activation underlies AMD, parameters of complement activation in blood plasma were determined together with disease-associated genetic markers in AMD patients. Plasma concentrations of activation products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor B and regulators factor H and factor D were quantified in patients (n = 112) and controls (n = 67). Subjects were analyzed for single nucleotide polymorphisms in factor H (CFH), factor B-C2 (BF-C2) and complement C3 (C3) genes which were previously found to be associated with AMD. All activation products, especially markers of chronic complement activation Ba and C3d (pAMD patients compared to controls. Similar alterations were observed in factor D, but not in C3, C4 or factor H. Logistic regression analysis revealed better discriminative accuracy of a model that is based only on complement activation markers Ba, C3d and factor D compared to a model based on genetic markers of the complement system within our study population. In both the controls' and AMD patients' group, the protein markers of complement activation were correlated with CFH haplotypes.This study is the first to show systemic complement activation in AMD patients. This suggests that AMD is a systemic disease with local disease manifestation at the ageing macula. Furthermore, the data provide evidence for an association of systemic activation of the alternative complement pathway with genetic variants of CFH that were previously linked to AMD susceptibility.

  6. Systemic complement activation in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Hendrik P N Scholl

    Full Text Available Dysregulation of the alternative pathway (AP of complement cascade has been implicated in the pathogenesis of age-related macular degeneration (AMD, the leading cause of blindness in the elderly. To further test the hypothesis that defective control of complement activation underlies AMD, parameters of complement activation in blood plasma were determined together with disease-associated genetic markers in AMD patients. Plasma concentrations of activation products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor B and regulators factor H and factor D were quantified in patients (n = 112 and controls (n = 67. Subjects were analyzed for single nucleotide polymorphisms in factor H (CFH, factor B-C2 (BF-C2 and complement C3 (C3 genes which were previously found to be associated with AMD. All activation products, especially markers of chronic complement activation Ba and C3d (p<0.001, were significantly elevated in AMD patients compared to controls. Similar alterations were observed in factor D, but not in C3, C4 or factor H. Logistic regression analysis revealed better discriminative accuracy of a model that is based only on complement activation markers Ba, C3d and factor D compared to a model based on genetic markers of the complement system within our study population. In both the controls' and AMD patients' group, the protein markers of complement activation were correlated with CFH haplotypes.This study is the first to show systemic complement activation in AMD patients. This suggests that AMD is a systemic disease with local disease manifestation at the ageing macula. Furthermore, the data provide evidence for an association of systemic activation of the alternative complement pathway with genetic variants of CFH that were previously linked to AMD susceptibility.

  7. Activation of the complement system and accumulation of hemoglobin-haptoglobin complexes in plasma during an adverse reaction to penicillin treatment.

    Science.gov (United States)

    Brandslund, I; Svehag, S E; Teisner, B; Hyltoft Petersen, P

    1983-01-01

    A patient treated with penicillin intravenously developed a serum sickness-like reaction. Classical pathway complement (C) activation was indicated by quantitation of the split products C3c and C3d as well as demonstration of C4 conversion. Circulating immune complexes could, however, not be detected by the solid-phase Clq and PEG-precipitation methods. A concomitant accumulation of circulating hemoglobin-haptoglobin complexes and a marked fall in serum-fibronectin concentrations suggested saturation of the reticuloendothelial system. The plasma became a deep-red color, and a diffuse intravascular coagulation followed. The patient recovered completely upon discontinuation of penicillin administration.

  8. Cryogenic Wind Tunnels.

    Science.gov (United States)

    1980-07-01

    50.1 1140 213 777 Methane 90.6 112 191 45.8 425 512 607 Ethane 89.9 185 305 48.2 550 401 Ethylene 104 169 283 50.9 568 486 476 Carbondioxide 195 195...up as the mercury is free to move inside the glass tube (Fig.3a). In contrast, a bi-metallic strip consists of two metals firmly fixed together, and...3(b) 3(c) 3(d) 3(g) Mercury in glass Bimetallic strip Bimetallic strip Dissimilar metals Similar metals at different thermometer unconstrained

  9. Superhigh Temperatures and Acoustic Cavitation

    CERN Document Server

    Belyaev, V B; Miller, M B; Sermyagin, A V; Topolnikov, A S

    2003-01-01

    The experimental results on thermonuclear synthesis under acoustic cavitation have been analyzed with the account of the latest data and their discussion. The analysis testifies that this avenue of research is a very promising one. The numerical calculations of the D(d, n)^{3}He reaction rate in the deuterated acetone (C_{3}D_{6}O) under the influence of ultrasound depending on T environment temperature within the range T=249-295 K have been carried out within the framework of hydrodynamic model. The results show that it is possible to improve substantially the effect/background relationship in experiments by decreasing the fluid temperature twenty-thirty degrees below zero.

  10. COMBINING A NEW 3-D SEISMIC S-WAVE PROPAGATION ANALYSIS FOR REMOTE FRACTURE DETECTION WITH A ROBUST SUBSURFACE MICROFRACTURE-BASED VERIFICATION TECHNIQUE

    Energy Technology Data Exchange (ETDEWEB)

    Bob Hardage; M.M. Backus; M.V. DeAngelo; R.J. Graebner; S.E. Laubach; Paul Murray

    2004-02-01

    Fractures within the producing reservoirs at McElroy Field could not be studied with the industry-provided 3C3D seismic data used as a cost-sharing contribution in this study. The signal-to-noise character of the converted-SV data across the targeted reservoirs in these contributed data was not adequate for interpreting azimuth-dependent data effects. After illustrating the low signal quality of the converted-SV data at McElroy Field, the seismic portion of this report abandons the McElroy study site and defers to 3C3D seismic data acquired across a different fractured carbonate reservoir system to illustrate how 3C3D seismic data can provide useful information about fracture systems. Using these latter data, we illustrate how fast-S and slow-S data effects can be analyzed in the prestack domain to recognize fracture azimuth, and then demonstrate how fast-S and slow-S data volumes can be analyzed in the poststack domain to estimate fracture intensity. In the geologic portion of the report, we analyze published regional stress data near McElroy Field and numerous formation multi-imager (FMI) logs acquired across McElroy to develop possible fracture models for the McElroy system. Regional stress data imply a fracture orientation different from the orientations observed in most of the FMI logs. This report culminates Phase 2 of the study, ''Combining a New 3-D Seismic S-Wave Propagation Analysis for Remote Fracture Detection with a Robust Subsurface Microfracture-Based Verification Technique''. Phase 3 will not be initiated because wells were to be drilled in Phase 3 of the project to verify the validity of fracture-orientation maps and fracture-intensity maps produced in Phase 2. Such maps cannot be made across McElroy Field because of the limitations of the available 3C3D seismic data at the depth level of the reservoir target.

  11. 求整数部分值的七法(初一、初二、初三)

    Institute of Scientific and Technical Information of China (English)

    王用燮

    2006-01-01

    1.直接计算例1 积(1+(1/(1×3))(1+(1/(2×4)) (1+(1/3×5))(1+(1/4×6))…(1+(1/98×100)) (1+(1/99×101))的值的整数部分为( ) (A)1. (B)2. (C)3. (D)4. (91年广州等五市初中联赛) 解原式=

  12. Impact of External Environmental Factors on Minuteman III Inertial Guidance System (NS-20) Failures

    Science.gov (United States)

    1975-08-01

    significant if the coefficient of determi- nation was .4 or higher. Mr. R. Genet (13), Aerospace Guidance and Metrology Center (AGMC...to .4 before the results could be considered of practical significance and warrant further study (27). Mr. Russell Genet , AGMC. Mr. Genet believed...4J Q CQ W 05 W (0 X >P id M ss Z < OQ CU D 1 H 0* D «0 "H w 04 D lOH WH ^ D J C 3 D J M 3 D ^ VH 3 < EH< 0« «^ W < OH 0 CX O H *J ftD O H

  13. Correlation of systemic lupus erythematosus disease activity with classical complement (CH50 function and related protein levels

    Directory of Open Access Journals (Sweden)

    Salesi M

    2008-09-01

    Full Text Available "nBackground: The components of the classical complement pathway play an important role in the pathogenesis of systemic lupus erythematosus (SLE and are reportedly useful biomarkers of disease activity. In this study, we evaluate disease activity, complement function (total hemolytic complement, CH50 and complement protein levels (C3, C4, C3d, C4d, SC5b-9, comparing the results of patients with active disease versus those with inactive disease."n"nMethods: This cross-sectional study included 78 hospitalized women with SLE, 24 of whom were in the active group, with SLE disease activity indexes (SLEDAI.2K of >6, and 54 in the inactive group, with SLEDAI.2K of ≤6. Serum CH50 was measured using a red blood cell hemolytic assay. C3 and C4 levels were determined by nephlometry and plasma levels of C3d, C4d, SC5b-9 by ELISA. The data were statistically analyzed using SPSS."n"nResults: The mean (±standard error C4d levels of the inactive group were significantly higher than those of the active group (23.39±1.1µg/ml and 16.9±1.6µg/ml, respectively; p=0.003. There was also a significant correlation between C3 and C4 levels (p=0.807. The mean values of the other proteins (C3, C4, CH50, SC5b-9, and C3d circulating immune complex concentrations were not significantly different between the inactive group vs. the active group: 89.35±6.8 vs. 85.54±7.6mg/dl, 18.33±2.3 vs. 20.45±2.4mg/dl, 149.03±4.3 vs. 157±4.3U, 1414.4±114.94 vs. 1471.1±216.9ng/ml, 9.43±0.96 vs. 13.31±3.16µgEq/ml, respectively (p>0.05."n"nConclusions: According to our results, C4d levels may be used as a biomarker of disease activity. The significant correlation between C3 and C4 may confirm the activity of the classical pathway in SLE patients."n"nKeywords: Systemic lupus erythematosus, CH50, C3, C4, C3d, C4d, SC5b-9, inactive, flare.

  14. Secondary metabolites from nudibranchs Tambja stegosauriformis, Hypselodoris lajenis and Okenia zoobotryon and from bryozoans Zoobotryon verticillatum and Bugula dentata from the Brazilian coastline; Metabolitos secundarios dos nudibranquios Tambja stegosauriformis, Hypselodoris lajensis e Okenia zoobotryon e dos briozoarios Zoobotryon verticillatum e Bugula dentata da costa do Brasil

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Fabio R.; Berlinck, Roberto G.S. [Universidade de Sao Paulo (IQSC/USP), Sao Carlos, SP (Brazil). Inst. de Quimica; Rodrigues Filho, Edson; Veloso, Katyuscya; Ferreira, Antonio G. [Universidade Federal de Sao Carlos (UFSCAR), SP (Brazil). Dept. de Quimica; Padula, Vinicius, E-mail: rgsberlinck@iqsc.usp.br [Zoologische Staatssammlung Muenchen, Mollusca Sektion, Muenchen (Germany)

    2012-07-01

    The chemical investigation of the MeOH extract from the bryozoan B. dentata MeOH yielded tambjamines A (1), C (3), D (4), K (6), aldehyde 8 and the new tambjamine J1(9), while the extract of its predator, the nudibranch Tambja stegosauriformis, yielded tambjamines C and K, along with aldehyde 8. Furodisinin lactone (11) was isolated from the nudibranch Hypselodoris lajensis, a compound previously isolated from Dysidea sponges. The alkaloid 2,5,6-tribromo-N-methylgramine (12) was isolated from the nudibranch Okenia zoobotryon and from its prey, the bryozoan Zoobotryon verticillatum, the only source of 12 previously known. (author)

  15. Warm autoimmune hemolytic anemia secondary to Plasmodium ovale infection: a case report and review of the literature.

    Science.gov (United States)

    Johnson, Adam S; Delisca, Gadini; Booth, Garrett S

    2013-12-01

    A three year old male from the Democratic Republic of the Congo was admitted to Monroe Carell Jr. Children's Hospital at Vanderbilt with a 10-day history of fever, emesis, and diarrhea. Examination demonstrated scleral icterus, splenomegaly, and anemia. By peripheral blood smear, the patient was diagnosed with Plasmodium ovale. Immunohematology demonstrated a positive direct antiglobulin test (DAT) for IgG and C3d with pan-agglutination on eluate. These findings, in combination with hemolytic labs, signified presence of an autoimmune hemolytic anemia (AIHA). We believe this to be the first reported case of P. ovale infection-mediated AIHA.

  16. Class 3 semaphorins expression and association with innervation and angiogenesis within the degenerate human intervertebral disc.

    Science.gov (United States)

    Binch, Abbie L A; Cole, Ashley A; Breakwell, Lee M; Michael, Anthony L R; Chiverton, Neil; Creemers, Laura B; Cross, Alison K; Le Maitre, Christine L

    2015-07-30

    Nerve and blood vessel ingrowth during intervertebral disc degeneration, is thought to be a major cause of low back pain, however the regulation of this process is poorly understood. Here, we investigated the expression and regulation of a subclass of axonal guidance molecules known as the class 3 semaphorins, and their receptors; plexins and neuropilins within human NP tissue and their regulation by pro-inflammatory cytokines. Importantly this determined whether semaphorin expression was associated with the presence of nerves and blood vessels in tissues from human intervertebral discs. The study demonstrated that semaphorin3A, 3C, 3D, 3E and 3F and their receptors were expressed by native NP cells and further demonstrated their expression was regulated by IL-1β but to a lesser extent by IL-6 and TNFα. This is the first study to identify sema3C, sema3D and their receptors within the nucleus pulposus of intervertebral discs. Immunopositivity shows significant increases in semaphorin3C, 3D and their receptor neuropilin-2 in degenerate samples which were shown to contain nerves and blood vessels, compared to non-degenerate samples without nerves and blood vessels. Therefore data presented here suggests that semaphorin3C may have a role in promoting innervation and vascularisation during degeneration, which may go on to cause low back pain.

  17. 3D imaging with an isocentric mobile C-arm comparison of image quality with spiral CT.

    Science.gov (United States)

    Kotsianos, Dorothea; Wirth, Stefan; Fischer, Tanja; Euler, Ekkehard; Rock, Clemens; Linsenmaier, Ulrich; Pfeifer, Klaus Jürgen; Reiser, Maximilian

    2004-09-01

    The purpose of this study was to evaluate the image quality of the new 3D imaging system (ISO-C-3D) for osteosyntheses of tibial condylar fractures in comparison with spiral CT (CT). Sixteen human cadaveric knees were examined with a C-arm 3D imaging system and spiral computed tomography. Various screws and plates of steel and titanium were used for osteosynthesis in these specimens. Image quality and clinical value of multiplanar (MP) reformatting of both methods were analyzed. In addition, five patients with tibial condylar fractures were examined for diagnosis and intra-operative control. The image quality of the C-arm 3D imaging system in the cadaveric study was rated as significantly worse than that of spiral CT with and without prostheses. After implantation of prostheses an increased incidence of artifacts was observed, but the diagnostic accuracy was not affected. Titanium implants caused the smallest number of artifacts. The image quality of ISO-C is inferior to CT, and metal artifacts were more prominent, but the clinical value was equal. ISO-C-3D can be useful in planning operative reconstructions and can verify the reconstruction of articular surfaces and the position of implants with diagnostic image quality.

  18. 3D imaging with an isocentric mobile C-arm. Comparison of image quality with spiral CT

    Energy Technology Data Exchange (ETDEWEB)

    Kotsianos, Dorothea; Wirth, Stefan; Fischer, Tanja; Euler, Ekkehard; Rock, Clemens; Linsenmaier, Ulrich; Pfeifer, Klaus Juergen; Reiser, Maximilian [Departments of Radiology and Surgery, Klinikum der Universitaet Muenchen, Innenstadt, Nussbaumstrasse 20, 80336, Munchen (Germany)

    2004-09-01

    The purpose of this study was to evaluate the image quality of the new 3D imaging system (ISO-C-3D) for osteosyntheses of tibial condylar fractures in comparison with spiral CT (CT). Sixteen human cadaveric knees were examined with a C-arm 3D imaging system and spiral computed tomography. Various screws and plates of steel and titanium were used for osteosynthesis in these specimens. Image quality and clinical value of multiplanar (MP) reformatting of both methods were analyzed. In addition, five patients with tibial condylar fractures were examined for diagnosis and intra-operative control. The image quality of the C-arm 3D imaging system in the cadaveric study was rated as significantly worse than that of spiral CT with and without prostheses. After implantation of prostheses an increased incidence of artifacts was observed, but the diagnostic accuracy was not affected. Titanium implants caused the smallest number of artifacts. The image quality of ISO-C is inferior to CT, and metal artifacts were more prominent, but the clinical value was equal. ISO-C-3D can be useful in planning operative reconstructions and can verify the reconstruction of articular surfaces and the position of implants with diagnostic image quality. (orig.)

  19. Detachment of human immunodeficiency virus type 1 from germinal centers by blocking complement receptor type 2.

    Science.gov (United States)

    Kacani, L; Prodinger, W M; Sprinzl, G M; Schwendinger, M G; Spruth, M; Stoiber, H; Döpper, S; Steinhuber, S; Steindl, F; Dierich, M P

    2000-09-01

    After the transition from the acute to the chronic phase of human immunodeficiency virus (HIV) infection, complement mediates long-term storage of virions in germinal centers (GC) of lymphoid tissue. The contribution of particular complement receptors (CRs) to virus trapping in GC was studied on tonsillar specimens from HIV-infected individuals. CR2 (CD21) was identified as the main binding site for HIV in GC. Monoclonal antibodies (MAb) blocking the CR2-C3d interaction were shown to detach 62 to 77% of HIV type 1 from tonsillar cells of an individual in the presymptomatic stage. Although they did so at a lower efficiency, these antibodies were able to remove HIV from tonsillar cells of patients under highly active antiretroviral therapy, suggesting that the C3d-CR2 interaction remains a primary entrapment mechanism in treated patients as well. In contrast, removal of HIV was not observed with MAb blocking CR1 or CR3. Thus, targeting CR2 may facilitate new approaches toward a reduction of residual virus in GC.

  20. Computer navigation assisted fixation in neglected C2-C3 dislocation in an adult

    Directory of Open Access Journals (Sweden)

    S Rajasekaran

    2011-01-01

    Full Text Available A 49-year-old male presented with neck pain and deformity following an industrial accident sustained two months back. His neurology was normal except for a minimal weakness in left biceps (grade 4/5. Radiographs, magnetic resonance imaging and computed tomographic scan revealed fracture dislocation of C2-C3 with significant lateral translation of C2 over C3 without disc herniation. In view of unsuccessful closed reduction and absent disc herniation at the level of dislocation, a posterior only reduction, stabilisation and fusion with Iso-C 3D computer navigation-assisted cervical pedicle screw fixation with transverse rod-screw construct was performed. At 6 months followup the patient was completely relieved of his symptoms and was able to return to his previous occupation. The rare case is reported for the management by Iso-C 3D computer navigation assisted cervical pedicle screw fixation and reduction with transverse rod-screw construct at each involved level.

  1. Assessment of in vivo complement activation on the Echinococcus granulosus hydatid cyst wall.

    Science.gov (United States)

    Ferreira, A M; Diaz, A; Fernandez, C; Sim, R B

    2001-12-01

    The larval stage of the parasite Echinococcus granulosus causes hydatid disease. The hydatid cyst is potentially capable of activating host complement, since it is a large, persistent, carbohydrate-rich structure, coated with host immunoglobulins, and localized in the host's internal organs. Nonetheless, in vitro studies have suggested that the cyst surface, the hydatid cyst wall (HCW), is a poor complement activator. In this study, we assessed the occurrence of in vivo complement activation on the hydatid cyst by measuring the levels of two complement activation products, C3d and complexes bearing a C9 activation neoepitope (TCC/MAC), in extracts from HCW of human origin. Low amounts of C3d and TCC/MAC were found in HCW in comparison with their levels in normal human plasma and activated human sera, suggesting that in vivo complement activation on HCW is efficiently down-regulated. This regulation may contribute to limit host inflammation which has been observed to correlate with parasite degeneration and death.

  2. A New Bio-Informatics Framework: Research on 3D Sensor Data of Human Activities

    Directory of Open Access Journals (Sweden)

    Sajid Ali

    2015-05-01

    Full Text Available Due to increasing attraction of motion capture systems technology and the usage of captured data in wide range of research-oriented applications, a framework has developed as an improved version of MOCAP TOOLBOX in Matlab platform. Firstly, we have introduced a faithful script to deal with public motion capture data, which will be friendly for us. Various functions through dynamic programming, by using the Body Segment Parameters (BSP are edited and they configured the position of markers according to data. It is used to visualize and refine without the MLS view and the C3D editor software. It has opened a valuable way of sensor data in many research aspects as gait movements, marker analysis, compression and motion pattern, bioinformatics, and animation. As a result, performed on CMU and ACCAD public mocap data, and achieved higher corrected configuration scheme of 3D markers when compared with the prior art, especially for C3D file. Another distinction of this work is that it handles the extra markers distortion, and provides the meaningful way to use captured data.

  3. Complement factor B expression profile in a spontaneous uveitis model.

    Science.gov (United States)

    Zipplies, Johanna K; Kirschfink, Michael; Amann, Barbara; Hauck, Stefanie M; Stangassinger, Manfred; Deeg, Cornelia A

    2010-12-01

    Equine recurrent uveitis serves as a spontaneous model for human autoimmune uveitis. Unpredictable relapses and ongoing inflammation in the eyes of diseased horses as well as in humans lead to destruction of the retina and finally result in blindness. However, the molecular mechanisms leading to inflammation and retinal degeneration are not well understood. An initial screening for differentially regulated proteins in sera of uveitic cases compared to healthy controls revealed an increase of the alternative pathway complement component factor B in ERU cases. To determine the activation status of the complement system, sera were subsequently examined for complement split products. We could demonstrate a significant higher concentration of the activation products B/Ba, B/Bb, Bb neoantigen, iC3b and C3d in uveitic condition compared to healthy controls, whereas for C5b-9 no differences were detected. Additionally, we investigated complement activation directly in the retina by immunohistochemistry, since it is the main target organ of this autoimmune disease. Interestingly, infiltrating cells co-expressed activated factor Bb neoantigen, complement split product C3d as well as CD68, a macrophage marker. In this study, we could demonstrate activation of the complement system both systemically as well as in the eye, the target organ of spontaneous recurrent uveitis. Based on these novel findings, we postulate a novel role for macrophages in connection with complement synthesis at the site of inflammation.

  4. The Staphylococcus aureus protein Sbi acts as a complement inhibitor and forms a tripartite complex with host complement Factor H and C3b.

    Directory of Open Access Journals (Sweden)

    Katrin Haupt

    2008-12-01

    Full Text Available The Gram-positive bacterium Staphylococcus aureus, similar to other pathogens, binds human complement regulators Factor H and Factor H related protein 1 (FHR-1 from human serum. Here we identify the secreted protein Sbi (Staphylococcus aureus binder of IgG as a ligand that interacts with Factor H by a-to our knowledge-new type of interaction. Factor H binds to Sbi in combination with C3b or C3d, and forms tripartite SbiratioC3ratioFactor H complexes. Apparently, the type of C3 influences the stability of the complex; surface plasmon resonance studies revealed a higher stability of C3d complexed to Sbi, as compared to C3b or C3. As part of this tripartite complex, Factor H is functionally active and displays complement regulatory activity. Sbi, by recruiting Factor H and C3b, acts as a potent complement inhibitor, and inhibits alternative pathway-mediated lyses of rabbit erythrocytes by human serum and sera of other species. Thus, Sbi is a multifunctional bacterial protein, which binds host complement components Factor H and C3 as well as IgG and beta(2-glycoprotein I and interferes with innate immune recognition.

  5. An outdated notion of antibody specificity is one of the major detrimental assumptions of the structure-based reverse vaccinology paradigm which prevented it from helping to develop an effective HIV-1 vaccine

    Directory of Open Access Journals (Sweden)

    Marc H V Van Regenmortel

    2014-11-01

    Full Text Available The importance of paradigms for guiding scientific research is explained with reference to the seminal work of Karl Popper and Thomas Kuhn. A prevalent paradigm, followed for more than a decade in HIV-1 vaccine research, which gave rise to the strategy known as structure-based reverse vaccinology is described in detail. Several reasons why this paradigm did not allow the development of an effective HIV-1 vaccine are analyzed. A major reason is the belief shared by many vaccinologists that antibodies possess a narrow specificity for a single epitope and are not polyspecific for a diverse group of potential epitopes. When this belief is abandoned, it becomes obvious that the one particular epitope structure observed during the crystallographic analysis of a neutralizing antibody-antigen complex does not necessarily reveal which immunogenic structure should be used to elicit the same type of neutralizing antibody.In the physical sciences, scientific explanations are usually presented as logical deductions derived from a relevant law of nature together with certain initial conditions. In immunology, causal explanations in terms of a single cause acting according to a law of nature are not possible because numerous factors always play a role in bringing about an effect. The implications of this state of affairs for the rational design of HIV vaccines are outlined. An alternative approach to obtain useful scientific understanding consists in intervening empirically in the immune system and it is suggested that manipulating the system experimentally is needed to learn to control it and achieve protective immunity by vaccination.

  6. Structure-Based Reverse Vaccinology Failed in the Case of HIV Because it Disregarded Accepted Immunological Theory

    Directory of Open Access Journals (Sweden)

    Marc H. V. Van Regenmortel

    2016-09-01

    Full Text Available Two types of reverse vaccinology (RV should be distinguished: genome-based RV for bacterial vaccines and structure-based RV for viral vaccines. Structure-based RV consists in trying to generate a vaccine by first determining the crystallographic structure of a complex between a viral epitope and a neutralizing monoclonal antibody (nMab and then reconstructing the epitope by reverse molecular engineering outside the context of the native viral protein. It is based on the unwarranted assumption that the epitope designed to fit the nMab will have acquired the immunogenic capacity to elicit a polyclonal antibody response with the same protective capacity as the nMab. After more than a decade of intensive research using this type of RV, this approach has failed to deliver an effective, preventive HIV-1 vaccine. The structure and dynamics of different types of HIV-1 epitopes and of paratopes are described. The rational design of an anti-HIV-1 vaccine is shown to be a misnomer since investigators who claim that they design a vaccine are actually only improving the antigenic binding capacity of one epitope with respect to only one paratope and not the immunogenic capacity of an epitope to elicit neutralizing antibodies. Because of the degeneracy of the immune system and the polyspecificity of antibodies, each epitope studied by the structure-based RV procedure is only one of the many epitopes that the particular nMab is able to recognize and there is no reason to assume that this nMab must have been elicited by this one epitope of known structure. Recent evidence is presented that the trimeric Env spikes of the virus possess such an enormous plasticity and intrinsic structural flexibility that it is it extremely difficult to determine which Env regions are the best candidate vaccine immunogens most likely to elicit protective antibodies.

  7. Detection of virus-specific intrathecally synthesised immunoglobulin G with a fully automated enzyme immunoassay system

    Directory of Open Access Journals (Sweden)

    Weissbrich Benedikt

    2007-05-01

    Full Text Available Abstract Background The determination of virus-specific immunoglobulin G (IgG antibodies in cerebrospinal fluid (CSF is useful for the diagnosis of virus associated diseases of the central nervous system (CNS and for the detection of a polyspecific intrathecal immune response in patients with multiple sclerosis. Quantification of virus-specific IgG in the CSF is frequently performed by calculation of a virus-specific antibody index (AI. Determination of the AI is a demanding and labour-intensive technique and therefore automation is desirable. We evaluated the precision and the diagnostic value of a fully automated enzyme immunoassay for the detection of virus-specific IgG in serum and CSF using the analyser BEP2000 (Dade Behring. Methods The AI for measles, rubella, varicella-zoster, and herpes simplex virus IgG was determined from pairs of serum and CSF samples of patients with viral CNS infections, multiple sclerosis and of control patients. CSF and serum samples were tested simultaneously with reference to a standard curve. Starting dilutions were 1:6 and 1:36 for CSF and 1:1386 and 1:8316 for serum samples. Results The interassay coefficient of variation was below 10% for all parameters tested. There was good agreement between AIs obtained with the BEP2000 and AIs derived from the semi-automated reference method. Conclusion Determination of virus-specific IgG in serum-CSF-pairs for calculation of AI has been successfully automated on the BEP2000. Current limitations of the assay layout imposed by the analyser software should be solved in future versions to offer more convenience in comparison to manual or semi-automated methods.

  8. Differential cellular expression of organic anion transporting peptides OATP1A2 and OATP2B1 in the human retina and brain: implications for carrier-mediated transport of neuropeptides and neurosteriods in the CNS.

    Science.gov (United States)

    Gao, Bo; Vavricka, Stephan R; Meier, Peter J; Stieger, Bruno

    2015-07-01

    Organic anion transporting polypeptides (OATPs) are polyspecific organic anion transporters, which are expressed in the blood-brain barrier, the choroid plexus, and other organs. The physiologic function of OATPs in extrahepatic tissues remains ambiguous. In rat retina, members of the OATP family are expressed. We therefore investigated the human retina for the expression of OATP1A2 and OATP2B1 and extended the study to human brain. Furthermore, we searched for peptide neurotransmitters as novel OATP substrates. OATP1A2 displayed a broad expression pattern in human retina as assessed by immunofluorescence localization. It is expressed in photoreceptor bodies and somas of amacrine cells. OATP1B2 expression is restricted to the inner nuclear layer and to the inner plexiform layer. Using paraffin sections from human cortex, cerebellum, and hippocampus, OATP1A2 was localized to neurons and neuronal processes, while OATP2B1 is expressed in endothelial cells of brain capillaries. Substance P and vasoactive intestinal peptide were identified as substrates for OATP1A2 and OATP2B1. Double-labeling immunofluorescence of human retina demonstrated the presence of substance P and of vasoactive intestinal peptides in neurons expressing OATP1A2 and OATP2B1, respectively. The expression of OATP1A2 and OATP2B1 in retinal neurons implies a role of these transporters in the reuptake of peptide neurotransmitters released from retinal neurons. The abundant expression of OATP1A2 in brain neurons points to the possibility that OATP1A2 could be involved in the homeostasis of neurosteroids. The high expression of OATP2B1 in brain capillaries supports an important function of OATPs in substance penetration across the blood-brain barrier.

  9. Why Does the Molecular Structure of Broadly Neutralizing Monoclonal Antibodies Isolated from Individuals Infected with HIV-1 not Inform the Rational Design of an HIV-1 Vaccine?

    Directory of Open Access Journals (Sweden)

    Marc H V Van Regenmortel

    2015-05-01

    Full Text Available It is commonly assumed that neutralizing Mabs that bind to the HIV-1 Env glycoprotein are more specific reagents than anti-HIV-1 polyclonal antisera and that knowledge of the structure of these Mabs facilitates the rational design of effective HIV-1 vaccine immunogens. However, after more than ten years of unsuccessful experimentation using the structure-based reverse vaccinology approach, it is now evident that it is not possible to infer from the structure of neutralizing Mabs which HIV immunogens induced their formation nor which vaccine immunogens will elicit similar Abs in an immunized host. The use of Mabs for developing an HIV-1 vaccine was counterproductive because it overlooked the fact that the apparent specificity of a Mab very much depends on the selection procedure used to obtain it and also did not take into account that an antibody is never monospecific for a single epitope but is always polyspecific for many epitopes. When the rationale of the proponents of the unsuccessful rational design strategy is analyzed, it appears that investigators who claim they are designing a vaccine immunogen are only improving the binding reactivity of a single epitope-paratope pair and are not actually designing an immunogen able to generate protective antibodies. The task of a designer consists in imagining what type of immunogen is likely to elicit a protective immune response but in the absence of knowledge regarding which features of the immune system are responsible for producing a functional neutralizing activity in antibodies, it is not feasible to intentionally optimize a potential immunogen candidate in order to obtain the desired outcome. The only available option is actually to test possible solutions by trial-and-error experiments until the preset goal is perhaps attained. Rational design and empirical approaches in HIV vaccine research should thus not be opposed as alternative options since empirical testing is an integral part of a so

  10. Human milk IgGs contain various combinations of different antigen-binding sites resulting in multiple variants of their bispecificity.

    Directory of Open Access Journals (Sweden)

    Sergey E Sedykh

    Full Text Available In the classic paradigm, immunoglobulins represent products of clonal B cell populations, each producing antibodies (Abs recognizing a single antigen. There is a common belief that IgGs in mammalian biological fluids are monovalent molecules having stable structures and two identical antigen-binding sites. However, human milk IgGs to different antigens undergo extensive half-molecule exchange. In the IgGs pool, only 33 ± 5% and 13 ± 5% of Abs contained light chains exclusively of kappa- or lambda-type, respectively, while 54 ± 10% of the IgGs contained both kappa- and lambda- light chains. All Ab preparations contained different amounts of IgGs of all four subclasses. Interestingly, lambda-IgGs contained an increased amount of IgG2 (87% and only 3-6% of each of IgG1, IgG3, and IgG4, while kappa-IgGs consisted of comparable (17-32% amounts of all IgG subtypes. Chimeric kappa-lambda-IgGs consisted of ~74% IgG1, ~16% IgG2, ~5% IgG3 and ~5% IgG4. As the result of the exchange, all IgG fractions eluted from several specific affinity sorbents under the conditions destroying strong immunocomplexes demonstrated high catalytic activities in hydrolysis of ATP, DNA, oligosaccharides, phosphorylation of proteins, lipids, and oligosaccharides. In vitro, an addition of reduced glutathione and milk plasma to two IgG fractions with different affinity for DNA-cellulose led to a transition of 25-60% of Ab of one fraction to the other fraction. Our data are indicative of the possibility of half-molecule exchange between milk IgGs of various subclasses, raised against different antigens (including abzymes, which explains the polyspecificity and cross-reactivity of these IgGs.

  11. Identification and characterization of a bacterial hydrosulphide ion channel

    Energy Technology Data Exchange (ETDEWEB)

    Czyzewski, Bryan K.; Wang, Da-Neng (NYUSM)

    2012-10-26

    The hydrosulphide ion (HS{sup -}) and its undissociated form, hydrogen sulphide (H{sub 2}S), which are believed to have been critical to the origin of life on Earth, remain important in physiology and cellular signalling. As a major metabolite in anaerobic bacterial growth, hydrogen sulphide is a product of both assimilatory and dissimilatory sulphate reduction. These pathways can reduce various oxidized sulphur compounds including sulphate, sulphite and thiosulphate. The dissimilatory sulphate reduction pathway uses this molecule as the terminal electron acceptor for anaerobic respiration, in which process it produces excess amounts of H{sub 2}S. The reduction of sulphite is a key intermediate step in all sulphate reduction pathways. In Clostridium and Salmonella, an inducible sulphite reductase is directly linked to the regeneration of NAD{sup +}, which has been suggested to have a role in energy production and growth, as well as in the detoxification of sulphite. Above a certain concentration threshold, both H{sub 2}S and HS{sup -} inhibit cell growth by binding the metal centres of enzymes and cytochrome oxidase, necessitating a release mechanism for the export of this toxic metabolite from the cell. Here we report the identification of a hydrosulphide ion channel in the pathogen Clostridium difficile through a combination of genetic, biochemical and functional approaches. The HS{sup -} channel is a member of the formate/nitrite transport family, in which about 50 hydrosulphide ion channels form a third subfamily alongside those for formate (FocA) and for nitrite (NirC). The hydrosulphide ion channel is permeable to formate and nitrite as well as to HS{sup -} ions. Such polyspecificity can be explained by the conserved ion selectivity filter observed in the channel's crystal structure. The channel has a low open probability and is tightly regulated, to avoid decoupling of the membrane proton gradient.

  12. Intravenous immunoglobulin in the therapeutic armamentarium of systemic lupus erythematosus: a systematic review and meta-analysis.

    Science.gov (United States)

    Sakthiswary, Rajalingham; D'Cruz, David

    2014-10-01

    Prepared from the plasma of thousands of blood donors, therapeutic intravenous immunoglobulin (IVIg) mostly consists of human polyspecific immunoglobulin G (IgG). The use of IVIg in systemic lupus erythematosus (SLE) is still considered experimental without any clear indications. The purpose of this systematic review is, therefore, to evaluate the available evidence to determine the therapeutic role of IVIg in SLE. A comprehensive, computerised search was performed in the MEDLINE (Pubmed), Scopus, EMBASE, and Cochrane controlled trials. The study eligibility criteria were randomized controlled trials, and prospective and retrospective observational studies that examined the efficacy of IVIg in adult patients with SLE who were considered the participants.IVIg therapy was the mode of intervention in these patients. Data abstracted included the study design, study population, changes in the disease activity scores (Systemic Lupus Erythematosus Disease Activity Index, Systemic Lupus Activity Measure, and Lupus Activity Index-Pregnancy), steroid dose, complement levels, autoantibodies, and renal function. Thereafter, data analysis established statistical procedures for meta-analysis. Thirteen studies (including 3 controlled and 10 observational) were eligible for inclusion. There was significant reduction in the SLE disease activity scores with IVIg therapy with a standard mean difference of 0.584 (P = 0.002, 95% confidence interval [CI] 0.221-0.947). In terms of rise in complement levels, the response rate was 30.9% (P = 0.001, 95 CI 22.1-41.3). The effects of IVIg on other clinical outcome measures including anti-double-stranded DNA, antinuclear antibody, average steroid dose, and renal function could not be determined because of the limited numbers of trials. The limitations of this review were lack of well-designed controlled trials with adequate sample size on the use of IVIg in SLE. In conclusion, the use of IVIg is associated with significant reduction in SLE

  13. Rationally evolving tRNAPyl for efficient incorporation of noncanonical amino acids.

    Science.gov (United States)

    Fan, Chenguang; Xiong, Hai; Reynolds, Noah M; Söll, Dieter

    2015-12-15

    Genetic encoding of noncanonical amino acids (ncAAs) into proteins is a powerful approach to study protein functions. Pyrrolysyl-tRNA synthetase (PylRS), a polyspecific aminoacyl-tRNA synthetase in wide use, has facilitated incorporation of a large number of different ncAAs into proteins to date. To make this process more efficient, we rationally evolved tRNA(Pyl) to create tRNA(Pyl-opt) with six nucleotide changes. This improved tRNA was tested as substrate for wild-type PylRS as well as three characterized PylRS variants (N(ϵ)-acetyllysyl-tRNA synthetase [AcKRS], 3-iodo-phenylalanyl-tRNA synthetase [IFRS], a broad specific PylRS variant [PylRS-AA]) to incorporate ncAAs at UAG codons in super-folder green fluorescence protein (sfGFP). tRNA(Pyl-opt) facilitated a 5-fold increase in AcK incorporation into two positions of sfGFP simultaneously. In addition, AcK incorporation into two target proteins (Escherichia coli malate dehydrogenase and human histone H3) caused homogenous acetylation at multiple lysine residues in high yield. Using tRNA(Pyl-opt) with PylRS and various PylRS variants facilitated efficient incorporation of six other ncAAs into sfGFP. Kinetic analyses revealed that the mutations in tRNA(Pyl-opt) had no significant effect on the catalytic efficiency and substrate binding of PylRS enzymes. Thus tRNA(Pyl-opt) should be an excellent replacement of wild-type tRNA(Pyl) for future ncAA incorporation by PylRS enzymes.

  14. Acute parvovirus B19 infection causes nonspecificity frequently in Borrelia and less often in Salmonella and Campylobacter serology, posing a problem in diagnosis of infectious arthropathy.

    Science.gov (United States)

    Tuuminen, Tamara; Hedman, Klaus; Söderlund-Venermo, Maria; Seppälä, Ilkka

    2011-01-01

    Several infectious agents may cause arthritis or arthropathy. For example, infection with Borrelia burgdorferi, the etiologic agent of Lyme disease, may in the late phase manifest as arthropathy. Infections with Campylobacter, Salmonella, or Yersinia may result in a postinfectious reactive arthritis. Acute infection with parvovirus B19 (B19V) may likewise initiate transient or chronic arthropathy. All these conditions may be clinically indistinguishable from rheumatoid arthritis. Here, we present evidence that acute B19V infection may elicit IgM antibodies that are polyspecific or cross-reactive with a variety of bacterial antigens. Their presence may lead to misdiagnosis and improper clinical management, exemplified here by two case descriptions. Further, among 33 subjects with proven recent B19V infection we found IgM enzyme immunoassay (EIA) positivity for Borrelia only; for Borrelia and Salmonella; for Borrelia and Campylobacter; and for Borrelia, Campylobacter, and Salmonella in 26 (78.7%), 1 (3%), 2 (6%), and 1 (3%), respectively; however, when examined by Borrelia LineBlot, all samples were negative. These antibodies persisted over 3 months in 4/13 (38%) patients tested. Likewise, in a retrospective comparison of the results of a diagnostic laboratory, 9/11 (82%) patients with confirmed acute B19V infection showed IgM antibody to Borrelia. However, none of 12 patients with confirmed borreliosis showed any serological evidence of acute B19V infection. Our study demonstrates that recent B19V infection can be misinterpreted as secondary borreliosis or enteropathogen-induced reactive arthritis. To obtain the correct diagnosis, we emphasize caution in interpretation of polyreactive IgM and exclusion of recent B19V infection in patients examined for infectious arthritis or arthropathy.

  15. Maternal anti-M induced hemolytic disease of newborn followed by prolonged anemia in newborn twins

    Directory of Open Access Journals (Sweden)

    Satyam Arora

    2015-01-01

    Full Text Available Allo-anti-M often has an immunoglobulin G (IgG component but is rarely clinically significant. We report a case of hemolytic disease of the fetus and newborn along with prolonged anemia in newborn twins that persisted for up to 70 days postbirth. The aim was to diagnose and successfully manage hemolytic disease of newborn (HDN due to maternal alloimmunization. Direct antiglobulin test (DAT, antigen typing, irregular antibody screening and identification were done by polyspecific antihuman globulin cards and standard tube method. At presentation, the newborn twins (T1, T2 had HDN with resultant low reticulocyte count and prolonged anemia, which continued for up to 70 days of life. Blood group of the twins and the mother was O RhD positive. DAT of the both newborns at birth was negative. Anti-M was detected in mothers as well as newborns. Type of antibody in mother was IgG and IgM type whereas in twins it was IgG type only. M antigen negative blood was transfused thrice to twin-1 and twice to twin-2. Recurring reduction of the hematocrit along with low reticulocyte count and normal other cell line indicated a pure red cell aplastic state. Anti-M is capable of causing HDN as well as prolonged anemia (red cell aplasia due to its ability to destroy the erythroid precursor cells. Newborns with anemia should be evaluated for all the possible causes to establish a diagnosis and its efficient management. Mother should be closely monitored for future pregnancies as well.

  16. Immunological compatibility between the chacma baboon and man.

    Science.gov (United States)

    Stark, J H; Smit, J A; Neethling, F A; Nortman, P J; Myburgh, J A

    1991-12-01

    Predictions of an increasing shortage of donor organs for the future has led to a resurgence of interest in xenotransplantation. We have methodically assessed the immunological compatibility of humans against the chacma baboon with a view to narrowing the gap of concordance by careful immunological screening. The necessity of major blood group compatibility in xenotransplantation is now established. While no group O universal donor exists in the baboon, groups A (45%), B (15%), and AB (40%) are well represented. Baboon histocompatibility antigens could not be precisely defined using human antisera. This does not necessarily imply lack of homology between the species, as we have shown specific crossreactivity of numerous antihuman monoclonal antibodies with baboon leukocytes. Normal humans do not exhibit preformed agglutinins to erythrocytes of the chacma baboon (Papio ursinus orientalis)) but cytotoxic antibodies are occasionally found. Sera from allosensitized patients may contain crossreacting hemagglutinins, leukoagglutinins and complement-dependent cytotoxic antibodies. Binding of human immunoglobulin-G and -M to baboon targets was demonstrated by flow cytometry. Negative crossmatch combinations for antibodies of the IgG subclass were easily found, but IgM antibodies from allosensitized patients were polyspecific in their action. In vitro assessment of lymphocyte mediated cytotoxicity showed that preformed cellular immunity between the species was rare. The response of human lymphocytes to xenoantigen stimulation in mixed lymphocyte cultures showed a normal distribution, permitting the selection of low-responding combinations. Screening for viruses, especially HTLV-1 and Coxsackie-BL34, is important. These findings demonstrate a closer degree of concordance than has previously been suspected.

  17. Mixed-species associations in cuxiús (genus Chiropotes).

    Science.gov (United States)

    Shaffer, Christopher A; Barnett, Adrian A; Gregory, Tremaine; de Melo, Fabiano; Moreira, Leandro; Alvim, Thiago H G; Moura, Viviane S; Filó, Anderson; Cardoso, Tatiane; Port-Carvalho, Marcio; Santos, Ricardo Rodrigues dos; Boyle, Sarah A

    2016-05-01

    Polyspecific or mixed-species associations, where two or more species come together to forage and travel as a unit, have been reported in many primate species. These associations appear to offer a number of benefits to the species involved including increased foraging efficiency and decreased risk of predation. While several researchers have suggested that cuxiús (genus Chiropotes) form mixed-species associations, previous studies have not identified the circumstances under which cuxiús form associations or whether they form associations more often than would be expected by chance. Here we present data on the formation of mixed-species associations by four species of cuxiús at eight different sites in Brazil, Suriname, and Guyana. We analyzed data from two of the study sites, (Biological Dynamics of Forest Fragments Project (BDFFP), Brazil and the Upper Essequibo Conservation Concession (UECC), Guyana, to assess whether associations occurred more than would be expected by chance encounters and identify the factors influencing their formation. Cuxiús showed a high degree of inter-site variation in the frequency of time spent in association (ranging from 2 to 26% of observation time) and duration of associations (mean duration from 22 min to 2.5 hr). Sapajus apella was the most common association partner at most sites. At BDFFP, cuxiús formed associations more frequently but not for longer duration than expected by chance. For much of the year at UECC, associations were not more frequent or longer than chance. However, during the dry season, cuxiús formed associations with S. apella significantly more often and for longer duration than predicted by chance. Cuxiús at UECC formed associations significantly more often when in smaller subgroups and when foraging for insects, and alarm called significantly less frequently during associations. We suggest cuxiús form mixed-species associations at some sites as an adaptive strategy to decrease predation risk and

  18. Defining the recognition elements of Lewis Y-reactive antibodies.

    Directory of Open Access Journals (Sweden)

    Somdutta Saha

    Full Text Available Antibody response to carbohydrate antigens is often independent of T cells and the process of affinity/specificity improvement is considered strictly dependent on the germinal centers. Antibodies induced during a T cell-independent type 2 (TI-2 response are less variable and less functionally versatile than those induced with T cell help. The antigen specificity consequences of accumulation of somatic mutations in antibodies during TI-2 responses of Marginal Zone (MZ B cells is a fact that still needs explanation. Germline genes that define carbohydrate-reactive antibodies are known to sculpt antibody-combining sites containing innate, key side-chain contacts that define the antigen recognition step. However, substitutions associated with MZ B cell derived antibodies might affect the mobility and polyspecificity of the antibody. To examine this hypothesis, we analyzed antibodies reactive with the neolactoseries antigen Lewis Y (LeY to define the residue subset required for the reactive repertoire for the LeY antigen. Our molecular simulation studies of crystallographically determined and modeled antibody-LeY complexes suggests that the heavy-chain germline gene VH7183.a13.20 and the light-chain Vκ cr1 germline gene are sufficient to account for the recognition of the trisaccharide-H determinant Types 1-4, while the specificity for LeY is driven by the CDR3 backbone conformation of the heavy chain and not the side chain interactions. These results confirm that these monoclonals use germline-encoded amino acids to recognize simple carbohydrate determinants like trisaccharide-H but relies on somatic mutations in the periphery of the combining site to modify affinity for LeY through electrostatic interactions that leads to their optimized binding. These observations bring further attention to the role of mutations in T-cell independent antibodies to distinguish self from non-self carbohydrate antigens.

  19. Defining the Recognition Elements of Lewis Y-Reactive Antibodies

    Science.gov (United States)

    Saha, Somdutta; Pashov, Anastas; Siegel, Eric R.; Murali, Ramachandran; Kieber-Emmons, Thomas

    2014-01-01

    Antibody response to carbohydrate antigens is often independent of T cells and the process of affinity/specificity improvement is considered strictly dependent on the germinal centers. Antibodies induced during a T cell-independent type 2 (TI-2) response are less variable and less functionally versatile than those induced with T cell help. The antigen specificity consequences of accumulation of somatic mutations in antibodies during TI-2 responses of Marginal Zone (MZ) B cells is a fact that still needs explanation. Germline genes that define carbohydrate-reactive antibodies are known to sculpt antibody-combining sites containing innate, key side-chain contacts that define the antigen recognition step. However, substitutions associated with MZ B cell derived antibodies might affect the mobility and polyspecificity of the antibody. To examine this hypothesis, we analyzed antibodies reactive with the neolactoseries antigen Lewis Y (LeY) to define the residue subset required for the reactive repertoire for the LeY antigen. Our molecular simulation studies of crystallographically determined and modeled antibody-LeY complexes suggests that the heavy-chain germline gene VH7183.a13.20 and the light-chain Vκ cr1 germline gene are sufficient to account for the recognition of the trisaccharide-H determinant Types 1–4, while the specificity for LeY is driven by the CDR3 backbone conformation of the heavy chain and not the side chain interactions. These results confirm that these monoclonals use germline-encoded amino acids to recognize simple carbohydrate determinants like trisaccharide-H but relies on somatic mutations in the periphery of the combining site to modify affinity for LeY through electrostatic interactions that leads to their optimized binding. These observations bring further attention to the role of mutations in T-cell independent antibodies to distinguish self from non-self carbohydrate antigens. PMID:25117628

  20. Basic Research in HIV vaccinology is hampered by reductionist thinking

    Directory of Open Access Journals (Sweden)

    Marc H V Van Regenmortel

    2012-07-01

    Full Text Available This review describes the structure-based reverse vaccinology approach aimed at developing vaccine immunogens capable of inducing antibodies that broadly neutralize HIV-1. Some basic principles of protein immunochemistry are reviewed and the implications of the extensive polyspecificity of antibodies for vaccine development are underlined. Although it is natural for investigators to want to know the cause of an effective immunological intervention, the classic notion of causality is shown to have little explanatory value for a system as complex as the immune system, where any observed effect always results from many interactions between a large number of components. Causal explanations are reductive because a single factor is singled out for attention and given undue explanatory weight on its own. Other examples of the negative impact of reductionist thinking on HIV vaccine development are discussed. These include 1 the failure to distinguish between the chemical nature of antigenicity and the biological nature of immunogenicity, 2 the belief that when an HIV-1 epitope is reconstructed by rational design to better fit a neutralizing Mab, this will produce an immunogen able to elicit Abs with the same neutralizing capacity as the Ab used as template for designing the antigen 3 the belief that protection against infection can be analysed at the level of individual molecular interactions although it has meaning only at the level of an entire organism.The numerous unsuccessful strategies that have been used to design HIV-1 vaccine immunogens are described and it is suggested that the convergence of so many negative experimental results, justifies the conclusion that reverse vaccinology is unlikely to lead to the development of a preventive HIV-1 vaccine. Immune correlates of protection in vaccinees have not yet been identified because this will become feasible only retrospectively once an effective vaccine exists.

  1. Mechanism of quinine-dependent monoclonal antibody binding to platelet glycoprotein IIb/IIIa.

    Science.gov (United States)

    Bougie, Daniel W; Peterson, Julie; Rasmussen, Mark; Aster, Richard H

    2015-10-29

    Drug-dependent antibodies (DDAbs) that cause acute thrombocytopenia upon drug exposure are nonreactive in the absence of the drug but bind tightly to a platelet membrane glycoprotein, usually α(IIb)/β3 integrin (GPIIb/IIIa) when the drug is present. How a drug promotes binding of antibody to its target is unknown and is difficult to study with human DDAbs, which are poly-specific and in limited supply. We addressed this question using quinine-dependent murine monoclonal antibodies (mAbs), which, in vitro and in vivo, closely mimic antibodies that cause thrombocytopenia in patients sensitive to quinine. Using surface plasmon resonance (SPR) analysis, we found that quinine binds with very high affinity (K(D) ≈ 10⁻⁹ mol/L) to these mAbs at a molar ratio of ≈ 2:1 but does not bind detectably to an irrelevant mAb. Also using SPR analysis, GPIIb/IIIa was found to bind monovalently to immobilized mAb with low affinity in the absence of quinine and with fivefold greater affinity (K(D) ≈ 2.2 × 10⁻⁶) when quinine was present. Measurements of quinine-dependent binding of intact mAb and fragment antigen-binding (Fab) fragments to platelets showed that affinity is increased 10 000- to 100 000-fold by bivalent interaction between antibody and its target. Together, the findings indicate that the first step in drug-dependent binding of a DDAb is the interaction of the drug with antibody, rather than with antigen, as has been widely thought, where it induces structural changes that enhance the affinity/specificity of antibody for its target epitope. Bivalent binding may be essential for a DDAb to cause thrombocytopenia.

  2. Thermodynamic stability and flexibility characteristics of antibody fragment complexes.

    Science.gov (United States)

    Li, Tong; Verma, Deeptak; Tracka, Malgorzata B; Casas-Finet, Jose; Livesay, Dennis R; Jacobs, Donald J

    2014-01-01

    Free energy landscapes, backbone flexibility and residue-residue couplings for being co-rigid or co-flexible are calculated from the minimal Distance Constraint Model (mDCM) on an exploratory dataset consisting of VL, scFv and Fab antibody fragments. Experimental heat capacity curves are reproduced markedly well, and an analysis of quantitative stability/flexibility relationships (QSFR) is applied to a representative VL domain and several complexes in the scFv and Fab forms. Global flexibility in the denatured ensemble typically decreases in the larger complexes due to domain-domain interfaces. Slight decreases in global flexibility also occur in the native state of the larger fragments, but with a concurrent large increase in correlated flexibility. Typically, a VL fragment has more co-rigid residue pairs when isolated compared to the scFv and Fab forms, where correlated flexibility appears upon complex formation. This context dependence on residue- residue couplings in the VL domain across length scales of a complex is consistent with the evolutionary hypothesis of antibody maturation. In comparing two scFv mutants with similar thermodynamic stability, local and long-ranged changes in backbone flexibility are observed. In the case of anti-p24 HIV-1 Fab, a variety of QSFR metrics were found to be atypical, which includes comparatively greater co-flexibility in the VH domain and less co-flexibility in the VL domain. Interestingly, this fragment is the only example of a polyspecific antibody in our dataset. Finally, the mDCM method is extended to cases where thermodynamic data is incomplete, enabling high throughput QSFR studies on large numbers of antibody fragments and their complexes.

  3. ADMET Evaluation in Drug Discovery. 16. Predicting hERG Blockers by Combining Multiple Pharmacophores and Machine Learning Approaches.

    Science.gov (United States)

    Wang, Shuangquan; Sun, Huiyong; Liu, Hui; Li, Dan; Li, Youyong; Hou, Tingjun

    2016-08-01

    Blockade of human ether-à-go-go related gene (hERG) channel by compounds may lead to drug-induced QT prolongation, arrhythmia, and Torsades de Pointes (TdP), and therefore reliable prediction of hERG liability in the early stages of drug design is quite important to reduce the risk of cardiotoxicity-related attritions in the later development stages. In this study, pharmacophore modeling and machine learning approaches were combined to construct classification models to distinguish hERG active from inactive compounds based on a diverse data set. First, an optimal ensemble of pharmacophore hypotheses that had good capability to differentiate hERG active from inactive compounds was identified by the recursive partitioning (RP) approach. Then, the naive Bayesian classification (NBC) and support vector machine (SVM) approaches were employed to construct classification models by integrating multiple important pharmacophore hypotheses. The integrated classification models showed improved predictive capability over any single pharmacophore hypothesis, suggesting that the broad binding polyspecificity of hERG can only be well characterized by multiple pharmacophores. The best SVM model achieved the prediction accuracies of 84.7% for the training set and 82.1% for the external test set. Notably, the accuracies for the hERG blockers and nonblockers in the test set reached 83.6% and 78.2%, respectively. Analysis of significant pharmacophores helps to understand the multimechanisms of action of hERG blockers. We believe that the combination of pharmacophore modeling and SVM is a powerful strategy to develop reliable theoretical models for the prediction of potential hERG liability.

  4. Rationally evolving tRNAPyl for efficient incorporation of noncanonical amino acids

    Science.gov (United States)

    Fan, Chenguang; Xiong, Hai; Reynolds, Noah M.; Söll, Dieter

    2015-01-01

    Genetic encoding of noncanonical amino acids (ncAAs) into proteins is a powerful approach to study protein functions. Pyrrolysyl-tRNA synthetase (PylRS), a polyspecific aminoacyl-tRNA synthetase in wide use, has facilitated incorporation of a large number of different ncAAs into proteins to date. To make this process more efficient, we rationally evolved tRNAPyl to create tRNAPyl-opt with six nucleotide changes. This improved tRNA was tested as substrate for wild-type PylRS as well as three characterized PylRS variants (Nϵ-acetyllysyl-tRNA synthetase [AcKRS], 3-iodo-phenylalanyl-tRNA synthetase [IFRS], a broad specific PylRS variant [PylRS-AA]) to incorporate ncAAs at UAG codons in super-folder green fluorescence protein (sfGFP). tRNAPyl-opt facilitated a 5-fold increase in AcK incorporation into two positions of sfGFP simultaneously. In addition, AcK incorporation into two target proteins (Escherichia coli malate dehydrogenase and human histone H3) caused homogenous acetylation at multiple lysine residues in high yield. Using tRNAPyl-opt with PylRS and various PylRS variants facilitated efficient incorporation of six other ncAAs into sfGFP. Kinetic analyses revealed that the mutations in tRNAPyl-opt had no significant effect on the catalytic efficiency and substrate binding of PylRS enzymes. Thus tRNAPyl-opt should be an excellent replacement of wild-type tRNAPyl for future ncAA incorporation by PylRS enzymes. PMID:26250114

  5. 凝胶直接抗球蛋白试验在自身免疫性溶血性贫血实验诊断中的应用%The Application of Microcolumn Coomb's Test in the Diagnosis of Autoimmune Hemolytic Anemia

    Institute of Scientific and Technical Information of China (English)

    罗广平; 丁浩强; 骆宏; 汪传喜; 叶欣; 夏文杰; 戎霞; 陈扬凯; 邓晶; 赵阳

    2009-01-01

    Objective To investigate the characteristic of the microcolumn Coomb's test and to observe its diagnosis significance in autoimmune hemolytic anemia (AIHA). Methods Competitive microcolumn gel and a routinely used direct antiglobulin test (DAT) were used to study IgG and C3d in 135 cases of AIHA. Results 19 cases were identified in positive by routine typing. 24 cases were identified in positive by microcolunm gel, incuding 13 cases in IgG positive. 4 cases in C3d positive and 7 cases both in IgG and C3d positive. There were statistically difference between the microcolumn gel and routine DAT. Conclusion Microcolumn Coomb's test is a sensitive and objective method for the diagnosis of AIHA.%目的 探讨凝胶直接抗球蛋白试验的特点及其在自身免疫性溶血性贫血(AIHA)实验诊断中的应用价值.提高致敏红细胞检出率.方法 检测临床诊断疑似AIHA标本135例.用Coomb's凝胶试剂卡对受检标本进行直接抗球蛋白试验.以试管法直接抗球蛋白试验作对照.凝胶法阳性者用单特异性IgG和C3d凝胶试剂卡进行分型.结果 试管法直接抗球蛋白试验阳性19例,Coomb's凝胶直接抗球蛋白试验(GDAT)阳性24例,两种检测方法间差异有统计学意义(P<0.05).对24份凝胶直接抗球蛋白试验阳性标本进行IgG和C3d分型,其中IgG+C3d型7例(29%),IgG型13例(54%),C3d型4例(17%).结论 凝胶直接抗球蛋白试验不需洗涤红细胞,操作简便,重复性好;检测致敏红细胞灵敏度优于试管法,在AIHA实验诊断中值得临床推广应用.

  6. Thermal-structural coupling analysis of disk brake%盘式制动器热结构耦合分析

    Institute of Scientific and Technical Information of China (English)

    朱永梅; 朱玉君; 王新国; 张奔

    2015-01-01

    The article expresses the direct thermal-structural coupling of disk brake by Abaqus .The C3D8T ele-ment has the degrees of freedom to calculate the temperature and structure , so we mesh the 3-dimensional disk brake model with the C3D8T element and analyze the initial conditions , boundary conditions and loads on the fi-nite element model .The selection and calculation of friction coefficient , function of heat flux and convection heat transfer coefficient are discussed in detail .The temperature contours are analized and the effects of different structural and material parameters of the brake disc are compared .The analysis provides a reliable basis for choosing the disc material , designing structural size , selecting braking conditions , and preventing brake disc fail-ure .%文中应用ABAQUS软件对盘式制动器进行热结构直接耦合分析,采用具有温度计算和结构计算所需自由度的C3 D8 T单元,对制动盘三维模型划分网格;分析了有限元模型的初始条件、边界条件和载荷施加,详细讨论了制动件之间摩擦系数、热流密度函数和对流散热系数的选取和计算;分析了制动盘制动模拟过程中的温度云图,比较制动盘的不同结构和材料参数对制动盘表面温升的影响。分析结果对制动盘材料选择、结构尺寸设计、制动工况选择、制动盘破坏预防等工作提供了可靠依据。

  7. Structural basis for simvastatin competitive antagonism of complement receptor 3

    DEFF Research Database (Denmark)

    Jensen, Maria Risager; Bajic, Goran; Zhang, Xianwei;

    2016-01-01

    The complement system is an important part of the innate immune response to infection, but may also cause severe complications during inflammation. Small molecule antagonists to complement receptor (CR)3 have been widely sought, but a structural basis for their mode of action is not available. We...... report here on the structure of the human CR3 ligand-binding I domain in complex with simvastatin. Simvastatin targets the metal ion-dependent adhesion site of the open, ligand-binding conformation of the CR3 I domain by direct contact with the chelated Mg2+ ion. Simvastatin antagonizes I domain binding...... to the complement fragments iC3b and C3d, but not to intercellular adhesion molecule-1. By virtue of the I domain's wide distribution in binding kinetics to ligands, it was possible to identify ligand binding kinetics as discriminator for simvastatin antagonism. In static cellular experiments, 15-25 μM simvastatin...

  8. Generation of a C3c specific monoclonal antibody and assessment of C3c as a putative inflammatory marker derived from complement factor C3

    DEFF Research Database (Denmark)

    Palarasah, Yaseelan; Skjodt, Karsten; Brandt, Jette;

    2010-01-01

    complex (C5b-C9) and quantification of complement split products by precipitation-in-gel techniques (e.g. C3d). We have developed a mouse monoclonal antibody (mAb) that is able to detect fluid phase C3c without interference from other products generated from the complement component C3. The C3c specific m......Ab was tested in different ELISA combinations with various types of in vitro activated sera and with plasma or serum samples from factor I deficient patients. The specificity of the mAb was evaluated in immunoprecipitation techniques and by analysis of eluted fragments of C3 after immunoaffinity chromatography...

  9. Studies on enzymatic hydrolysis extraction of collagen from grass carp fish scale%酶解法提取草鱼鱼鳞胶原蛋白的工艺研究

    Institute of Scientific and Technical Information of China (English)

    邱小明

    2014-01-01

    对酶解法提取草鱼鱼鳞胶原蛋白的工艺进行了研究,以胶原蛋白提取率作为评价指标,选择选择酶解温度、pH值、加酶量、酶解时间作为考察因素,进行了正交试验,确定最佳的提取工艺方案为A2B2C3D1,即酶解温度30℃,pH值4,加酶量2%,酶解时间1h.在该条件下草鱼鱼鳞胶原蛋白提取率为92.28%.

  10. Synthesis and biological activity of novel tiliroside derivants.

    Science.gov (United States)

    Qin, Nan; Li, Chun-Bao; Jin, Mei-Na; Shi, Li-Huan; Duan, Hong-Quan; Niu, Wen-Yan

    2011-10-01

    A series of new tiliroside derivatives were synthesized and characterized by analytical (1)H NMR, (13)C NMR and mass spectrometry. All of the compounds were evaluated for anti-diabetic properties in vitro using HepG2 cells. Compounds 3c, 3d, and 3i-l caused significant enhancements in glucose consumption by insulin-resistant HepG2 cells compared with control cells and cells that were exposed to metformin (an anti-diabetic drug). Moreover, compound 3l significantly activated adenosine 5'-monophosphate-activated protein kinase activity and reduced acetyl-CoA carboxylase activity. Thus, the tiliroside derivative 3l offers potential to be developed as a new approach for treating type II diabetes.

  11. Electron Thermal Capacity in Plasma Generated at Cavitation Bubble Collapse in D-acetone

    CERN Document Server

    Kostenko, B F

    2004-01-01

    The latest experimental data on nuclear reaction product registration at cavitation bubble collapse in deuterated acetone (C$_3$D$_6$O) still argue in favour of existence of a new possibility to realize the thermonuclear synthesis. Theoretical description based on numerical solution of simultaneous conservation equations for gaseous and liquid phases also confirms this possibility, although it requires further more precise definitions. In particular, description of electron degrees of freedom in very dense nonequilibrium plasma generated at the final stage of bubble collapse needs specification. In the present paper, calculations of electron thermal capacity in the deuterated acetone multiple ionization region at electron temperatures $T_e \\simeq 10^4 $ K and above and compression range $\\rho/\\rho_0 \\simeq 1 \\div 100$ have been fulfilled on the basis of direct numerical solution of equation for chemical potential.

  12. The CC stretching band ν6 of allene- d4

    Science.gov (United States)

    Plíva, J.; Rousan, K.; Polo, S. R.

    1983-10-01

    The infrared spectrum of C 3D 4 was measured in the region of the paralled band of the CC stretching vibration ν6 centered at ν0 = 1920.2332 cm -1 on a high-resolution Fourier transform spectrometer and deconvolved to a linewidth of ˜ {1}/{2} of the Doppler width (˜0.0023 cm -1). The high resolution reveals the presence of strong perturbations in the K = 4 and K = 8 to 12 levels of the ν6 upper state. For a quantitative treatment of the observed transitions, a Hamiltonian matrix including six different perturbing states was constructed and used to refine the 6 spectroscopic constants of the ν6 state and 20 of the constants for the perturbing states. Measurement of the hot band ν6 + ν11 - ν11 whose band center is at 1916.200 cm -1 yielded the anharmonic constant x6,11 = -4.033 cm -1.

  13. Three-dimensional microscopic light field particle image velocimetry

    Science.gov (United States)

    Truscott, Tadd T.; Belden, Jesse; Ni, Rui; Pendlebury, Jonathon; McEwen, Bryce

    2017-03-01

    A microscopic particle image velocimetry (μ {PIV}) technique is developed based on light field microscopy and is applied to flow through a microchannel containing a backward-facing step. The only hardware difference from a conventional μPIV setup is the placement of a microlens array at the intermediate image plane of the microscope. The method combines this optical hardware alteration with post-capture computation to enable 3D reconstruction of particle fields. From these particle fields, we measure three-component velocity fields, but find that accurate velocity measurements are limited to the two in-plane components at discrete depths through the volume (i.e., 2C-3D). Results are compared with a computational fluid dynamics simulation.

  14. Assessment of left heart and pulmonary circulation flow dynamics by a new pulsed mock circulatory system

    Science.gov (United States)

    Tanné, David; Bertrand, Eric; Kadem, Lyes; Pibarot, Philippe; Rieu, Régis

    2010-05-01

    We developed a new mock circulatory system that is able to accurately simulate the human blood circulation from the pulmonary valve to the peripheral systemic capillaries. Two independent hydraulic activations are used to activate an anatomical-shaped left atrial and a left ventricular silicon molds. Using a lumped model, we deduced the optimal voltage signals to control the pumps. We used harmonic analysis to validate the experimental pulmonary and systemic circulation models. Because realistic volumes are generated for the cavities and the resulting pressures were also coherent, the left atrium and left ventricle pressure-volume loops were concordant with those obtained in vivo. Finally we explored left atrium flow pattern using 2C-3D+T PIV measurements. This gave a first overview of the complex 3D flow dynamics inside realistic left atrium geometry.

  15. Effects of three-dimensional navigation on intraoperative management and early postoperative outcome after open reduction and internal fixation of displaced acetabular fractures

    DEFF Research Database (Denmark)

    Oberst, Michael; Hauschild, Oliver; Konstantinidis, Lukas;

    2012-01-01

    BACKGROUND: This study was conducted to evaluate whether intraoperative procedure and/or early postoperative results after open reduction and internal fixation (ORIF) of displaced acetabulum fractures are influenced by the use of a three-dimensional (3D) image intensifier in combination with a na....... In addition, the complication rate in the navigated group was significantly lower. CONCLUSION: We support the use of navigation systems and a 3D image intensifier as helpful tools during ORIF of displaced acetabular fractures. LEVEL OF EVIDENCE: Therapeutic study, level III....... acetabular fractures led to a significant increase in skin-to-skin time. Postoperative radiolographic analysis revealed an improvement in the quality of fracture reduction in the 3D navigation group. Navigation in combination with the 3D images of the ISO-C 3D limited the need for extended approaches...

  16. 半边旗药材提取工艺的研究%Study on Extraction Process in Pteris semipinnata L.

    Institute of Scientific and Technical Information of China (English)

    典灵辉; 梁念慈

    2007-01-01

    目的 优选半边旗的提取工艺.方法 采用L9(34)正交试验,考察乙醇浓度(A)、提取时间(B)、提取次数(C)和溶剂用量(D)4个影响因素,以5F(11β-hydroxy-15-oxo-ent-kaur-16-en-19-oic acid)含量为评价指标,并采用薄层扫描法进行含量测定.结果 半边旗回流提取的最佳工艺为A2B2C3D3,即加12倍量70%乙醇,回流提取3次,每次2h.结论 优选出的工艺稳定可行.

  17. Design and synthesis of novel triazole antifungal derivatives based on the active site of fungal lanosterol 14a-demethylase (CYP51)

    Institute of Scientific and Technical Information of China (English)

    Zhi Gang Dan; Jun Zhang; Shi Chong Yu; Hong Gang Hu; Xiao Yun Chai; Qing Yan Sun; Qiu Ye Wu

    2009-01-01

    A series of 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-(N-isoproyl-N-substituted-amino)-2-propanols have been designed and synthesized on the basis of the active site of lanosterol 14a-demethylase (CYP51). Their structures were confirmed by MS and 1H NMR. In vitro antifungal activities of these synthesized compounds were evaluated against eight human pathogenic fungi. The results showed that all title compounds exhibited activity against fungi tested to some extent. Compounds 3c, 3d, 7a, 7b and 7c exhibited more potent antifungal activities against nearly all fungi tested except Aspergillus fumigatus than fluconazole.

  18. Growth of ZnO nanostructures on Au-coated Si: Influence of growth temperature on growth mechanism and morphology

    DEFF Research Database (Denmark)

    Kumar, Rajendra; McGlynn, E.; Biswas, M.;

    2008-01-01

    ZnO nanostructures were grown on Au-catalyzed Si silicon substrates using vapor phase transport at growth temperatures from 800 to 1150 degrees C. The sample location ensured a low Zn vapor supersaturation during growth. Nanostructures grown at 800 and 850 degrees C showed a faceted rodlike...... growth tended to dominate resulting in the formation of a porous, nanostructured morphology. In all cases growth was seen only on the Au-coated region. Our results show that the majority of the nanostructures grow via a vapor-solid mechanism at low growth temperatures with no evidence of Au nanoparticles...... morphology with mainly one-dimensional (1D) growth along the nanorod axis. Samples grown at intermediate temperatures (900, 950, and 1050 degrees C) in all cases showed significant three dimensional (3D) growth at the base of 1D nanostructures. At higher growth temperatures (1100 and 1150 degrees C) 3D...

  19. Complement's participation in acquired immunity

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Leslie, Robert Graham Quinton

    2002-01-01

    of the B cell receptor for antigen (BCR), a complex composed of the iC3b/C3d fragment-binding complement type 2 receptor (CR2, CD21) and its signaling element CD19 and the IgG-binding receptor FcgammaRIIb (CD32). The positive or negative outcome of signaling through this triad is determined by the context...... in which antigen is seen, be it alone or in association with natural or induced antibodies and/or C3-complement fragments. The aim of this review is to describe the present status of our understanding of complement's participation in acquired immunity and the regulation of autoimmune responses....

  20. Relative role of upstream regulators of Akt, ERK and CREB in NCAM- and FGF2-mediated signalling

    DEFF Research Database (Denmark)

    Ditlevsen, D.K.; Owczarek, S.; Berezin, V.

    2008-01-01

    demonstrated previously to be involved in NCAM signalling. For comparison, we also evaluated the role of upstream signalling cascades on fibroblast growth factor 2 (FGF2)-mediated phosphorylation of ERK, Akt, and CREB and found that FGF2 required the activity of both FGFR and Src-family kinases...... for phosphorylation of ERK, Akt, and CREB. MEK was required for phosphorylation of ERK and CREB, but not Akt, whereas G(0)/G(i)-proteins were necessary for phosphorylation of Akt and CREB, and cGMP was necessary for Akt phosphorylation. We thus demonstrate that even though NCAM and FGF2 have many signalling features...... in common, and even though both are known to activate FGFR, there are a number of differences in the intracellular signalling network activated by the NCAM ligand C3d and the FGFR ligand FGF2....

  1. Steroids from Dysoxylum grande (Meliaceae) leaves.

    Science.gov (United States)

    Wah, Low Kok; Abas, Faridah; Cordell, Geoffrey A; Ito, Hideyuki; Ismail, Intan Safinar

    2013-02-01

    Seven new 23-oxo-cholestane derivatives named as grandol A (1), B (2), C (3), D (4), E (5), F (6), and G (7) were isolated from Dysoxylum grande leaves alongside with a new 3,4-secodammar-4(28)-en-3-oic acid derivative (8). The structures of the compounds were elucidated based on the interpretation of spectroscopic data, and their relative configurations were established by NOESY 2D NMR data. All of the isolates were tested for anti-acetylcholinesterase activity using thin layer chromatography (TLC)-bioautography with fast blue B salt. Only grandol A (1) and B (2) showed positive results, with clear discoloration at a concentration of 12.5 ppm. However, the obtained IC(50) values for grandol A and B, when using Ellman's method, were not significant (>200 μg/ml).

  2. THE KFIB EXPERIMENT

    Energy Technology Data Exchange (ETDEWEB)

    Youngblood, Gerald E.; Senor, David J.; Jones, Russell H.; Kowbel, W.; Kohyama, A.

    2000-06-30

    Several rod-shaped specimens with uniaxially packed fibers (Hi-Nicalon™, Hi-Nicalon™ Type S, Tyranno™ SA and Amoco K1100™ types) in a pre-ceramic polymer matrix were fabricated. By using appropriate analytic models, the bare fiber thermal conductivity (Kf) will be determined as a function of temperature up to 1000°C before and after irradiation for samples cut from these rods. Preliminary thermal conductivity data for unirradiated fibers (Hi-Nicalon™ and Tyranno™ SA-B SiC and K1100™ graphite) and for three types of unirradiated composites made from these fibers (2D-Nicalon S/SiC multilayer/CVI-SiC, 3D-Nicalon S/PIP-SiC, and 2D-8HS Tyrannohex™ HP) are presented.

  3. 高频堆焊耐磨覆层正交试验研究%Orthogonal Experimental Study of High-frequency Induction Overlaying Welding Wear-resisting Coating

    Institute of Scientific and Technical Information of China (English)

    汪选国

    2006-01-01

    对高频堆焊耐磨覆层材料主要化学成分进行了正交设计,对每种成分的高频覆层试样进行了耐磨性试验.对正交试验结果进行了极差和方差分析,两种分析方法得出的结论一致.得出的最优方案为A3B2C3D2:即C3.0%,Cr27%,Mo1.5%,ReSi1.0%,对最优方案的耐磨性进行了数值估计.通过验证试验表明:最优方案的相对耐磨性达到45钢的11.73倍,与理论分析一致.

  4. Serum amyloid P component-DNA complexes are decreased in systemic lupus erythematosus. inverse association with anti-dsDNA antibodies

    DEFF Research Database (Denmark)

    Voss, Anne; Nielsen, Ellen Holm; Svehag, Sven Erik;

    2008-01-01

    OBJECTIVE: To study serum levels of serum amyloid P component (SAP) and SAP-DNA complexes in a population-based cohort of patients with systemic lupus erythematosus (SLE). METHODS: The study population comprised 82 unselected patients of predominantly Scandinavian ancestry with SLE according......-DNA-negative patients tended to have lower leukocyte counts and complement C3 levels, and higher erythrocyte sedimentation rates and C3d levels versus SAP-DNA-positive patients. There was an inverse association between the occurrence of anti-double-stranded DNA (anti-dsDNA) antibodies and SAP-DNA complexes. Co......-occurrence of SAP-DNA complexes and anti-dsDNA antibodies was demonstrated in only one SLE patient, implying that 81/82 patients were discordant for the presence of anti-dsDNA antibodies and SAP-DNA complexes. CONCLUSION: The decreased level of SAP-DNA complexes in SLE patients and the inverse relationship between...

  5. Orthogonal Experiment of the Extraction of Triterpenoids from Stems of Hyptis suaveolens with Microwave%微波提取毛老虎茎中总三萜酸的正交实验研究

    Institute of Scientific and Technical Information of China (English)

    黄秀香; 林翠梧; 陈丽芬; 袁霞; 宁自华

    2008-01-01

    目的:研究微波法提取毛老虎茎中总三萜酸的最佳工艺.方法:采用正交实验,考察时间(A)、温度(B)、固液比(C)、NaOH浓度(D)4个因素的影响.结果:微波提取优化工艺条件是A1B2C3D2.结论:微波提取具有提取率高,提取速率快,提取温度低,能量消耗小等特点,用于中草药的提取应用前景广阔.

  6. Study on the Extracting Technique of Flavonoids from Rumex Acetosa Linn.%正交设计提取酸模中黄酮化合物

    Institute of Scientific and Technical Information of China (English)

    王绪英

    2012-01-01

    To study the flavonoid Rumex acetosa Linn. extraction process,to establish the best extraction conditions with orthogonal test method Conclusion: tlavonoid Rumex acetosa Linn best flavonoid extraction technology A2B3C3D. That with 10 times the amount of 85% ethanol bath reflux 3h.%采用正交设计法对酸模(Rumexacetosa Linn.)中黄酮类化合物的最佳提取工艺进行了初步研究。结果显示最佳提取工艺组合为,即乙醇浓度85%、提取时间3h、料液比1:10。影响提取的因素依次为:提取时间〉乙醇浓度〉溶媒倍数。

  7. Synthesis and bactericidal activities of novel pyrazole-l-carbothioamide derivatives

    Institute of Scientific and Technical Information of China (English)

    LIU Xinhua; WANG Shifan; SONG Baoan

    2007-01-01

    4-(2-Hydroxy-phenyl)-but-3-en-2-one (1) was prepared via condensation of salicylaldehyde with acetone,and then reaction of the ketone 1 with thiosemicarbazide was accompanied by cyclization to give substituted pyrazole (2).Seven new 5-(2-hydroxy-phenyl)-3-methyl-4,5-dihydropyrazole- 1-carbothioamide derivatives (3a-3g) were synthesized by the acylation of 2 and characterized by means of elemental analysis,infrared (IR),and 1H nuclear magnetic resonance (NMR).The compounds 3c,3d,and 3g showed certain bactericidal activity against E.coli;while compound 3g showed certain bactericidal activity against P.vulgaris.

  8. Activation of Complement Following Total Hip Replacement.

    Science.gov (United States)

    Thordardottir, S; Vikingsdottir, T; Bjarnadottir, H; Jonsson, H; Gudbjornsson, B

    2016-03-01

    The aim of this study was to investigate whether complement activation, via the classical and alternative pathways, occurs following a cemented total hip replacement (THR) surgery due to osteoarthritis. Blood samples were collected systematically from 12 patients - six male and six women, with a median age of 75 (range: 59-90 years) - preoperatively, 6 h post-operatively and on the first, second and third post-operative day. Total function of classical (CH50) and alternative pathways (AH50) was evaluated, along with the determination of serum concentrations of the complement proteins C3, C4, C3d, the soluble terminal complement complex (sTCC) sC5b-9, as well as C-reactive protein (CRP) and albumin. Measurements of CRP and albumin levels elucidated a marked inflammatory response following the operation. The CH50, AH50 and C3 and C4 levels were significantly lower 6 h after the surgery compared with the preoperative levels, but elevated above the preoperative levels during the following 3 days. The complement activation product C3d levels increased continually during the whole observation period, from 13.5 AU/ml (range: 8-19 AU/ml) preoperative to 20 AU/ml (range: 12-34 AU/ml) on the third post-operative day. Furthermore, we observed an increase in the sC5b-9 levels between the preoperative and the third post-operative day. These results demonstrate a significant activation of the complement system following cemented THR. Further studies are needed to elucidate the time frame and the pathogenic role of this observed complement activation.

  9. Intra-operative computer navigation guided cervical pedicle screw insertion in thirty-three complex cervical spine deformities

    Directory of Open Access Journals (Sweden)

    S Rajasekaran

    2010-01-01

    Full Text Available Background: Cervical pedicle screw fixation is challenging due to the small osseous morphometrics and the close proximity of neurovascular elements. Computer navigation has been reported to improve the accuracy of pedicle screw placement. There are very few studies assessing its efficacy in the presence of deformity. Also cervical pedicle screw insertion in children has not been described before. We evaluated the safety and accuracy of Iso-C 3D-navigated pedicle screws in the deformed cervical spine. Materials and Methods: Thirty-three patients including 15 children formed the study group. One hundred and forty-five cervical pedicle screws were inserted using Iso-C 3D-based computer navigation in patients undergoing cervical spine stabilization for craniovertebral junction anomalies, cervico-thoracic deformities and cervical instabilities due to trauma, post-surgery and degenerative disorders. The accuracy and containment of screw placement was assessed from postoperative computerized tomography scans. Results: One hundred and thirty (89.7% screws were well contained inside the pedicles. Nine (6.1% Type A and six (4.2% Type B pedicle breaches were observed. In 136 levels, the screws were inserted in the classical description of pedicle screw application and in nine deformed vertebra, the screws were inserted in a non-classical fashion, taking purchase of the best bone stock. None of them had a critical breach. No patient had any neurovascular complications. Conclusion: Iso-C navigation improves the safety and accuracy of pedicle screw insertion and is not only successful in achieving secure pedicle fixation but also in identifying the best available bone stock for three-column bone fixation in altered anatomy. The advantages conferred by cervical pedicle screws can be extended to the pediatric population also.

  10. Complement activation in Ghanaian children with severe Plasmodium falciparum malaria

    Directory of Open Access Journals (Sweden)

    Ofori Michael F

    2007-12-01

    Full Text Available Abstract Background Severe anaemia (SA, intravascular haemolysis (IVH and respiratory distress (RD are severe forms of Plasmodium falciparum malaria, with RD reported to be of prognostic importance in African children with malarial anaemia. Complement factors have been implicated in the mechanism leading to excess anaemia in acute P. falciparum infection. Methods The direct Coombs test (DCT and flow cytometry were used to investigate the mean levels of RBC-bound complement fragments (C3d and C3bαβ and the regulatory proteins [complement receptor 1 (CD35 and decay accelerating factor (CD55] in children with discrete clinical forms of P. falciparum malaria. The relationship between the findings and clinical parameters including coma, haemoglobin (Hb levels and RD were investigated. Results Of the 484 samples tested, 131(27% were positive in DCT, out of which 115/131 (87.8% were positive for C3d alone while 16/131 (12.2% were positive for either IgG alone or both. 67.4% of the study population were below 5 years of age and DCT positivity was more common in this age group relative to children who were 5 years or older (Odds ratio, OR = 3.8; 95%CI, 2.2–6.7, p Conclusion These results suggest that complement activation contributed to anaemia in acute childhood P. falciparum malaria, possibly through induction of erythrophagocytosis and haemolysis. In contrast to other studies, this study did not find association between levels of the complement regulatory proteins, CD35 and CD55 and malarial anaemia. These findings suggest that complement activation could also be involved in the pathogenesis of RD but larger studies are needed to confirm this finding.

  11. Ultrasonic-assisted extraction technology of papaya seed oil%超声波辅助提取木瓜籽油的工艺研究

    Institute of Scientific and Technical Information of China (English)

    王鑫; 赵梅; 慕鸿雁

    2015-01-01

    Papaya seedoil was extracted by ultrasound method. Theoptimal ultrasound–assisted extraction processingconditions were explored by single–factor andorthogonal experiments. The result showed that theorderof primary and secondary factors that effected the extraction rateof papaya seed oil wasB>C>A>D,that was to say the extraction temperature was the most important,followed by extraction time,ratioof solid–liquid and ultrasonic power. Theoptimumconditionof extraction rate of papaya seedoil wasA2B1C3D1,that was to say ratioof solid–liquid was 1∶10 g/mL,extraction temperature was 50℃,extraction time was 30 minutes and ultrasonic power was 175 W. Under this condition,the yieldof papaya seedoil was up to 29.36%.%采用超声波辅助提取木瓜籽油,并用单因素试验和正交试验筛选最佳提取条件。结果表明:影响木瓜籽油出油率的因素主次顺序是B>C>A>D,即超声温度>超声时间>料液比>超声波功率。最佳提取工艺条件为,A2B1C3D1,即料液比1∶10 g/mL、超声温度50℃、超声时间30 min、超声功率175 W。在此工艺条件下,木瓜籽油出油率为29.36%。

  12. Communication energy-aware research of star cluster NoC%片上网络的星型簇结构通信能耗研究

    Institute of Scientific and Technical Information of China (English)

    刘琪; 李东生

    2012-01-01

    相对于传统的平面结构,三维片上网络具有更好的集成度和性能.提出一种基于三维网格的星型簇结构的片上网络( 3D SCBM-NoC),3D SCBM-NoC可以减少路由节点,降低处理节点间的通信代价.通过分析3DSCBM-NoC的拓扑结构,建立了针对星型簇结构的片上网络通信能耗模型,分别使用顺序方法和蚁群算法实现了片上网络映射.实验结果表明,相对于处理节点规模相同且数目为16的3D Mesh-NoC和2D Mesh-NoC,3D SCBM-NoC的通信能耗明显降低.%Comparing with the traditional planar structure, 3D NoC are capable of achieving better performance and packaging density. This paper advanced a new style of NoC structure called star cluster NoC based on three dimensions Mesh(3D SCBM-NoC) , which could reduce the number of router nodes, and saved the cost of communication. By analyzing the topology of the 3D SCBM-NoC, this paper presented the communication energy model of star-cluster structure, and achieved the mapping of NoC using the sequence method and ant arithmetic. When the number of processor nodes is 16,comparing with 3D Mesh-NoC and 2D Mesh-NoC,the communication energy of 3D SCBM-NoC is the lowest.

  13. Complement C3 deficiency attenuates chronic hypoxia-induced pulmonary hypertension in mice.

    Directory of Open Access Journals (Sweden)

    Eileen M Bauer

    Full Text Available Evidence suggests a role of both innate and adaptive immunity in the development of pulmonary arterial hypertension. The complement system is a key sentry of the innate immune system and bridges innate and adaptive immunity. To date there are no studies addressing a role for the complement system in pulmonary arterial hypertension.Immunofluorescent staining revealed significant C3d deposition in lung sections from IPAH patients and C57Bl6/J wild-type mice exposed to three weeks of chronic hypoxia to induce pulmonary hypertension. Right ventricular systolic pressure and right ventricular hypertrophy were increased in hypoxic vs. normoxic wild-type mice, which were attenuated in C3-/- hypoxic mice. Likewise, pulmonary vascular remodeling was attenuated in the C3-/- mice compared to wild-type mice as determined by the number of muscularized peripheral arterioles and morphometric analysis of vessel wall thickness. The loss of C3 attenuated the increase in interleukin-6 and intracellular adhesion molecule-1 expression in response to chronic hypoxia, but not endothelin-1 levels. In wild-type mice, but not C3-/- mice, chronic hypoxia led to platelet activation as assessed by bleeding time, and flow cytometry of platelets to determine cell surface P-selectin expression. In addition, tissue factor expression and fibrin deposition were increased in the lungs of WT mice in response to chronic hypoxia. These pro-thrombotic effects of hypoxia were abrogated in C3-/- mice.Herein, we provide compelling genetic evidence that the complement system plays a pathophysiologic role in the development of PAH in mice, promoting pulmonary vascular remodeling and a pro-thrombotic phenotype. In addition we demonstrate C3d deposition in IPAH patients suggesting that complement activation plays a role in the development of PAH in humans.

  14. The 15 SCR flexible extracellular domains of human complement receptor type 2 can mediate multiple ligand and antigen interactions.

    Science.gov (United States)

    Gilbert, Hannah E; Asokan, Rengasamy; Holers, V Michael; Perkins, Stephen J

    2006-10-01

    Complement receptor type 2 (CR2, CD21) is a cell surface protein that links the innate and adaptive immune response during the activation of B cells. The extracellular portion of CR2 comprises 15 or 16 short complement regulator (SCR) domains, for which the overall arrangement in solution is unknown. This was determined by constrained scattering and ultracentrifugation modelling. The radius of gyration of CR2 SCR 1-15 was determined to be 11.5 nm by both X-ray and neutron scattering, and that of its cross-section was 1.8 nm. The distance distribution function P(r) showed that the overall length of CR2 SCR 1-15 was 38 nm. Sedimentation equilibrium curve fits gave a mean molecular weight of 135,000 (+/- 13,000) Da, in agreement with a fully glycosylated structure. Velocity experiments using the g*(s) derivative method gave a sedimentation coefficient of 4.2 (+/- 0.1) S. In order to construct a model of CR2 SCR 1-15 for constrained fitting, homology models for the 15 SCR domains were combined with randomised linker peptides generated by molecular dynamics simulations. Using an automated procedure, the analysis of 15,000 possible CR2 SCR 1-15 models showed that only those models in which the 15 SCR domains were flexible but partially folded back accounted for the scattering and sedimentation data. The best-fit CR2 models provided a visual explanation for the versatile interaction of CR2 with four ligands C3d, CD23, gp350 and IFN-alpha. The flexible location of CR2 SCR 1-2 is likely to facilitate interactions of C3d-antigen complexes with the B cell receptor.

  15. Half molecular exchange of IgGs in the blood of healthy humans: chimeric lambda-kappa-immunoglobulins containing HL fragments of antibodies of different subclasses (IgG1-IgG4).

    Science.gov (United States)

    Sedykh, Sergey E; Lekchnov, Evgenii A; Prince, Viktor V; Buneva, Valentina N; Nevinsky, Georgy A

    2016-10-20

    In the classic paradigm, immunoglobulins represent products of clonal B cell populations, each producing antibodies recognizing a single antigen (monospecific). There is a common belief that IgGs in mammalian biological fluids are monospecific molecules having stable structures and two identical antigen-binding sites. But the issue concerning the possibility of exchange by HL-fragments between the antibody molecules in human blood is still unexplored. Different physico-chemical and immunological methods for analysis of half-molecule exchange between human blood IgGs were used. Using eighteen blood samples of healthy humans we have shown unexpected results for the first time: blood antibodies undergo extensive post-transcriptional half-molecule exchange and IgG pools on average consist of 62.4 ± 6.5% IgGs containing kappa light chains (kappa-kappa-IgGs), 29.8.6 ± 5.4% lambda light chains (lambda-lambda-IgGs), and 8.8 ± 2.7% (range 2.6-16.8%) IgGs containing both kappa- and lambda-light chains. Kappa-kappa-IgGs and lambda-lambda-IgGs contained on average (%): IgG1 (36.0 and 32.3), IgG2 (50.9 and 51.4), IgG3 (9.7 and 9.9), and IgG4 (6.5 and 5.7), while chimeric kappa-lambda-IgGs consisted of (%): 25.5 ± 4.2 IgG1, 50.8 ± 3.9 IgG2, 9.1 ± 2.1 IgG3, and 14.5 ± 2.2 IgG4. Our unexpected data are indicative of the possibility of half-molecule exchange between blood IgGs of various subclasses, raised against different antigens. The existence of blood chimeric bifunctional IgGs with different binding sites destroys the classic paradigm. Due to the phenomenon of polyspecificity and cross-reactivity of bifunctional IgGs containing HL-fragments of different types to different antigens, such IgGs may be important in human blood for widening their different biological functions.

  16. Human placenta: relative content of antibodies of different classes and subclasses (IgG1-IgG4) containing lambda- and kappa-light chains and chimeric lambda-kappa-immunoglobulins.

    Science.gov (United States)

    Lekchnov, Evgenii A; Sedykh, Sergey E; Dmitrenok, Pavel S; Buneva, Valentina N; Nevinsky, Georgy A

    2015-06-01

    The specific organ placenta is much more than a filter: it is an organ that protects, feeds and regulates the growth of the embryo. Affinity chromatography, ELISA, SDS-PAGE and matrix-assisted laser desorption ionization mass spectrometry were used. Using 10 intact human placentas deprived of blood, a quantitative analysis of average relative content [% of total immunoglobulins (Igs)] was carried out for the first time: (92.7), IgA (2.4), IgM (2.5), kappa-antibodies (51.4), lambda-antibodies (48.6), IgG1 (47.0), IgG2 (39.5), IgG3 (8.8) and IgG4 (4.3). It was shown for the first time that placenta contains sIgA (2.5%). In the classic paradigm, Igs represent products of clonal B-cell populations, each producing antibodies recognizing a single antigen. There is a common belief that IgGs in mammalian biological fluids are monovalent molecules having stable structures and two identical antigen-binding sites. However, similarly to human milk Igs, placenta antibodies undergo extensive half-molecule exchange and the IgG pool consists of 43.5 ± 15.0% kappa-kappa-IgGs and 41.6 ± 17.0% lambda-lambda-IgGs, while 15.0 ± 4.0% of the IgGs contained both kappa- and lambda-light chains. Kappa-kappa-IgGs and lambda-lambda-IgGs contained, respectively (%): IgG1 (47.7 and 34.4), IgG2 (36.3 and 44.5), IgG3 (7.4 and 11.8) and IgG4 (7.5 and 9.1), while chimeric kappa-lambda-IgGs consisted of (%): 43.5 IgG1, 41.0 IgG2, 5.6 IgG3 and 7.9 IgG4. Our data are indicative of the possibility of half-molecule exchange between placenta IgGs of various subclasses, raised against different antigens, which explains a very well-known polyspecificity and cross-reactivity of different human IgGs.

  17. Antibody producing B lineage cells invade the central nervous system predominantly at the time of and triggered by acute Epstein-Barr virus infection: A hypothesis on the origin of intrathecal immunoglobulin synthesis in multiple sclerosis.

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    Otto, Carolin; Hofmann, Jörg; Ruprecht, Klemens

    2016-06-01

    Patients with multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS), typically have an intrathecal synthesis of immunoglobulin (Ig)G. Intrathecal IgG is produced by B lineage cells that entered the CNS, but why and when these cells invade the CNS of patients with MS is unknown. The intrathecal IgG response in patients with MS is polyspecific and part of it is directed against different common viruses (e.g. measles virus, rubella virus, varicella zoster virus). Strong and consistent evidence suggests an association of MS and Epstein-Barr virus (EBV) infection and EBV seroprevalence in patients with MS is practically 100%. However, intriguingly, despite of the universal EBV seroprevalence, the frequency of intrathecally produced IgG to EBV in patients with MS is much lower than that of intrathecally produced IgG to other common viruses. The acute phase of primary EBV infection is characterized by a strong polyclonal B cell activation. As typical for humoral immune responses against viruses, EBV specific IgG is produced only with a temporal delay after acute EBV infection. Aiming to put the above facts into a logical structure, we here propose the hypothesis that in individuals going on to develop MS antibody producing B lineage cells invade the CNS predominantly at the time of and triggered by acute primary EBV infection. Because at the time of acute EBV infection EBV IgG producing B lineage cells have not yet occurred, the hypothesis could explain the universal EBV seroprevalence and the low frequency of intrathecally produced IgG to EBV in patients with MS. Evidence supporting the hypothesis could be provided by large prospective follow-up studies of individuals with symptomatic primary EBV infection (infectious mononucleosis). Furthermore, the clarification of the molecular mechanism underlying an EBV induced invasion of B lineage cells into the CNS of individuals going on to develop MS could corroborate it, too. If true, our

  18. Randomised controlled double-blind non-inferiority trial of two antivenoms for saw-scaled or carpet viper (Echis ocellatus envenoming in Nigeria.

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    Isa S Abubakar

    Full Text Available BACKGROUND: In West Africa, envenoming by saw-scaled or carpet vipers (Echis ocellatus causes great morbidity and mortality, but there is a crisis in supply of effective and affordable antivenom (ISRCTN01257358. METHODS: In a randomised, double-blind, controlled, non-inferiority trial, "EchiTAb Plus-ICP" (ET-Plus equine antivenom made by Instituto Clodomiro Picado was compared to "EchiTAb G" (ET-G ovine antivenom made by MicroPharm, which is the standard of care in Nigeria and was developed from the original EchiTAb-Fab introduced in 1998. Both are caprylic acid purified whole IgG antivenoms. ET-G is monospecific for Echis ocellatus antivenom (initial dose 1 vial and ET-Plus is polyspecific for E. ocellatus, Naja nigricollis and Bitis arietans (initial dose 3 vials. Both had been screened by pre-clinical and preliminary clinical dose-finding and safety studies. Patients who presented with incoagulable blood, indicative of systemic envenoming by E. ocellatus, were recruited in Kaltungo, north-eastern Nigeria. Those eligible and consenting were randomly allocated with equal probability to receive ET-Plus or ET-G. The primary outcome was permanent restoration of blood coagulability 6 hours after the start of treatment, assessed by a simple whole blood clotting test repeated 6, 12, 18, 24 and 48 hr after treatment. Secondary (safety outcomes were the incidences of anaphylactic, pyrogenic and late serum sickness-type antivenom reactions. FINDINGS: Initial doses permanently restored blood coagulability at 6 hours in 161/194 (83.0% of ET-Plus and 156/206 (75.7% of ET-G treated patients (Relative Risk [RR] 1.10 one-sided 95% CI lower limit 1.01; P = 0.05. ET-Plus caused early reactions on more occasions than did ET-G [50/194 (25.8% and 39/206 (18.9% respectively RR (1.36 one-sided 95% CI 1.86 upper limit; P = 0.06. These reactions were classified as severe in 21 (10.8% and 11 (5.3% of patients, respectively. CONCLUSION: At these doses, ET-Plus was

  19. Influence of SLC22A1 rs622342 genetic polymorphism on metformin response in South Indian type 2 diabetes mellitus patients.

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    Umamaheswaran, Gurusamy; Praveen, Ramakrishnan Geethakumari; Damodaran, Solai Elango; Das, Ashok Kumar; Adithan, Chandrasekaran

    2015-11-01

    Metformin is an oral antidiabetic drug, commonly used for treating type 2 diabetes mellitus (T2DM) patients. It is transported into the hepatocytes by polyspecific organic cation transporter 1, which is encoded by the gene SLC22A1. It has been hypothesized that genetic variations of SLC22A1 gene will influence inter-individual variation in glucose lowering efficacy of metformin. Previous studies have demonstrated this in other populations with conflicting results, but it remains to be elucidated in Indian population. Henceforth, the objective of the study was to evaluate the impact of SLC22A1 rs622342 gene polymorphism on the clinical efficacy of metformin in South Indian T2DM patients. A total of 122 newly detected, treatment naive T2DM patients of either sex were included in this study. The patients were started on metformin monotherapy and followed up for 12 weeks. Genotype was determined using qRT-PCR. Before and after treatment with metformin, body mass index (BMI), serum lipid profile, glycated hemoglobin (HbA1c), fasting and postprandial glucose level, and blood pressure (BP) were measured. The study cohort mean age was 49.57 ± 9.88 years. Of the 122 T2DM patients, 93 were classified as responders and 29 as non-responders based on fall in HbA1c levels. Interestingly, carriers of one variant allele 'C' (AC) of rs622342 polymorphism were less among the responders than those who did not (44.8 vs. 22.6 %). The response was even lesser (13.8 vs. 4.3 %) in carriers of two copies of "C" allele (CC). On the contrary, patients with two copies of allele 'A' (AA) had 5.6 times greater chance of responding to metformin treatment. A similar trend was observed when the proportion was analyzed under different genetic models (OR 3.85, 95 % CI 1.61-9.19 for dominant; OR 3.56, 95 % CI 0.83-15.26 for recessive; OR 0.35, 95 % CI 0.14-0.86 for over-dominant; and OR 4.10, 95 % CI 1.78-9.43 for additive). Further, metformin showed significant beneficial effects on BMI, HbA1c, FPG

  20. Frequency patterns of T-cell exposed motifs in immunoglobulin heavy chain peptides presented by MHCs

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    Robert D. Bremel

    2014-10-01

    Full Text Available Immunoglobulins are highly diverse protein sequences that are processed and presented to T-cells by B-cells and other antigen presenting cells. We examined a large dataset of immunoglobulin heavy chain variable regions (IGHV to assess the diversity of T-cell exposed motifs (TCEM. TCEM comprise those amino acids in a MHC-bound peptide which face outwards, surrounded by the MHC histotope, and which engage the T-cell receptor. Within IGHV there is a distinct pattern of predicted MHC class II binding and a very high frequency of re-use of the TCEMs. The re-use frequency indicates that only a limited number of different cognate T-cells are required to engage many different clonal B-cells. The amino acids in each outward-facing TCEM are intercalated with the amino acids of inward-facing MHC groove-exposed motifs (GEM. Different GEM may have differing, allele-specific, MHC binding affinities. The intercalation of TCEM and GEM in a peptide allows for a vast combinatorial repertoire of epitopes, each eliciting a different response. Outcome of T-cell receptor binding is determined by overall signal strength, which is a function of the number of responding T-cells and the duration of engagement. Hence, the frequency of T-cell exposed motif re-use appears to be an important determinant of whether a T-cell response is stimulatory or suppressive. The frequency distribution of TCEMs implies that somatic hypermutation is followed by clonal expansion that develop along repeated pathways. The observations of TCEM and GEM derived from immunoglobulins suggest a relatively simple, yet powerful, mechanism to correlate T-cell polyspecificity, through re-use of TCEMs, with a very high degree of specificity achieved by combination with a diversity of GEMs. The frequency profile of TCEMs also points to an economical mechanism for maintaining T-cell memory, recall, and self-discrimination based on an endogenously generated profile of motifs.

  1. Tick parasites of rodents in Romania: host preferences, community structure and geographical distribution

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    Mihalca Andrei D

    2012-11-01

    Full Text Available Abstract Background Ticks are among the most important vectors of zoonotic diseases in temperate regions of Europe, with widespread distribution and high densities, posing an important medical risk. Most ticks feed on a variety of progressively larger hosts, with a large number of small mammal species typically harbouring primarily the immature stages. However, there are certain Ixodidae that characteristically attack micromammals also during their adult stage. Rodents are widespread hosts of ticks, important vectors and competent reservoirs of tick-borne pathogens. Micromammal-tick associations have been poorly studied in Romania, and our manuscript shows the results of a large scale study on tick infestation epidemiology in rodents from Romania. Methods Rodents were caught using snap-traps in a variety of habitats in Romania, between May 2010 and November 2011. Ticks were individually collected from these rodents and identified to species and development stage. Frequency, mean intensity, prevalence and its 95% confidence intervals were calculated using the EpiInfo 2000 software. A p value of Results We examined 423 rodents (12 species collected from six counties in Romania for the presence of ticks. Each collected tick was identified to species level and the following epidemiological parameters were calculated: prevalence, mean intensity and mean abundance. The total number of ticks collected from rodents was 483, with eight species identified: Ixodes ricinus, I. redikorzevi, I. apronophorus, I. trianguliceps, I. laguri, Dermacentor marginatus, Rhipicephalus sanguineus and Haemaphysalis sulcata. The overall prevalence of tick infestation was 29.55%, with a mean intensity of 3.86 and a mean abundance of 1.14. Only two polyspecific infestations were found: I. ricinus + I. redikorzevi and I. ricinus + D. marginatus. Conclusions Our study showed a relatively high diversity of ticks parasitizing rodents in Romania. The most common tick in rodents

  2. Interaction of environmental contaminants with zebrafish organic anion transporting polypeptide, Oatp1d1 (Slco1d1)

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    Popovic, Marta; Zaja, Roko [Laboratory for Molecular Ecotoxicology, Division for Marine and Environmental Research, Rudjer Boskovic Institute, Bijenicka 54, 10 000 Zagreb (Croatia); Fent, Karl [University of Applied Sciences Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz (Switzerland); Swiss Federal Institute of Technology (ETH Zürich), Department of Environmental System Sciences, Institute of Biogeochemistry and Pollution Dynamics, CH-8092 Zürich (Switzerland); Smital, Tvrtko, E-mail: smital@irb.hr [Laboratory for Molecular Ecotoxicology, Division for Marine and Environmental Research, Rudjer Boskovic Institute, Bijenicka 54, 10 000 Zagreb (Croatia)

    2014-10-01

    Polyspecific transporters from the organic anion transporting polypeptide (OATP/Oatp) superfamily mediate the uptake of a wide range of compounds. In zebrafish, Oatp1d1 transports conjugated steroid hormones and cortisol. It is predominantly expressed in the liver, brain and testes. In this study we have characterized the transport of xenobiotics by the zebrafish Oatp1d1 transporter. We developed a novel assay for assessing Oatp1d1 interactors using the fluorescent probe Lucifer yellow and transient transfection in HEK293 cells. Our data showed that numerous environmental contaminants interact with zebrafish Oatp1d1. Oatp1d1 mediated the transport of diclofenac with very high affinity, followed by high affinity towards perfluorooctanesulfonic acid (PFOS), nonylphenol, gemfibrozil and 17α-ethinylestradiol; moderate affinity towards carbaryl, diazinon and caffeine; and low affinity towards metolachlor. Importantly, many environmental chemicals acted as strong inhibitors of Oatp1d1. A strong inhibition of Oatp1d1 transport activity was found by perfluorooctanoic acid (PFOA), chlorpyrifos-methyl, estrone (E1) and 17β-estradiol (E2), followed by moderate to low inhibition by diethyl phthalate, bisphenol A, 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4 tetrahydronapthalene and clofibrate. In this study we identified Oatp1d1 as a first Solute Carrier (SLC) transporter involved in the transport of a wide range of xenobiotics in fish. Considering that Oatps in zebrafish have not been characterized before, our work on zebrafish Oatp1d1 offers important new insights on the understanding of uptake processes of environmental contaminants, and contributes to the better characterization of zebrafish as a model species. - Highlights: • We optimized a novel assay for determination of Oatp1d1 interactors • Oatp1d1 is the first SLC characterized fish xenobiotic transporter • PFOS, nonylphenol, diclofenac, EE2, caffeine are high affinity Oatp1d1substrates • PFOA, chlorpyrifos

  3. Molecular characterization of zebrafish Oatp1d1 (Slco1d1), a novel organic anion-transporting polypeptide.

    Science.gov (United States)

    Popovic, Marta; Zaja, Roko; Fent, Karl; Smital, Tvrtko

    2013-11-22

    The organic anion-transporting polypeptide (OATP/Oatp) superfamily includes a group of polyspecific transporters that mediate transport of large amphipathic, mostly anionic molecules across cell membranes of eukaryotes. OATPs/Oatps are involved in the disposition and elimination of numerous physiological and foreign compounds. However, in non-mammalian species, the functional properties of Oatps remain unknown. We aimed to elucidate the role of Oatp1d1 in zebrafish to gain insights into the functional and structural evolution of the OATP1/Oatp1 superfamily. We show that diversification of the OATP1/Oatp1 family occurs after the emergence of jawed fish and that the OATP1A/Oatp1a and OATP1B/Oatp1b subfamilies appeared at the root of tetrapods. The Oatp1d subfamily emerged in teleosts and is absent in tetrapods. The zebrafish Oatp1d1 is similar to mammalian OATP1A/Oatp1a and OATP1B/Oatp1b members, with the main physiological role in transport and balance of steroid hormones. Oatp1d1 activity is dependent upon pH gradient, which could indicate bicarbonate exchange as a mode of transport. Our analysis of evolutionary conservation and structural properties revealed that (i) His-79 in intracellular loop 3 is conserved within OATP1/Oatp1 family and is crucial for the transport activity; (ii) N-glycosylation impacts membrane targeting and is conserved within the OATP1/Oatp1 family with Asn-122, Asn-133, Asn-499, and Asn-512 residues involved; (iii) the evolutionarily conserved cholesterol recognition interaction amino acid consensus motif is important for membrane localization; and (iv) Oatp1d1 is present in dimeric and possibly oligomeric form in the cell membrane. In conclusion, we describe the first detailed characterization of a new Oatp transporter in zebrafish, offering important insights into the functional evolution of the OATP1/Oatp1 family and the physiological role of Oatp1d1.

  4. Generation of Long-Lived Bone Marrow Plasma Cells Secreting Antibodies Specific for the HIV-1 gp41 Membrane-Proximal External Region in the Absence of Polyreactivity

    Science.gov (United States)

    Donius, Luke R.; Cheng, Yuxing; Choi, Jaewon; Sun, Zhen-Yu J.; Hanson, Melissa; Zhang, Michael; Gierahn, Todd M.; Marquez, Susanna; Uduman, Mohammed; Kleinstein, Steven H.; Irvine, Darrell; Love, J. Christopher; Reinherz, Ellis L.

    2016-01-01

    their fine specificities require a structural fitness of the antibody combining site involving heavy and light chain variable domains shaped by somatic hypermutation and affinity maturation of B cells in the germinal center. Perhaps more importantly, our results demonstrate that the majority of MPER-specific antibodies are not inherently polyspecific and/or autoreactive, suggesting that polyreactivity of MPER-specific antibodies is separable from their antigen specificity. PMID:27466419

  5. Modelling staphylococcal pneumonia in a human 3D lung tissue model system delineates toxin-mediated pathology.

    Science.gov (United States)

    Mairpady Shambat, Srikanth; Chen, Puran; Nguyen Hoang, Anh Thu; Bergsten, Helena; Vandenesch, Francois; Siemens, Nikolai; Lina, Gerard; Monk, Ian R; Foster, Timothy J; Arakere, Gayathri; Svensson, Mattias; Norrby-Teglund, Anna

    2015-11-01

    Staphylococcus aureus necrotizing pneumonia is recognized as a toxin-mediated disease, yet the tissue-destructive events remain elusive, partly as a result of lack of mechanistic studies in human lung tissue. In this study, a three-dimensional (3D) tissue model composed of human lung epithelial cells and fibroblasts was used to delineate the role of specific staphylococcal exotoxins in tissue pathology associated with severe pneumonia. To this end, the models were exposed to the mixture of exotoxins produced by S. aureus strains isolated from patients with varying severity of lung infection, namely necrotizing pneumonia or lung empyema, or to purified toxins. The necrotizing pneumonia strains secreted high levels of α-toxin and Panton-Valentine leukocidin (PVL), and triggered high cytotoxicity, inflammation, necrosis and loss of E-cadherin from the lung epithelium. In contrast, the lung empyema strain produced moderate levels of PVL, but negligible amounts of α-toxin, and triggered limited tissue damage. α-toxin had a direct damaging effect on the epithelium, as verified using toxin-deficient mutants and pure α-toxin. Moreover, PVL contributed to pathology through the lysis of neutrophils. A combination of α-toxin and PVL resulted in the most severe epithelial injury. In addition, toxin-induced release of pro-inflammatory mediators from lung tissue models resulted in enhanced neutrophil migration. Using a collection of 31 strains from patients with staphylococcal pneumonia revealed that strains producing high levels of α-toxin and PVL were cytotoxic and associated with fatal outcome. Also, the strains that produced the highest toxin levels induced significantly greater epithelial disruption. Of importance, toxin-mediated lung epithelium destruction could be inhibited by polyspecific intravenous immunoglobulin containing antibodies against α-toxin and PVL. This study introduces a novel model system for study of staphylococcal pneumonia in a human setting. The

  6. Modelling staphylococcal pneumonia in a human 3D lung tissue model system delineates toxin-mediated pathology

    Directory of Open Access Journals (Sweden)

    Srikanth Mairpady Shambat

    2015-11-01

    Full Text Available Staphylococcus aureus necrotizing pneumonia is recognized as a toxin-mediated disease, yet the tissue-destructive events remain elusive, partly as a result of lack of mechanistic studies in human lung tissue. In this study, a three-dimensional (3D tissue model composed of human lung epithelial cells and fibroblasts was used to delineate the role of specific staphylococcal exotoxins in tissue pathology associated with severe pneumonia. To this end, the models were exposed to the mixture of exotoxins produced by S. aureus strains isolated from patients with varying severity of lung infection, namely necrotizing pneumonia or lung empyema, or to purified toxins. The necrotizing pneumonia strains secreted high levels of α-toxin and Panton-Valentine leukocidin (PVL, and triggered high cytotoxicity, inflammation, necrosis and loss of E-cadherin from the lung epithelium. In contrast, the lung empyema strain produced moderate levels of PVL, but negligible amounts of α-toxin, and triggered limited tissue damage. α-toxin had a direct damaging effect on the epithelium, as verified using toxin-deficient mutants and pure α-toxin. Moreover, PVL contributed to pathology through the lysis of neutrophils. A combination of α-toxin and PVL resulted in the most severe epithelial injury. In addition, toxin-induced release of pro-inflammatory mediators from lung tissue models resulted in enhanced neutrophil migration. Using a collection of 31 strains from patients with staphylococcal pneumonia revealed that strains producing high levels of α-toxin and PVL were cytotoxic and associated with fatal outcome. Also, the strains that produced the highest toxin levels induced significantly greater epithelial disruption. Of importance, toxin-mediated lung epithelium destruction could be inhibited by polyspecific intravenous immunoglobulin containing antibodies against α-toxin and PVL. This study introduces a novel model system for study of staphylococcal pneumonia in a

  7. Effects of the glial cell line-derived neurotrophic factor family on chronic constrictive injury in rats%胶质细胞源性神经营养因子家族在大鼠坐骨神经慢性压榨损伤中的作用

    Institute of Scientific and Technical Information of China (English)

    胡玉萍; 杨建军; 李伟彦; 稽晴

    2011-01-01

    目的 研究大鼠坐骨神经慢性压榨损伤(chronic constrictive injury,CCI)中胶质细胞源性神经营养因子(glialcell line-derived neurotrophic factor,GDNF)和神经细胞黏附分子(neural cell adhesion molecule,NCAM)表达的变化,以及鞘内注射NCAM相似肽c3d、NCAM反义寡核甘酸(Anti)对神经病理性疼痛(neuropathic pain,NP)的影响,探讨GDNF、NCAM在NP中的作用及可能机制. 方法 实验1:成年雄性SD大鼠42只,随机分为2组(每组21只):疼痛组和对照组.疼痛组大鼠行左侧坐骨神经结扎术,建立CCI模型,对照组行假手术.分别于术前1d和术后1、3、5、7、14、21d测机械痛阈(mechanicalwithdrawl threshold,MWT)和热痛阈(thermal withdrawal latency,TWL).采用免疫组织化学染色和RT-PCR技术检测背根神经节(dorsal root ganglion,DRG)中GDNF和NCAM的表达变化.实验2:成年雄性SD大鼠24只,随机分为4组(每组6只):生理盐水(normal saline,NS)对照组、NS+ GDNF组、c3d+GDNF组、Anti-NCAM+ GDNF组.各组大鼠于建立CCI模型后3d鞘内注射上述制剂,观察其痛阈变化. 结果 实验1:与对照组相比,疼痛组大鼠术前1d、术后1、21 d MWT和TWL差异无统计学意义(P>0.05);术后3、5、7、14d MWT和TWL均降低,其中术后7d阈值最低(P<0.01);术后3、5、7、14d GDNF和NCAM的表达均升高,其中7d表达最高(P<0.01).实验2:与NS对照组相比,NS+ GDNF组、c3d+ GDNF组MWT和TWL明显降低(P<0.01),Anti-NCAM+ GDNF组差异无统计学意义(P>0.05);NS+ GDNF组、c3d+ GDNF组与给药前相比,MWT和TWL明显降低(P<0.01);Anti-NCAM+ GDNF组差异无统计学意义(P>0.05). 结论 大鼠CCI后出现痛阈下降,DRG中GDNF和NCAM表达增高;外源性GDNF可缓解NP,阻断NCAM表达可消减GDNF的镇痛作用,提示GDNF和NCAM信号通路参与了NP的发生和调节.%Objective The present study was to investigate the changes in the expressions of the glial cell line-derived neuro-trophic factor (GDNF) and

  8. Curso clínico da anemia hemolítica auto-imune: um estudo descritivo Clinical course of autoimmune hemolytic anemia: an observational study

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    Maria Christina L. A. Oliveira

    2006-02-01

    identify the clinical, immunological and outcome characteristics of autoimmune hemolytic anemia patients treated at the (HC-UFMG Pediatric Hematology Unit and the Hemocentro de Belo Horizonte. METHODS: We evaluated 17 patients younger than 15 years old admitted from 1988 to 2003 were evaluated. Autoimmune hemolytic anemia diagnosis was based on the presence of acquired hemolysis and confirmed by positive direct Coombs polyspecific test results. Clinical, laboratory, and outcome data were obtained from patient records. RESULTS: The median age at diagnosis was 10.5 months. The direct Coombs polyspecific test was positive in 13 and negative in four patients. Monospecific testing was performed for 14 patients. The most frequent red cell autoantibody was IgG (five patients, followed by IgM in two. Thirteen patients had severe anemia and needed blood transfusions. Underlying diseases were identified in four patients: systemic lupus erythematosus, Hodgkin's lymphoma, autoimmune hepatitis and Langerhans cell histiocytosis. The remaining patients were classified as having primary disease. The median follow-up period was 11 months (5 to 23 months. Three children died, two after splenectomy and one with complications of the underlying disease. CONCLUSION: Autoimmune hemolytic anemia is rare in children and adolescents. Although patients usually respond to corticosteroids and/or immunoglobulin, fatal cases can occur. Prognosis is worse in patients with chronic underlying diseases.

  9. Applications of direct antiglobulin test with microcolumn gel in the diagnosis of autoimmune hemolytic anemia disease%微柱凝胶直接抗人球蛋白试验对自身免疫性溶血性贫血诊断的应用

    Institute of Scientific and Technical Information of China (English)

    刘凌; 李流娇; 莫水群

    2012-01-01

    Objective To analyze the effects of direct antiglobulin test with microcolumn gel in the diagnosis of autoimmune hemolytic anemia disease in order to provide references for clinic.Methods The blood specimens of 208 cases with positive blood cross-matching were selected.The tested akaryocyte were invided into ablution group and unablution group.We tested the effects of direct antiglobulin test with microcolumn gel.Meanwhile,the type of IgG and C3d was carried in 186 positive cases.In control group,the direct antiglobulin test with traditional tube was used; in the observation group there was direct antiglobulin test with microcolumn gel.Results The tested positive rate was 89.4% in the observation group and 53.8% in the control group; the checking method in the observation group was significantly better than that in the control group (P < 0.05).Saline washed red blood cells had no effects on the results of antiglobulin test with microcolumn gel,including the same positive 186 cases.The type of IgG,C3d,IgG + C3d was 46.77% (87/186),3.23% (6/186),50.00% (93/186) respectively.Conclusion The direct antiglobulin test with microcolumn gel has high clinical application value in diagnosis of autoimmune hemolytic anemia disease.%目的 分析微柱凝胶直接抗人球蛋白试验对自身免疫性溶血性贫血诊断的效果,以便为临床提供参考.方法 选择208例交叉配血次侧阳性的标本为观察组,采用微柱凝胶直接抗人球蛋白试验;将受检红细胞分成洗涤组和非洗涤组,检测红细胞洗涤对微柱凝胶直接抗人球蛋白试验的影响;同时对此检测方法阳性结果的186例红细胞进行IgG和C3d分型.对照组(208名)采用试管法直接抗人球蛋白试验.结果 观察组与对照组阳性率比较差异有统计学意义[ 89.4%( 186/208)与53.8% (112/208),P<0.05].微柱凝胶直接抗人球蛋白试验生理盐水洗涤和非洗涤组受检红细胞的208份血液样本中同

  10. Diagnóstico laboratorial da anemia hemolítica auto-imune: características do teste manual direto do PolybreneÒ Laboratory diagnosis of auto-immune hemolytic anemia: characteristics of the manual direct test of PolybreneTM

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    G.W. Braga

    1998-03-01

    Full Text Available O teste manual direto do PolybreneÒ (TDP e o teste de Coombs direto (TCD foram utilizados para a detecção de IgG na superfície de hemácias de pacientes com diagnóstico clínico e laboratorial de anemia hemolítica auto-imune (AHAI. OBJETIVO: Comparar a sensibilidade e especificidade do TPD e do TCD no diagnóstico da AHAI. MÉTODO: Foram estudados 18 pacientes com diagnóstico clínico-laboratorial de AHAI. Como indivíduos controles, foram testados 20 doadores de sangue assintomáticos e 20 pacientes com anemia falciforme. RESULTADOS: O TCD foi positivo em 14 pacientes e negativo em quatro indivíduos, enquanto o TDP foi positivo em 17 pacientes e negativo em um indivíduo que apresentava TCD positivo devido a fixação de complemento (C3d nas hemácias. Todos os eluatos positivos realizados com a técnica de diclorometano revelaram anticorpos quentes com especificidade "anti-Rh". A sensibilidade do TDP (94% para detectar fixação de IgG in vivo foi significantemente maior (pThe direct manual PolybreneTM test (DPT and the direct antiglobulin tests (DAT were employed to detect antibody sensitizing red blood cell (RCB in patients with clinical and laboratorial findings of autoimmune hemolytic anemia (AIHA. PURPOSE: To compare the sensitivity and specificity of DPT and DAT in the diagnosis of AIHA. METHODS: Eighteen consecutive patients with diagnosis of AIHA were evaluated. The control group consisted of 20 normal volunteers blood donors and 20 patients with sickle cell anemia. All patients and controls were submitted to DPT and DAT. All DAT positive samples were further tested using monospecific reagents ( anti-IgG heavy chain and anti-C3d. Positive samples for either DPT or DAT were evaluated by eluate technique using. The dichloromethane (DCM. RESULTS: The DAT was positive in 14 patients and negative in 4 subjects, while the DPT was positive in 17 patients and negative in 1 individual who had a positive DAT owing to complement (C3d. All

  11. Reaserch on the Production of Kvass Yogurt%饮用型格瓦斯酸奶的研制

    Institute of Scientific and Technical Information of China (English)

    胡姝敏; 张冰

    2014-01-01

    Through orthogonal experimental design and sensory evaluation, use of different dosage fermentation culture(A), fermentation temperature(B)and time(C)and the amount of liquid malt extract(D), four factors and three levels orthogonal design experiments and the sensory evaluation of products as evaluation criteria, to selected horizontal preferred combination of factors. The results shows that the order of factors affecting as A> D> C ≈ B, optimum process parameters of kvass yogurt is A2B1C3D3, namely as fermentation culture in an amount of 0.004%, fermentation temperature at 28 degrees, fermentation time with 14 hours, and liquid malt extract was 3%. Production-proven, above the level of factors that can get better delicate soft curds with a unique keifr lfavor and mild toasted bread lfavor of kvass yogurt.%通过正交试验设计和感官评分,选用不同的发酵剂添加量(A)、发酵温度(B)和时间(C)、液体麦精量(D),采用四因素三水平进行正交试验,以产品的感官评分为评价指标,筛选出因素水平最佳组合。结果显示:因素影响排序为:A>D>C≈B;格瓦斯酸奶的最佳工艺参数为A2B1C3D3,即发酵剂添加量0.004%,发酵温度28℃,发酵时间14 h,液体麦精添加量3%。经生产验证,上述较佳因素水平组合能够获得细腻柔软的凝乳,并带有独特开菲尔风味及温和烤面包风味的饮用型格瓦斯酸奶。

  12. Studies on extracting technics of essential oils from Allium Mngolicum Regel%沙葱挥发油提取工艺的研究

    Institute of Scientific and Technical Information of China (English)

    乌仁张嘎; 张兴夫; 敖长金

    2011-01-01

    It is carried through research on extracting technics of essential oil from Allium Mngolicum Regel. In this paper using Allium Mngolicum Regel powder as raw material ,adopting vapor distillation,on the base of result analysis of single-factor test ,taking extraction yield of essential oil as target,the soaking time (A),ratio of materiol and water (B),Ultrasonic extraction time (C),distillation time (D) as factor making orthogonal expriment,the optimizing technics of extracting essential oil was built up. The result was shown that effect on extracting rate by different expriment factors, influence degree Ultrasonic extraction time, ratio of materiol and water, distillation time, soaking time in turn. The optimum combination was A1B3C3D3, that was to say ,the optimized condition is soaking 1.5 h, adding water 11 times, Ultrasonic extraction time 20 min,and steam distillation 3.5 h. A maximum extraction yield of essential oil of 0.46% was obtained under the optimized conditions. The optimizing technics of extracting were steady and reasonable by validate test.%文章对沙葱挥发油的提取工艺进行了研究,以沙葱粉为原料,采用水蒸气蒸馏法,在单因素试验结果与分析的基础上,以挥发油得率为指标,以浸泡时间(A)、料液比(B)、超声波处理时间(C)、蒸馏时间(D)为因素进行L9(34)正交试验,研究确定了提取沙葱挥发油的最佳工艺.试验结果表明,各因素影响沙葱挥发油提取率的程度由大到小的顺序为超声波处理时间>料液比=蒸馏时间>浸泡时间;最佳组合为A1B3C3D3,即浸泡时间1.5 h、料液比1∶11、超声波处理时间20 min、蒸馏时间3.5 h.在此最佳工艺条件下提取率为0.46%.通过验证试验表明,所选的最佳提取工艺稳定、可行.

  13. Clonal dissemination of the multi-drug resistant Salmonella enterica serovar Braenderup, but not the serovar Bareilly, of prevalent serogroup C1 Salmonella from Taiwan

    Directory of Open Access Journals (Sweden)

    Tsay Jwu-Guh

    2009-12-01

    Full Text Available Abstract Background Nontyphoidal Salmonella is the main cause of human salmonellosis. In order to study the prevalent serogroups and serovars of clinical isolates in Taiwan, 8931 Salmonellae isolates were collected from 19 medical centers and district hospitals throughout the country from 2004 to 2007. The pulsed-field eletrophoresis types (PFGE and antibiotic resistance profiles of Salmonella enterica serovars Bareilly (S. Bareilly and Braenderup (S. Braenderup were compared, and multi-drug resistance (MDR plasmids were characterized. Results Over 95% of human salmonellosis in Taiwan was caused by five Salmonella serogroups: B, C1, C2-C3, D1, and E1. S. Typhymurium, S. Enteritidis, S. Stanley and S. Newport were the four most prevalent serovars, accounting for about 64% of isolates. While only one or two major serovars from four of the most prevalent serogroups were represented, four predominant serovars were found in serogroup C1 Salmonellae. The prevalence was decreasing for S. Choleraeuis and S. Braenderup, and S. Virchow and increasing for S. Bareilly. S. Braenderup mainly caused gastroenteritis in children; in contrast, S. Bareiley infected children and elderly people. Both serovars differed by XbaI-PFGE patterns. Almost all S. Bareilly isolates were susceptible to antibiotics of interest, while all lacked plasmids and belonged to one clone. Two distinct major clones in S. Braenderup were cluster A, mainly including MDR isolates with large MDR plasmid from North Taiwan, and cluster B, mainly containing susceptible isolates without R plasmid from South Taiwan. In cluster A, there were two types of conjugative R plasmids with sizes ranging from 75 to 130 kb. Type 1 plasmids consisted of replicons F1A/F1B, blaTEM, IS26, and a class 1 integron with the genes dfrA12-orfF-aadA2-qacEΔ1-sulI. Type 2 plasmids belonged to incompatibility group IncI, contained tnpA-blaCMY-2-blc-sugE genetic structures and lacked both IS26 and class 1 integrons

  14. KHELASI PLUMBUM (Pb DAN CADMIUM (Cd MENGGUNAKAN ASAM SITRAT PADA BIJI KEDELA (Chelation of Plumbum and Cadmium by Citric acid in Soybean Seeds

    Directory of Open Access Journals (Sweden)

    Sapto Priyadi

    2014-02-01

    Full Text Available A study on the chelation of plumbum and cadmium by citric acid in soybean seeds, it was aimed to identify the effect of chelation treatment (chelating ratio, time contact and seeds condition on plumbum reduction and cadmium in soybean seeds. A factors of research covering 1st chelating ratio (citric acid/”C” consisting of three (1, 2 and 3 grams of citric acid; 2nd the time contact (“D” consisting of three (90, 120 and 180 minutes and the 3rd factors is condition of the seeds (“E” consisting of three standard (whole qualify e.i. passing sieve of 0.3 inch and restrained at 0.2 inch, ruptured e.i. restrained for sieve at 10 mesh, and flour qualify for pass for sieves 50 mesh. The result showed that the combination of three factors were able to reduce Cd maximaly (non detected/detect limit 0.01 ppm. Reduction Pb maximaly (non detected /detect limit 0.09 ppm occured in treatment C1D1E1, C1D1E2, C1D2E1, C1D2E2, C1D2E2, C2D1E1, C2D1E2, C2D2E1, C2D3E1, C2D3E2, C3D1E1 and C3D2E1. A combination of citric acid chelation (C with the time contact (D showing significant difference and both showed interactions, the reduction of the highest was C1D1 treatment. A combination of citric acid chelation (C with the condition of the nut (E showed significant difference and both no interaction, the reduction of the highest was C2E1 treatment. The combination between the time of contact (D with the condition of the seed (E showed significant difference and both no interaction, the reduction of the highest were D1E1 and D2E1 treatments. Keywords: chelation, plumbum, cadmium and soybean   ABSTRAK Telah dilakukan penelitian tentang khelasi plumbum (pb dan cadmium (cd menggunakan asam sitrat pada biji kedelai, dengan tujuan untuk mengetahui pengaruh faktor perlakuan khelasi (ratio pengkhelat, waktu kontak dan kondisi biji dalam mereduksi Pb dan Cd pada biji kedelai. Faktor penelitian meliputi 1 rasio pengkhelat (asam sitrat/C yang terdiri dari tiga taraf (1

  15. The Humoral Theory of Transplantation: Epitope Analysis and the Pathogenicity of HLA Antibodies

    Science.gov (United States)

    Farber, John L.

    2016-01-01

    Central to the humoral theory of transplantation is production of antibodies by the recipient against mismatched HLA antigens in the donor organ. Not all mismatches result in antibody production, however, and not all antibodies are pathogenic. Serologic HLA matching has been the standard for solid organ allocation algorithms in current use. Antibodies do not recognize whole HLA molecules but rather polymorphic residues on the surface, called epitopes, which may be shared by multiple serologic HLA antigens. Data are accumulating that epitope analysis may be a better way to determine organ compatibility as well as the potential immunogenicity of given HLA mismatches. Determination of the pathogenicity of alloantibodies is evolving. Potential features include antibody strength (as assessed by antibody titer or, more commonly and inappropriately, mean fluorescence intensity) and ability to fix complement (in vitro by C1q or C3d assay or by IgG subclass analysis). Technical issues with the use of solid phase assays are also of prime importance, such as denaturation of HLA antigens and manufacturing and laboratory variability. Questions and controversies remain, and here we review new relevant data. PMID:28070526

  16. Dosimetry of cone beam computed tomography scanning for diagnosis and planning in implant dentistry

    Energy Technology Data Exchange (ETDEWEB)

    Santos Pinto de A, E. L.; Manzi, F. R.; Goncalves Z, E. [Pontifical Catholic University of Minas Gerais, Av. Jose Gaspar 500, 30535-901 Belo Horizonte, Minas Gerais (Brazil); Nogueira, M. S.; Fernandes Z, M. A., E-mail: madelon@cdtn.br [Development Center of Nuclear Technology / CNEN, Av. Pte. Antonio Carlos 6627, 31270-901Belo Horizonte, Minas Gerais (Brazil)

    2015-10-15

    Full text: The radiation dose and estimate the radiation induced risk of cancer and morpho functional alterations according to BEIR VII (2006) and recommendations of the ICRP 103 (2007) were measured in cone beam computed tomography (CBCT) scanning (Tc Kodak 9000C 3D) in different oral and maxillofacial regions for diagnosis and planning in implant dentistry for each examination protocol: jaw full, maxilla full and jaw and maxilla full associated. Thermoluminescent dosimeters (TLD- 100 H) were placed in an Alderson-Rando in regions corresponding to the crystalline, parotid, submandibular and thyroid glands and ovaries. The highest values for entrance skin dose were observed in the region of the parotid and submandibular glands, 9.612 mGy to 7.912 mGy and 8.818 mGy to 0.483 mGy, respectively. All examination protocols presented on the right and left sides in the region of the submandibular gland the highest values for absorbed dose (D). In the jaw full exam the thyroid glands on both sides presented highest dose values than maxilla full exam. This study allowed measuring the entrance skin dose and the absorbed dose (D) highlighting a dosimetric preponderance to the salivary glands. With danger of to radiation that induces cancer risk was observed that the age group most likely to have to risk of cancer was 20 years, compared to 30, 40, 50, 60,70 and 80 years. (Author)

  17. Approximation of Convex Bodies by Convex Bodies%凸体间的逼近

    Institute of Scientific and Technical Information of China (English)

    国起; Sten Kaijser

    2003-01-01

    For the affine distance d(C,D)between two convex bodies C,D(∈)Rn,which reduces to the Banach-Mazur distance for symmetric convex bodies, the bounds of d(C,D)have been studied for many years. Some well known estimates for the upper-bounds are as follows: F. John proved d(C,D)≤n1/2 if one is an ellipsoid and another is symmetric,d(C,D)≤n if both are symmetric, and fromF. John's result and d(C1,C2)≤d(C1,C3)d(C2,C3) one has d(C,D)≤n2 for general convex bodies;M.Lassak proved d(C,D)≤(2n-1) if one of them is symmetric.In this paper we get an estimate which includes all the results above as special cases and refines some of them in terms of measures of asymmetry for convex bodies.

  18. DHMPIV and Tomo-PIV measurements of three-dimensional structures in a turbulent boundary layer

    Science.gov (United States)

    Amili, O.; Atkinson, C.; Soria, J.

    In turbulent boundary layers, a large portion of total turbulence production happens in the near wall region, y/δ Tomo-PIV) was used to extract the 3C-3D velocity field using a rapid and less memory intensive reconstruction algorithm. It is based on a multiplicative line-of-sight (MLOS) estimation that determines possible particle locations in the volume, followed by simultaneous iterative correction. Application of MLOS-SART and MART to a turbulent boundary layer at Refθ=2200 using a 4 camera Tomo-PIV system with a volume of 1000×1000×160 voxels is discussed. In addition, near wall velocity measurement attempt made by digital holographic microscopic particle image velocimetry (DHMPIV). The technique provides a solution to overcome the poor axial accuracy and the low spatial resolution which are common problems in digital holography [5]. By reducing the depth of focus by at least one order of magnitude as well as increasing the lateral spatial resolution, DHMPIV provides the opportunity to resolve the small-scale structures existing in near wall layers.

  19. 胸腰椎三维非线性有限元模型的建立%Building an effective nonlinear three-dimensional finite-element model of human thoracolumbar spine

    Institute of Scientific and Technical Information of China (English)

    曾至立; 程黎明; 朱睿; 王建杰; 于研

    2011-01-01

    Objective To build an effective nonlinear three-dimensional finite-element (FE) model of T11 - L3 segments for a further biomechanical study of thoracolumbar spine. Methods The CT ( computed tomography) scan images of healthy adult T11 - L3 segments were imported into software Simpleware 2. 0 to generate a triangular mesh model. Using software Geomagic 8 for model repair and optimization, a solid model was generated into the finite element software Abaqus 6. 9. The reasonable element C3D8 was selected for bone structures. Created between bony endplates, the intervertebral disc was subdivided into nucleus pulposus and annulus fibrosus (44% nucleus, 56% annulus). The nucleus was filled with 5 layers of 8-node solid elements and annulus reinforced by 8 crisscross collagenous fiber layers. The nucleus and annulus were meshed by C3D8RH while the collagen fibers meshed by two node-truss elements. The anterior (ALL) and posterior (PLL) longitudinal ligaments, flavum (FL), supraspinous (SSL), interspinous (ISL) and intertransverse (ITL) ligaments were modeled with S4R shell elements while capsular ligament (GL) was modeled with 3-node shell element. All surrounding ligaments were represented by envelops of 1 mm uniform thickness. The discs and bone structures were modeled with hyper-elastic and elasto-plastic material laws respectively while the ligaments governed by visco-elastic material law. The nonlinear three-dimensional finite-element model of T11 - L3 segments was generated and its efficacy verified through validating the geometric similarity and disc load-displacement and stress distribution under the impact of violence. Using ABAQUS/EXPLICIT 6. 9 the explicit dynamic finite element solver, the impact test was simulated in vitro. Results In this study, a 3-demensional, nonlinear FE model including 5 vertebrae, 4 intervertebral discs and 7 ligaments consisted of 78 887 elements and 71 939 nodes. The model had good geometric similarity under the same conditions. The

  20. Ectopic Germinal Centers and IgG4-Producing Plasmacytes Observed in Synovia of HLA-B27+ Ankylosing Spondylitis Patients with Advanced Hip Involvement

    Directory of Open Access Journals (Sweden)

    Xiugao Feng

    2015-01-01

    Full Text Available Introduction. Ectopic lymphoid neogenesis and the presence of IgG4-positive plasmacytes have been confirmed in chronic inflammatory sclerosing diseases. This study aims to investigate hip synovial tissues of ankylosing spondylitis (AS patients for IgG4-positive plasma cells and ectopic lymphoid tissues with germinal centers (GCs. Methods. Synovial samples were collected from 7 AS patients who received total hip replacement and were evaluated using immunohistochemistry for the presence of CD20+ B-cells, CD3+ T-cells, CD21+ follicular dendritic cells (FDC, and CD38+ plasma cells. Furthermore, immunoglobulin G (IgG and IgG4, IgA, IgM, and complement components C3d and C4d in synovia were evaluated. Both synovial CD21+ FDCs and IgG4-producing plasmacytes were analyzed. Results. All seven patients had severe fibrosis. Massive infiltrations of lymphocytes were found in 5 out of 7 patients’ synovia. Ectopic lymphoid tissues with CD21+ FDC networks and IgG4-positive plasma cells were observed coincidentally in two patients’ synovia. Conclusion. The pathophysiological mechanism of AS patients’ hip damage might be related to the coincidental presence of ectopic lymphoid tissue with FDCs network and IgG4-positive plasma cells identified here for the first time in AS patients’ inflamed synovial tissue.

  1. Up-regulated production and activation of the complement system in Alzheimer's disease brain.

    Science.gov (United States)

    Yasojima, K; Schwab, C; McGeer, E G; McGeer, P L

    1999-03-01

    We used reverse transcriptase-polymerase chain reaction and Western blotting techniques to measure the levels of complement mRNAs and their protein products in Alzheimer's disease (AD) brain compared with non-AD brain. mRNAs for C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, and C9 were detected in the 11 regions of brain that were investigated. The mRNA levels were markedly up-regulated in affected areas of AD brain. In the entorhinal cortex, hippocampus, and midtemporal gyrus, which had dense accumulations of plaques and tangles, C1q mRNA was increased 11- to 80-fold over control levels, and C9 mRNA 10- to 27-fold. These levels were substantially higher than in the livers of the same cases. Western blot analysis of AD hippocampus established the presence of all of the native complement proteins as well as their activation products C4d, C3d, and the membrane attack complex. These data indicate that high levels of complement are being produced in affected areas of AD brain, that full activation of the classical complement pathway is continuously taking place, and that this activation may be contributing significantly to AD pathology.

  2. Percolation transition of short-ranged square well fluids in bulk and confinement.

    Science.gov (United States)

    Neitsch, Helge; Klapp, Sabine H L

    2013-02-14

    Using grand canonical Monte Carlo simulations, we investigate the percolation behavior of a square-well fluid with an ultra-short range of attraction in three dimension (3D) and in confined geometry. The latter is defined through two parallel and structureless walls (slit-pore). We focus on temperatures above the critical temperature of the (metastable) condensation transition of the 3D system. Investigating a broad range of systems sizes, we first determine the percolation thresholds, i.e., the critical packing fraction for percolation η(c). For the slit-pore systems, η(c) is found to vary with the wall separation L(z) in a continuous but non-monotonic way, η(c)(L(z)→∞)=η(c)(3D). We also report results for critical exponents of the percolation transition, specifically, the exponent ν of the correlation length ξ and the two fisher exponents τ and σ of the cluster-size distribution. These exponents are obtained from a finite-size analysis involving the cluster-size distribution and the radii of gyration distribution at the percolation threshold. Within the accuracy of our simulations, the values of the critical exponents of our 3D system are comparable to those of 3D random percolation theory. For narrow slit-pores, the estimated exponents are found to be close to those obtained from the random percolation theory in two dimensions.

  3. Production of resistant starch by extrusion cooking of acid-modified normal-maize starch.

    Science.gov (United States)

    Hasjim, Jovin; Jane, Jay-Lin

    2009-09-01

    The objective of this study was to utilize extrusion cooking and hydrothermal treatment to produce resistant starch (RS) as an economical alternative to a batch-cooking process. A hydrothermal treatment (110 degrees C, 3 d) of batch-cooked and extruded starch samples facilitated propagation of heat-stable starch crystallites and increased the RS contents from 2.1% to 7.7% up to 17.4% determined using AOAC Method 991.43 for total dietary fiber. When starch samples were batch cooked and hydrothermally treated at a moisture content below 70%, acid-modified normal-maize starch (AMMS) produced a greater RS content than did native normal-maize starch (NMS). This was attributed to the partially hydrolyzed, smaller molecules in the AMMS, which had greater mobility and freedom than the larger molecules in the NMS. The RS contents of the batch-cooked and extruded AMMS products after the hydrothermal treatment were similar. A freezing treatment of the AMMS samples at -20 degrees C prior to the hydrothermal treatment did not increase the RS content. The DSC thermograms and the X-ray diffractograms showed that retrograded amylose and crystalline starch-lipid complex, which had melting temperatures above 100 degrees C, accounted for the RS contents.

  4. De Novo Donor-Specific HLA Antibodies Developing Early or Late after Transplant Are Associated with the Same Risk of Graft Damage and Loss in Nonsensitized Kidney Recipients

    Science.gov (United States)

    Cioni, Michela; Nocera, Arcangelo; Innocente, Annalisa; Tagliamacco, Augusto; Trivelli, Antonella; Basso, Sabrina; Quartuccio, Giuseppe; Fontana, Iris; Magnasco, Alberto; Drago, Francesca; Gurrado, Antonella; Guido, Ilaria; Compagno, Francesca; Garibotto, Giacomo; Klersy, Catherine; Verrina, Enrico; Ghiggeri, Gian Marco; Cardillo, Massimo

    2017-01-01

    De novo posttransplant donor-specific HLA-antibody (dnDSA) detection is now recognized as a tool to identify patients at risk for antibody-mediated rejection (AMR) and graft loss. It is still unclear whether the time interval from transplant to DSA occurrence influences graft damage. Utilizing sera collected longitudinally, we evaluated 114 consecutive primary pediatric kidney recipients grafted between 2002 and 2013 for dnDSA occurrence by Luminex platform. dnDSAs occurred in 39 patients at a median time of 24.6 months. In 15 patients, dnDSAs developed within 1 year (early-onset group), while the other 24 seroconverted after the first posttransplant year (late-onset group). The two groups were comparable when considering patient- and transplant-related factors, as well as DSA biological properties, including C1q and C3d complement-binding ability. Only recipient age at transplant significantly differed in the two cohorts, with younger patients showing earlier dnDSA development. Late AMR was diagnosed in 47% of the early group and in 58% of the late group. Graft loss occurred in 3/15 (20%) and 4/24 (17%) patients in early- and late-onset groups, respectively (p = ns). In our pediatric kidney recipients, dnDSAs predict AMR and graft loss irrespective of the time elapsed between transplantation and antibody occurrence. PMID:28367453

  5. A shock tube study of the branching ratios of propene + OH reaction.

    Science.gov (United States)

    Badra, Jihad; Khaled, Fethi; Giri, Binod Raj; Farooq, Aamir

    2015-01-28

    Absolute rate coefficients for the reaction of the OH radical with propene (C3H6) and five deuterated isotopes, propene-1-D1 (CDHCHCH3), propene-1,1-D2 (CD2CHCH3), propene-1,1,2-D3 (CD2CDCH3), propene-3,3,3-D3 (CH2CHCD3), and propene-D6 (C3D6), were measured behind reflected shock waves over the temperature range of 818-1460 K and pressures near 1 atm. The reaction progress was followed by monitoring the OH radical near 306.7 nm using UV laser absorption. Kinetic isotope effects in the measured rate coefficients are discussed and rationalized for the site-specific H-abstraction by the OH radical. The first experimental measurements for the branching ratio of the title reaction are reported and compared with transition state theory calculations. The allylic H-atom abstraction of propene by OH radicals was found to be the most dominant reaction pathway followed by propen-1-yl and propen-2-yl channels over the entire temperature range of this study. The derived Arrhenius expressions for various site-specific rate coefficients over 818-1442 K are (the subscript in the rate coefficient identifies the position of H or D atom according to the IUPAC nomenclature of alkenes):

  6. Dyshidrotic eczema: relevance to the immune response in situ

    Directory of Open Access Journals (Sweden)

    Frank J. Pinto

    2009-08-01

    Full Text Available Context: Pompholyx (called dyshidrosis by some is one of the most common conditions and its immune response is presently poorly understood. Case report: We describe a 58 year old African American female with a clinical history of rheumatoid arthritis and type II diabetes who presented a chronic five-year, itchy vesicular/blistering rash involving her hands and feet. A lesional skin biopsy was taken for hematoxylin and eosin (H & E analysis. In addition, a multicolor direct immunofluorescence (MDIF and immunohistochemistry (IHC studies were performed. The major findings to be reported were: the H & E examination revealed spongiotic dermatitis and pompholix. IHC and MDIF studies demonstrated focally deposits of positive CD45, CD3, CD8, anti myeloperoxidase (MPO, and anti-human IgE, C3C, C3D and anti-human-fibrinogen within the epidermal spongiotic process, as well as around the blood vessels surrounding the inflammatory process especially at the sweat glands and respective ductus. The patient began mycophenolate mofetil therapy, with successful clearing of the palms and soles. Conclusion: The significance of our findings indicates a complex immunological process including complement, MPO and T-cell immune response. In addition, possibly a secondary allergic process for the presence of IgE immune response and possibly aggravation by application of other medicines. Further immunological studies on pompholyx are needed

  7. Dyshidrotic eczema: Relevance to the immune response in situ

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2009-01-01

    Full Text Available Context: Pompholyx (called dyshidrosis by some is one of the most common conditions and its immune response is presently poorly understood. Case report: We describe a 58 year old African American female with a clinical history of rheumatoid arthritis and type II diabetes who presented a chronic five-year, itchy vesicular/blistering rash involving her hands and feet. A lesional skin biopsy was taken for hematoxylin and eosin (H & E analysis. In addition, a multicolor direct immunofluorescence (MDIF and immunohistochemistry (IHC studies were performed. The major findings to be reported were: the H & E examination revealed spongiotic dermatitis and pompholix. IHC and MDIF studies demonstrated focally deposits of positive CD45, CD3, CD8, anti myeloperoxidase (MPO, and anti-human IgE, C3C, C3D and anti-human-fibrinogen within the epidermal spongiotic process, as well as around the blood vessels surrounding the inflammatory process especially at the sweat glands and respective ductus. The patient began mycophenolate mofetil therapy, with successful clearing of the palms and soles. Conclusion : The significance of our findings indicates a complex immunological process including complement, MPO and T-cell immune response. In addition, possibly a secondary allergic process for the presence of IgE immune response and possibly aggravation by application of other medicines. Further immunological studies on pompholyx are needed. (Abreu Velez AM, Pinto FJ, Howard MS.

  8. 重质燃料油中主要芳烃在自然条件下的风化规律%Weathering of Main Aromatic Hydrocarbon in Heavy Fuel Oil under Natural Conditions

    Institute of Scientific and Technical Information of China (English)

    倪张林; 马启敏; 程海鸥

    2007-01-01

    文章在自然环境条件下对重质燃料油进行了风化模拟实验,采用气质(GC/MS)联用仪分析了重质燃料油中主要芳烃组分及其变化.结果表明:该重质燃料油中主要芳烃为苯类(CnB)、萘(CnN)类、菲(CnP)类、二苯并噻吩(CnD)类;在自然条件下,经过1周的风化,CnB和C0N完全损失;经过6周风化,C1N完全损失;经过12周的风化,C2N完全损失,3环的PAHs无明显变化.同时指出C2D/C2P和C3D/C,P的比值以及烷基化二苯并噻吩的同分异构体分布可用于区别其它油品,并且风化后变化不大,仍可较好地用于油品的鉴定.

  9. The Biomarker Changes of a Heavy Fuel Oil After Different Weathering Times

    Institute of Scientific and Technical Information of China (English)

    MA Qimin; NI Zhanglin; YU Zhigang

    2009-01-01

    This paper presents the experimental results of composition changes of heavy fuel oil by simulating weathering in static seawater under natural environmental conditions. The results indicate: n-C10 to n-C15 were lost gradually in 24 weeks and the relative abundance of alkanes with long chains (n-C19) increased markedly. The aromatic compounds with less than two rings (except C4N) were completely lost in 24 weeks and CnP and CnD became the main aromatics in the heavy fuel oil after 24 weeks. The ratios of n-C17/Pristane (Pr) and n-C18/Phytane (Ph) were suitable for identifying lightly weathered (3 weeks) heavy fuel oil. The ratios of n-C17/n-C18 and Pr/Ph were suitable for identifying moderately weathered heavy fuel oil (12 weeks); the ratios of C2D/C2P and C3D/C3P did not change significantly in 24 weeks and were more suitable for identifying moderately weathered heavy fuel oil (24 weeks).

  10. Complement and Humoral Adaptive Immunity in the Human Choroid Plexus: Roles for Stromal Concretions, Basement Membranes, and Epithelium.

    Science.gov (United States)

    Moore, G R Wayne; Laule, Cornelia; Leung, Esther; Pavlova, Vladimira; Morgan, B Paul; Esiri, Margaret M

    2016-05-01

    The choroid plexus (CP) provides a barrier to entry of toxic molecules from the blood into the brain and transports vital molecules into the cerebrospinal fluid. While a great deal is known about CP physiology, relatively little is known about its immunology. Here, we show immunohistochemical data that help define the role of the CP in innate and adaptive humoral immunity. The results show that complement, in the form of C1q, C3d, C9, or C9neo, is preferentially deposited in stromal concretions. In contrast, immunoglobulin (Ig) G (IgG) and IgA are more often found in CP epithelial cells, and IgM is found in either locale. C4d, IgD, and IgE are rarely, if ever, seen in the CP. In multiple sclerosis CP, basement membrane C9 or stromal IgA patterns were common but were not specific for the disease. These findings indicate that the CP may orchestrate the clearance of complement, particularly by deposition in its concretions, IgA and IgG preferentially via its epithelium, and IgM by either mechanism.

  11. A CD21 low phenotype, with no evidence of autoantibodies to complement proteins, is consistent with a poor prognosis in CLL.

    Science.gov (United States)

    Nichols, Eva-Maria; Jones, Rachel; Watson, Rachael; Pepper, Chris J; Fegan, Chris; Marchbank, Kevin J

    2015-10-20

    B-cell chronic lymphocytic leukemia (CLL) is characterized by differential BCR signaling and autoimmune complications. Complement modulates B-cell function via C3d and CD21 cross-linked to the B-cell receptor (BCR). We hypothesized that CD21 contributes to BCR signaling and participates in the autoimmunity associated with CLL. We analyzed CD21 expression on 106 CLL patient samples and matched serum from 50 patients for the presence of soluble CD21 and autoantibodies to CR2, CR1, MCP and FH. CD21 expression on CLL B-cells was significantly lower than that expressed on B-cells from age-matched controls (P complement regulator. Low CD21 expression correlated to prognostic subsets of CLL patients, i.e. cases with unmutated IGHV genes (P = 0.0006), high CD38 (P = 0.02) and high ZAP70 expression (P = 0.0017). Low CD21 expression was inversely correlated to the levels of phosphotyrosine induced in CLL cells following BCR ligation with αIgM (r2 = -0.21). Importantly, lower CD21 expression was also predictive for reduced overall survival (P = 0.005; HR = 2.7). In conclusion, we showed that reduced expression of CD21 on CLL B-cells appears functionally relevant and was associated with poor clinical outcomes.

  12. Novel thermostable lipase from Bacillus circulans IIIB153: comparison with the mesostable homologue at sequence and structure level.

    Science.gov (United States)

    Johri, S; Bhat, A; Sayed, S; Nargotra, A; Jain, A; Qazi, G N

    2012-01-01

    Thermophilic Bacillus circulans IIIB153 isolated from hot springs of North West Himalayas, India, produced an extracellular lipase, which exhibited significant biofilm disruption property on the static biofilm disruption model with a single species of Actinomyces viscosous. The gene encoding the lipase was cloned and overexpressed in Escherichia coli. Recombinant Bacillus circulans lipase (BCL), a monomer with molecular mass of 43 kDa also exhibited significant biofilm disruption activity. The enzyme was optimally active at 60°C, pH 8.5 and retained >70% of its original activity after 1 h incubation at 60°C. 3D structure of BCL developed by homology modeling showed a typical α/β hydrolase fold, a characteristic feature of lipolytic enzymes. Comparison of thermostable BCL with mesostable lipase from Chromobacterium viscosum at the sequence and structure level showed distinct variations in the structural features, with the presence of a high content of proline residues, aromatic amino acids and salt bridges. These features along with the presence of zinc-binding site observed in BCL structure could have a potential role in thermal stability of the enzyme.

  13. Investigation of Spectral Band Requirements for Improving Retrievals of Phytoplankton Functional Types

    Directory of Open Access Journals (Sweden)

    Aleksandra Wolanin

    2016-10-01

    Full Text Available Studying phytoplankton functional types (PFTs from space is possible due to recent advances in remote sensing. Though a variety of products are available, the limited number of wavelengths available compared to the number of model parameters needed to be retrieved is still a major problem in using ocean-color data for PFT retrievals. Here, we investigated which band placement could improve retrievals of three particular PFTs (diatoms, coccolithophores and cyanobacteria. In addition to analyzing dominant spectral features in the absorption spectra of the target PFTs, two previously-developed methods using measured spectra were applied to simulated data. Such a synthetic dataset allowed for significantly increasing the number of scenarios and enabled a full control over parameters causing spectral changes. We evaluated the chosen band placement by applying an adapted ocean reflectance inversion, as utilized in the generalized inherent optical properties (GIOP retrieval. Results show that the optimal band settings depend on the method applied to determine the bands placement, as well as on the internal variability of the dataset investigated. Therefore, continuous hyperspectral instruments would be most beneficial for discriminating multiple PFTs, though a small improvement in spectral sampling and resolution does not significantly modify the results. Bands, which could be added to future instruments (e.g., Ocean and Land Colour Instrument (OLCI instrument on the upcoming Sentinel-3B,-3C,-3D, etc., and further satellites in order to enhance PFT retrieval capabilities, were also determined.

  14. 番茄红素的超临界二氧化碳萃取研究%Study on Extraction of Lycopene by Supercritical Carbon Dioxide

    Institute of Scientific and Technical Information of China (English)

    袁永俊; 李培骏; 芮光伟; 陈斌; 李洪湖

    2005-01-01

    对超临界CO2萃取番茄红素进行了研究,结果表明:采用70 ℃常温鼓风干燥时,番茄原料经0.5%的亚硫酸钠溶液浸泡能够减少番茄红素的损失,干燥后的番茄片经粉碎过40目筛有利于番茄红素的超临界萃取,过40目筛的番茄粉经有机溶剂乙醚浸泡、研磨后,番茄红素的萃取量增加幅度较大.在实验范围内,影响超临界CO2萃取的主要因素的显著性关系为C(流量)>B(温度)>D(时间)>A(压力),各因素的最佳水平组合为A3B3C3D2.

  15. Gravitational Effects on Multi-component Droplet Evaporation

    Science.gov (United States)

    Habchi, Chawki; Ebrahimian, Vahid

    2012-06-01

    This paper focuses on the analysis of multi-component droplet heating and evaporation under microgravity and normal gravity conditions. This analysis is based on the conventional conservation equations of species and energy for the gas phase, and the energy balance equation at the liquid-gas interface. The species diffusion is based on the Hirschfelder law, rather than on the less general Fick's equation. Moreover, the heat flux due to species diffusion is taken into account in addition to the classical conduction heat flux between the gas and the liquid droplets. The liquid phase analysis is based on the infinite thermal conductivity liquid phase model, which has been justified by a reasonably good agreement between the predicted and experimental results. Indeed, the developed evaporation model has been validated against experimental data reported by Chauveau et al. (2008), where the droplets evaporation has been observed in microgravity and normal gravity conditions. The effects of gravity have been taken into account by introducing the Grashof number in the expressions of the Sherwood and Nusselt numbers. This model has been implemented in the multidimensional IFP-C3D industrial software. The modeling and experimental results have been shown to be reasonably close and the gravitational effects have been revealed to be significant especially for multi-component liquids including heavy components.

  16. The cationic peptide LL-37 binds Mac-1 (CD11b/CD18) with a low dissociation rate and promotes phagocytosis.

    Science.gov (United States)

    Zhang, Xianwei; Bajic, Goran; Andersen, Gregers R; Christiansen, Stig Hill; Vorup-Jensen, Thomas

    2016-05-01

    As a broad-spectrum anti-microbial peptide, LL-37 plays an important role in the innate immune system. A series of previous reports implicates LL-37 as an activator of various cell surface receptor-mediated functions, including chemotaxis in integrin CD11b/CD18 (Mac-1)-expressing cells. However, evidence is scarce concerning the direct binding of LL-37 to these receptors and investigations on the associated binding kinetics is lacking. Mac-1, a member of the β2 integrin family, is mainly expressed in myeloid leukocytes. Its critical functions include phagocytosis of complement-opsonized pathogens. Here, we report on interactions of LL-37 and its fragment FK-13 with the ligand-binding domain of Mac-1, the α-chain I domain. LL-37 bound the I-domain with an affinity comparable to the complement fragment C3d, one of the strongest known ligands for Mac-1. In cell adhesion assays both LL-37 and FK-13 supported binding by Mac-1 expressing cells, however, with LL-37-coupled surfaces supporting stronger cell adhesion than FK-13. Likewise, in phagocytosis assays with primary human monocytes both LL-37 and FK-13 enhanced uptake of particles coupled with these ligands but with a tendency towards a stronger uptake by LL-37.

  17. Optimal Design for Improving Thermo-Mechanical Fatigue Reliability of Solder Joint of PBGA Component Based on Robust Design%基于稳健设计的PBGA器件焊点热机械疲劳可靠性的优化设计

    Institute of Scientific and Technical Information of China (English)

    周继承; 肖小清; 恩云飞; 何小琦

    2007-01-01

    基于稳健设计与有限元法,研究了加速热循环测试条件下塑封球栅阵列(PBGA)焊点的热机械疲劳可靠性.考虑PCB大小(A)、基板厚度(D)、芯片热膨胀系数(G)、焊点热膨胀系数(H)等八个控制因素,使用L18(21×37)混合正交表,以对焊点热机械疲劳寿命的考核为目标,对PBGA焊点进行了优化设计.结果表明,影响焊点可靠性的显著性因素依次是基板热膨胀系数、焊点的热膨胀系数、基板厚度、芯片的热膨胀系数;最优方案组合为A1B2C3D1E2F1G3H1.进一步的验证试验结果表明,与原始方案相比,该优化方案的最大等效应变降低了66%,信噪比提高了22.4%.

  18. Effect of Wire-EDM cutting parameters on material removal rate of titanium alloy (Ti6Al4V)

    Science.gov (United States)

    Azam, N.; Afendi, M.

    2016-07-01

    In this study, titanium alloy (Ti6Al4V) which is also known as difficult to cut material is used as workpiece. Seven main parameters namely pulse duration (A), pulse interval (B), servo voltage (C), ignition pulse current (D), wire tension (E), wire speed (F) and dielectric pressure (G) have been experimentally studied by using Taguchi method as well as the determination of optimum parameters for material removal rate (MRR). Analysis of variance (ANOVA) has been used for recognizing the level of significant of WEDM cutting parameter for optimizing MRR and the result found that pulse duration and servo voltage give significant effect on MRR. While according to Signal to Noise (S/N) ratio response table for MRR, the parameters combination of A3B3C3D3E1F3G3 give the optimum value for MRR. It is also observed that the predicted results agree with the experimental values within an error of 4.6 %.

  19. Fluctuations in the microwave conductivity of YBa{sub 2}Cu{sub 3}O{sub 7{minus}{delta}} single crystals in zero dc magnetic field

    Energy Technology Data Exchange (ETDEWEB)

    Anlage, S.M.; Mao, J.; Booth, J.C.; Wu, D.H.; Peng, J.L. [Center for Superconductivity Research, Department of Physics, University of Maryland, College Park, Maryland 20742-4111 (United States)

    1996-02-01

    We present a quantitative analysis of finite frequency fluctuation conductivity above and below {ital T}{sub {ital c}} in cuprate superconductors in zero dc magnetic field. In a YBa{sub 2}Cu{sub 3}O{sub 7{minus}{delta}} crystal showing a linear in temperature increase of the penetration depth at low temperatures, we find that two-dimensional (2D) finite frequency Gaussian conductivity fluctuations above {ital T}{sub {ital c}} cross over into a slower divergence of the conductivity as {ital T}{sub {ital c}} is approached from above. We find that the critical regime above {ital T}{sub {ital c}} is less than about 0.6 K wide. At and below {ital T}{sub {ital c}}, 3D fluctuations dominate the conductivity, with evidence of 3D {ital XY} critical scaling of the imaginary part of the conductivity down to 5 K below {ital T}{sub {ital c}}. {copyright} {ital 1996 The American Physical Society.}

  20. The mode of action of immunological adjuvants.

    Science.gov (United States)

    Allison, A C

    1998-01-01

    Adjuvants augment immune responses to antigens and influence the balance between cell-mediated and humoral responses, as well as the isotypes of antibodies formed. New adjuvant formulations include antigen-carrying vehicles and small molecules with immunomodulating activity. Widely used two-phase vehicles comprise liposomes and microfluidized squalene or squalane emulsions. These are believed to target antigens to antigen-presenting cells, including dendritic cells (DC), follicular dendritic cells (FDC) and B-lymphocytes. Activation of complement generates C3d, which binds CR2 (CD21) on FDC and B-lymphocytes, thereby stimulating the proliferation of the latter and the generation of B-memory. Targeting of antigens to DC may favour cell-mediated immunity. Immunomodulating agents induce the production of cytokine cascades. In a primary cascade at injection sites TNF-alpha, GM-CSF and IL-1 are produced. TNF-alpha promotes migration of DC to lymphoid tissues, while GM-CSF and IL-1 accelerate the maturation of DC into efficient antigen-presenting cells for T-lymphocytes. In a secondary cytokine cascade in draining lymph nodes, DC produce IL-12, which induces Th1 responses with the production of IFN-gamma. The cytokines elicit cell-mediated immune responses and the formation of antibodies of protective isotypes, such as IgG2a in the mouse and IgG1 in humans. Antibodies of these isotypes activate complement and collaborate with antibody-dependent effector cells in protective immune responses.

  1. 后路C2/C3椎弓根螺钉固定治疗Hangman骨折%Posterior C2/C3 pedicle screw fixation and fusion for treatment of Hangman fracture

    Institute of Scientific and Technical Information of China (English)

    胡临; 田伟; 刘波; 李勤; 李志宇; 袁强; 王永庆

    2010-01-01

    目的 探讨后路C2/C3椎弓根螺钉固定治疗Hangman骨折的应用指征及疗效.方法 采用后路C2/C3椎弓根螺钉固定治疗18例Ⅱ型及Ⅱa型Hangman骨折患者,其中3例采用基于CT的导航,14例采用基于ICO-C 3D C臂的导航.结果 全部患者达到骨性愈合,没有出现椎动脉和神经损伤及其他合并症.结论 后路C2/C3椎弓根螺钉固定对于治疗Hangman骨折是一种有效的方法,术中导航技术使其更加准确和安全.

  2. Structural optimization and evaluation of butenolides as potent antifouling agents: modification of the side chain affects the biological activities of compounds

    KAUST Repository

    Li, Yongxin

    2012-09-01

    A recent global ban on the use of organotin compounds as antifouling agents has increased the need for safe and effective antifouling compounds. In this study, a series of new butenolide derivatives with various amine side chains was synthesized and evaluated for their anti-larval settlement activities in the barnacle, Balanus amphitrite. Side chain modification of butenolide resulted in butenolides 3c-3d, which possessed desirable physico-chemical properties and demonstrated highly effective non-toxic anti-larval settlement efficacy. A structure-activity relationship analysis revealed that varying the alkyl side chain had a notable effect on anti-larval settlement activity and that seven to eight carbon alkyl side chains with a tert-butyloxycarbonyl (Boc) substituent on an amine terminal were optimal in terms of bioactivity. Analysis of the physico-chemical profile of butenolide analogues indicated that lipophilicity is a very important physico-chemical parameter contributing to bioactivity. © 2012 Copyright Taylor and Francis Group, LLC.

  3. [Vitreo-retinal surgery for complicated retinal detachment].

    Science.gov (United States)

    Wang, J Z

    1993-07-01

    93 eyes (93 patients) of complicated retinal detachment were treated with vitreo-retinal surgery. Among the series, 75 eyes were rhegmatogenous with PVR C3-D3 in 66 eyes (88.0%), while the remaining 18 eyes were traction induced. None of the cases had giant tears or complicating diabetes. On discharge from the hospital, the operation was effective in 62 cases (66.7%), in whom the retina was totally reattached or only a small amount of subretinal fluid remained. In a group of 40 eyes where the inert gas SF6 was used, the operation was effective in 30 cases (75.0%). 41 cases were followed up postoperatively for over 3 months, averaging 13.7 months, to find the operative results stable in 33 eyes (80.5%), with the visual acuity improved in 22 cases (66.7%), unchanged in 9 cases (27.3%), and decreased in 2 cases (6.0%). The operative procedures, the peeling of pre-retinal membrane, the effect of PVR severity on the operative results, and the promotion of operative efficacy by application of wide encircling buckle and inert gas tamponade were discussed.

  4. Measurements of K Shell Emission of Highly Charged Ions with the XRS at EBIT

    Science.gov (United States)

    Porter, F. Scott; Beiersdorfer, P.; Boyce, K.; Brown, G. V.; Chen, H.; Kahn, S.; Kelley, R.; Kilbourne, C. A.

    2004-01-01

    The XRS/EBIT is a 32 channel microcalorimeter spectrometer operating at the electron beam ion trap (EBIT) facility at Lawrence Livermore National Laboratory. The system contains a flight candidate detector array from the XRS instrument for the Astro-E2 mission. The detector array in the XRS/EBIT is functionally identical to the flight array integrated into the XRS instrument and benefits from the enormous amount of calibration data from the XRS program. Since the XRSEBIT was upgraded with the new detector array in October 2003, the system has been used for a number of experiments including a survey of the K shell emission from He-like and H-like O, Ne, Ar, Fe, Ni and Kr as well as for L shell emission to measure the 3C/3D line ratio in Ni. Here we present some basic operational parameters of the instrument as well as direct excitation and simulated maxwellian spectra of He-like and E-like Fe. We show that the XRS instrument can resolve the Lyal and Lya2 lines from each other as well as from the dielectronic recombination satellites in thermal H-like Fe. We also show exactly how well the XRS instrument on Astro-E2 will resolve the thermal He-like triplet in collisionally excited Fe. This work was funded under NASA's Research Opportunities in Space Science program.

  5. Kinetic plasma turbulence during the nonlinear stage of the Kelvin-Helmholtz instability

    CERN Document Server

    Kemel, Koen; Lapenta, Giovanni; Califano, Francesco; Markidis, Stefano

    2014-01-01

    Using a full kinetic, implicit particle-in-cell code, iPiC3D, we studied the properties of plasma kinetic turbulence, such as would be found at the interface between the solar wind and the Earth magnetosphere at low latitude during northwards periods. In this case, in the presence of a magnetic field B oriented mostly perpendicular to the velocity shear, turbulence is fed by the disruption of a Kelvin-Helmholtz vortex chain via secondary instabilities, vortex pairing and non-linear interactions. We found that the magnetic energy spectral cascade between ion and electron inertial scales, $d_i$ and $d_e$, is in agreement with satellite observations and other previous numerical simulations; however, in our case the spectrum ends with a peak beyond $d_e$ due to the occurrence of the lower hybrid drift instability. The electric energy spectrum is influenced by effects of secondary instabilities: anomalous resistivity, fed by the development of the lower hybrid drift instability, steepens the spectral decay and, de...

  6. Three-dimensional illumination system for tomographic particle image velocimetry

    Science.gov (United States)

    Zhang, Fen; Song, Yang; Qu, Xiangju; Ji, Yunjing; Li, Zhenhua; He, Anzhi

    2016-10-01

    Tomographic particle image velocimetry (Tomo-PIV) is a new developed technique for three-component threedimensional (3C-3D) velocity measurement of the flow field based on the optical tomographic reconstruction method, and has been received extensive attention of the related industries. Three-dimensional light source illuminating the tracer particles of flow field is a critical application for tomographic particle image velocimetry. Three-dimensional light source not only determines the size of measurement volume and the range of the scope of application, but also has a great influence on the image quality. In this work, we propose a rectangular light amplification system using powell lens, prisms and two reflectors. The system can be optimized if given the system parameters based on the theoretical model. The rectangular light amplification system will be verified experimentally by measuring the cross section size of the illuminated light source. A 60mm×25mm cross section of rectangular three-dimensional light source can be obtained by using the rectangular light amplification system. The experiments demonstrate the the feasibility the proposed system.

  7. Myocarditis in patients with subarachnoid hemorrhage: A histopathologic study.

    Science.gov (United States)

    van der Bilt, Ivo A C; Vendeville, Jean-Paul; van de Hoef, Tim P; Begieneman, Mark P V; Lagrand, Wim K; Kros, Johan M; Wilde, Arthur A M; Rinkel, Gabriel J E; Niessen, Hans W M

    2016-04-01

    Cardiac abnormalities after subarachnoid hemorrhage (SAH) such as electrocardiographic changes, echocardiographic wall motion abnormalities, and elevated troponin levels are independently associated with a poor prognosis. They are caused by catecholaminergic stress coinciding with influx of inflammatory cells into the heart. These abnormalities could be a sign of a myocarditis, potentially giving insight in pathophysiology and treatment options. These inflammatory cells are insufficiently characterized, and it is unknown whether myocarditis is associated with SAH. Myocardium of 25 patients who died of SAH and 18 controls was stained with antibodies identifying macrophages (CD68), lymphocytes (CD45), and neutrophil granulocytes (myeloperoxidase). Myocytolysis was visualized using complement staining (C3d). CD31 was used to identify putative thrombi. We used Mann-Whitney U testing for analysis. In the myocardium of SAH patients, the amount of myeloperoxidase-positive (P Myocarditis, consisting of an influx of neutrophil granulocytes, lymphocytes, and macrophages, coinciding with myocytolysis and thrombi in intramyocardial arteries, occurs in patients with SAH but not in controls. These findings might explain the cardiac abnormalities after SAH and may have implications for treatment.

  8. Detection of Salmonella invA gene in shrimp enrichment culture by polymerase chain reaction.

    Science.gov (United States)

    Upadhyay, Bishnu Prasad; Utrarachkij, Fuangfa; Thongshoob, Jarinee; Mahakunkijcharoen, Yuvadee; Wongchinda, Niracha; Suthienkul, Orasa; Khusmith, Srisin

    2010-03-01

    Contamination of seafood with salmonellae is a major public health concern. Detection of Salmonella by standard culture methods is time consuming. In this study, an enrichment culture step prior to polymerase chain reaction (PCR) was applied to detect 284 bp fragment of Salmonella invA in comparison with the conventional culture method in 100 shrimp samples collected from four different shrimp farms and fresh food markets around Bangkok. Samples were pre-enriched in non-selective lactose broth (LB) and selective tetrathionate broth (TTB). PCR detection limit was 10 pg and 10(4) cfu/ml of viable salmonellae with 100% specificity. PCR assay detected 19 different Salmonella serovars belonging to 8 serogroups (B, C1, C2-C3, D1, E1, E4 and K) commonly found in clinical and environmental samples in Thailand. The detection rate of PCR following TTB enrichment (24%) was higher than conventional culture method (19%). PCR following TTB, but not in LB enrichment allowed salmonella detection with 84% sensitivity, 90% specificity and 89% accuracy. Shrimp samples collected from fresh food markets had higher levels of contaminated salmonellae than those from shrimp farms. The results indicated that incorporation of an enrichment step prior to PCR has the potential to be applied for detection of naturally contaminated salmonellae in food, environment and clinical samples.

  9. Green synthesis of novel quinoline based imidazole derivatives and evaluation of their antimicrobial activity

    Directory of Open Access Journals (Sweden)

    N.C. Desai

    2014-12-01

    Full Text Available We have described the conventional and microwave method for the synthesis of N-(4-((2-chloroquinolin-3-ylmethylene-5-oxo-2-phenyl-4,5-dihydro-1H-imidazol-1-yl(arylamides 3a–l. It is observed that the solvent-free microwave thermolysis is a convenient, rapid, high-yielding, and environmental friendly protocol for the synthesis of quinoline based imidazole derivatives when compared with conventional reaction in a solution phase. Antimicrobial activity of the newly synthesized compounds is screened in vitro on the following microbial cultures: Escherichia coli (MTCC 443, Pseudomonas aeruginosa (MTCC 1688, Staphylococcus aureus (MTCC 96, Streptococcus pyogenes (MTCC 442, Candida albicans (MTCC 227, Aspergillus niger (MTCC 282, Aspergillus clavatus (MTCC 1323. All the synthesized bio-active molecules are tested for their in vitro antimicrobial activity by bioassay namely serial broth dilution. Among these compounds 3c, 3d, 3f, 3h and 3j show significant potency against different microbial strains. All the compounds have been characterized by IR, 1H NMR, 13C NMR and mass spectral data. On the basis of statistical analysis, it is observed that these compounds give significant co-relation.

  10. Genetic control of the alternative pathway of complement in humans and age-related macular degeneration.

    Science.gov (United States)

    Hecker, Laura A; Edwards, Albert O; Ryu, Euijung; Tosakulwong, Nirubol; Baratz, Keith H; Brown, William L; Charbel Issa, Peter; Scholl, Hendrik P; Pollok-Kopp, Beatrix; Schmid-Kubista, Katharina E; Bailey, Kent R; Oppermann, Martin

    2010-01-01

    Activation of the alternative pathway of complement is implicated in common neurodegenerative diseases including age-related macular degeneration (AMD). We explored the impact of common variation in genes encoding proteins of the alternative pathway on complement activation in human blood and in AMD. Genetic variation across the genes encoding complement factor H (CFH), factor B (CFB) and component 3 (C3) was determined. The influence of common haplotypes defining transcriptional and translational units on complement activation in blood was determined in a quantitative genomic association study. Individual haplotypes in CFH and CFB were associated with distinct and novel effects on plasma levels of precursors, regulators and activation products of the alternative pathway of complement in human blood. Further, genetic variation in CFH thought to influence cell surface regulation of complement did not alter plasma complement levels in human blood. Plasma markers of chronic activation (split-products Ba and C3d) and an activating enzyme (factor D) were elevated in AMD subjects. Most of the elevation in AMD was accounted for by the genetic variation controlling complement activation in human blood. Activation of the alternative pathway of complement in blood is under genetic control and increases with age. The genetic variation associated with increased activation of complement in human blood also increased the risk of AMD. Our data are consistent with a disease model in which genetic variation in the complement system increases the risk of AMD by a combination of systemic complement activation and abnormal regulation of complement activation in local tissues.

  11. Prelimary Study on Using Compound Biological Insecticides to Control Dendrolimus kikuchii%复合生物杀虫剂防治思茅松毛虫的初步研究

    Institute of Scientific and Technical Information of China (English)

    邓秀明

    2002-01-01

    应用白僵菌、苏云金杆菌、马尾松毛虫质型多角体病毒(DCPV)和15%保丰等4种杀虫剂对2~3龄思茅松毛虫幼虫进行了毒力测定.并通过林间正交试验设计筛选出了复合生物杀虫剂最佳组合A3B1C3D1,即白僵菌1.4×106孢子*ml-1+苏云金杆菌1.6×108孢子*ml-1+DCPV 5×106PIB*ml-1+15%保丰4000倍液.研究表明在复合杀虫剂中保丰、苏云金杆菌对防治效果有显著影响.林间大面积防治试验表明,复合杀虫剂的防治效果优于单一生物杀虫剂.

  12. Clinical and serological characterization of cold agglutinin syndrome in a Tertiary Care Hospital in Eastern India

    Directory of Open Access Journals (Sweden)

    Sudipta Sekhar Das

    2015-01-01

    Full Text Available Background and Aim: Cold agglutinin syndrome (CAS primary or secondary represents approximately 16-32% of autoimmune hemolytic anemia cases. Most patients present with mild, chronic hemolytic anemia with exacerbation of the condition in the cold environment. Red cell transfusions are only indicated when there is a life-threatening anemia causing crisis. We studied the clinical and serological characterization of CAS with the aim that the information gained from this study would help in proper diagnosis and management of these patients. Materials and Methods: The prospective study included nine patients who were admitted with severe anemia. Detailed work-up were conducted to establish the diagnosis, severity of in vivo hemolysis and transfusion management. Results: All patients presented with pallor, weakness, fatigue and painful fingers and toes with exacerbation of symptoms in winter months. Secondary CAS was observed in three patients suffering from malignant lymphoma. Red cells of all patients were coated with complements (C3 more specifically C3d. In one patient suffering from malignant lymphoma, the cold autoagglutinin titer was as high as 4096. Autoantibody in seven patients was specific to "I" antigen and one to "i" antigen. Conclusions: We conclude that detailed clinical and serological characterization is needed to diagnose and manage CAS. Whereas avoidance of cold exposure is the primary therapy, but no critical patient should be denied blood transfusion due to serological complications. All transfusion services should follow the correct protocol to maximize blood safety in CAS.

  13. Shock tube measurements of the branching ratios of propene + OH -> products

    KAUST Repository

    Khaled, Fathi

    2014-07-25

    Absolute rate coefficients for the reaction of OH radical with propene (C3H6) and five deutrated isotopes, propene-1-d1 (CDHCHCH3), propene-1,1-d2 (CD2CHCH3), propene-2-d1 (CH2CDCH3), propene-3,3,3-d3 (CH2CHCD3), and propene-d6 (C3D6), were measured in a shock tube behind reflected shock conditions over the temperature range of 812 K – 1460 K and pressures near 1 atm. The reaction progress was followed by monitoring OH radical near 306.7 nm using UV laser absorption. The first experimental measurements for the branching ratio of the title reaction are reported and compared with theoretical calculations. The allylic H atom abstraction of propene by OH radicals was found to be the most dominant reaction pathway followed by propen-1-yl and propen-2-yl channels over the entire temperature range of this study which is in line with theoretical predictions. Arrhenius parameters for various site-specific rate coefficients are provided for kinetic modeling.

  14. Fluctuations in the Microwave Conductivity of YBCO Single Crystals in Zero DC Magnetic Field

    Science.gov (United States)

    Anlage, Steven; Mao, Jian; Booth, James; Wu, Dong-Ho; Peng, J. L.

    1996-03-01

    We present a quantitative analysis of finite frequency fluctuation conductivity above and below Tc in cuprate superconductors in zero dc magnetic field.(S. M. Anlage, J. Mao, J. C. Booth, D. H. Wu, and J. L. Peng, Phys. Rev. B 53), Feb. 1, 1996. In a YBa_2Cu_3O_7-δ crystal showing a linear in temperature increase of the magnetic penetration depth at low temperatures, we find that two-dimensional finite-frequency Gaussian conductivity fluctuations above Tc cross over into a slower divergence of the conductivity as Tc is approached from above. We find that the critical regime above Tc is less than about 0.6 K wide, although inhomogeneities in the crystal may also dominate the conductivity in this temperature range. At and below T_c, 3D fluctuations dominate the conductivity, with evidence of 3D XY critical scaling of the imaginary part of the conductivity down to 5 K below T_c. Supported by the NSF NYI program (DMR-9258183), and NSF grant DMR-9123198.

  15. A Simple and Novel Strategy for the Production of a Pan-specific Antiserum against Elapid Snakes of Asia

    Science.gov (United States)

    Ratanabanangkoon, Kavi; Tan, Kae Yi; Eursakun, Sukanya; Tan, Choo Hock; Simsiriwong, Pavinee; Pamornsakda, Teeraporn; Wiriyarat, Witthawat; Klinpayom, Chaiya; Tan, Nget Hong

    2016-01-01

    Snakebite envenomation is a serious medical problem in many tropical developing countries and was considered by WHO as a neglected tropical disease. Antivenom (AV), the rational and most effective treatment modality, is either unaffordable and/or unavailable in many affected countries. Moreover, each AV is specific to only one (monospecific) or a few (polyspecific) snake venoms. This demands that each country to prepare AV against its local snake venoms, which is often not feasible. Preparation of a ‘pan-specific’ AV against many snakes over a wide geographical area in some countries/regions has not been possible. If a ‘pan-specific’ AV effective against a variety of snakes from many countries could be prepared, it could be produced economically in large volume for use in many countries and save many lives. The aim of this study was to produce a pan-specific antiserum effective against major medically important elapids in Asia. The strategy was to use toxin fractions (TFs) of the venoms in place of crude venoms in order to reduce the number of antigens the horses were exposed to. This enabled inclusion of a greater variety of elapid venoms in the immunogen mix, thus exposing the horse immune system to a diverse repertoire of toxin epitopes, and gave rise to antiserum with wide paraspecificity against elapid venoms. Twelve venom samples from six medically important elapid snakes (4 Naja spp. and 2 Bungarus spp.) were collected from 12 regions/countries in Asia. Nine of these 12 venoms were ultra-filtered to remove high molecular weight, non-toxic and highly immunogenic proteins. The remaining 3 venoms were not ultra-filtered due to limited amounts available. The 9 toxin fractions (TFs) together with the 3 crude venoms were emulsified in complete Freund’s adjuvant and used to immunize 3 horses using a low dose, low volume, multisite immunization protocol. The horse antisera were assayed by ELISA and by in vivo lethality neutralization in mice. The findings

  16. Epitope reactions can be gauged by relative antibody discriminating specificity (RADS values supported by deletion, substitution and cysteine bridge formation analyses: potential uses in pathogenesis studies

    Directory of Open Access Journals (Sweden)

    Falconar Andrew K I

    2012-07-01

    Full Text Available Abstract Background Epitope-mapping of infectious agents is essential for pathogenesis studies. Since polyclonal antibodies (PAbs and monoclonal antibodies (MAbs are always polyspecific and can react with multiple epitopes, it is important to distinguish between specific and non-specific reactions. Relative antibody discriminating specificity (RADS values, obtained from their relative ELISA reactions with L-amino acid peptides prepared in the natural versus reverse orientations (x-fold absorbance natural/absorbance reverse = RADS value may be valuable for this purpose. PAbs generated against the dengue type-2 virus (DENV-2 nonstructural-1 (NS1 glycoprotein candidate vaccine also reacted with both DENV envelope (E glycoproteins and blood-clotting proteins. New xKGSx/xSGKx amino acid motifs were identified on DENV-2 glycoproteins, HIV-1 gp41 and factor IXa. Their potential roles in DENV and HIV-1 antibody-enhanced replication (AER and auto-immunity were assessed. In this study, a RADS values were determined for MAbs and PAbs, generated in congeneic (H2: class II mice against DENV NS1 glycoprotein epitopes, to account for their cross-reaction patterns, and b MAb 1G5.3 reactions with xKGSx/xSGKx motifs present in the DENV-4 NS1, E and HIV-1 glycoproteins and factor IXa were assessed after the introduction of amino acid substitutions, deletions, or intra-/inter-cysteine (C-C bridges. Results MAbs 1H7.4, 5H4.3, 3D1.4 and 1G5.3 had high (4.23- to 16.83-fold RADS values against single epitopes on the DENV-2 NS1 glycoprotein, and MAb 3D1.4 defined the DENV complex-conserved LX1 epitope. In contrast, MAbs 1G5.4-A1-C3 and 1C6.3 had low (0.47- to 1.67-fold RADS values against multiple epitopes. PAb DENV complex-reactions occurred through moderately-high (2.77- and 3.11-fold RADS values against the LX1 epitope. MAb 1G5.3 reacted with xSGKx motifs present in DENV-4 NS1 and E glycoproteins, HIV-1 gp41 and factor IXa, while natural C-C bridge formations or

  17. A Simple and Novel Strategy for the Production of a Pan-specific Antiserum against Elapid Snakes of Asia.

    Directory of Open Access Journals (Sweden)

    Kavi Ratanabanangkoon

    2016-04-01

    Full Text Available Snakebite envenomation is a serious medical problem in many tropical developing countries and was considered by WHO as a neglected tropical disease. Antivenom (AV, the rational and most effective treatment modality, is either unaffordable and/or unavailable in many affected countries. Moreover, each AV is specific to only one (monospecific or a few (polyspecific snake venoms. This demands that each country to prepare AV against its local snake venoms, which is often not feasible. Preparation of a 'pan-specific' AV against many snakes over a wide geographical area in some countries/regions has not been possible. If a 'pan-specific' AV effective against a variety of snakes from many countries could be prepared, it could be produced economically in large volume for use in many countries and save many lives. The aim of this study was to produce a pan-specific antiserum effective against major medically important elapids in Asia. The strategy was to use toxin fractions (TFs of the venoms in place of crude venoms in order to reduce the number of antigens the horses were exposed to. This enabled inclusion of a greater variety of elapid venoms in the immunogen mix, thus exposing the horse immune system to a diverse repertoire of toxin epitopes, and gave rise to antiserum with wide paraspecificity against elapid venoms. Twelve venom samples from six medically important elapid snakes (4 Naja spp. and 2 Bungarus spp. were collected from 12 regions/countries in Asia. Nine of these 12 venoms were ultra-filtered to remove high molecular weight, non-toxic and highly immunogenic proteins. The remaining 3 venoms were not ultra-filtered due to limited amounts available. The 9 toxin fractions (TFs together with the 3 crude venoms were emulsified in complete Freund's adjuvant and used to immunize 3 horses using a low dose, low volume, multisite immunization protocol. The horse antisera were assayed by ELISA and by in vivo lethality neutralization in mice. The

  18. A Simple and Novel Strategy for the Production of a Pan-specific Antiserum against Elapid Snakes of Asia.

    Science.gov (United States)

    Ratanabanangkoon, Kavi; Tan, Kae Yi; Eursakun, Sukanya; Tan, Choo Hock; Simsiriwong, Pavinee; Pamornsakda, Teeraporn; Wiriyarat, Witthawat; Klinpayom, Chaiya; Tan, Nget Hong

    2016-04-01

    Snakebite envenomation is a serious medical problem in many tropical developing countries and was considered by WHO as a neglected tropical disease. Antivenom (AV), the rational and most effective treatment modality, is either unaffordable and/or unavailable in many affected countries. Moreover, each AV is specific to only one (monospecific) or a few (polyspecific) snake venoms. This demands that each country to prepare AV against its local snake venoms, which is often not feasible. Preparation of a 'pan-specific' AV against many snakes over a wide geographical area in some countries/regions has not been possible. If a 'pan-specific' AV effective against a variety of snakes from many countries could be prepared, it could be produced economically in large volume for use in many countries and save many lives. The aim of this study was to produce a pan-specific antiserum effective against major medically important elapids in Asia. The strategy was to use toxin fractions (TFs) of the venoms in place of crude venoms in order to reduce the number of antigens the horses were exposed to. This enabled inclusion of a greater variety of elapid venoms in the immunogen mix, thus exposing the horse immune system to a diverse repertoire of toxin epitopes, and gave rise to antiserum with wide paraspecificity against elapid venoms. Twelve venom samples from six medically important elapid snakes (4 Naja spp. and 2 Bungarus spp.) were collected from 12 regions/countries in Asia. Nine of these 12 venoms were ultra-filtered to remove high molecular weight, non-toxic and highly immunogenic proteins. The remaining 3 venoms were not ultra-filtered due to limited amounts available. The 9 toxin fractions (TFs) together with the 3 crude venoms were emulsified in complete Freund's adjuvant and used to immunize 3 horses using a low dose, low volume, multisite immunization protocol. The horse antisera were assayed by ELISA and by in vivo lethality neutralization in mice. The findings were: a

  19. Study of Ultraviolet System Purify Bacteria in Crassostrea rivularis%紫外线系统净化近江牡蛎(Crassostrearivularis)中细菌的研究

    Institute of Scientific and Technical Information of China (English)

    蒋伟明; 吴卫君; 番志忠; 丁兆坤; 李咏梅; 陈秀荔; 何为; 吴铁军

    2011-01-01

    In order to ensure food safety, ultraviolet system was used to disinfect sea water, Crassostrea rivularis was taken as materials and purified in the purification tank by artificial inoculation, cleaning, and roughly election processes. The best environmental condition of purification on Crassostrea rivularis was researched by experiment of each purification conditions and orthogonal experiment,with coliform group and total bacteria taken as index. The result showed that ultraviolet system could be used to disinfect sea water and purify Crassostrea rivularis. Optimal combination of orthogonal experiment were group 6 A2B3C, D2 (temperature 25 °C , salinity 25 "he, water exchange rate 1 time/4 h, shellfish to water ratio 1:6) and group 7 A3 B, C3 D2 (temperature 30 *C , salinity 15 %e, water exchange rate 1 time/8 h, shellfish to water ratio 1:4). But considered purification effect and economic benefit comprehensively, temperature 30 t, salinity 25 %o, water exchange rate 1 time/4 h, shellfish to water ratio 1:4, purification time 36 h could be selected as optimization condition to purify bacterias in Crassostrea rivularis.%为保证食品安全,研究采用紫外线系统杀菌海水,以近江牡蛎为试验材料,经人工接菌、清洗、粗选等流程后,进行各净化处理条件试验及正交试验筛选,以大肠菌群和菌落总数为指标,探讨净化的最佳环境条件.结果表明,利用紫外线系统能达到海水杀菌的效果,可用于贝类净化.正交试验最优组合为第6组A2 B3 C1 D2(温度25℃、盐度25‰、换水率1次/4h、贝水比1∶6)和第7组A3B1C3D2(温度30℃、盐度15%、换水率1次/8 h、贝水比1∶4).但综合考虑净化效果及经济效益,可选取温度30℃、盐度25‰、换水率1次/4h、贝水比1∶4,净化时间36 h作为近江牡蛎细菌净化的优化条件.

  20. The comparison analysis of microtube column agglutination technology and conventional tube technique for autoimmune hemolytic anemia detection%抗人球蛋白试验的微柱凝集法与传统试管法在自身免疫性溶血性贫血检测中的对比研究

    Institute of Scientific and Technical Information of China (English)

    刘洋; 雷婷; 陈双; 张正昊; 曹薇; 郭新红

    2013-01-01

    Objective To evaluate the clinic value of Microtube column agglutination technology antiglobu-lin test in dignosis of autoimmune hemolytic anemia (AIHA ) . Methods Specimens of 146 suspected AIHA patients were performed antiglobulin test by Microtube column agglutination technology and con-ventional tube .The results of the two tests have been comparatively analyzed .Results Among 46 patients who were diagnosed as AIHA ,under the test of MCAT ,DAT positive cases are 44 (95 .7% ) and IAT positive cases were 12 (26 .1% );while under the test of MCAT ,DAT positive cases were 22 cases (47 .8% ) and IAT positive cases were 2 cases (4 .3% ) .Among 44 cases detected by MCAT ,IgG+ C3d was positive in 23 cases (52 .3% ) ,IgG was positive in 8 cases (18 .2% ) and C3d was positive in 13 cases (29 .5% ) .The positive rate of MCAT was significantly higher than the CTT method ,the difference was statistically significant (P<0 .05) .It has been obviously observed that detection rate in positive of Micro-tube column agglutination technology is much higher .The difference is statistically significant .Conclusion Compared with conventional tube ,the microtube column agglutination technology for antiglobulin test is more sensitive ,easier to perform and standardized in diagnosis of AIHA .%目的:探讨微柱凝集法(Microtube column agglutination technology ,MCAT )抗人球蛋白试验(antiglobulin test ,AGT)在自身免疫性溶血性贫血(autoimmune hemolytic anemia ,AIHA)诊断中的临床意义。方法收集146例临床疑为AIHA患者的外周血标本,采用微柱凝集法和传统试管法(conventional tube technique ,CTT)进行抗人球蛋白试验,并对2种方法AGT试验检测AIHA结果进行比较分析。结果46例临床最终诊断 AIHA病例中, MCAT法检出DAT阳性44例(95.7%),IAT阳性12例(26.1%);CTT 法检出DAT 阳性22例(47.8%),IAT阳性2例(4.3%);在MCAT法检出的44

  1. Microdureza de resinas em função da cor e luz halógena Microhardness of resins as a function of color and halogen light

    Directory of Open Access Journals (Sweden)

    Fábio Martins

    2002-09-01

    Full Text Available O objetivo desse trabalho foi avaliar a influência da intensidade da luz e cor de uma resina composta no grau de dureza Knoop. Corpos-de-prova foram confeccionados utilizando-se matrizes de poliéster envoltas por um anel de cobre, contendo uma cavidade padronizada de 6 mm de diâmetro por 2 mm de espessura. Estas cavidades foram preenchidas com resina composta selecionada, Fill Magic - Vigodent, com as cores A3, B3, C3, D3 e I, fotopolimerizadas através de um fotopolimerizador Elipar, calibrado para produzir 3 intensidades de luz diferentes: 450 mW/cm², 800 mW/cm² e uma intensidade de luz crescente de 100 a 800 mW/cm². Foram confeccionados 90 corpos-de-prova em que o tempo de exposição da resina à luz halógena foi de 40 s. As amostras foram armazenadas em tubos de ensaio com água destilada a 37 ± 1ºC. Após este período, foram realizados os testes de dureza Knoop na região de superfície e fundo. Os resultados mostraram que houve diferença estatística em relação a intensidade de luz, entretanto em relação a cor, não houve diferença estatística. Os autores concluíram que a cor do compósito não influencia a dureza Knoop e que a intensidade progressiva promoveu os melhores resultados de dureza Knoop.The aim of this study was to evaluate the influence of light intensity and the influence of the color of a composite resin on Knoop hardness. Samples were confected utilizing polyester matrices with 6 mm of diameter and 2 mm of depth. The matrices were filled with composite resin (Fill Magic - Vigodent, colors A3, B3, C3, D3 and I, and light-cured by means of an Elipar light-curing unit in three different light intensities: 450 mW/cm2, 800 mW/cm² and an increasing intensity setup of 100 mW/cm² to 800 mW/cm². Ninety test specimens were confected, with the standard curing time of 40 seconds. The specimens were stored at 37 ± 1ºC and immersed in distillate water. The Knoop test was carried out in superficial and deep areas

  2. Analysis of Serum proteom before and after Intravenous Injection of wild ginseng herbal acupuncture

    Directory of Open Access Journals (Sweden)

    Tae-Sik Kang

    2004-12-01

    Full Text Available Objectives : To observe changes in the serum proteins before and after intravenous injection of wild ginseng herbal acupuncture. Methods : Blood was collected before and after the administration of wild ginseng herbal acupuncture and only the serum was centrifuged. Then differences in the spots on the scanned image after running 2-Dimensional electrophoresis were located and conducted mass analysis and protein identification. Results : Following results were obtained from the comparative analysis of serum proteins before and after the administration of wild ginseng herbal acupuncture. 1. 28 spots were identified before and after the administration. 2. In confirming manifestation degree, spots with more than two-times increase were 204, 803, 1505, 2205, 3105, 7104, 9001 spots, with more than one-time increase were 1101, 1302, 2013, 3009, 3010, 4002, 4009, 6706, 7103, 8006, 8101, and spots with decrease were 205, 801, 3205, 5202, 6105. 3. After conducting protein identification, proteins 205, 804, 1302, 4009, 6105, 6106 are unidentified yet, and 1101 is unnamed protein. Protein 204 is identified as complement receptor CR2-C3d, 801 as YAP1 protein, 803 as antitrypsin polymer, 1505 as PRO0684, 2013 and 3010 as proapolipoprotein, 2205 as USP48, 2403 as vitamin D binding protein, 3009 as complement component 4A preprotein, 3105 as immunoglobulin lambda chain, 3205 as transthyretin, 4002 as Ras-related protein Ral-A, 4204 as beta actin, 5202 and 7104 as apolipoprotein L1, 6704 as alpha 2 macroglobulin precursor, 7103 as complement component 3 precursor, 8006 as testis-specific protein Y, 8101 as transferrin, 9001 as (Alpha-Oxy, Beta-(C112gdeoxy T-State Human Hemoglobin, and 9003 as human hemoglobin. 4. Immune protein CR2-C3d, which acts against microbes and pathogenic organisms, and Antitrypsin(803, which is secreted with inflammatory response in the lungs, were increased by more than 200% after the administration of herbal acupuncture. 5

  3. 三维片上网络拓扑结构研究综述%Survey on Topologies of Three-Dimensional Network on Chip

    Institute of Scientific and Technical Information of China (English)

    张大坤; 宋国治; 王莲莲; 黄翠

    2015-01-01

    Three-dimensional network on chip (3D NoC) is developed based on three-dimensional integrated circuit (3D IC), system on chip (SoC) and two-dimensional network on chip (2D NoC). 3D NoC is mainly used to solve the problems such as communication bottleneck of highly integrated chips. It has attracted great attention from both aca-demia and industry at home and abroad. 3D NoC topology structure reflects the layout and connectivity of communi-cations node in the chip, which is crucial for the performance of 3D chip. This paper introduces 2D NoC, the evolu-tion from 2D NoC to 3D NoC, the advantages and problems of adopting 3D NoC and the key technical issues which can be solved by 3D NoC, and analyzes the overall development of 3D NoC. 3D topology is one of the key prob-lems in the design of 3D NoC. This paper mainly studies the different classification methods for 3D NoC topology and divides 3D NoC topologies into 9 categories in terms of communication, then gives a thorough study of 3D NoC topology structures with comparison and analysis of the characteristics for each topology structure. Finally, this paper indicates the possible future research development of 3D NoC topology.%三维片上网络(three-dimensional network on chip ,3D NoC)是在三维集成电路(three-dimensional integrated circuit,3D IC)、片上系统(system on chip,SoC)和二维片上网络(two-dimensional network on chip,2D NoC)的基础上发展起来的,主要解决高集成度芯片通信瓶颈等问题,已引起国内外学术界和产业界的高度重视。3D NoC拓扑结构体现了通信节点在芯片中的布局与连接,对三维芯片性能起决定性作用。简介了2D NoC、2D NoC到3D NoC的演变、3D NoC的优点与存在的问题以及3D NoC解决的关键技术问题,分析了3D NoC总体发展状况。三维拓扑结构是3D NoC设计中的关键问题之一,重点研究了3D NoC拓扑结构的分类方法,从通信角度将3D No

  4. Analysis of Serum Proteom after Intravenous Injection of cultivated wild ginseng pharmacopuncture

    Directory of Open Access Journals (Sweden)

    Dong-Hee,Lee

    2006-06-01

    Full Text Available Objectives : To observe the changes in the serum proteins after intravenous injection of cultivated wild ginseng pharmacopuncture. Methods : Blood was collected before and after the administration of cultivated wild ginseng pharmacopuncture and only the serum was taken. Then differences in the spots on the scanned image after carrying out 2-Dimensional electrophoresis were located and conducted mass analysis and protein identification. Results : Following results were obtained from the comparative analysis of serum proteins before and after the administration of cultivated wild ginseng pharmacopuncture. 1. 28 spots were identified before and after the administration. 2. In confirming manifestation degree, spots with more than two-times increase were 204, 1302, 2205, 3105, 7104, 8006, spots with more than one-time increase were 1101, 1505, 2013, 2403, 3009, 3010, 4002, 4009, 6704, 8101, and spots with decrease were 205, 801, 803, 3205, 5202, 6105, 6106, 7103, 9001, 9003. 3. After conducting protein identification, proteins 205, 804, 1302, 4009, 6105, 6106 are unidentified yet, and 1l01 is unnamed protein. Protein 204 is identified as complement receptor CR2-C3d, 801 as YAPl protein, 803 as antitrypsin polymer, 1505 as PRO0684, 2013 and 3010 as proapolipoprotein, 2205 as USP48, 2403 as vitamin D binding protein, 3009 as complement component 4A preprotein, 3105 as immunoglobulin lambda chain, 3205 as transthyretin, 4002 as Ras-related protein Ral-A, 4204 as beta actin, 5202 and 7104 as apolipoprotein Ll, 6704 as alpha 2 macroglobulin precursor, 7103 as complement component 3 precursor, 8006 as testis-specific protein Y, 8101 as transferrin, 9001 as (Alpha-Oxy, Beta-(Cl12gdeoxy T-State Human Hemoglobin, and 9003 as human hemoglobin. 4. Immune protein CR2-C3d(204, which acts against microbes and pathogenic organisms, was increased by more than two-times after the administration of pharmacopuncture. 5. Antitrypsin(803, which is secreted with

  5. Quantitative comparison of cancer and normal cell adhesion using organosilane monolayer templates: an experimental study on the anti-adhesion effect of green-tea catechins.

    Science.gov (United States)

    Sakamoto, Rumi; Kakinuma, Eisuke; Masuda, Kentaro; Takeuchi, Yuko; Ito, Kosaku; Iketaki, Kentaro; Matsuzaki, Takahisa; Nakabayashi, Seiichiro; Yoshikawa, Hiroshi Y; Yamamoto, Hideaki; Sato, Yuko; Tanii, Takashi

    2016-09-01

    The main constituent of green tea, (-)-Epigallocatechin-3-O-gallate (EGCG), is known to have cancer-specific chemopreventive effects. In the present work, we investigated how EGCG suppresses cell adhesion by comparing the adhesion of human pancreatic cancer cells (AsPC-1 and BxPC-3) and their counterpart, normal human embryonic pancreas-derived cells (1C3D3), in catechin-containing media using organosilane monolayer templates (OMTs). The purpose of this work is (1) to evaluate the quantitativeness in the measurement of cell adhesion with the OMT and (2) to show how green-tea catechins suppress cell adhesion in a cancer-specific manner. For the first purpose, the adhesion of cancer and normal cells was compared using the OMT. The cell adhesion in different type of catechins such as EGCG, (-)-Epicatechin-3-O-gallate (ECG) and (-)-Epicatechin (EC) was also evaluated. The measurements revealed that the anti-adhesion effect of green-tea catechins is cancer-specific, and the order is EGCG≫ECG>EC. The results agree well with the data reported to date, showing the quantitativeness of the new method. For the second purpose, the contact area of cells on the OMT was measured by reflection interference contrast microscopy. The cell-OMT contact area of cancer cells decreases with increasing EGCG concentration, whereas that of normal cells remains constant. The results reveal a twofold action of EGCG on cancer cell adhesion-suppressing cell attachment to a candidate adhesion site and decreasing the contact area of the cells-and validates the use of OMT as a tool for screening cancer cell adhesion.

  6. Hydrothermal synthesis and characterization of the first mixed alkali borate-nitrate K{sub 3}Na[B{sub 6}O{sub 9}(OH){sub 3}]NO{sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Ortner, Teresa S.; Wurst, Klaus [Institut für Allgemeine, Anorganische und Theoretische Chemie, Leopold-Franzens-Universität Innsbruck, Innrain 80-82, A-6020 Innsbruck (Austria); Perfler, Lukas; Tribus, Martina [Institut für Mineralogie und Petrographie, Leopold-Franzens-Universität Innsbruck, Innrain 52, A-6020 Innsbruck (Austria); Huppertz, Hubert, E-mail: Hubert.Huppertz@uibk.ac.at [Institut für Allgemeine, Anorganische und Theoretische Chemie, Leopold-Franzens-Universität Innsbruck, Innrain 80-82, A-6020 Innsbruck (Austria)

    2015-01-15

    The first mixed alkali borate-nitrate K{sub 3}Na[B{sub 6}O{sub 9}(OH){sub 3}]NO{sub 3} was synthesized under hydrothermal conditions from Na{sub 2}B{sub 4}O{sub 7}·10H{sub 2}O and K{sub 2}B{sub 4}O{sub 7}·4H{sub 2}O using KNO{sub 3} as a nitrate source. The compound crystallizes in the space group Pnnm (no. 58) with the lattice parameters a=1320.8(3), b=910.7(2), and c=1232.5(3) pm (Z=4). Isolated Sechserrings formed by BO{sub 4} and BO{sub 3} groups are linked through hydrogen bridges to form a three-dimensional network. - Graphical abstract: The first mixed alkali borate-nitrate K{sub 3}Na[B{sub 6}O{sub 9}(OH){sub 3}]NO{sub 3} was synthesized under hydrothermal conditions from Na{sub 2}B{sub 4}O{sub 7}·10H{sub 2}O and K{sub 2}B{sub 4}O{sub 7}·4H{sub 2}O using KNO{sub 3} as a nitrate source. - Highlights: • The first mixed alkali borate-nitrate K{sub 3}Na[B{sub 6}O{sub 9}(OH){sub 3}]NO{sub 3} is reported. • Hydrothermal conditions (240 °C, 3d) were used for the synthesis of K{sub 3}Na[B{sub 6}O{sub 9}(OH){sub 3}]NO{sub 3}. • Borate Sechserrings are interconnected through hydrogen-bonding.

  7. Using gray-based Taguchi method to construct multi-objective optimal model in super-resolution near-field photolithography.

    Science.gov (United States)

    Yang, Ching-Been; Chiang, Hsiu-Lu

    2013-01-01

    This study integrated thermally induced super-resolution into near-field photolithography and conducted simulation and analysis on line segment fabrication. This technique involves passing a laser beam through an aluminum-plated optical fiber probe onto a thin film of indium (approximately 10 nm thick). The indium film opens a melted aperture narrower than the width of the laser beam, creating a melted region and a crystalline region. The difference in penetration rate between the two regions leads to the generation of thermally induced super-resolution. This paper proposes a combination of Taguchi method with gray relational analysis, in which S/N ratios obtained using the Taguchi method are converted into gray relational grades to identify an optimal combination of parameters capable of meeting multiple quality objectives. This optimal combination includes a probe aperture of 100 nm (A1), exposure energy/μm of 0.002nJ/μm (B2), development time of 60 s (C3), and indium film with a thickness of 7 nm (D1). The optimal parameters were (A1B2C3D1) for the gray relational analysis and (A1B1C1D1) for the Taguchi method. Results showed a negative improvement of -14.3% in line width from 126.2 (Taguchi method) to 144.2 nm (gray relational analysis). Working depth, however, showed a significantly improvement of 140.4% from 5.7 (Taguchi method) to 13.7 nm (gray relational analysis). The proposed approach resolves the conflicts that commonly occur among factor levels in Taguchi analysis under the requirements of multiple quality requirements.

  8. Influence of time interval between surgery and radiotherapy on tumor regrowth

    Energy Technology Data Exchange (ETDEWEB)

    Cividalli, A.; Ceciarelli, F.; Tirindelli Danesi, D. [ENEA, Rome (Italy). Casaccia Research Center, Section of Toxicology and Biomedical Sciences; Creton, G. [Clinica Villa Flaminia, Rome (Italy). Dept. of Radiotheraphy; Stringari, L.; Benassi, M. [Regina Elena Cancer Institute, Rome (Italy). Division of Medical Physics

    2005-03-15

    In order to evaluate the influence of time intervals between tumor cell injection and radiotherapy on tumor control and regrowth after surgery, we performed two kinds of experiments on C3D2F1 mice bearing a mammary carcinoma inoculated in the foot or leg. 1. experiment: tumor in foot. End point: Tumor Control Probability (TCP). Single dose radiation treatments (RT) were administered at different period times from injection time of tumor cells (day 1). 1. group: unirradiated control, 2. group: RT on day 2 (TCP50 29{+-}2.1 Gy), 3. group: RT on day 7 (TCP 52.5{+-}2.9 Gy), 4. group: RT on day 12 (TCP50 61.9{+-}2.4 Gy). 2. experiment: tumor in leg. End point: percentage of tumor regrowth. Mice were randomly assigned to three groups: 1. control group (tumor growth in all mice), 2. surgical excision of macroscopically evident tumor on day 7-9 from injection (tumor regrowth in 85% of mice), 3. as the previous group plus 30 Gy radiation treatment within 24 hours from excision (tumor regrowth in 33% of cases). The radiation dose was selected on the basis of TCP50 observed in the 1. experiment for mice with sub-clinical disease. These data indicate that the radiation dose able to control 50% of tumors increases with the time interval between tumor cells injection and RT. A short time interval between surgery and RT should increase the probability of local control, supporting the rationale of intraoperative radiation therapy (IORT) as adjuvant therapy after surgical resection, when subclinical residual cells are suspected.

  9. Lateral Pressure of RC Silos with Static and Dynamic Granular Materials

    Institute of Scientific and Technical Information of China (English)

    Lingkai Meng

    2015-01-01

    This paper aims at analyzing material⁃induced lateral pressure of RC cylinder silo in both static and dynamic condition using the finite element method (FEM).In the finite element software ABAQUS, concrete material is modeled by concrete damaged plasticity model, and stored materials in silo is modeled by the hypoplastic theory.In terms of numerical model, shell elements (S4R) and solid elements (C3D8) are applied for model silo wall and stored materials respectively. The interaction between silo wall and stored materials is simulated by Coulomb friction model and penalty contact constrain provided by ABAQUS.The numerical results are verified with the existing experimental data that are designed to ensure the validation of such numerical model using FEM and it obtains good agreements between numerical results and experimental data. Then the material parameters are analyzed in both static and dynamic condition.According to the analysis, it is clear that critical friction angle, initial void ratio and minimum void ratio have an obvious effect on static lateral pressure while all the material parameters affect dynamic lateral pressure at different levels. In addition, differences of silo wall between elastic and plastic state are analyzed in dynamic condition. The numerical results show that it contributes to increasing dynamic pressure when silo wall enters into the plastic state. Finally, this paper discusses the time⁃history lateral pressure at different heights along silo wall, and analytical results indicate that larger acceleration values play main roles in producing the maximum lateral pressure at higher part of the silo wall.

  10. Discovery and evaluation of asymmetrical monocarbonyl analogs of curcumin as anti-inflammatory agents

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2014-04-01

    Full Text Available Yali Zhang,1,2,* Chengguang Zhao,1,2,* Wenfei He,2,* Zhe Wang,2 Qilu Fang,2 Bing Xiao,2 Zhiguo Liu,2 Guang Liang,2 Shulin Yang1 1School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu, People's Republic of China; 2Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, University Town, Wenzhou, Zhejiang, People's Republic of China *These authors contributed equally to this work Abstract: Sepsis is a systemic inflammatory response syndrome and is mainly caused by lipopolysaccharides (LPS – a component of the cell walls of gram-negative bacteria, via toll-like receptor 4–mitogen-activated protein kinases/nuclear factor-kappa B-dependent proinflammatory signaling pathway. Here, we synthesized 26 asymmetric monocarbonyl analogs of curcumin and evaluated their anti-inflammatory activity by inhibiting the LPS-induced secretion of tumor necrosis factor-α and interleukin-6 in mouse RAW264.7 macrophages. Five active compounds (3a, 3c, 3d, 3j, and 3l exhibited dose-dependent inhibition against the release of tumor necrosis factor-α and interleukin-6, and they also showed much higher chemical stability than curcumin in vitro. The anti-inflammatory activity of analogs 3a and 3c may be associated with their inhibition of the phosphorylation of extracellular signal-regulated kinase and the activation of nuclear factor-kappa B. In addition, 3c exhibited significant protection against LPS-induced septic death in vivo. These results indicate that asymmetrical monocarbonyl curcumin analogs may be utilized as candidates for the treatment of acute inflammatory diseases. Keywords: sepsis, inflammatory cytokines, anti-inflammation, quantitative structure–activity relationship

  11. Role of complement receptor 1 (CR1; CD35) on epithelial cells: A model for understanding complement-mediated damage in the kidney.

    Science.gov (United States)

    Java, Anuja; Liszewski, M Kathryn; Hourcade, Dennis E; Zhang, Fan; Atkinson, John P

    2015-10-01

    The regulators of complement activation gene cluster encodes a group of proteins that have evolved to control the amplification of complement at the critical step of C3 activation. Complement receptor 1 (CR1) is the most versatile of these inhibitors with both receptor and regulatory functions. While expressed on most peripheral blood cells, the only epithelial site of expression in the kidney is by the podocyte. Its expression by this cell population has aroused considerable speculation as to its biologic function in view of many complement-mediated renal diseases. The goal of this investigation was to assess the role of CR1 on epithelial cells. To this end, we utilized a Chinese hamster ovary cell model system. Among our findings, CR1 reduced C3b deposition by ∼ 80% during classical pathway activation; however, it was an even more potent regulator (>95% reduction in C3b deposition) of the alternative pathway. This inhibition was primarily mediated by decay accelerating activity. The deposited C4b and C3b were progressively cleaved with a t½ of ∼ 30 min to C4d and C3d, respectively, by CR1-dependent cofactor activity. CR1 functioned intrinsically (i.e, worked only on the cell on which it was expressed). Moreover, CR1 efficiently and stably bound but didn't internalize C4b/C3b opsonized immune complexes. Our studies underscore the potential importance of CR1 on an epithelial cell population as both an intrinsic complement regulator and an immune adherence receptor. These results provide a framework for understanding how loss of CR1 expression on podocytes may contribute to complement-mediated damage in the kidney.

  12. Development and validation of an Eulerian model towards the simulation of fuel injection in internal combustion engines; Developpement et validation d'un modele eulerien en vue de la simulation des jets de carburants dans les moteurs a combustion interne

    Energy Technology Data Exchange (ETDEWEB)

    Truchot, B.

    2005-12-15

    The objective of this work is to develop an Eulerian two phase model to improve the prediction of fuel injection in internal combustion engines, particularly the dense liquid zone close to the nozzle. Lagrangian models, usually used in engine simulations, are based on the assumption of dispersed two phase flows with low liquid volume fraction, which is not fulfilled in the case of direct injection engine technology. Different Eulerian approaches are available in the literature. Physical phenomena that occur near the nozzle and characteristics of each model lead to the choice of a two fluids two pressures model. Several open terms appear in the equations of the model: exchange between the two phases and turbulent correlations. Closures of exchange terms are based on the spherical droplets hypothesis while a RANS approach is adopted to close turbulent correlations. This model has been integrated in the IFP CFD code, IFP-C3D. Several numerical tests and analytical validations (for single and two phase flows) have been then carried out in order to check the correct implementation of equations and the predictivity of the model and closures. Modifications in the turbulent model of the gas have required validations in both the gas phase (flow behind a sudden enlargement) and the liquid phase (pure liquid injection). A two phase mixing layer has been then used to validate the whole model. Finally, injection tests have been achieved under realistic conditions (similar to those encountered in automotive engines) in order to check the feasibility of engine computations using the developed Eulerian approach. These tests have also allowed to check the compatibility of this approach with the specificities of engine simulations (especially mesh movement). (author)

  13. Maternal antibodies: clinical significance, mechanism of interference with immune responses, and possible vaccination strategies

    Directory of Open Access Journals (Sweden)

    Stefan eNiewiesk

    2014-09-01

    Full Text Available Neonates have an immature immune system which cannot adequately protect against infectious diseases. Early in life, immune protection is accomplished by maternal antibodies transferred from mother to offspring. However, decaying maternal antibodies inhibit vaccination as is examplified by the inhibition of seroconversion after measles vaccination. This phenomenon has been described in both human and veterinary medicine and is independent of the type of vaccine being used. This review will discuss the use of animal models for vaccine research. I will review clinical solutions for inhibition of vaccination by maternal antibodies, and the testing and development of potentially effective vaccines. These are based on new mechanistic insight about the inhibitory mechanism of maternal antibodies. Maternal antibodies inhibit the generation of antibodies whereas the T cell response is usually unaffected. B cell inhibition is mediated through a cross-link between B-cell receptor (BCR with the Fcg receptor IIB (FcgRIIB by a vaccine-antibody complex. In animal experiments, this inhibition can be partially overcome by injection of a vaccine-specific monoclonal IgM antibody. IgM stimulates the B-cell directly through cross-linking the BCR via complement protein C3d and antigen to the complement receptor 2 (CR2 signaling complex. In addition, it was shown that interferon alpha binds to the CD21 chain of CR2 as well as the interferon receptor and that this dual receptor usage drives B cell responses in the presence of maternal antibodies. In lieu of immunizing the infant the concept of maternal immunization as a strategy to protect neonates has been proposed. This approach would still not solve the question of how to immunize in the presence of maternal antibodies but would defer the time of infection to an age where infection might not have such a detrimental outcome as in neonates. I will review successful examples and potential challenges of implementing

  14. Genetics and evolution of the Salmonella galactose-initiated set of o antigens.

    Directory of Open Access Journals (Sweden)

    Peter R Reeves

    Full Text Available This paper covers eight Salmonella serogroups, that are defined by O antigens with related structures and gene clusters. They include the serovars that are now most frequently isolated. Serogroups A, B1, B2, C2-C3, D1, D2, D3 and E have O antigens that are distinguished by having galactose as first sugar, and not N-acetyl glucosamine or N-acetyl galactosamine as in the other 38 serogroups, and indeed in most Enterobacteriaceae. The gene clusters for these galactose-initiated appear to have entered S. enterica since its divergence from E. coli, but sequence comparisons show that much of the diversification occurred long before this. We conclude that the gene clusters must have entered S. enterica in a series of parallel events. The individual gene clusters are discussed, followed by analysis of the divergence for those genes shared by two or more gene clusters, and a putative phylogenic tree for the gene clusters is presented. This set of O antigens provides a rare case where it is possible to examine in detail the relationships of a significant number of O antigens. In contrast the more common pattern of O-antigen diversity within a species is for there to be only a few cases of strains having related gene clusters, suggesting that diversity arose through gain of individual O-antigen gene clusters by lateral gene transfer, and under these circumstances the evolution of the diversity is not accessible. This paper on the galactose-initiated set of gene clusters gives new insights into the origins of O-antigen diversity generally.

  15. Fisetin extraction process of cotinus coggygria's active ingredients%黄栌有效成分漆黄素提取工艺研究

    Institute of Scientific and Technical Information of China (English)

    李建华; 段丹丹; 马聪玲

    2012-01-01

    Objective: To select out the optimal extraction process of fisetin of cotinus coggygria. Methods: We adopted a single factor and L, (34) orthogonal experimental design method. The index was the content of fisetin in cotinus coggygria. We took four factors (extraction solvent, extraction time, solvent pH, solvent volume), three levels, preferred extraction process of fisetin. Results: The optimum extraction was A2B,C]D3 which used 65% and 25 times amount of ethanol at pH9 as extraction solvent, and extracted 2 times, 90min each time. Conclusion: The optimized extraction process is stable and feasible, with good reproducibility, high extraction rate (1.03%), provided a reference for further exploitation of the medicinal resources of the cotinus coggygria.%目的:筛选黄栌中有效成分漆黄素最佳提取工艺的研究.方法:采用单因素考察和L9(34)正交试验设计法,以黄栌中漆黄素的含量为考察指标,取4因素(提取溶媒、提取时间、溶媒pH、溶媒量)3水平,优选漆黄素提取工艺.结果:最佳提取工艺为A2B3C3D3,即以65%、25倍药材量的乙醇为提取溶媒,调pH9,每次90min以提取2次为宜.结论:该提取工艺设计合理、可行,工艺稳定,重现性好,提取率高( 1.03%),为进一步开发利用黄栌药用资源提供指导.

  16. Identification of Eight Different Isoforms of the Glucocorticoid Receptor in Guinea Pig Placenta: Relationship to Preterm Delivery, Sex and Betamethasone Exposure.

    Directory of Open Access Journals (Sweden)

    Zarqa Saif

    Full Text Available The placental glucocorticoid receptor (GR is central to glucocorticoid signalling and for mediating steroid effects on pathways associated with fetal growth and lung maturation but the GR has not been examined in the guinea pig placenta even though this animal is regularly used as a model of preterm birth and excess glucocorticoid exposure. Guinea pig dams received subcutaneous injections of either vehicle or betamethasone at 24 and 12 hours prior to preterm or term caesarean-section delivery. At delivery pup and organ weights were recorded. Placentae were dissected, weighed and analysed using Western blot to examine GR isoform expression in nuclear and cytoplasmic extracts. A comparative examination of the guinea pig GR gene identified it is capable of producing seven of the eight translational GR isoforms which include GRα-A, C1, C2, C3, D1, D2, and D3. GRα-B is not produced in the Guinea Pig. Total GR antibody identified 10 specific bands from term (n = 29 and preterm pregnancies (n = 27. Known isoforms included GRγ, GRα A, GRβ, GRP, GRA and GRα D1-3. There were sex and gestational age differences in placental GR isoform expression. Placental GRα A was detected in the cytoplasm of all groups but was significantly increased in the cytoplasm and nucleus of preterm males and females exposed to betamethasone and untreated term males (KW-ANOVA, P = 0.0001, P = 0.001. Cytoplasmic expression of GRβ was increased in female preterm placentae and preterm and term male placentae exposed to betamethasone (P = 0.01. Nuclear expression of GRβ was increased in all placentae exposed to betamethasone (P = 0.0001. GRα D2 and GRα D3 were increased in male preterm placentae when exposed to betamethasone (P = 0.01, P = 0.02. The current data suggests the sex-specific placental response to maternal betamethasone may be dependent on the expression of a combination of GR isoforms.

  17. Molecular analysis of three Ljungan virus isolates reveals a new, close-to-root lineage of the Picornaviridae with a cluster of two unrelated 2A proteins.

    Science.gov (United States)

    Johansson, Susanne; Niklasson, Bo; Maizel, Jacob; Gorbalenya, Alexander E; Lindberg, A Michael

    2002-09-01

    Ljungan virus (LV) is a suspected human pathogen recently isolated from bank voles (Clethrionomys glareolus). In the present study, it is revealed through comparative sequence analysis that three newly determined Swedish LV genomes are closely related and possess a deviant picornavirus-like organization: 5' untranslated region-VP0-VP3-VP1-2A1-2A2-2B-2C-3A-3B-3C-3D-3' untranslated region. The LV genomes and the polyproteins encoded by them exhibit several exceptional features, such as the absence of a predicted maturation cleavage of VP0, a conserved sequence determinant in VP0 that is typically found in VP1 of other picornaviruses, and a cluster of two unrelated 2A proteins. The 2A1 protein is related to the 2A protein of cardio-, erbo-, tescho-, and aphthoviruses, and the 2A2 protein is related to the 2A protein of parechoviruses, kobuviruses, and avian encephalomyelitis virus. The unprecedented association of two structurally different 2A proteins is a feature never previously observed among picornaviruses and implies that their functions are not mutually exclusive. Secondary polyprotein processing of the LV polyprotein is mediated by proteinase 3C (3C(pro)) possessing canonical affinity to Glu and Gln at the P1 position and small amino acid residues at the P1' position. In addition, LV 3C(pro) appears to have unique substrate specificity to Asn, Gln, and Asp and to bulky hydrophobic residues at the P2 and P4 positions, respectively. Phylogenetic analysis suggests that LVs form a separate division, which, together with the Parechovirus genus, has branched off the picornavirus tree most closely to its root. The presence of two 2A proteins indicates that some contemporary picornaviruses with a single 2A may have evolved from the ancestral multi-2A picornavirus.

  18. Classical Complement Pathway Activation in the Kidneys of Women With Preeclampsia.

    Science.gov (United States)

    Penning, Marlies; Chua, Jamie S; van Kooten, Cees; Zandbergen, Malu; Buurma, Aletta; Schutte, Joke; Bruijn, Jan Anthonie; Khankin, Eliyahu V; Bloemenkamp, Kitty; Karumanchi, S Ananth; Baelde, Hans

    2015-07-01

    A growing body of evidence suggests that complement dysregulation plays a role in the pathogenesis of preeclampsia. The kidney is one of the major organs affected in preeclampsia. Because the kidney is highly susceptible to complement activation, we hypothesized that preeclampsia is associated with renal complement activation. We performed a nationwide search for renal autopsy material in the Netherlands using a computerized database (PALGA). Renal tissue was obtained from 11 women with preeclampsia, 25 pregnant controls, and 14 nonpregnant controls with hypertension. The samples were immunostained for C4d, C1q, mannose-binding lectin, properdin, C3d, C5b-9, IgA, IgG, and IgM. Preeclampsia was significantly associated with renal C4d-a stable marker of complement activation-and the classical pathway marker C1q. In addition, the prevalence of IgM was significantly higher in the kidneys of the preeclamptic women. No other complement markers studied differed between the groups. Our findings in human samples were validated using a soluble fms-like tyrosine kinase 1 mouse model of preeclampsia. The kidneys in the soluble fms-like tyrosine kinase 1-injected mice had significantly more C4 deposits than the control mice. The association between preeclampsia and renal C4d, C1q, and IgM levels suggests that the classical complement pathway is involved in the renal injury in preeclampsia. Moreover, our finding that soluble fms-like tyrosine kinase 1-injected mice develop excess C4 deposits indicates that angiogenic dysregulation may play a role in complement activation within the kidney. We suggest that inhibiting complement activation may be beneficial for preventing the renal manifestations of preeclampsia.

  19. Effects of Different Culture Substrates on Seedling Growth of the Ocimum basilicum var basilicum%不同基质配方对盆栽罗勒生长的影响

    Institute of Scientific and Technical Information of China (English)

    田小霞; 毛培春; 孟林

    2012-01-01

    通过4因素3水平正交试验,设计9种不同基质处理,另增设纯土为对照,研究不同基质配方对盆栽罗勒(Ocimum basilicum var basilicum)萌发与生长的影响.结果表明,与纯土盆栽比较,9种配方基质对罗勒盆栽苗的生长均有明显的促进作用.不同基质条件下罗勒生长量变化趋势基本保持一致,但对出苗率、株高和根系指标的生长影响不同,对出苗率和株高来说,S1基质最好;对于根系总长度和总表面积来说,S7基质最好;且均显著高于对照.通过极差方差分析和回归分析得出最适合盆栽罗勒生长的基质为A3B1C3D1,即V(草炭):V(纯土):V(珍珠岩):V(蛭石)=3:1:3:1.对于根冠比来说,A为主要影响因素,其次为B因素;对于根系总长度来说,B为主要影响因素,其次是C和D因素.

  20. The dual role of complement in the progression of renal disease in NZB/W F(1) mice and alternative pathway inhibition.

    Science.gov (United States)

    Sekine, Hideharu; Ruiz, Phillip; Gilkeson, Gary S; Tomlinson, Stephen

    2011-10-01

    Complement plays a dual role in the progression of systemic lupus erythematosus since it has important protective functions, such as the clearance of immune complexes and apoptotic cells, but is also a mediator of renal inflammation. To investigate this balance in a clinically relevant setting, we investigated how targeted inhibition of all complement pathways vs. targeted inhibition of only the alternative pathway impacts immune and therapeutic outcomes in NZB/W F(1) mice. Following onset of proteinuria, mice were injected twice weekly with CR2-fH (inhibits alternative pathway), CR2-Crry (inhibits all pathways at C3 activation step), sCR2 (C3d targeting vehicle) or saline. Sera were analyzed every 2 weeks for anti-dsDNA antibody levels, and urinary albumin excretion was determined. Kidneys were collected for histological evaluation at 32 weeks. Compared to the control group, all CR2-fH, CR2-Crry and sCR2 treated groups showed significantly reduced serum anti-dsDNA antibody levels and strong trends towards reduced glomerular IgG deposition levels. Glomerular C3 deposition levels were also significantly reduced in all three-treated groups. However, significant reductions of disease activity (albuminuria and glomerulonephritis) were only seen in the CR2-fH treated group. These data highlight the dual role played by complement in the pathogenesis of lupus, and demonstrate a benefit of selectively inhibiting the alternative complement pathway, presumably because of protective contributions from the classical and/or lectin pathways. The sCR2 targeting moiety appears to be contributing to therapeutic outcome via modulation of autoimmunity. Furthermore, these results are largely consistent with our previous data using the MRL/lpr lupus model, thus broadening the significance of these findings.

  1. Isolating the Epstein-Barr virus gp350/220 binding site on complement receptor type 2 (CR2/CD21).

    Science.gov (United States)

    Young, Kendra A; Chen, Xiaojiang S; Holers, V Michael; Hannan, Jonathan P

    2007-12-14

    Complement receptor type 2 (CR2/CD21) is essential for the attachment of Epstein-Barr virus (EBV) to the surface of B-lymphocytes in an interaction mediated by the viral envelope glycoprotein gp350. The heavily glycosylated structure of EBV gp350 has recently been elucidated by x-ray crystallography, and the CR2 binding site on this protein has been characterized. To identify the corresponding gp350 binding site on CR2, we have undertaken a site-directed mutagenesis study targeting regions of CR2 that have previously been implicated in the binding of CR2 to the C3d/C3dg fragments of complement component C3. Wild-type or mutant forms of CR2 were expressed on K562 cells, and the ability of these CR2-expressing cells to bind gp350 was measured using flow cytometry. Mutations directed toward the two N-terminal extracellular domains of CR2 (SCR1-2) reveal that a large contiguous surface of CR2 SCR1-2 is involved in gp350 binding, including a number of positively charged residues (Arg-13, (Arg-28, (Arg-36, Lys-41, Lys-57, Lys-67, and Arg-83). These data appear to complement the CR2 binding site on gp350, which is characterized by a preponderance of negative charge. In addition to identifying the importance of charge in the formation of a CR2-gp350 complex, we also provide evidence that both SCR1 and SCR2 make contact with gp350. Specifically, two anti-CR2 monoclonal antibodies, designated as monoclonal antibodies 171 and 1048 whose primary epitopes are located within SCR2, inhibit binding of wild-type CR2 to EBV gp350; with regard to SCR1, both K562 cells expressing an S15P mutation and recombinant S15P CR2 proteins exhibit diminished gp350 binding.

  2. Efficacy of Targeted Complement Inhibition in Experimental C3 Glomerulopathy

    Science.gov (United States)

    Ruseva, Marieta M.; Peng, Tao; Lasaro, Melissa A.; Bouchard, Keith; Liu-Chen, Susan; Sun, Fang; Yu, Zhao-Xue; Marozsan, Andre; Wang, Yi

    2016-01-01

    C3 glomerulopathy refers to renal disorders characterized by abnormal accumulation of C3 within the kidney, commonly along the glomerular basement membrane (GBM). C3 glomerulopathy is associated with complement alternative pathway dysregulation, which includes functional defects in complement regulator factor H (FH). There is no effective treatment for C3 glomerulopathy. We investigated the efficacy of a recombinant mouse protein composed of domains from complement receptor 2 (CR2) and FH (CR2-FH) in two models of C3 glomerulopathy with either preexisting or triggered C3 deposition along the GBM. FH-deficient mice spontaneously develop renal pathology associated with abnormal C3 accumulation along the GBM and secondary plasma C3 deficiency. CR2-FH partially restored plasma C3 levels in FH-deficient mice 2 hours after intravenous injection. CR2-FH specifically targeted glomerular C3 deposits, reduced the linear C3 reactivity assessed with anti-C3 and anti-C3b/iC3b/C3c antibodies, and prevented further spontaneous accumulation of C3 fragments along the GBM. Reduction in glomerular C3d and C9/C5b-9 reactivity was observed after daily administration of CR2-FH for 1 week. In a second mouse model with combined deficiency of FH and complement factor I, CR2-FH prevented de novo C3 deposition along the GBM. These data show that CR2-FH protects the GBM from both spontaneous and triggered C3 deposition in vivo and indicate that this approach should be tested in C3 glomerulopathy. PMID:26047789

  3. Optimization of temperature and time for drying and carbonization to increase calorific value of coconut shell using Taguchi method

    Science.gov (United States)

    Musabbikhah, Saptoadi, H.; Subarmono, Wibisono, M. A.

    2016-03-01

    Fossil fuel still dominates the needs of energy in Indonesia for the past few years. The increasing scarcity of oil and gas from non-renewable materials results in an energy crisis. This condition turns to be a serious problem for society which demands immediate solution. One effort which can be taken to overcome this problem is the utilization and processing of biomass as renewable energy by means of carbonization. Thus, it can be used as qualified raw material for production of briquette. In this research, coconut shell is used as carbonized waste. The research aims at improving the quality of coconut shell as the material for making briquettes as cheap and eco-friendly renewable energy. At the end, it is expected to decrease dependence on oil and gas. The research variables are drying temperature and time, carbonization time and temperature. The dependent variable is calorific value of the coconut shell. The method used in this research is Taguchi Method. The result of the research shows thus variables, have a significant contribution on the increase of coconut shell's calorific value. It is proven that the higher thus variables are higher calorific value. Before carbonization, the average calorific value of coconut shell reaches 4,667 call/g, and a significant increase is notable after the carbonization. The optimization is parameter setting of A2B3C3D3, which means that the drying temperature is 105 °C, the drying time is 24 hours, the carbonization temperature is 650 °C and carbonization time is 120 minutes. The average calorific value is approximately 7,744 cal/g. Therefore, the increase of the coconut shell's calorific value after the carbonization is 3,077 cal/g or approximately 60 %. The charcoal of carbonized coconut shell has met the requirement of SNI, thus it can be used as raw material in making briquette which can eventually be used as cheap and environmental friendly fuel.

  4. Molecular Characterization and SYBR Green Ⅰ-Based Quantitative PCR for Duck Hepatitis Virus Type 1

    Institute of Scientific and Technical Information of China (English)

    LUO Yu-jun; ZHANG Gui-hong; XU Xiao-qin; CHEN Jian-hong; LIAO Ming

    2008-01-01

    To determine the genomic sequence of a duck hepatitis virus type 1 (DHV-1) strain,real-time quantitative polyrnerase chain reaction (RTQ-PCR) assay based on SYBR Green Ⅰ technology was developed to target 3D gene of DHV-1.Comparative sequence analysis showed that the genome has a typical picornarivus genetic organization,and strain DHV-1 R genetic organaiztion is 5' untranslated region (UTR)-VPO-VP3-VP1-2A1-2A2-2B-2C-3A-3B-3C-3D-3' UTR,DHV-1 R has close relationship with Parechovirus,and has 95.1-99.1% nucleotide sequence identity with other DHV-1 strains.Based on the DHV-1 sequences in GenBank,three pairs of specific primers were designed to amplify DHV-1 using real-time PCR.The results showed that real-time PCR Tm value is 85.6℃ and the real-time PCR provides a broad dynamic range,detecting from 102 to 109 copies of DHV-1 cDNA per reaction.No cross-reactions were found in specimens containing DPV,AIV and NDV.It is concluded that DHV-1 belongs to a new group of the family Picornaviridae that may form a separate genus most closely related to the genus Parechovirus.All results showed that the real-time PCR has high sensitivity and specificity to detect DHV-1 using SYBR Green Ⅰ dissociation curve analysis,isolates can be distinguished by their melting temperature.These methods are rapid,sensitive,and reliable,and can be readily adapted for detection of DHV-1 from other clinical samples.

  5. Identification and complete genome analysis of a novel bovine picornavirus in Japan.

    Science.gov (United States)

    Nagai, Makoto; Omatsu, Tsutomu; Aoki, Hiroshi; Kaku, Yoshihiro; Belsham, Graham J; Haga, Kei; Naoi, Yuki; Sano, Kaori; Umetsu, Moeko; Shiokawa, Mai; Tsuchiaka, Shinobu; Furuya, Tetsuya; Okazaki, Sachiko; Katayama, Yukie; Oba, Mami; Shirai, Junsuke; Katayama, Kazuhiko; Mizutani, Tetsuya

    2015-12-02

    We identified novel viruses in feces from cattle with diarrhea collected in 2009 in Hokkaido Prefecture, Japan, by using a metagenomics approach and determined the (near) complete sequences of the virus. Sequence analyses revealed that they had a standard picornavirus genome organization, i.e. 5' untranslated region (UTR) - L- P1 (VP4- VP3- VP2- VP1) - P2 (2A- 2B- 2C) - P3 (3A- 3B- 3C-3D) - 3'UTR- poly(A). They are closely related to other unclassified Chinese picornaviruses; bat picornaviruses group 1-3, feline picornavirus, and canine picornavirus, sharing 45.4-51.4% (P1), 38.0-44.9% (P2), and 49.6-53.3% (P3) amino acid identities, respectively. The phylogenetic analyses and detailed genome characterization showed that they, together with the unclassified Chinese picornaviruses, grouped as a cluster for the P1, 2C, 3CD and VP1 coding regions. These viruses had conserved features (e.g. predicted protein cleavage sites, presence of a leader protein, 2A, 2C, 3C, and 3D functional domains), suggesting they have a common ancestor. Reverse-transcription-PCR assays, using specific primers designed from the 5'UTR sequence of these viruses, showed that 23.0% (20/87) of fecal samples from cattle with diarrhea were positive, indicating the prevalence of these picornavirus in the Japanese cattle population in Hokkaido Prefecture. However, further studies are needed to investigate the pathogenic potential and etiological role of these viruses in cattle.

  6. Alternative complement pathway deficiency ameliorates chronic smoke-induced functional and morphological ocular injury.

    Directory of Open Access Journals (Sweden)

    Alex Woodell

    Full Text Available BACKGROUND: Age-related macular degeneration (AMD, a complex disease involving genetic variants and environmental insults, is among the leading causes of blindness in Western populations. Genetic and histologic evidence implicate the complement system in AMD pathogenesis; and smoking is the major environmental risk factor associated with increased disease risk. Although previous studies have demonstrated that cigarette smoke exposure (CE causes retinal pigment epithelium (RPE defects in mice, and smoking leads to complement activation in patients, it is unknown whether complement activation is causative in the development of CE pathology; and if so, which complement pathway is required. METHODS: Mice were exposed to cigarette smoke or clean, filtered air for 6 months. The effects of CE were analyzed in wildtype (WT mice or mice without a functional complement alternative pathway (AP; CFB(-/- using molecular, histological, electrophysiological, and behavioral outcomes. RESULTS: CE in WT mice exhibited a significant reduction in function of both rods and cones as determined by electroretinography and contrast sensitivity measurements, concomitant with a thinning of the nuclear layers as measured by SD-OCT imaging and histology. Gene expression analyses suggested that alterations in both photoreceptors and RPE/choroid might contribute to the observed loss of function, and visualization of complement C3d deposition implies the RPE/Bruch's membrane (BrM complex as the target of AP activity. RPE/BrM alterations include an increase in mitochondrial size concomitant with an apical shift in mitochondrial distribution within the RPE and a thickening of BrM. CFB(-/- mice were protected from developing these CE-mediated alterations. CONCLUSIONS: Taken together, these findings provide clear evidence that ocular pathology generated in CE mice is dependent on complement activation and requires the AP. Identifying animal models with RPE/BrM damage and verifying

  7. 鼠李糖乳杆菌GG(LGG)高密度培养基优化%Optimization of Lactobacillus rhamnosus GG (LGG) high-density medium

    Institute of Scientific and Technical Information of China (English)

    王智鼎; 刘艳秋; 李岳飞; 孙德军

    2013-01-01

    鼠李糖乳杆菌GG是国家认可的第3代益生菌的一种,因其可在肠道定植并且有耐酸碱等特性而得到广泛应用.实验希望优化其培养基,使鼠李糖乳杆菌GG能用较低的成本来进行高密度培养.首先以MRS培养基为基础,根据物种特性进行碳源(麦芽糖∶葡萄糖∶乳糖∶蔗糖)、氮源(胰蛋白胨∶牛肉膏∶酵母粉)和增菌物质(黄瓜汁∶西红柿汁)的成分分别调整,之后进行单因素分析.在相同的条件下,经过37℃厌氧、恒温培养16 h后,测OD600来比较增菌效果.实验发现胰蛋白胨、酵母粉、葡萄糖、西红柿汁这4种物质增菌明显.在以上述4种物质设计4因素3水平L9(34)的正交分析,结果为鼠李糖乳杆菌GG影响性西红柿汁>胰蛋白胨>葡萄糖>酵母粉,其中最佳配比方案为A3B1C3D 2 (2.5%胰蛋白胨+1.5%酵母粉+2.5%葡萄糖+20%西红柿汁).在优化配方下鼠李糖乳杆菌GG可达9.4×109 cfu/mL.

  8. Solución adyuvante CM-95 tratada magnéticamente en comparación con el adyuvante de Freund para la obtención del suero de Coombs en conejo

    Directory of Open Access Journals (Sweden)

    Clara Martínez

    2009-12-01

    Full Text Available En este trabajo se evaluó la aplicación de la solución CM-95 tratada magnéticamente como adyuvante inmunológico, en comparación con el adyuvante de Freund, para la obtención del suero de Coombs en conejos, de gran demanda en bancos de sangre y hospitales, para el diagnóstico clínico de conflictos Rh y la enfermedad hemolítica del recién nacido, entre otras. Conejos Nueva Zelanda Blancos se inocularon por la vía subcutánea con suero humano obtenido de 30 donantes O+, unido con la solución CM-95 tratada magnéticamente como adyuvante inmunológico. Se empleó un esquema de inmunización de 40 días, donde se evaluó la dinámica en el título de anticuerpos anti IgG humano por la técnica de hemoaglutinación en tubos. Al antisuero se le determinó la calidad inmunológica por el título de heteroaglutininas de los grupos sanguíneos A, B y O, de anticuerpos anticomplemento C3b, C3d y C4b y anti IgG, antes y después de su purificación. El suero de Coombs con la solución adyuvante CM-95 tratada magnéticamente mostró valores similares a los obtenidos con el adyuvante de Freund. En el mismo se cumplió con los requisitos establecidos por el Centro Estatal para el Control de la Calidad de los Medicamentos, según las normativas de la FDA para este diagnosticador. Estos resultados abren nuevas perspectivas para el uso de la solución adyuvante en la obtención del suero de Coombs.

  9. Synthesis and antitumor activity of camptothecin-20-O-β-aminopropionates%喜树碱20-O-β-胺基丙酸酯类衍生物的合成及抗肿瘤活性

    Institute of Scientific and Technical Information of China (English)

    李玉艳; 尤启冬; 陈晟; 王磊; 陈晓光; 李燕; 李洪燕

    2009-01-01

    目的:研究Topo Ⅰ抑制剂喜树碱β-胺基酸酯类衍生物的合成、抗肿瘤活性和血液稳定性,寻找高效低毒的肿瘤治疗药物.方法:通过喜树碱、9-硝基喜树碱和7-乙基喜树碱的20位羟基与丙烯酰氯反应得化合物1a~3a,然后与仲胺进行Michael加成,产物与盐酸成盐分别制得目标化合物1b~1e,2b~2e,3b~3e.采用MTT法对上述化合物进行4个瘤株KB,HT-29,HCT-8,Bel 7402的抗肿瘤活性测定.以化合物1b和1e为代表检测了目标化合物在人血液中的稳定性.结果:合成了12个新的化合物,其结构经IR、1H NMR、MS等确证.所有目标化合物都有较好的抗肿瘤活性,其中7个化合物1b,3b,1c,3c,3d,2e和3e的抗肿瘤活性强于羟基喜树碱,化合物1c,3b和3d的抗肿瘤活性与喜树碱相当.与喜树碱相比,化合物1b和1e的血液稳定性从5.2%增加到66.6%和55.1%.结论:Topo Ⅰ抑制剂喜树碱β-氨基酸酯类衍生物有较好的抗肿瘤活性,20位成酯增加在血液中的稳定性,且有利于降低毒性.化合物1c,3b和3d的活性较强,值得进一步研究.

  10. IMMUNOHISTOCHEMISTRY VERSUS IMMUNOFLUORESENCE IN THE DIAGNOSIS OF AUTOIMMUNE BLISTERING DISEASES

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2013-11-01

    Full Text Available Introduction: In patients with autoimmune skin blistering diseases (ABDs, the diagnostic gold standard has classically been direct and indirect immunofluorescence (DIF and IIF, despite inherent technical problems of autofluorescence. Aim: We sought to overcome autofluorescence issues and compare the reliability of immunofluorescence versus immunohistochemistry (IHC staining in the diagnoses of these diseases. Methods: We tested via IHC for anti-human IgG, IgM, IgA, IgD, IgE, Kappa light chains, Lambda light chains, Complement/C3c, Complement/C1q, Complement/C3d, albumin and fibrinogen in 30 patients affected by a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre-EPF, and 30 control biopsies from the endemic area. We also tested archival biopsies from patients with ABDs whose diagnoses were made clinically, histopathologically and by DIF/IIF studies from 2 independent dermatopathology laboratories in the USA. Specifically, we tested 34 patients with bullous pemphigoid (BP, 18 with pemphigus vulgaris (PV, 8 with pemphigus foliaceus (PF, 14 with dermatitis herpetiformis (DH and 30 control skin samples from plastic esthetic surgery reduction surgeries. Results: The diagnostic correlation between IHC and DIF-IIF was almost 98% in most cases. IHC revealed evidence of autofluorescence around dermal blood vessels, dermal eccrine glands and neurovascular packages feeding skin appendices in ABDs; this autofluorescence may represent a non-specific immune response. Strong patterns of positivity were seen also in endothelial-mesenchymal cell junction-like structures, as well as between dermal fibrohistiocytic cells. In PV, we noted strong reactivity to neurovascular packages supplying sebaceous glands, as well as apocrine glands with edematous changes. Conclusions: We suggest that IHC is as reliable as DIF or IIF for the diagnosis of ABDs; our findings further suggest that what has previously been considered DIF/IIF autofluorescence

  11. Beyond Flory theory: Distribution functions for interacting lattice trees

    Science.gov (United States)

    Rosa, Angelo; Everaers, Ralf

    2017-01-01

    While Flory theories [J. Isaacson and T. C. Lubensky, J. Physique Lett. 41, 469 (1980), 10.1051/jphyslet:019800041019046900; M. Daoud and J. F. Joanny, J. Physique 42, 1359 (1981), 10.1051/jphys:0198100420100135900; A. M. Gutin et al., Macromolecules 26, 1293 (1993), 10.1021/ma00058a016] provide an extremely useful framework for understanding the behavior of interacting, randomly branching polymers, the approach is inherently limited. Here we use a combination of scaling arguments and computer simulations to go beyond a Gaussian description. We analyze distribution functions for a wide variety of quantities characterizing the tree connectivities and conformations for the four different statistical ensembles, which we have studied numerically in [A. Rosa and R. Everaers, J. Phys. A: Math. Theor. 49, 345001 (2016), 10.1088/1751-8113/49/34/345001 and J. Chem. Phys. 145, 164906 (2016), 10.1063/1.4965827]: (a) ideal randomly branching polymers, (b) 2 d and 3 d melts of interacting randomly branching polymers, (c) 3 d self-avoiding trees with annealed connectivity, and (d) 3 d self-avoiding trees with quenched ideal connectivity. In particular, we investigate the distributions (i) pN(n ) of the weight, n , of branches cut from trees of mass N by severing randomly chosen bonds; (ii) pN(l ) of the contour distances, l , between monomers; (iii) pN(r ⃗) of spatial distances, r ⃗, between monomers, and (iv) pN(r ⃗|l ) of the end-to-end distance of paths of length l . Data for different tree sizes superimpose, when expressed as functions of suitably rescaled observables x ⃗=r ⃗/√{ } or x =l / . In particular, we observe a generalized Kramers relation for the branch weight distributions (i) and find that all the other distributions (ii-iv) are of Redner-des Cloizeaux type, q (x ⃗) =C |x| θexp(-(K|x |) t) . We propose a coherent framework, including generalized Fisher-Pincus relations, relating most of the RdC exponents to each other and to the contact and Flory

  12. In-vitro antimicrobial screening and molecular docking studies of synthesized 2-chloro-N-(4-phenylthiazol-2-ylacetamide derivatives

    Directory of Open Access Journals (Sweden)

    Rahmat Ali

    2015-01-01

    Full Text Available Introduction: Glucosamine-6-phosphate (GlcN6P synthase biosynthetic pathway has been identified as potential targets for the development of new antimicrobial agents. Aim: A series of 2-chloro-N-(42-phenylthiazol-25-ylacetamide derivatives (3a-r was synthesized and evaluated their antimicrobial activity. Materials and Methods: The 2-chloro-N-(Para substituted phenylthiazol-25-yl acetamide (2a-c were synthesized by stirring intermediates (1a-c with 2-chloroacetylchloride in dichloromethane in the presence of K2CO3. The intermediate (2a-c were further reacted with different secondary amine such as pyrrolidine, N-methyl piperazine, N-ethyl piperazine, thiomorpholine, morpholine, piperidine etc in ethanol in presence of TEA Triethylamine (TEA to get desired compounds (3a-r. Compounds were characterized by a spectroscopic technique such as Fourier transform infraredFTIR, 1 H-NMR, 13 C-NMR, and mass spectrometry. The synthesized thiazole derivatives (3a-r were screened for anti-bacterial and anti-fungal activity against Escherichia coli, Staphylococcus aureus NCTC 6571, Pseudomonas aeruginosa NCTC 10662, CandidaC. albicans (MTCC-183, AspergillusA. niger (MTCC 281 NCTC 10418 and AspergillusA. flavus (MTCC 277. Result and Conclusion: The results of anti-bacterial screening revealed that among all the screened compounds, eight compounds viz. 3b, 3c, 3d, 3e, 3i, 3j, 3k, and 3p showed moderate to good anti-bacterial and antifungal activity having minimum inhibitory concentration (MIC between 6.25- and 25 µg/ml. While compound 3d showed the most promising antibacterial activity against E. coli and S. aureus, while the compound 3j showed promising antifungal activity with MIC value 6.25 µg/ml against C. albicans, A. niger and A. flavus. In addition, all these eight potential molecules were also examined for possible binding on enzyme GlcN6Pglucosamine-6-phosphate synthase by molecular docking studies on (PDB ID 1JXA.

  13. On thermonuclear processes in cavitation bubbles

    Science.gov (United States)

    Nigmatulin, R. I.; Lahey, R. T., Jr.; Taleyarkhan, R. P.; West, C. D.; Block, R. C.

    2014-09-01

    The theoretical and experimental foundations of so-called bubble nuclear fusion are reviewed. In the nuclear fusion process, a spherical cavitation cluster ˜ 10-2 m in diameter is produced of spherical bubbles at the center of a cylindrical chamber filled with deuterated acetone using a focused acoustic field having a resonant frequency of about 20 kHz. The acoustically-forced bubbles effectuate volume oscillations with sharp collapses during the compression stage. At the final stages of collapse, the bubble cluster emits 2.5 MeV D-D fusion neutron pulses at a rate of ˜ 2000 per second. The neutron yield is ˜ 10^5 s -1. In parallel, tritium nuclei are produced at the same yield. It is shown numerically that, for bubbles having sufficient molecular mass, spherical shock waves develop in the center of the cluster and that these spherical shock waves (microshocks) produce converging shocks within the interior bubbles, which focus energy on the centers of the bubbles. When these shock waves reflect from the centers of the bubbles, extreme conditions of temperature ( ˜ 10^8 K) and density ( ˜ 10^4 kg m -3) arise in a (nano)spherical region ( ˜ 10-7 m in size) that last for ˜ 10-12 s, during which time about ten D-D fusion neutrons and tritium nuclei are produced in the region. A paradoxical result in our experiments is that it is bubble cluster (not streamer) cavitation and the sufficiently high molecular mass of (and hence the low sound speed in) D-acetone ( C3D6O) vapor (as compared, for example, to deuterated water D2O) which are necessary conditions for the formation of convergent spherical microshock waves in central cluster bubbles. It is these waves that allow the energy to be sufficiently focused in the nanospherical regions near the bubble centers for fusion events to occur. The criticism to which the concept of 'bubble fusion' has been subjected in the literature, in particular, most recently in Uspekhi Fizicheskikh Nauk (Physics - Uspekhi) journal, is

  14. Heterologous prime-boost-boost immunisation of Chinese cynomolgus macaques using DNA and recombinant poxvirus vectors expressing HIV-1 virus-like particles

    Directory of Open Access Journals (Sweden)

    Anson Donald S

    2011-09-01

    Full Text Available Abstract Background There is renewed interest in the development of poxvirus vector-based HIV vaccines due to the protective effect observed with repeated recombinant canarypox priming with gp120 boosting in the recent Thai placebo-controlled trial. This study sought to investigate whether a heterologous prime-boost-boost vaccine regimen in Chinese cynomolgus macaques with a DNA vaccine and recombinant poxviral vectors expressing HIV virus-like particles bearing envelopes derived from the most prevalent clades circulating in sub-Saharan Africa, focused the antibody response to shared neutralising epitopes. Methods Three Chinese cynomolgus macaques were immunised via intramuscular injections using a regimen composed of a prime with two DNA vaccines expressing clade A Env/clade B Gag followed by boosting with recombinant fowlpox virus expressing HIV-1 clade D Gag, Env and cholera toxin B subunit followed by the final boost with recombinant modified vaccinia virus Ankara expressing HIV-1 clade C Env, Gag and human complement protein C3d. We measured the macaque serum antibody responses by ELISA, enumerated T cell responses by IFN-γ ELISpot and assessed seroneutralisation of HIV-1 using the TZM-bl β-galactosidase assay with primary isolates of HIV-1. Results This study shows that large and complex synthetic DNA sequences can be successfully cloned in a single step into two poxvirus vectors: MVA and FPV and the recombinant poxviruses could be grown to high titres. The vaccine candidates showed appropriate expression of recombinant proteins with the formation of authentic HIV virus-like particles seen on transmission electron microscopy. In addition the b12 epitope was shown to be held in common by the vaccine candidates using confocal immunofluorescent microscopy. The vaccine candidates were safely administered to Chinese cynomolgus macaques which elicited modest T cell responses at the end of the study but only one out of the three macaques

  15. 霍乱毒素A亚单位基因的原核表达及单克隆抗体的制备%Prokaryotic expression of cholera toxin subunit A gene and preparation of monoclonal antibody

    Institute of Scientific and Technical Information of China (English)

    陈健; 韦雨杏; 解晓燕; 朱召芹; 万延民; 徐建青

    2014-01-01

    目的 原核表达并纯化霍乱毒素A亚单位(cholera toxin subunitA,CTA)基因,建立分泌CTA单克隆抗体的杂交瘤细胞系,并制备单克隆抗体.方法 构建原核表达质粒pET30a-CTA,转化大肠埃希菌(E.coli)BL21(DE3),IPTG诱导表达6h,表达产物经12% SDS-PAGE分析后,用Ni2+亲和层析柱纯化;将纯化的重组CTA蛋白免疫C57BL/6小鼠,运用杂交瘤细胞技术制备抗CTA的单抗,采用Western blot法及体外阻断实验检测抗CTA单抗的特异性及对CT毒性作用的体外阻断.结果 原核表达质粒pET30a-CTA经PCR及双酶切鉴定,证明构建正确;表达的重组CTA蛋白在相对分子质量25 000 ~ 35 000之间可见明显的目的蛋白条带,纯化后的重组CTA蛋白纯度达90%以上;获得1株可分泌抗CTA单抗的杂交瘤细胞株G6C3-D10,可与CTA蛋白特异性结合,在相对分子质量25 000 ~ 35 000之间可见明显的特异条带;杂交瘤培养上清中CTA特异性抗体滴度为54,与CT混合后,可明显抑制CT所诱导的细胞内环腺苷酸(cyclic adenosine monophosphate,cAMP)水平的升高(P<0.01).结论 原核表达并纯化了CTA基因,获得了能够分泌具有阻断CT毒性作用的单抗的细胞株,为CTA毒性作用和佐剂机制的进一步研究提供了参考.

  16. Site-Specific Rate Constant Measurements for Primary and Secondary H- and D-Abstraction by OH Radicals: Propane and n -Butane

    KAUST Repository

    Badra, Jihad

    2014-07-03

    Site-specific rate constants for hydrogen (H) and deuterium (D) abstraction by hydroxyl (OH) radicals were determined experimentally by monitoring the reaction of OH with two normal and six deuterated alkanes. The studied alkanes include propane (C3H8), propane 2,2 D2 (CH 3CD2CH3), propane 1,1,1-3,3,3 D6 (CD 3CH2CD3), propane D8 (C3D 8), n-butane (n-C4H10), butane 2,2-3,3 D4 (CH3CD2CD2CH3), butane 1,1,1-4,4,4 D6 (CD3CH2CH2CD3), and butane D10 (C4D10). Rate constant measurements were carried out over 840-1470 K and 1.2-2.1 atm using a shock tube and OH laser absorption. Previous low-temperature data were combined with the current high-temperature measurements to generate three-parameter fits which were then used to determine the site-specific rate constants. Two primary (P1,H and P 1,D) and four secondary (S00,H, S00,D, S 01,H, and S01,D) H- and D-abstraction rate constants, in which the subscripts refer to the number of C atoms connected to the next-nearest-neighbor C atom, are obtained. The modified Arrhenius expressions for the six site-specific abstractions by OH radicals are P1,H = 1.90 × 10-18T2.00 exp(-340.87 K/T) cm 3molecule-1s-1 (210-1294 K); P1,D= 2.72 × 10-17 T1.60 exp(-895.57 K/T) cm 3molecule-1s-1 (295-1317 K); S00,H = 4.40 × 10-18 T1.93 exp(121.50 K/T) cm 3molecule-1s-1 (210-1294 K); S00,D = 1.45 × 10-20 T2.69 exp(282.36 K/T) cm 3molecule-1s-1 (295-1341 K); S01,H = 4.65 × 10-17 T1.60 exp(-236.98 K/T) cm 3molecule-1s-1 (235-1407 K); S01,D = 1.26 × 10-18 T2.07 exp(-77.00 K/T) cm 3molecule-1s-1 (294-1412 K). © 2014 American Chemical Society.

  17. 长时间降雨工况下亚黏土路堤边坡稳定性研究%The Analysis of sub Clay Embankment Slope Stability under the Condition of Long Time Small Rainfall Infiltration

    Institute of Scientific and Technical Information of China (English)

    李丽华; 彭振斌

    2016-01-01

    降雨是诱发边坡失稳的主要因素,为研究长时间降雨工况下,亚黏土路堤边坡的稳定性,提出综合考虑基质吸力变化、重度修正以及软化效应的修正饱和-非饱和抗剪强度理论;利用Geo-studio中的seep模块模拟渗流,再将渗流计算结果导入FLA C3D,利用FLA C3D内置的fish语言编程反映边坡的重度变化、基质吸力变化、软化效应。研究结果表明:(1)随降雨时间的增加边坡内部水位线从坡脚逐渐上升且坡脚处水位线上升的速率大于路基中心线处水位线上升的速率;(2)降雨过程中,边坡内水位线以下的基质吸力逐渐消散并逐渐转变为正孔隙水压力;(3)随降雨的持续进行,边坡逐渐变为失稳状态。%Rainfall is the main factor that affects the stability of slope. In order to analyse sub clay embankment slope stability under the condition of the long-term rainfall infiltration, took matric suction dissipation, severe correction and softening effect into consideration and came up with the corrected saturated-unsaturated shear strength theory. Use the seep module of geo-studio to simulate seepage and introduce the seepage calculation results into FLAC3D. Fish language was used to reflect the effect of matric suction dissipation, softening effect. The results show that: (1) with the duration of rainfall increased, slope internal water line increased gradually from the foot of the slope and the foot of the slope water level rising rate is greater than the roadbed along the centerline of the water level rising rate. (2)During the process of rainfall infiltration, the slope’s matric suction dissipate into positive pore water pressure;(3)with rainfall infiltration going on, slope gradually changed into unstable state.

  18. The regulatory SCR-1/5 and cell surface-binding SCR-16/20 fragments of factor H reveal partially folded-back solution structures and different self-associative properties.

    Science.gov (United States)

    Okemefuna, Azubuike I; Gilbert, Hannah E; Griggs, Kim M; Ormsby, Rebecca J; Gordon, David L; Perkins, Stephen J

    2008-01-01

    Factor H (FH) is a plasma glycoprotein that plays a central role in regulation of the alternative pathway of complement. It is composed of 20 short complement regulator (SCR) domains. The SCR-1/5 fragment is required for decay acceleration and cofactor activity, while the SCR-16/20 fragment possesses binding sites for complement C3d and heparin. X-ray scattering and analytical ultracentrifugation showed that SCR-1/5 was monomeric, while SCR-16/20 formed dimers. The Guinier radius of gyration R(G) of 4.3 nm for SCR-1/5 and those of 4.7 nm and about 7.8 nm for monomeric and dimeric SCR-16/20, respectively, showed that their structures are partially folded back and bent. The distance distribution function P(r) showed that SCR-1/5 has a maximum dimension of 15 nm while monomeric and dimeric SCR-16/20 are 17 nm and about 27 nm long, respectively. The sedimentation coefficient of 2.4 S for SCR-1/5 showed no concentration-dependence, while that for SCR-16/20 was 2.8 S for the monomer and 3.9 S for the dimer. Sedimentation equilibrium data showed that SCR-1/5 is monomeric while SCR-16/20 exhibited a weak monomer-dimer equilibrium with a dissociation constant of 16 microM. The constrained scattering and sedimentation modelling of SCR-1/5 and SCR-16/20 showed that partially folded-back and bent flexible SCR arrangements fitted both data sets better than extended linear arrangements, and that the dimer was best modelled in the SCR-16/20 model by an end-to-end association of two SCR-20 domains. The SCR-1/5 and SCR-16/20 models were conformationally similar to the previously determined partially folded-back structure for intact wild-type FH, hence suggesting a partial explanation of the intact FH structure. Comparison of the SCR-16/20 model with the crystal structure of C3b clarified reasons for the distribution of mutations leading to atypical haemolytic uraemic syndrome.

  19. Synthesis of O'-SiAlON-BN Composite by Reaction Sintering

    Institute of Scientific and Technical Information of China (English)

    ZHEN Qiang; YAN Kai; ZHANG Dahai; LI Wenchao

    2006-01-01

    By using micron α-Si3N4, SiO2, Al2O3 and h-BN as starting materials, O' -SiAlON-BN ( Si2-ZAlzO1+zN2-z, z = 0.3) composite was synthesized by reaction sintering. According to theoretical proportion ratio:n(SiO2)/n(α-Si3N4) = 1, the effects of two sintering aid comtosites, Y2O3+B2O3 and Y2O3+TiO2 at 1700℃ for 2h, were studied. The results indicate that Y2O3+TiO2 as sintering aid can accelerate reaction sintering of O'-SiAlON-BN more effectively than Y2O3+B2O3, and the relative density of the composites declined with the increase of BN addition (10%, 20% and30% respectively); XRD analysis found that excessive β-Si3N4 existed in the O' -SiAlON-BN composite. Therefore, in order to get more pure O' -SiAlON and BN phases in the composites ore SiO2 is needed. When Y2O3+TiO2 was used as sintering aid and addition of BN was 10%, the result of cross experiment on condition of A n(SiO2)/n(α-Si3N4) was 1.05, 1.1 and1.2; B addition of sintering aid was 2%, 4% and 6%; C firing temperature was 1600℃, 1650℃ and 1700℃ ;D-soaking time was 1h, 2h and 3h, shows that the sintering properties were influenced by factors of firing temperature, soaking time, addition of sintering aid and n(SiO2)/n(α-Si3N4) in order of importance. In addition, the technical parameter A3B3C3D3 can achieve the highest relative density. Besides, using Pattern Recognition method, the optimized parameter range to form pure O' -SiAlON and BN without β-Si3N4 remained was determined as Y > 1024X2 - 230.400X+11.088 ( X =0.9999A-0.0006C-0.0163D, Y =0.0163A +0.0009B -0.0014C+0.9999D).

  20. Three-Dimensional High-Frequency Ultrasonography for Early Detection and Characterization of Embryo Implantation Site Development in the Mouse

    Science.gov (United States)

    Peavey, Mary C.; Reynolds, Corey L.; Szwarc, Maria M.; Gibbons, William E.; Valdes, Cecilia T.

    2017-01-01

    Ultrasonography is a powerful tool to non-invasively monitor in real time the development of the human fetus in utero. Although genetically engineered mice have served as valuable in vivo models to study both embryo implantation and pregnancy progression, such studies usually require sacrifice of parous mice for subsequent phenotypic analysis. To address this issue, we used three-dimensional (3-D) reconstruction in silico of high-frequency ultrasound (HFUS) imaging data for early detection and characterization of murine embryo implantation sites and their development in utero. With HFUS imaging followed by 3-D reconstruction, we were able to precisely quantify embryo implantation site number and embryonic developmental progression in pregnant C57BL6J/129S mice from as early as 5.5 days post coitus (d.p.c.) through to 9.5 d.p.c. using a VisualSonics Vevo 2100 (MS550S) transducer. In addition to measurements of implantation site number, location, volume and spacing, embryo viability via cardiac activity monitoring was also achieved. A total of 12 dams were imaged with HFUS with approximately 100 embryos examined per embryonic day. For the post-implantation period (5.5 to 8.5 d.p.c.), 3-D reconstruction of the gravid uterus in mesh or solid overlay format enabled visual representation in silico of implantation site location, number, spacing distances, and site volume within each uterine horn. Therefore, this short technical report describes the feasibility of using 3-D HFUS imaging for early detection and analysis of post-implantation events in the pregnant mouse with the ability to longitudinally monitor the development of these early pregnancy events in a non-invasive manner. As genetically engineered mice continue to be used to characterize female reproductive phenotypes, we believe this reliable and non-invasive method to detect, quantify, and characterize early implantation events will prove to be an invaluable investigative tool for the study of female

  1. A shock tube study of the branching ratios of propene + OH reaction

    KAUST Repository

    Badra, Jihad

    2014-12-01

    Absolute rate coefficients for the reaction of the OH radical with propene (C3H6) and five deuterated isotopes, propene-1-D1 (CDHCHCH3), propene-1,1-D2 (CD2CHCH3), propene-1,1,2-D3 (CD2CDCH3), propene-3,3,3-D3 (CH2CHCD3), and propene-D6 (C3D6), were measured behind reflected shock waves over the temperature range of 818-1460 K and pressures near 1 atm. The reaction progress was followed by monitoring the OH radical near 306.7 nm using UV laser absorption. Kinetic isotope effects in the measured rate coefficients are discussed and rationalized for the site-specific H-abstraction by the OH radical. The first experimental measurements for the branching ratio of the title reaction are reported and compared with transition state theory calculations. The allylic H-atom abstraction of propene by OH radicals was found to be the most dominant reaction pathway followed by propen-1-yl and propen-2-yl channels over the entire temperature range of this study. The derived Arrhenius expressions for various site-specific rate coefficients over 818-1442 K are (the subscript in the rate coefficient identifies the position of H or D atom according to the IUPAC nomenclature of alkenes):k3,H = 2.32 × 10-11 exp(-2341 K/T) cm3 molecule-1 s-1k3,D = 1.96 × 10-11 exp(-2420 K/T) cm3 molecule-1 s-1k1,H = 1.39 × 10-11 exp(-2270 K/T) cm3 molecule-1 s-1k1,D = 1.95 × 10-11 exp(-2868 K/T) cm3 molecule-1 s-1k2,H = 7.2 × 10-12 exp(-2282 K/T) cm3 molecule-1 s-1k2,D = 7.69 × 10-12 exp(-2575 K/T) cm3 molecule-1 s-1 This journal is

  2. 计算机导航辅助骨样骨瘤的外科治疗%Computer navigation-guided excision of osteoid osteomas

    Institute of Scientific and Technical Information of China (English)

    王涛; 张清; 牛晓辉; 鱼锋; 李远; 赵海涛; 刘巍峰; 马珂; 杨发军

    2011-01-01

    目的 探讨计算机导航技术在骨样骨瘤外科治疗中的意义.方法 回顾性分析2008年1月至2009年12月应用计算机导航辅助切除骨样骨瘤手术26例患者的临床资料,其中男性23例,女性3例,平均年龄18岁(7~35岁).26例患者肿瘤位于股骨干9例、股骨粗隆部4例、股骨颈2例、胫骨干5例、胫骨近端干骺端1例、髋臼2例、耻骨1例、脊柱附件1例、桡骨干1例.术前均经局部X线及CT扫描明确诊断.其中4例采用CT数据导航,22例采用Iso-C 3D C型臂术中实时导航.术中导航指引定位,精确切除瘤巢.结果 全部病例均完成导航手术,其中行开窗刮除12例、整块切除14例;植骨21例、未植骨5例.26例患者均经术中肉眼判定、术中导航指引器确认、术后X线和(或)CT扫描确认瘤巢去除充分.全部病例均经组织病理学确诊为骨样骨瘤,术后疼痛即刻缓解.全部病例均获随访,平均随访20.6个月(12~35个月),未见肿瘤复发和疼痛复发.结论 将计算机导航技术应用于骨样骨瘤的外科治疗,不仅使术中瘤巢定位更精确,而且对于复杂部位瘤巢的切除可以达到骨结构微创治疗的目的.对于骨干部位的骨样骨瘤,Iso-C 3D C型臂术中实时导航较CT数据导航更有帮助.%Objective To report the experience for the precision osteoid osteoma resection using computer navigation system. Methods Between January 2008 and December 2009, 26 surgical resections were performed for 26 patients who had osteoid osteoma with computer navigation system. There were 23 males and 3 females with an average age of 18 years (7 to 35). Tumors were located at femoral shaft 9,femoral trochanter 4, femoral neck 2, tibial shaft 5, metaphysic of proximal tibia 1, acetabulum 2, pubis 1,vertebral appendix 1 and radial shaft 1. Pre-operative X-ray and CT of each patient was performed to confirm the diagnosis. It was carried out intraoperatively the process of CT-based navigation in 4

  3. Development and Calibration of New 3-D Vector VSP Imaging Technology: Vinton Salt Dome, LA

    Energy Technology Data Exchange (ETDEWEB)

    Kurt J. Marfurt; Hua-Wei Zhou; E. Charlotte Sullivan

    2004-09-01

    Vinton salt dome is located in Southwestern Louisiana, in Calcasieu Parish. Tectonically, the piercement dome is within the salt dome minibasin province. The field has been in production since 1901, with most of the production coming from Miocene and Oligocene sands. The goal of our project was to develop and calibrate new processing and interpretation technology to fully exploit the information available from a simultaneous 3-D surface seismic survey and 3-C, 3-D vertical seismic profile (VSP) survey over the dome. More specifically the goal was to better image salt dome flanks and small, reservoir-compartmentalizing faults. This new technology has application to mature salt-related fields across the Gulf Coast. The primary focus of our effort was to develop, apply, and assess the limitations of new 3-C, 3-D wavefield separation and imaging technology that could be used to image aliased, limited-aperture, vector VSP data. Through 2-D and 3-D full elastic modeling, we verified that salt flank reflections exist in the horizontally-traveling portion of the wavefield rather than up- and down-going portions of the wavefield, thereby explaining why many commercial VSP processing flow failed. Since the P-wave reflections from the salt flank are measured primarily on the horizontal components while P-wave reflections from deeper sedimentary horizons are measured primarily on the vertical component, a true vector VSP analysis was needed. We developed an antialiased discrete Radon transform filter to accurately model P- and S-wave data components measured by the vector VSP. On-the-fly polarization filtering embedded in our Kirchhoff imaging algorithm was effective in separating PP from PS wave images. By the novel application of semblance-weighted filters, we were able to suppress many of the migration artifacts associated with low fold, sparse VSP acquisition geometries. To provide a better velocity/depth model, we applied 3-D prestack depth migration to the surface data

  4. 骨性Ⅲ类错(牙合)下前牙区牙槽骨形态的锥形束CT分析%Preliminary cone-beam computed tomography study of alveolar bone of anterior mandible in adults with skeletal Class Ⅲ malocclusion

    Institute of Scientific and Technical Information of China (English)

    张莉; 王博; 房兵

    2012-01-01

    PURPOSE: To evaluate the thickness of alveolar bone of mandibular anterior teeth in adults with skeletal Class Ⅲ malocclusion by a method of detailed cone-beam computed tomography (CBCT) images. METHODS: The subjects were 45 untreated patients with skeletal Class III malocclusion and 45 untreated patients with skeletal Class I malocclusion. They were divided into 2 groups: skeletal Class III and skeletal Class I patients. Tomography was carried out using KODAK9000C 3D volume scanner before orthodontic treatment. Three-dimensional CBCT software (Kodak dental imaging software 3D module v 2.4, Eastman Kodak Company, French) was used to measure the labial, lingual and total thickness of alveolar bone of mandibular anterior teeth by 6 reference points. The thicknesses of alveolar bone of both groups were measured along an axial plane at mandibular anterior teeth root apex levels from a CBCT image. Differences between the 2 groups were analyzed by using group t test with SPSS16.0 software package. RESULTS: The thickness of the alveolar bone of mandibular anterior teeth was greater in the skeletal Class I than the skeletal Class III subjects. There was significant (P<0.05) difference between the two groups. CONCLUSIONS: The thickness of alveolar bone of mandibular anterior segment was obviously thinner in the skeletal Class III malocclusion than that in Class I. More attention was recommended to be paid in skeletal Glass HI patient. Supported by National Natural Science of China (10972142), Research Fund of Science and Technology Commission of Shanghai Municipality (08411961600) and Program for Innovative Research Team of Shanghai Municipal Education Commission.%目的:应用锥形束CT(cone-beam computed tomography,CBCT)评价骨性Ⅲ类和骨性I类错猞患者下颌切牙区 牙槽骨形态的差异。方法:选取45例恒牙期骨性Ⅲ类错治病例及45例恒牙期骨性I类错骀病例矫治前的CBCT图 像,测量下切牙区

  5. 饥饿和再投喂对中间球海胆代谢和生长的影响%Effects of starvation and refeeding on metabolism and growth in sea urchin, Strongylocentrotus intermedius

    Institute of Scientific and Technical Information of China (English)

    秦艳杰; 李霞; 吴立新; 周一兵

    2011-01-01

    The sea urchin (Strongylocentrotus intermedins) with body weight of (5. 72±0. 23) g was starved for 0 (control group, C) , 3 d (S3) , 6 d (S6) , 9 d (S9) and 12 d (S12) , and then re-fed until the 30th d to evaluate the effects of starvation on growth and metabolism in the sea urchin. The wet weight of whole body and gonad, special growth rate of body and gonad, the oxygen consumption rate, ammonia excretion rate and the food conversion efficiency were measured and calculated every five days in control group, on the day at the end of starvation, and 2,4,8 and 12 days after re-fed in four starved groups. Results showed that there were no significant differences in body wet weight between S3, S6 and C groups at the end of the experiment, but significantly lower in S9 and S12 than those in the control. There was significantly lower in gonad wet weight in S6, S9 and S12 compared to C and S3 at the end. The sea urchin in S6, S9 and S12 showed a peak in special growth rate in body and gonad after re-fed and lasted 3-5 days. The oxygen consumption rate and ammonia excretion rate were found to decrease for 4-8 days in S6, S9 and S12 at the beginning of re-fed. The food conversion efficiencies were increased in varying degrees after re-fed in the four experimental groups. It is indicated that the food deprivation for 6 d, 9 d and 12 d leads to part compensatory growth in the sea urchin, which are contributed in the significant decrease in metabolic rate and the increase in the food conversion efficiency during the initial stage of refeeding.%将体质量为(5.72±0.23)g的中间球海胆Strongylocentrotus intermedius分别饥饿0、3、6、9、12 d(分别记为C、S3、S6、S9、S12)后再饱食投喂至30 d,研究了饥饿与再投喂过程中海胆的代谢率、生长率、摄食率、食物转化率的变化.结果表明:在饥饿和再投喂过程中,S3组各指标与对照组无明显差异;S6、S9、S12组在恢复投喂过程中的一段时间内代谢率均维

  6. Seismic Technology Adapted to Analyzing and Developing Geothermal Systems Below Surface-Exposed High-Velocity Rocks Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Hardage, Bob A. [Univ. of Texas, Austin, TX (United States). Bureau of Economic Geology; DeAngelo, Michael V. [Univ. of Texas, Austin, TX (United States). Bureau of Economic Geology; Ermolaeva, Elena [Univ. of Texas, Austin, TX (United States). Bureau of Economic Geology; Hardage, Bob A. [Univ. of Texas, Austin, TX (United States). Bureau of Economic Geology; Remington, Randy [Univ. of Texas, Austin, TX (United States). Bureau of Economic Geology; Sava, Diana [Univ. of Texas, Austin, TX (United States). Bureau of Economic Geology; Wagner, Donald [Univ. of Texas, Austin, TX (United States). Bureau of Economic Geology; Wei, Shuijion [Univ. of Texas, Austin, TX (United States). Bureau of Economic Geology

    2013-02-01

    applications by inserting into this report a small part of the interpretation we have done with 3C3D data across Wister geothermal field in the Imperial Valley of California. This interpretation shows that P-SV data reveal faults (and by inference, also fractures) that cannot be easily, or confidently, seen with P-P data, and that the combination of P-P and P-SV data allows VP/VS velocity ratios to be estimated across a targeted reservoir interval to show where an interval has more sandstone (the preferred reservoir facies). The conclusion reached from this investigation is that S-wave seismic technology can be invaluable to geothermal operators. Thus we developed a strong interest in understanding the direct-S modes produced by vertical-force sources, particularly vertical vibrators, because if it can be demonstrated that direct-S modes produced by vertical-force sources can be used as effectively as the direct-S modes produced by horizontal-force sources, geothermal operators can acquire direct-S data across many more prospect areas than can be done with horizontal-force sources, which presently are limited to horizontal vibrators. We include some of our preliminary work in evaluating direct-S modes produced by vertical-force sources.

  7. Establishment of an adolescent idiopathic scoliosis model using 3-dimensional finite element method%三维有限元法构建青少年特发性脊柱侧弯模型

    Institute of Scientific and Technical Information of China (English)

    汪学松; 吴志宏; 王以朋; 阎家智; 刑泽军; 王储; 邱贵兴

    2008-01-01

    背景:目前国外有很多脊柱柞侧凸方面的有限元研究,均是在建立良好的有限元脊柱侧凸模型基础上进行的,但是国内尚未有建立脊柱侧凸有限兀模型的报道.目的:利用有限元分析软件abaqus建立青少年特发件脊柱侧弯三维实体有限无模型.设计、时间及地点:三维有限元建模,于2007-08/2008 05在北京协和医院生物力学实验室完成.对象经北京协和医院选取女性志愿者1名,17岁,发现脊柱侧凸4年,为双弯畸形.上弯为胸弯,下弯为腰弯,Risser征Ⅳ度.方法:获得青少年特发性脊柱测弯患者的CT资料,导入医学建模软件mimics11.11,获得医学仿真模型.利用获得青少年特发性脊柱侧弯患者医学仿真模型,导入有限元分析软件 abaqus6.7,通过表面网格体网格化、定义材质属性、定义接触、定义连接、模拟6韧带等建言PUMCⅡd Ⅱ型青少年特发性脊柱侧弯患者有限元分析模型.主要观察指标:建立模型的节点和单元数、韧带的弹簧单元模拟数目、表面接触数目.结果:建立的特发性脊柱侧弯有限元模型,共包含节点数648 034,单元数3 074 881,单元类型为C3D4,为一阶单元,其计定义表面224个,表面间接触34对,表面间绑定78对(tie接触),定义弹簧单元162个.结论:利用计算机软件abaqus成功地建立特发性脊柱侧弯的有限元模型,具有良好的仿生效果及生物逼真度.

  8. 炎痛平透皮软膏的制备及活血作用的探讨%Preparation and promoting blood circulation effect of Yantongping transdermal ointments

    Institute of Scientific and Technical Information of China (English)

    何爱明; 徐洁; 王艺辉; 林世明

    2012-01-01

    Objective To find out the best prescription method for Yantongping transdermal ointments through orthogonal design and research on the effect of promoting blood circulation. Methods With 60 minutes in vitro cumulative penetration rate, using L9(34) orthogonal experiment, the best formula and technology were found out through grinding method, and quality thereafter was e-valuated. Mice was picked up as blank groups and model groups, each respectively was divided into six smaller groups as Vaseline, Vaseline and Fatty Alcohol, Yantongping transdermal ointments( low dosage) , Yantongping transdermal ointments( medium dosage) , Yantongping transdermal ointments( high dosage) and Voltaren Emulsions. A A and AV were measured before and after modeling by microcirculation method and microscopic micro-distance measuring method , while the blood circulation function of each medicine by the scoring of the blood of veinule was compared. Results The best prescription was confirmed by A2B2C3D2, that was with the weight of the traditional Chinese drugs (TCD) Vaseline ratioes ( A) to 50% , with the weight of TCD and Fatty Alcohol ratios ( B) to 25% , the order of reagent was as follow; Fatty Alcohol, TCD, Vaseline . The grinding temperature was 80 X. , and it passed five quality evaluation as physical appearance, melting point, water value, stability, irritation. Before modeling, in the A A level measured, Yantongping group (low dosage) had statistical significance over Vaseline and Fatty Alcohol group in 30 min(P<0.05= ,while Yantongping group (medium dosage and high dosage) had obviously statistical significance over Vaseline and Fatty Alcohol group in different time periods in the A A and A V level (P<0. 01=. In the blood flow quality evaluation measured, Yantongping group (low dosage) had statistical significance over Vaseline and Fatty Alcohol group in 20 min, 30 min ( P<0. 05 ) ; while Yantongping group ( medium and high dosage) had obviously significant

  9. Determination of Optimal Double Sampling Plan using Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Sampath Sundaram

    2012-03-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 Designing double sampling plan requires identification of sample sizes and acceptance numbers. In this paper a genetic algorithm has been designed for the selection of optimal acceptance numbers and sample sizes for the specified producer’s risk and consumer’s risk. Implementation of the algorithm has been illustrated numerically for different choices of quantities involved in a double sampling plan