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Sample records for anti-igg c3d polyspecific

  1. A novel antihuman C3d monoclonal antibody with specificity to the C3d complement split product

    DEFF Research Database (Denmark)

    Rasmussen, Karina Juhl; Skjødt, Mikkel-Ole; Vitved, Lars

    2017-01-01

    The complement component C3 and the cleavage products of C3b/iC3b, C3c and C3d are used as biomarkers in clinical diagnostics. Currently, no specific antibodies are able to differentiate C3d from other fragments, although such a distinction could be very valuable considering that they may reflect...

  2. 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.

  3. C3d enhanced DNA vaccination induced humoral immune response to glycoprotein C of pseudorabies virus

    International Nuclear Information System (INIS)

    Tong Tiezhu; Fan Huiying; Tan Yadi; Xiao Shaobo; Ling Jieyu; Chen Huanchun; Guo Aizhen

    2006-01-01

    Murine C3d were utilized to enhance immunogenicity of pseudorabies virus (PrV) gC DNA vaccination. Three copies of C3d and four copies of CR2-binding domain M28 4 were fused, respectively, to truncated gC gene encoding soluble glycoprotein C (sgC) in pcDNA3.1. BALB/c mice were, respectively, immunized with recombinant plasmids, blank vector, and inactivated vaccine. The antibody ELISA titer for sgC-C3d 3 DNA was 49-fold more than that for sgC DNA, and the neutralizing antibody obtained 8-fold rise. Protection of mice from death after lethal PrV (316 LD 5 ) challenge was augmented from 25% to 100%. Furthermore, C3d fusion increased Th2-biased immune response by inducing IL-4 production. The IL-4 level for sgC-C3d 3 DNA immunization approached that for the inactivated vaccine. Compared to C3d, M28 enhanced sgC DNA immunogenicity to a lesser extent. In conclusion, we demonstrated that murine C3d fusion significantly enhanced gC DNA immunity by directing Th1-biased to a balanced and more effective Th1/Th2 response

  4. [Iso-C(3D0-assisted) navigated implantation of pedicle screws in thoracic lumbar vertebrae].

    Science.gov (United States)

    Wendl, K; von Recum, J; Wentzensen, A; Grützner, P A

    2003-11-01

    The mobile Siremobil Iso-C(3D) C-arm (Siemens AG, Medical Solutions, Erlangen) is the first device that permits the intraoperative three-dimensional (3D) representation of bone structures. A high-resolution isotropic 3D data cube in the isocenter with an edge length of approximately 12 cm is calculated simultaneously. The Siremobil Iso-C(3D) is linked to navigation with the integrated NaviLink interface (Siemens AG, Medical Solutions, Erlangen). This makes it possible to transfer the generated 3D data directly to the linked navigation system Surgigate (Medivision, Oberndorf, Switzerland). In this prospective clinical trial we evaluated the accuracy of pedicle screw placement using the Siremobil Iso-C(3D) C-arm. The results were compared to the conventional approach and other computer-assisted procedures (CT-based navigation, C-arm-based 2D navigation) in historical control groups. A total of 141 pedicle screws were placed in 30 patients (70 thoracic spine, 71 lumbar spine). Only in one single case was misplacement shown in the postoperative control CT scan (0.71%), the lowest rate of incorrect placements of all techniques. Also the lowest average fluoroscopy time (1.28+/-0.56 min) was achieved during the placement of pedicle screws on the spine with Iso-C(3D) navigation at a comparable average OR duration (103.26+/-23.3 min). There were no postoperative neurological complications in all 30 patients. From these data we conclude that Iso-C(3D) navigation of pedicle screws is a very accurate method in the correct placement of pedicle screws.

  5. Intra-operative assessment of femoral antetorsion using ISO-C 3D: a cadaver study.

    Science.gov (United States)

    Hawi, Nael; Suero, Eduardo M; Liodakis, Emmanouil; Decker, Sebastian; Krettek, Christian; Citak, Musa

    2014-03-01

    The aim of this study was to check the feasibility and accuracy of measuring antetorsion during surgery using a mobile image intensifier (IF) with computed tomography (CT) function (ISO-C 3D; Siemens, Erlangen, Germany) in comparison to a conventional multi-slice CT scanner (LightSpeed QX/I CT; GE Healthcare, VA, USA). A total of 10 intact femora with intact soft tissue of five fresh frozen cadavers were used. After fixation on a surgical table, IF CT scans of the hip and knee were performed at both 190° and 120° of scanning rotation. Afterwards, a conventional CT scan was performed. Antetorsion was calculated according to the method of Jend et al. Analysis of variance (ANOVA) and Lin's concordance correlation coefficient (LCC) were used to test the agreement between the three measurement techniques. There was no significant difference in femoral antetorsion angle measurements between the different techniques (P>0.05). The mean time required to perform a scan using the ISO-C 3D was 9±3 min. The mean time required to measure antetorsion was 8±2 min. We found a high positive correlation between CT-based measurements and measurements performed using both the ISO-C 3D at 190° (LCC=0.99; mean difference=0.02°±1.8°) and the ISO-C 3D at 120° (LCC=0.99; mean difference=0.6°±1.5°), and a high positive correlation was also seen between both ISO-C 3D methods (LCC=0.99; mean difference=0.6°±1.7°). Measuring femoral antetorsion using an intra-operative IF with CT function is a feasible and accurate method. This technique could be used when there is doubt about the antetorsion angle in the operated femur and it could help decrease the need for a separate revision surgery. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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

  7. 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

  8. 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

    2014-11-25

    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.

  9. The 3C/3D Line Ratio in Ni XIX: New Ab Initio Theory and Experimental Results

    International Nuclear Information System (INIS)

    Chen, G. X.; Kirby, K.; Silver, E.; Brickhouse, N. S.; Gillaspy, J. D.; Tan, J. N.; Pomeroy, J. M.; Laming, J. M.

    2006-01-01

    We report a fully relativistic close-coupling calculation of the electron impact excitation of Ni xix to derive the 3C/3D line intensity ratio, with an uncertainty of 5%. Convergence of the calculation with respect to both channel coupling effects and the many interacting Rydberg series of resonances has been achieved. New measurements in an electron beam ion trap agree with our calculation. We show that the 3C/3D x-ray line ratio depends sensitively on both electron energy and beamwidth in an optically thin plasma. Accounting for this dependence improves the accuracy of the Ni abundance determination in astrophysical sources

  10. Antigen fusion with C3d3 augments or inhibits humoral immunity to AAV genetic vaccines in a transgene-dependent manner.

    Science.gov (United States)

    Logan, Grant J; Wang, Lina; Zheng, Maolin; Coppel, Ross L; Alexander, Ian E

    2010-02-01

    Genetic fusion of tandem repeats of the complement molecule C3d has been shown to considerably enhance immune responses to genetic vaccines. We have investigated the applicability of this approach to augment humoral immune responses toward vaccines delivered by recombinant adeno-associated virus (AAV) vectors. C3d(3)-fusion was found to markedly decrease antibody responses to merozoite surface protein 4/5 from Plasmodium yoelii and contrasted with greater than 50-fold enhancement in responses when this strategy was similarly applied to another AAV-encoded model antigen, hen egg lysozyme. These data indicate that the efficacy of the C3d(3) strategy operates in an antigen-dependent manner. Additional studies also showed that homologous recombination events between the C3d tandem repeats occurred during vector packaging and transduction resulting in expression of C3d(1)-, C3d(2)-, C3d(3)- and C3d(4)-fused antigen. This is the first report to apply the C3d approach to augment responses against a recombinant viral vector system and the consequences of these findings are discussed.

  11. Histamine Clearance Through Polyspecific Transporters in the Brain.

    Science.gov (United States)

    Yoshikawa, Takeo; Yanai, Kazuhiko

    2017-01-01

    Histamine plays an important role as a neurotransmitter in diverse brain functions, and clearance of histamine is essential to avoid excessive histaminergic neuronal activity. Histamine N-methyltransferase, which is an enzyme in the central nervous system that metabolizes histamine, is localized to the cytosol. This suggests that a histamine transport process is essential to inactivate histamine. Previous reports have shown the importance of astrocytes for histamine transport, although neuronal histamine transport could not be ruled out. High-affinity and selective histamine transporters have not yet been discovered, although it has been reported that the following three polyspecific transporters transport histamine: organic cation transporter (OCT) 2, OCT3, and plasma membrane monoamine transporter (PMAT). The K m values of human OCT2, OCT3, and PMAT are 0.54, 0.64, and 4.4 mM, respectively. The three transporters are expressed in the brain, and their regional distribution is different. Recent studies revealed the contribution of OCT3 and PMAT to histamine transport by primary human astrocytes. Several investigations using mice supported the importance of OCT3 for histamine clearance in the brain. However, further studies are required to elucidate the detailed mechanism of histamine transport in the brain.

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

    International Nuclear Information System (INIS)

    Soria, J; Atkinson, C

    2008-01-01

    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

  13. Construction, expression and immunoassay detection of recombinant plasmid encoding fusion protein of Roman chicken complement C3d and Newcastle disease virus F gene.

    Science.gov (United States)

    Liu, D; Niu, Z-X

    2008-12-01

    The terminal degradation product (C3d) of mammalian complement component C3 plays an important role in modulation of the adaptive immune response through the interaction with complement receptor type 2 (CR2) on B cells. In this study, the gene fragment coding for the complement protein C3d (chC3d) from Roman chicken was cloned and expressed as a fusion protein for its application in the vaccine study of chicken, and for in vitro experiments. The chC3d fragment strengthened B-cell responses when complexed with antigen. Three potential vaccine construct units were engineered to contain two, four and six copies of chC3d coding gene linked to the F gene of Newcastle disease virus (NDV), an economically important pathogen of chicken that is classified as a list A contagious disease of poultry by the Office International des Epizooties. The cloned chC3d protein and different repeats of C3d proteins in addition to the F gene of NDV were generated separately in Escherichia coli and chicken embryo fibroblast cells with the help of expression vectors. All recombinant proteins were analysed by SDS-PAGE and Western blotting. Analysis of the immunogenicity of different repeats of C3d revealed that chC3d had an enhancing effect on the immunogenicity of antigens, and that six or more repeats of C3d may be necessary for efficient enhancement of antigen-specific immune responses. To date, published research into the adjuvant activities of C3d has been limited to experiments in mice, rabbits and cattle. The adjuvant properties of C3d have not been assessed in poultry using homologous C3d in association with antigens relevant to the target species. The Roman chicken C3d fusion proteins described in this study is the first report and will provide a basis for immunization trials in chicken, studies of receptor binding and cell activation of chicken lymphocytes, and investigations of new types of vaccines, including recombinant vaccines and DNA vaccines for future use against other

  14. DNA vaccines expressing soluble CD4-envelope proteins fused to C3d elicit cross-reactive neutralizing antibodies to HIV-1

    International Nuclear Information System (INIS)

    Bower, Joseph F.; Green, Thomas D.; Ross, Ted M.

    2004-01-01

    DNA vaccines expressing the envelope (Env) of the human immunodeficiency virus type 1 (HIV-1) have been relatively ineffective at generating high-titer, long-lasting, neutralizing antibodies in a variety of animal models. In this study, DNA vaccines were constructed to express a fusion protein of the soluble human CD4 (sCD4) and the gp120 subunit of the HIV-1 envelope. To enhance the immunogenicity of the expressed fusion protein, three copies of the murine C3d (mC3d 3 ) were added to the carboxyl terminus of the complex. Monoclonal antibodies that recognize CD4-induced epitopes on gp120 efficiently bound to sCD4-gp120 or sCD4-gp120-mC3d 3 . In addition, both sCD4-gp120 and sCD4-gp120-mC3d 3 bound to cells expressing appropriate coreceptors in the absence of cell surface hCD4. Mice (BALB/c) vaccinated with DNA vaccines expressing either gp120-mC3d 3 or sCD4-gp120-mC3d 3 elicited antibodies that neutralized homologous virus infection. However, the use of sCD4-gp120-mC3d 3 -DNA elicited the highest titers of neutralizing antibodies that persisted after depletion of anti-hCD4 antibodies. Interestingly, only mice vaccinated with DNA expressing sCD4-gp120-mC3d 3 had antibodies that elicited cross-protective neutralizing antibodies. The fusion of sCD4 to the HIV-1 envelope exposes neutralizing epitopes that elicit broad protective immunity when the fusion complex is coupled with the molecular adjuvant, C3d

  15. Isolation of the C3 complement component and its C3d subunit from IY-1 fraction of Cohn's fractionation of human plasma.

    Science.gov (United States)

    Matveevskaya, N S; Alyoshkin, V A; Rozina, M N

    1995-02-03

    C3 complement component and its C3d subunit were isolated from the IY-1 Cohn's fraction, which is the waste of industrially produced albumin and immunoglobulins. The first step was the fractionation of precipitate IY-1 by polyethylene glycol (PEG) 4000 to a final concentration of 16% PEG. The precipitate formed was separated by centrifugation. The supernatant contained the C3d subunit of C3, and the redissolved 16% PEG precipitate contained the C3 component. Then the supernatant and the dissolved precipitate were subjected to anion-exchange chromatography on DEAE-Toyopearl 650 M. In the last step fractions containing C3 and C3d concentrated by ultrafiltration were chromatographed on Sephacryl S-200.

  16. Molecular Basis of Substrate Polyspecificity of the Candida albicans Mdr1p Multidrug/H+Antiporter.

    Science.gov (United States)

    Redhu, Archana Kumari; Banerjee, Atanu; Shah, Abdul Haseeb; Moreno, Alexis; Rawal, Manpreet Kaur; Nair, Remya; Falson, Pierre; Prasad, Rajendra

    2018-03-02

    The molecular basis of polyspecificity of Mdr1p, a major drug/H + antiporter of Candida albicans, is not elucidated. We have probed the nature of the drug-binding pocket by performing systematic mutagenesis of the 12 transmembrane segments. Replacement of the 252 amino acid residues with alanine or glycine yielded 2/3 neutral mutations while 1/3 led to the complete or selective loss of resistance to drugs or substrates transported by the pump. Using the GlpT-based 3D-model of Mdr1p, we roughly categorized these critical residues depending on their type and localization, 1°/ main structural impact ("S" group), 2°/ exposure to the lipid interface ("L" group), 3°/ buried but not facing the main central pocket, inferred as critical for the overall H + /drug antiport mechanism ("M" group) and finally 4°/ buried and facing the main central pocket ("B" group). Among "B" category, 13 residues were essential for the large majority of drugs/substrates, while 5 residues were much substrate-specific, suggesting a role in governing polyspecificity (P group). 3D superposition of the substrate-specific MFS Glut1 and XylE with the MDR substrate-polyspecific MdfA and Mdr1p revealed that the B group forms a common substrate interaction core while the P group is only found in the 2 MDR MFS transporters, distributed into 3 areas around the B core. This specific pattern has let us to propose that the structural basis for polyspecificity of MDR MFS transporters is the extended capacity brought by residues located at the periphery of a binding core to accomodate compounds differing in size and type. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. C4d and C3d immunohistochemical evaluation on formalin-fixed paraffin-embedded tissue for the diagnosis of bullous pemphigoid: systematic review of the literatures

    Directory of Open Access Journals (Sweden)

    Mahsa Akbari Oryani

    2017-01-01

    Full Text Available Introduction: Several methods are available for the diagnosis of autoimmune bullous disease. Since the immunohistochemistry of complement component is easy and more accessible compared to other methods, it is thought that this technique as an efficient method can replace other difficult, and time-consuming procedures. Therefore, in this study we aimed to systematically review the literatures in which the diagnostic value of complement component 3d (C3d and C4d had been investigated in bullous pemphigoid. Methods: A systematic search was conducted in the PubMed, Google scholar, and Scopus using following search method (((C3d OR C4d OR complement component 3d OR complement component 4d immunohistochemistry OR (C3d OR C4d marker OR complement component 3d OR complement component 4d marker AND (bullous pemphigoid OR cutaneous pemphigoid to evaluate the diagnostic value of C3d and/or C4d for early and accurate detection of bullous pemphigoid on November 2015. Subsequently, the extracted data were described.Result: Total of 28 documents were collected and reviewed based on the purpose of this study. Of the collected articles, 21 documents were excluded in several steps of article selection process and only 7 relevant articles were included for data assessment. The results showed that the deposits of C3d and/or C4d in skin biopsies were found in 125 of 134 patients, indicating that immunohistochemistry is a reliable technique for the diagnosis of inflammatory skin diseases.Conclusion: The results of this review showed that C3d and/or C4d immunohistochemistry in skin biopsies is a reliable technique for the diagnosis of inflammatory skin diseases, particularly bullous pemphigoid.

  18. 3D-imaging of the facial skeleton with an isocentric mobile C-arm system (Siremobil Iso-C3D).

    Science.gov (United States)

    Heiland, M; Schulze, D; Adam, G; Schmelzle, R

    2003-01-01

    The purpose of this study was to compare three-dimensional (3D) imaging of the facial skeleton using an isocentric mobile C-arm system vs CT. A dried human skull was scanned using a Siremobil Iso-C3D and a multi-detector CT (SOMATOM Volume Zoom; Siemens Medical Solutions, Erlangen, Germany) to compare reconstructed data sets. For each group of scans a standard protocol and a high resolution protocol were used. Image quality was analysed using six anatomical and six virtual structures in the primary reconstructed axial images of both data sets of the Siremobil Iso-C3D compared with CT. A receiver operating characteristic (ROC) study was performed with six examiners. The original categorical response data revealed no significant differences in sensitivity and specificity (P < 0.05). However, image quality of the reconstructed images of the Siremobil Iso-C3D was inferior to the CT images, with metal artefacts having a more prominent negative effect. The Siremobil Iso-C3D produces 3D images of the facial skeleton suitable for imaging osseous structures. No significant differences were found in sensitivity or specificity between the two methods. Metal objects degrade the image from the Iso-C method to a greater extent than those from CT.

  19. [Expression of NA of influenza virus and C3d fusion gene in replication-defective recombinant adenovirus and its immune efficacy analysis].

    Science.gov (United States)

    Han, Feng; Wang, Xuan; Wang, Yan; Zhao, Xiao-dong; Wu, Shu-hua

    2013-02-01

    To construct a replication-defective recombinant adenovirus expressing the fusion gene of neuraminidase (NA) gene in influenza virus A/FM/1/47 and C3d and to evaluate the induced immune efficacy. NA-C3d was cloned into shutter vector pAdTrack-CMV, which was cotransformated with adenovirus DNA into E. coli BJ5183. The recombinant adenovirus genomic DNA was generated through homological recombination. The recombinant adenovirus was produced by transfecting 293 cell line with the genomic DNA and the induced immune efficacy in mice were analyzed. The integration of NA-C3d in the adenovirus genomic DNA and its expression were confirmed by PCR and Western-Blot assays respectively. After intranasal immunization, the serum IgG was induced at a titer of 1: 1000 and 1:100 000 in BALB/c mice at primary and secondary immunization respectively. The vaccinated mice were completely survived when challenged with wide influenza virus. recombinant adenovirus expressing NA-C3d was successfully constructed and it could induce desired immune efficacy.

  20. Fusion of C3d molecule with neutralization epitope(s) of hepatitis E virus enhances antibody avidity maturation and neutralizing activity following DNA immunization.

    Science.gov (United States)

    Yang, Shucai; Wang, Chunling; Fang, Xuefeng; Zhai, Lijie; Dong, Chen; Ding, Lei; Meng, Jihong; Wang, Lixin

    2010-08-01

    Previous studies have identified that a hepatits E virus peptide (HEV-p179), spanning amino acids (aa) 439-617 in the 660-aa protein encoded by open reading frame 2(ORF2) of the Chinese epidemic strain (genotype 4), is the minimal size fragment of conformation-dependent neutralization epitope(s). We report here the successful immunization of mice with DNA vaccines expressing the secreted form of HEV-p179 (fused with a human tissue plasminogen activator (tPA) signal sequence) and the tPA-p179-C3d fusion protein (fused with three tandem copies of the murine complement C3d). Analysis of antibody responses in vaccinated mice revealed that immunizations with tPA-p179-C3d3 DNA vaccine dramatically increased both the level and avidity maturation of antibodies against HEV-p179 compared to p179 and tPA-p179 DNA vaccines. In addition, this increased antibody response correlated with neutralizing titers in a PCR-based cell culture neutralization assay. These results indicate that vaccination with C3d conjugated p179 DNA vaccine enhances antibody responses to HEV, and this approach may be applied to overcome the poor immunogenicity of DNA vaccines to generate HEV neutralizing antibodies. Copyright 2010 Elsevier B.V. All rights reserved.

  1. [Detection of tibial condylar fractures using 3D imaging with a mobile image amplifier (Siemens ISO-C-3D): Comparison with plain films and spiral CT].

    Science.gov (United States)

    Kotsianos, D; Rock, C; Wirth, S; Linsenmaier, U; Brandl, R; Fischer, T; Euler, E; Mutschler, W; Pfeifer, K J; Reiser, M

    2002-01-01

    To analyze a prototype mobile C-arm 3D image amplifier in the detection and classification of experimental tibial condylar fractures with multiplanar reconstructions (MPR). 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 degrees 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 Müller AO classification. To confirm the results, the specimens were finally surgically dissected. 97 % of the tibial condylar fractures were easily seen and correctly classified according to the Müller 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. The evaluation of fractures with the ISO-C is better than with plain films alone and comparable to CT scans. The three-dimensional reconstruction of the ISO-C can provide important information which cannot be obtained from plain films. The ISO-C-3D may be useful in planning operative reconstructions and evaluating surgical results in orthopaedic surgery of the limbs.

  2. Non-equilibrium Modeling of the Fe XVII 3C/3D Line Ratio in an Intense X-Ray Free-Electron Laser Excited Plasma

    Science.gov (United States)

    Loch, S. D.; Ballance, C. P.; Li, Y.; Fogle, M.; Fontes, C. J.

    2015-03-01

    Recent measurements using an X-ray Free Electron Laser (XFEL) and an Electron Beam Ion Trap at the Linac Coherent Light Source facility highlighted large discrepancies between the observed and theoretical values for the Fe xvii 3C/3D line intensity ratio. This result raised the question of whether the theoretical oscillator strengths may be significantly in error, due to insufficiencies in the atomic structure calculations. We present time-dependent spectral modeling of this experiment and show that non-equilibrium effects can dramatically reduce the predicted 3C/3D line intensity ratio, compared with that obtained by simply taking the ratio of oscillator strengths. Once these non-equilibrium effects are accounted for, the measured line intensity ratio can be used to determine a revised value for the 3C/3D oscillator strength ratio, giving a range from 3.0 to 3.5. We also provide a framework to narrow this range further, if more precise information about the pulse parameters can be determined. We discuss the implications of the new results for the use of Fe xvii spectral features as astrophysical diagnostics and investigate the importance of time-dependent effects in interpreting XFEL-excited plasmas.

  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. 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.

  5. Studies on image quality, high contrast resolution and dose for the axial skeleton and limbs with a new, dedicated CT system (ISO-C-3D); Untersuchungen zur Bildqualitaet, Hochkontrastaufloesung und Dosis am Stamm- und Gliedmassenskelett mit einem neuen dedizierten CT-System (ISO-C-3D)

    Energy Technology Data Exchange (ETDEWEB)

    Rock, C.; Kotsianos, D.; Linsenmaier, U. [Klinikum der Universitaet Muenchen, Muenchen (Germany). Inst. fuer Klinische Radiologie; Fischer, T. [Klinikum der Universitaet Muenchen, Muenchen (DE). Inst. fuer Klinische Radiologie] (and others)

    2002-02-01

    Purpose: Evaluation of 3D-CT imaging of the axial skeleton and different joints of the lower and upper extremities with a new dedicated CT system (ISO-C-3D) based on a mobile isocentric C-arm image amplifier. Material and Methods: 27 cadaveric specimes of different joints of the lower and upper extremities and of the spinal column were examined with 3D-CT imaging (ISO-C-3d). All images were evaluated by 3 radiologists for image quality using a semiquantitative score (score value 1: poor quality; score value 4: excellent quality). In addition, dose measurements and measurements of high contrast resolution were performed in comparison to conventional and low-dose spiral CT using a high contrast phantom (Catphan, Phantom Laboratories). Results: Adequate image quality (mean score values 3-4) could be achieved with an applied dose comparable to low-dose CT in smaller joints such as wrist, elbow, ankle and knee. A remarkably inferior image quality resulted in imaging of the hip, lumbar and thoracic spine (mean score values 2-3) in spite of almost doubling the dose (dose increased by 85 percent). The image quality of shoulder examinations was insufficient (mean score value 1). Phantom studies showed a high-contrast resolution comparable to helical CT in the xy-axis (9 lp/cm). Conclusion: Preliminary results show, that image quality of C-arm-based CT-imaging (ISO-C-3D) seems to be adequate in smaller joints. ISO-C-3D images of the hip and axial skeleton show a decreased image quality, which does not seem to be sufficient for diagnosing subtle fractures. (orig.) [German] Zielsetzung: Evaluierung der 3D-CT-Bildgebung mit einem C-Bogen-basierten dedizierten CT-System (ISO-C-3D, Fa. Siemens) an Extremitaetengelenken und am Stammskelett. Methodik: 27 humane Leichenpraeparate der unteren und oberen Extremitaet sowie des Stammskeletts wurden am ISO-C-3D untersucht und die Bilddaten anhand eines Bildqualitaetsscores von 3 Untersuchern semiquantitativ evaluiert (Score 1: nicht

  6. Structure of P-Glycoprotein Reveals a Molecular Basis for Poly-Specific Drug Binding

    Energy Technology Data Exchange (ETDEWEB)

    Aller, Stephen G.; Yu, Jodie; Ward, Andrew; Weng, Yue; Chittaboina, Srinivas; Zhuo, Rupeng; Harrell, Patina M.; Trinh, Yenphuong T.; Zhang, Qinghai; Urbatsch, Ina L.; Chang, Geoffrey; (Scripps); (TTU)

    2009-04-22

    P-glycoprotein (P-gp) detoxifies cells by exporting hundreds of chemically unrelated toxins but has been implicated in multidrug resistance (MDR) in the treatment of cancers. Substrate promiscuity is a hallmark of P-gp activity, thus a structural description of poly-specific drug-binding is important for the rational design of anticancer drugs and MDR inhibitors. The x-ray structure of apo P-gp at 3.8 angstroms reveals an internal cavity of -6000 angstroms cubed with a 30 angstrom separation of the two nucleotide-binding domains. Two additional P-gp structures with cyclic peptide inhibitors demonstrate distinct drug-binding sites in the internal cavity capable of stereoselectivity that is based on hydrophobic and aromatic interactions. Apo and drug-bound P-gp structures have portals open to the cytoplasm and the inner leaflet of the lipid bilayer for drug entry. The inward-facing conformation represents an initial stage of the transport cycle that is competent for drug binding.

  7. Construction and immunogenicity of DNA vaccines encoding fusion protein of murine complement C3d-p28 and GP5 gene of porcine reproductive and respiratory syndrome virus.

    Science.gov (United States)

    Zhang, Deqing; Xia, Qingxiang; Wu, Jiaqiang; Liu, Dong; Wang, Xiaolong; Niu, Zhongxiang

    2011-01-17

    Porcine reproductive and respiratory syndrome virus (PRRSV) has recently caused catastrophic losses in swine industry worldwide. The commercial vaccines only provide a limited protection against PRRSV infection. At present, DNA vaccine is the focus on the new vaccines. The gene fragment (p28) coding for the molecular adjuvants complement protein C3d (mC3d) from BALB/c mouse was cloned and expressed as a fusion protein for its application in the vaccine study of mice. Three potential vaccines construct units were engineered to contain two, four and six copies of mC3d-p28 coding gene linked to the GP5 gene of PRRSV and one vaccine expressing GP5 alone (pcDNA3.1-GP5) was constructed. Subsequently, the vaccines' abilities to elicit the humoral and cellular immune responses were investigated in mice. These results showed that significantly enhanced GP5-specific ELISA antibody, GP5-specific neutralizing antibody, IFN-γ level, and IL-4 level, could be induced in mice immunized with DNA construct units encoding the pcDNA3.1-C3d-p28.n-GP5 than those received DNA vaccine expressing GP5 alone (pcDNA3.1-GP5). Analysis of the immunogenicity of different repeats of mC3d-p28 revealed that mC3d-p28 had an enhancing effect on the immunogenicity of antigens, and that six or more repeats of mC3d-p28 may be necessary for efficient enhancement of antigen specific immune responses. This approach may provide a new strategy for the development of efficient vaccines against the PRRSV for pigs in the future. Copyright © 2010 Elsevier Ltd. All rights reserved.

  8. [A study on the construction, expression and immunosterility of Lagurus laguru zona pellucida 3 DNA vaccine pVAX1-sig-LTB-lZP3-C3d3].

    Science.gov (United States)

    Li, Chen-Chen; Yu, Ji-Yun; Jiang, Min; Tu, Yi-Xian; Ma, Xiao-Lin; Zhang, Fu-Chun

    2011-09-01

    To enhance the immunocontraceptive effect of Lagurus lagurus zona pellucida 3 DNA vaccine, and to achieve the prospect of application through the pVAX1-sig-LTB-lZP3-C3d3 different immunity pathway. Two adjuvant molecules were constructed into the recombinant plasmid pVAX1-sig-LTB-lZP3-C3d3 as DNA vaccine which contains Escherichia coli heat-labile enterotoxin B subunit and the molecular adjuvant 3 copies of C3d. The results of RT-PCR and western blot showed that the DNA vaccine was expressed in mRNA and protein level. The female C57BL/6 mice were immunized by three ways: intramuscular injection, intranasal or oral route.Antibody levels and types were detected by ELISA. ELISA results showed that recombinant plasmid pVAX1-sig-LTB-lZP3-C3d3 immunization induced specific IgG, IgA levels were significantly different comparing with control (Psig-LTB-lZP3-C3d3 can induce the specific immune response efficiently and enhance the immunocontraceptive effects.

  9. 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

    2015-01-01

    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. PMID:26405039

  10. 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. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Polyspecific associations between squirrel monkeys (Saimiri sciureus) and other primates in eastern Amazonia.

    Science.gov (United States)

    Pinheiro, Tatyana; Ferrari, Stephen F; Lopes, Maria Aparecida

    2011-11-01

    One of the most common types of polyspecific association observed in Neotropical primate communities is that between squirrel monkeys (Saimiri) and capuchins (Cebus). The present study focused on association patterns in two Saimiri sciureus groups in eastern Brazilian Amazonia, between March and October, 2009. The associations were analyzed in terms of the species involved, the degree of association, and niche breadth and overlap. The study involved two S. sciureus groups (B4 and GI) on the right and left bank of the Tocantins River, respectively, within the area of the Tucuruí reservoir in southeastern Pará. Relations between species were classified as associations (individuals within 50 m and moving in the same direction), and encounters (individuals within 50 m and no coordinated movement). Group B4 was in association with Cebus apella during 100% of monitoring, and with Chiropotes satanas in 20.2%. By contrast, Group GI associated with Cebus 54.8% of the time, and with Chiropotes utahickae 2.5%. Encounters with Alouatta belzebul and Saguinus niger were recorded at both sites, with Aotus azarae and Dasyprocta prymnolopha at B4, and with Callicebus moloch, Dasyproct aleporina, Mazama gouazoubira, and Nasua nasua at GI. Overall, Saimiri had a broader niche than Cebus in terms of vertical spacing and diet, but not for substrate use. This pattern did not appear to be affected by association. While group GI spent significantly (P < 0.05) more time in association with Cebus during the wet season, group B4 associated with Chiropotes more during the dry season. Despite the higher association rates, niche overlap was greater for all variables at B4. This may reflect differences in the ranging and foraging patterns at the two sites, and the varying potential benefits of association for Saimiri. © 2011 Wiley Periodicals, Inc.

  12. [3-D imaging with a mobile surgical image enhancement equipment (ISO-C-3D). Initial examples of fracture diagnosis of peripheral joints in comparison with spiral CT and conventional radiography].

    Science.gov (United States)

    Kotsianos, D; Rock, C; Euler, E; Wirth, S; Linsenmaier, U; Brandl, R; Mutschler, W; Pfeifer, K J

    2001-09-01

    To analyze a prototype mobile C-arm image amplifier (Iso-C3D) in the evaluation of different joint fractures of the upper and lower limbs using multiplanar reconstruction (MPR). Different cadaver joint specimens (n = 14) were examined with a prototype (Iso-C3D, Siemens AG, Erlangen, Germany), plain radiographs (CR), and spiral computed tomography (CT). The motorized C-arm provides fluoroscopic images during a 190 degrees orbital rotation computing a 119-mm data cube. These three-dimensional data sets yielded MPR images, which were evaluated by two readers for the detection and extent of fracture lines. Initial data show that fractures were easily depicted and correctly classified on MPR images with the Iso-C3D and that there was no difference between the Iso-C and CT in the detection of fractures. The preliminary results suggest a remarkably good detection of joint fractures with the Iso-C3D. Studies in an adequate number of patients are required to elucidate whether these promising results can also be obtained in a clinical setting.

  13. Quinoxaline-substituted chalcones as new inhibitors of breast cancer resistance protein ABCG2: polyspecificity at B-ring position

    Science.gov (United States)

    Winter, Evelyn; Gozzi, Gustavo Jabor; Chiaradia-Delatorre, Louise Domeneghini; Daflon-Yunes, Nathalia; Terreux, Raphael; Gauthier, Charlotte; Mascarello, Alessandra; Leal, Paulo César; Cadena, Silvia M; Yunes, Rosendo Augusto; Nunes, Ricardo José; Creczynski-Pasa, Tania Beatriz; Di Pietro, Attilio

    2014-01-01

    A series of chalcones substituted by a quinoxaline unit at the B-ring were synthesized and tested as inhibitors of breast cancer resistance protein-mediated mitoxantrone efflux. These compounds appeared more efficient than analogs containing other B-ring substituents such as 2-naphthyl or 3,4-methylenedioxyphenyl while an intermediate inhibitory activity was obtained with a 1-naphthyl group. In all cases, two or three methoxy groups had to be present on the phenyl A-ring to produce a maximal inhibition. Molecular modeling indicated both electrostatic and steric positive contributions. A higher potency was observed when the 2-naphthyl or 3,4-methylenedioxyphenyl group was shifted to the A-ring and methoxy substituents were shifted to the phenyl B-ring, indicating preferences among polyspecificity of inhibition. PMID:24920885

  14. Comparison of the effect of Crotalus simus and Crotalus durissus ruruima venoms on the equine antibody response towards Bothrops asper venom: implications for the production of polyspecific snake antivenoms.

    Science.gov (United States)

    Dos-Santos, Maria Cristina; Arroyo, Cynthia; Solano, Sergio; Herrera, María; Villalta, Mauren; Segura, Alvaro; Estrada, Ricardo; Gutiérrez, José María; León, Guillermo

    2011-02-01

    Antivenoms are preparations of immunoglobulins purified from the plasma of animals immunized with snake venoms. Depending on the number of venoms used during the immunization, antivenoms can be monospecific (if venom from a single species is used) or polyspecific (if venoms from several species are used). In turn, polyspecific antivenoms can be prepared by purifying antibodies from the plasma of animals immunized with a mixture of venoms, or by mixing antibodies purified from the plasma of animals immunized separately with single venom. The suitability of these strategies to produce polyspecific antibothropic-crotalic antivenoms was assessed using as models the venoms of Bothrops asper, Crotalus simus and Crotalus durissus ruruima. It was demonstrated that, when used as co-immunogen, C. simus and C. durissus ruruima venoms exert a deleterious effect on the antibody response towards different components of B. asper venom and in the neutralization of hemorrhagic and coagulant effect of this venom when compared with a monospecific B. asper antivenom. Polyspecific antivenoms produced by purifying immunoglobulins from the plasma of animals immunized with venom mixtures showed higher antibody titers and neutralizing capacity than those produced by mixing antibodies purified from the plasma of animals immunized separately with single venom. Thus, despite the deleterious effect of Crotalus sp venoms on the immune response against B. asper venom, the use of venom mixtures is more effective than the immunization with separate venoms for the preparation of polyspecific bothropic-crotalic antivenoms. Copyright © 2010 Elsevier Ltd. All rights reserved.

  15. Crystal structure of Yersinia pestis virulence factor YfeA reveals two polyspecific metal-binding sites.

    Science.gov (United States)

    Radka, Christopher D; DeLucas, Lawrence J; Wilson, Landon S; Lawrenz, Matthew B; Perry, Robert D; Aller, Stephen G

    2017-07-01

    Gram-negative bacteria use siderophores, outer membrane receptors, inner membrane transporters and substrate-binding proteins (SBPs) to transport transition metals through the periplasm. The SBPs share a similar protein fold that has undergone significant structural evolution to communicate with a variety of differentially regulated transporters in the cell. In Yersinia pestis, the causative agent of plague, YfeA (YPO2439, y1897), an SBP, is important for full virulence during mammalian infection. To better understand the role of YfeA in infection, crystal structures were determined under several environmental conditions with respect to transition-metal levels. Energy-dispersive X-ray spectroscopy and anomalous X-ray scattering data show that YfeA is polyspecific and can alter its substrate specificity. In minimal-media experiments, YfeA crystals grown after iron supplementation showed a threefold increase in iron fluorescence emission over the iron fluorescence emission from YfeA crystals grown from nutrient-rich conditions, and YfeA crystals grown after manganese supplementation during overexpression showed a fivefold increase in manganese fluorescence emission over the manganese fluorescence emission from YfeA crystals grown from nutrient-rich conditions. In all experiments, the YfeA crystals produced the strongest fluorescence emission from zinc and could not be manipulated otherwise. Additionally, this report documents the discovery of a novel surface metal-binding site that prefers to chelate zinc but can also bind manganese. Flexibility across YfeA crystal forms in three loops and a helix near the buried metal-binding site suggest that a structural rearrangement is required for metal loading and unloading.

  16. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Preclinical efficacy against toxic activities of medically relevant Bothrops sp. (Serpentes: Viperidae) snake venoms by a polyspecific antivenom produced in Mexico.

    Science.gov (United States)

    Segura, Álvaro; Herrera, María; Vargas, Mariángela; Villalta, Mauren; Uscanga-Reynell, Alfredo; León, Guillermo; Gutiérrez, José María

    2017-03-01

    The assessment of the preclinical neutralizing ability of antivenoms in Latin America is necessary to determine their scope of efficacy. This study was aimed at analyzing the neutralizing efficacy of a polyspecific bothropic-crotalic antivenom manufactured by BIRMEX in Mexico against lethal, hemorrhagic, defibrinogenating and in vitro coagulant activities of the venoms of Bothrops jararaca (Brazil), B. atrox (Perú and Colombia), B. diporus (Argentina), B. mattogrossensis (Bolivia), and B. asper (Costa Rica). Standard laboratory tests to determine these activities were used. In agreement with previous studies with bothropic antivenoms in Latin America, a pattern of cross-neutralization of heterologous venoms was observed. However, the antivenom had low neutralizing potency against defibrinogenating effect of the venoms of B. atrox (Colombia) and B. asper (Costa Rica), and failed to neutralize the in vitro coagulant activity of the venom of B. asper (Costa Rica) at the highest antivenom/venom ratio tested. It is concluded that, with the exception of coagulant and defibrinogenating activities of B. asper (Costa Rica) venom, this antivenom neutralizes toxic effects of various Bothrops sp venoms. Future studies are necessary to assess the efficacy of this antivenom against other viperid venoms.

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

    Science.gov (United States)

    Rangel, Luciana Pereira; Winter, Evelyn; Gauthier, Charlotte; Terreux, Raphaël; Chiaradia-Delatorre, Louise D; Mascarello, Alessandra; Nunes, Ricardo J; Yunes, Rosendo A; Creczynski-Pasa, Tania B; Macalou, Sira; Lorendeau, Doriane; Baubichon-Cortay, Hélène; Ferreira-Pereira, Antonio; Di Pietro, Attilio

    2013-01-01

    Adenosine triphosphate-binding cassette subfamily G member 2 (ABCG2) plays a major role in cancer cell multidrug resistance, which contributes to low eifficacy 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 3polyspecificity 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. The presence of a large O-benzyl substituent at position 4 and a 2′-naphthyl as A-ring markedly decreased the cytotoxicity, giving a high therapeutic ratio, which constitutes a critical requirement for future in-vivo assays in animal models. PMID:24109177

  19. Contributions of the snake venoms of Bothrops asper, Crotalus simus and Lachesis stenophrys to the paraspecificity of the Central American polyspecific antivenom (PoliVal-ICP).

    Science.gov (United States)

    Solano, Gabriela; Gómez, Aarón; Corrales, Greivin; Chacón, Danilo; Estrada, Ricardo; León, Guillermo

    2018-03-15

    PoliVal-ICP antivenom is produced from plasma of horses immunized toward the venoms of Bothrops asper, Crotalus simus and Lachesis stenophrys. The antibody response induced by these venoms confers PoliVal-ICP the capacity to neutralize the venoms of the most important Central American viperids, including not only homologous venoms (i.e., venoms used as immunogen), but many heterologous venoms (i.e., venoms not used as immunogen). In this work, the individual contributions of homologous venoms to the paraspecificity of PoliVal-ICP were inferred from the capacity of experimental monospecific antivenoms toward venoms of B. asper (anti-Ba), C. simus (anti-Cs) and L. stenophrys (anti-Ls), and an experimental polyspecific antivenom (anti-Ba/Cs/Ls) to neutralize the lethality induced by different venoms in mice. It was found that all antivenoms neutralized their corresponding homologous venoms. Moreover, the anti-Ba antivenom cross-neutralized the venoms of Agkistrodon howardgloydi, Atropoides picadoi, Bothriechis lateralis, Bothriechis supraciliaris and Porthidium ophryomegas; the anti-Cs antivenom cross-neutralized the venoms of B. lateralis, B. supraciliaris, Cerrophidion sasai and Porthidium nasutum; and the anti-Ls antivenom cross-neutralized the venoms of B. lateralis, B. supraciliaris, C. sasai and Lachesis melanocephala. All venoms neutralized by any monospecific antivenom were also neutralized by the anti-Ba/Cs/Ls antivenom. Venoms of Atropoides mexicanus, Bothriechis nigroviridis and Bothriechis schlegelii were not neutralized by any experimental antivenom, thus explaining the limitations of PoliVal-ICP to neutralize these venoms. Consequently, an enlargement of the neutralization scope of PoliVal-ICP could be achieved by including these venoms in the group of those used as immunogens. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Crystal structure of Yersinia pestis virulence factor YfeA reveals two polyspecific metal-binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Radka, Christopher D.; DeLucas, Lawrence J.; Wilson, Landon S.; Lawrenz, Matthew B.; Perry, Robert D.; Aller, Stephen G.

    2017-06-30

    Gram-negative bacteria use siderophores, outer membrane receptors, inner membrane transporters and substrate-binding proteins (SBPs) to transport transition metals through the periplasm. The SBPs share a similar protein fold that has undergone significant structural evolution to communicate with a variety of differentially regulated transporters in the cell. InYersinia pestis, the causative agent of plague, YfeA (YPO2439, y1897), an SBP, is important for full virulence during mammalian infection. To better understand the role of YfeA in infection, crystal structures were determined under several environmental conditions with respect to transition-metal levels. Energy-dispersive X-ray spectroscopy and anomalous X-ray scattering data show that YfeA is polyspecific and can alter its substrate specificity. In minimal-media experiments, YfeA crystals grown after iron supplementation showed a threefold increase in iron fluorescence emission over the iron fluorescence emission from YfeA crystals grown from nutrient-rich conditions, and YfeA crystals grown after manganese supplementation during overexpression showed a fivefold increase in manganese fluorescence emission over the manganese fluorescence emission from YfeA crystals grown from nutrient-rich conditions. In all experiments, the YfeA crystals produced the strongest fluorescence emission from zinc and could not be manipulated otherwise. Additionally, this report documents the discovery of a novel surface metal-binding site that prefers to chelate zinc but can also bind manganese. Flexibility across YfeA crystal forms in three loops and a helix near the buried metal-binding site suggest that a structural rearrangement is required for metal loading and unloading.

  1. 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

  2. Cross-reactivity and cross-immunomodulation between venoms of the snakes Bothrops asper, Crotalus simus and Lachesis stenophrys, and its effect in the production of polyspecific antivenom for Central America.

    Science.gov (United States)

    Arroyo, Cynthia; Solano, Sergio; Segura, Álvaro; Herrera, María; Estrada, Ricardo; Villalta, Mauren; Vargas, Mariángela; Gutiérrez, José María; León, Guillermo

    2017-11-01

    A mixture of the venoms of Bothrops asper, Crotalus simus and Lachesis stenophrys is used as immunogen to produce the polyspecific Central American antivenom (PoliVal-ICP). In this work, we studied the ability of each of these venoms to modulate the antibody response induced by the other two venoms included in the immunization mixture. For that, equine monospecific, bispecific and polyspecific antivenoms were prepared and compared regarding their ability to neutralize the phospholipase A 2 , coagulant and lethal activities of each venom, and their anti-venom antibodies concentration. Results indicate that there is low cross-reactivity and cross-neutralization between venoms of B. asper, C. simus and L. stenophrys, hence justifying the use of all of them as immunogens for the production of the Central American antivenom. It was also found that the venom of B. asper reduces the anti-crotalic response while the venom of C. simus does not affect the anti-bothropic response. On the other hand, the venoms of B. asper and C. simus increase the anti-lachesic response, and L. stenoprhys venom reduced both the anti-bothropic and anti-crotalic responses. On the basis of these results, the immunization strategy can be adjusted by preventing or taking advantage of cross-immunomodulation between venoms, in order to maximize the antibody response towards all venoms. Immune responses can be improved by injecting horses with several immunogen mixtures, composed by one or two of the three venoms, and administering them at different times during the immunization, eventually generating a high titer against the three venoms. Our results suggest that addressing the issue of immunomodulation by venoms might improve antivenom manufacture worldwide. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Laboratory Study of the Diagnostic Utility of the 3C/3D Line Ratio in Fe XVII

    Science.gov (United States)

    Brown, G. V.; Beiersdorfer, P.; Chen, H.; Chen, M., II; Reed, K. J.

    2002-01-01

    Fe XVII X-ray emission is present in a multitude of sources, such as the corona of the Sun, Capella, and Procyon. Two of the strongest lines observed in these spectra are the resonance and intercombination lines located at 15.01 and 15.26 A, respectively. As part of the laboratory astrophysics program at the electron beam ion traps EBIT-I & EBIT-II located at the Lawrence Livermore National Laboratory we have measured this line ratio for the case where the relative abundance of Fe XVI to Fe XVII is approx. 1. Our results show that an Fe XVI innershell satellite line coincides with the intercombination line and can significantly reduce the relative intensity, R, of the resonance to intercombination line. The fact that the apparent relative intensity of the resonance and intercombination line in Fe XVII is sensitive to the strength of an Fe XVI innershell satellite, and therefore, tho relative abundance of Fe XVI to Fe XVII, makes the line ratio a diagnostic of temperature, and explains the anomalously low ratios observed in the solar and stellar coronae.

  4. Plasma C3d levels of young farmers correlate with respirable dust exposure levels during normal work in swine confinement buildings

    DEFF Research Database (Denmark)

    Hoffmann, Hans Jürgen; Iversen, Martin; Brandslund, Ivan

    2003-01-01

    Work in swine confinement buildings leads to an inflammatory response and may be associated with increased levels of acute phase proteins. We compared the inflammatory response of a control group of young former farm workers with age-matched former farm workers who had previously developed the lo...

  5. Local order in fully deuterated liquid N-methylacetamide (C3D7NO) as studied by neutron diffraction and density-functional theory calculations.

    Science.gov (United States)

    Trabelsi, Sahbi; Nasr, Salah; Bahri, Mohamed; Bellissent-Funel, Marie-Claire

    2006-12-14

    A structural investigation of fully deuterated liquid N-methylacetmide (NMAd7) is performed at 308 K and atmospheric pressure by using neutron diffraction together with density-functional theory (DFT). The analysis of experimental data yields the total structure factor SM(Q), the molecular form factor F1(Q), and the distinct pair correlation function gL(r). The DFT calculations are performed to study the relative stability of the two possible isomers (trans and cis) and to examine some possible clusters recently published that may describe the intermolecular arrangement in the liquid state. Neutron measurements can be interpreted in terms of trans linear trimer (T1) and cis cyclic trimer (T2) where the total number of hydrogen bonds is respectively equal to two and three. The theoretical structure factors obtained on the basis of intermolecular arrangements agree fairly well with the experimental one beyond Q = 2 A-1. All through the study, a comparison is made with complementary X-ray results.

  6. Plasma C3d levels of young farmers correlate with respirable dust exposure levels during normal work in swine confinement buildings

    DEFF Research Database (Denmark)

    Hoffmann, Hans Jürgen; Iversen, Martin; Brandslund, Ivan

    2003-01-01

    Work in swine confinement buildings leads to an inflammatory response and may be associated with increased levels of acute phase proteins. We compared the inflammatory response of a control group of young former farm workers with age-matched former farm workers who had previously developed...

  7. Polyspecific drug and steroid clearance by an organic anion transporter of mammalian liver

    NARCIS (Netherlands)

    Bossuyt, [No Value; Muller, M; Hagenbuch, B; Meier, PJ

    An organic anion-transporting polypeptide that mediates sodium-independent uptake of negatively charged sulfobromophthalein and bile salts has recently been cloned from rat liver (Jacquemin et al., 1994). In this study we have extended the substrate specificity studies to neutral and positively

  8. Poly-specific association of the olive baboon ( Papio anubis ) group ...

    African Journals Online (AJOL)

    black and white colobus monkey Colobus polykomos, putty nosed monkey Cercopithecus nictitans, squirrel-Protoxerus stangeri, mona monkey Cercopithecus mona, human being Homo sapien, chimpanzee Pan troglodytes, and red river hog Potamochoerus porcus with poly specific association percentage of 32. 7, 19.4 ...

  9. Polyspecific organic anion transporting polypeptides mediate hepatic uptake of amphipathic type II organic cations

    NARCIS (Netherlands)

    van Montfoort, J.E; Hagenbuch, B; Fattinger, K.E; Muller, M; Groothuis, Geny; Meijer, D.K F; Meier, P.J

    1999-01-01

    Hepatic uptake of albumin-bound amphipathic organic cations has been suggested to be mediated by multispecific bile salt and organic anion transport systems. Therefore, we investigated whether the recently cloned rat organic anion transporting polypeptides 1 and 2 as well as the human organic anion

  10. Structural basis for polyspecificity in the POT family of proton-coupled oligopeptide transporters

    DEFF Research Database (Denmark)

    Lyons, Joseph A.; Parker, Joanne L.; Solcan, Nicolae

    2014-01-01

    An enigma in the field of peptide transport is the structural basis for ligand promiscuity, as exemplified by PepT1, the mammalian plasma membrane peptide transporter. Here, we present crystal structures of di‐ and tripeptide‐bound complexes of a bacterial homologue of PepT1, which reveal at least...

  11. Innovative immunization protocols using chimeric recombinant protein for the production of polyspecific loxoscelic antivenom in horses.

    Science.gov (United States)

    Figueiredo, Luís F M; Dias-Lopes, Camila; Alvarenga, Larissa M; Mendes, Thais M; Machado-de-Ávila, Ricardo A; McCormack, Jessica; Minozzo, João C; Kalapothakis, Evanguedes; Chávez-Olórtegui, Carlos

    2014-08-01

    A chimeric protein (rCpLi) was constructed expressing three epitopes of rLiD1, a dermonecrotic toxin from the venom of Loxosceles intermedia spider. We have analyzed the neutralization potential of sera obtained by immunization of horses with rCpLi and rCpLi combined with initial doses of venoms and compared these with antivenom traditionally produced in horses using crude Loxosceles gaucho, Loxosceles laeta and L. intermedia venoms as antigens. We have demonstrated by ELISA that horses immunized with three initial doses of crude venom containing mixtures of L. intermedia, L. gaucho and L. laeta followed by nine doses of rCpLi generate antibodies with the same reactivity as those produced following immunization with traditional antivenom, towards the venoms of the three Loxosceles sp. species. Results from in vivo and in vitro neutralization assays showed that the new horse sera are able to neutralize the dermonecrotic activity of Loxosceles venoms, which are of medical importance in Brazil and some of these sera are capable of meeting the necessary potency requirements that could allow for their therapeutic use in humans. This immunization strategy combining both antigens used approximately 67% less crude Loxosceles venoms compared to traditional immunization protocol and can mean the development of Loxosceles antivenoms with the consequent reduction of devastation of arachnid fauna. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Cross-recognition of a pit viper (Crotalinae) polyspecific antivenom explored through high-density peptide microarray epitope mapping

    DEFF Research Database (Denmark)

    Engmark, Mikael; Lomonte, Bruno; Gutiérrez, José María

    2017-01-01

    Snakebite antivenom is a 120 years old invention based on polyclonal mixtures of antibodies purified from the blood of hyper-immunized animals. Knowledge on antibody recognition sites (epitopes) on snake venom proteins is limited, but may be used to provide molecular level explanations...... for antivenom cross-reactivity. In turn, this may help guide antivenom development by elucidating immunological biases in existing antivenoms. In this study, we have identified and characterized linear elements of B-cell epitopes from 870 pit viper venom protein sequences by employing a high......-throughput methodology based on custom designed high-density peptide microarrays. By combining data on antibody-peptide interactions with multiple sequence alignments of homologous toxin sequences and protein modelling, we have determined linear elements of antibody binding sites for snake venom metalloproteases (SVMPs...

  13. Lachesis stenophrys venom reduces the equine antibody response towards Bothrops asper venom used as co-immunogen in the production of polyspecific snake antivenom.

    Science.gov (United States)

    Arroyo, Cynthia; Solano, Sergio; Herrera, María; Segura, Álvaro; Estrada, Ricardo; Vargas, Mariángela; Villalta, Mauren; Gutiérrez, José María; León, Guillermo

    2015-09-01

    The anti-bothropic activity of an antivenom prepared from the plasma of horses immunized with Bothrops asper venom (anti-B antivenom) was compared with a similar formulation produced from the plasma of horses immunized with a mixture of B. asper and Lachesis stenophrys venoms (anti-BL antivenom). Likewise, a comparison between the anti-lachesic activity of the anti-BL antivenom and a similar formulation prepared from horses immunized only with L. stenophrys venom (anti-L antivenom) was performed. The anti-BL antivenom had lower concentration of anti-bothropic antibodies than the anti-B antivenom. This difference was associated to a lower response towards all components of B. asper venom, but particularly towards some D49-phospholipases A2 (PLA2s) and PIII-metalloproteinases. Consequently, the anti-BL antivenom was less effective neutralizing lethal, coagulant, defibrinogenating, PLA2, and myotoxic activities of B. asper venom. On the other hand, anti-BL and anti-L antivenoms showed similar concentration of anti-lachesic antibodies, and similar capacity to recognize the HPLC fractions of L. stenophrys venom and to neutralize lethal, coagulant, proteolytic, hemorrhagic, PLA2 and myotoxic activities induced by this venom. It is concluded that, when used as co-immunogens, the venom of L. stenophrys reduces the antibody response towards B. asper venom, whereas the latter does not affect the anti-lachesic response. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Resolution of Serologic Problems Due to Cold Agglutinins in Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Javed, Rizwan; Datta, Suvro Sankha; Basu, Sabita; Chakrapani, Anupam

    2016-06-01

    Autoimmune hemolytic anemia can be classified depending on presence of warm, cold or mixed type of autoantibodies that are directed against antigens on the red blood cell surface. Here we report a case of pathological cold agglutinin disease which was eventually detected due to blood group discrepancy. A request was sent to the blood bank for two units of packed red cells in a diagnosed case of CLL which showed type IV discrepancy during blood grouping.The discrepancy was subsequently resolved after warm saline washing of red cells along with repetition of reverse grouping with pre-warmed serum. The direct antiglobulin test was positive and revealed autoanibodies against C3b/C3d only. Indirect antiglobulin test was performed with 3-cell panel in a polyspecific gel card (IgG+C3d) showed a pan-reactive pattern along with a positive autocontrol. Subsequently a cold agglutinin titration was performed and titers of 1024 at 4 °C; titer of 2 at room temperature were detected. Dithiothreitol (DTT) treatment of serum was undertaken and IgM type of autoantibody was detected in this case confirming a case of secondary cold agglutinin disease in this patient. Two units of red cells were transfused to this patient after successfully performing cross-match with pre-warmed serum. It was advised from the blood bank that the blood should be transfused slowly through a blood-warmer and patient should be kept in warm condition to avoid in-vivo hemolysis due to high titer of cold agglutinin. The transfusion was uneventful and patient is on regular follow-up till now. Thus we concluded that serological discrepancies observed in blood bank can successfully guide the bedside transfusion protocol in case of cold agglutinin disease.

  15. Frequency of Red Cell Alloimmunization and Autoimmunization in Thalassemia Patients: A Report from Eastern India.

    Science.gov (United States)

    Datta, Suvro Sankha; Mukherjee, Somnath; Talukder, Biplabendu; Bhattacharya, Prasun; Mukherjee, Krishnendu

    2015-01-01

    Introduction. Red blood cell (RBC) alloimmunization and autoimmunization remain a major problem in transfusion dependent thalassemic patients. There is a paucity of data on the incidence of RBC alloimmunization and autoimmunization in thalassemic patients from eastern part of India, as pretransfusion antibody screening is not routinely performed. Aims. To assess the incidence of RBC alloimmunization and autoimmunization in transfusion dependent thalassemic patients in eastern India. Materials and Methods. Total 500 thalassemia cases were evaluated. The antibody screening and identification were performed with commercially available panel cells (Diapanel, Bio-rad, Switzerland) by column agglutination method. To detect autoantibodies, autocontrol and direct antiglobulin tests were carried out using polyspecific coombs (IgG + C3d) gel cards in all patients. Results. A total of 28 patients developed RBC alloimmunization (5.6%) and 5 patients had autoantibodies (1%). Alloantibody against c had the highest incidence (28.57%) followed by E (21.42%). Five out of 28 (17.85%) patients had developed antibodies against both c and E. Conclusion. Data from this study demonstrate that the RBC alloantibody and autoantibody development rates are significant in our region. Thus, pretransfusion antibody screening needs to be initiated in eastern India in order to ensure safe transfusion practice.

  16. Frequency of Red Cell Alloimmunization and Autoimmunization in Thalassemia Patients: A Report from Eastern India

    Directory of Open Access Journals (Sweden)

    Suvro Sankha Datta

    2015-01-01

    Full Text Available Introduction. Red blood cell (RBC alloimmunization and autoimmunization remain a major problem in transfusion dependent thalassemic patients. There is a paucity of data on the incidence of RBC alloimmunization and autoimmunization in thalassemic patients from eastern part of India, as pretransfusion antibody screening is not routinely performed. Aims. To assess the incidence of RBC alloimmunization and autoimmunization in transfusion dependent thalassemic patients in eastern India. Materials and Methods. Total 500 thalassemia cases were evaluated. The antibody screening and identification were performed with commercially available panel cells (Diapanel, Bio-rad, Switzerland by column agglutination method. To detect autoantibodies, autocontrol and direct antiglobulin tests were carried out using polyspecific coombs (IgG + C3d gel cards in all patients. Results. A total of 28 patients developed RBC alloimmunization (5.6% and 5 patients had autoantibodies (1%. Alloantibody against c had the highest incidence (28.57% followed by E (21.42%. Five out of 28 (17.85% patients had developed antibodies against both c and E. Conclusion. Data from this study demonstrate that the RBC alloantibody and autoantibody development rates are significant in our region. Thus, pretransfusion antibody screening needs to be initiated in eastern India in order to ensure safe transfusion practice.

  17. Alloimmunization and autoimmunization in transfusion dependent thalassemia major patients: Study on 319 patients.

    Science.gov (United States)

    Dhawan, Hari Krishan; Kumawat, Vijay; Marwaha, Neelam; Sharma, Ratti Ram; Sachdev, Suchet; Bansal, Deepak; Marwaha, Ram Kumar; Arora, Satyam

    2014-07-01

    The development of anti-red blood cell antibodies (both allo-and autoantibodies) remains a major problem in thalassemia major patients. We studied the frequency of red blood cell (RBC) alloimmunization and autoimmunization among thalassemia patients who received regular transfusions at our center and analyzed the factors, which may be responsible for development of these antibodies. The study was carried out on 319 multiply transfused patients with β-thalassemia major registered with thalassemia clinic at our institute. Clinical and transfusion records of all the patients were examined for age of patients, age at initiation of transfusion therapy, total number of blood units transfused, transfusion interval, status of splenectomy or other interventions. Alloantibody screening and identification was done using three cell and 11 cell panel (Diapanel, Bio-rad, Switzerland) respectively. To detect autoantibodies, autocontrol was carried out using polyspecific coombs (IgG + C3d) gel cards. Eighteen patients out of total 319 patients (5.64%) developed alloantibodies and 90 (28.2%) developed autoantibodies. Nine out of 18 patients with alloantibodies also had autoantibodies. Age at first transfusion was significantly higher in alloimmunized than non-immunized patients (P = 0.042). Out of 23 alloantibodies, 52.17% belonged to Rh blood group system (Anti-E = 17%, Anti D = 13%, Anti-C = 13%, Anti-C(w) = 9%), 35% belonged to Kell blood group system, 9% of Kidd and 4% of Xg blood group system. Alloimmunization was detected in 5.64% of multitransfused thalassemia patients. Rh and Kell blood group system antibodies accounted for more than 80% of alloantibodies. This study re-emphasizes the need for RBC antigen typing before first transfusion and issue of antigen matched blood (at least for Rh and Kell antigen). Early institution of transfusion therapy after diagnosis is another means of decreasing alloimmunization.

  18. Alloimmunization and autoimmunization in transfusion dependent thalassemia major patients: Study on 319 patients

    Directory of Open Access Journals (Sweden)

    Hari Krishan Dhawan

    2014-01-01

    Full Text Available Background: The development of anti-red blood cell antibodies (both allo-and autoantibodies remains a major problem in thalassemia major patients. We studied the frequency of red blood cell (RBC alloimmunization and autoimmunization among thalassemia patients who received regular transfusions at our center and analyzed the factors, which may be responsible for development of these antibodies. Materials and Methods: The study was carried out on 319 multiply transfused patients with β-thalassemia major registered with thalassemia clinic at our institute. Clinical and transfusion records of all the patients were examined for age of patients, age at initiation of transfusion therapy, total number of blood units transfused, transfusion interval, status of splenectomy or other interventions. Alloantibody screening and identification was done using three cell and 11 cell panel (Diapanel, Bio-rad, Switzerland respectively. To detect autoantibodies, autocontrol was carried out using polyspecific coombs (IgG + C3d gel cards. Results: Eighteen patients out of total 319 patients (5.64% developed alloantibodies and 90 (28.2% developed autoantibodies. Nine out of 18 patients with alloantibodies also had autoantibodies. Age at first transfusion was significantly higher in alloimmunized than non-immunized patients (P = 0.042. Out of 23 alloantibodies, 52.17% belonged to Rh blood group system (Anti-E = 17%, Anti D = 13%, Anti-C = 13%, Anti-C w = 9%, 35% belonged to Kell blood group system, 9% of Kidd and 4% of Xg blood group system. Conclusion: Alloimmunization was detected in 5.64% of multitransfused thalassemia patients. Rh and Kell blood group system antibodies accounted for more than 80% of alloantibodies. This study re-emphasizes the need for RBC antigen typing before first transfusion and issue of antigen matched blood (at least for Rh and Kell antigen. Early institution of transfusion therapy after diagnosis is another means of decreasing

  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...

  20. Activity budgets on social and reproductive behaviour of olive baboons

    African Journals Online (AJOL)

    The study was conducted to investigate the activity budgets on social interactions and reproductive behaviour of olive baboon (Papio anubis) at Gashaka Gumti ... Results of polyspecific association shows that the baboons spent 14.29% of the time in association with red flanked duikers, 14.29% with black-and-white ...

  1. 374-IJBCS-Article-Sylvie Djego

    African Journals Online (AJOL)

    User

    et Marie Curie, Paris, pp 226. Galat-Luong A, Galat G. 2006. Résistance pugnance des colobes bai du Saloum. Journal de l'IRD. Gautier-Hion A, Quris R, Gautier JP. 1983. Monospecific vs polyspecific life: a comparative study of foraging and antipredatory tactics in a community of. Cercopithecus monkeys. Behav. Ecol.

  2. Immunoglobulin G for patients with necrotising soft tissue infection (INSTINCT)

    DEFF Research Database (Denmark)

    Madsen, Martin B.; Hjortrup, Peter B.; Hansen, Marco B.

    2017-01-01

    Purpose: The aim of the INSTINCT trial was to assess the effect of intravenous polyspecific immunoglobulin G (IVIG) compared with placebo on self-reported physical function in intensive care unit (ICU) patients with necrotising soft tissue infection (NSTI). Methods: We randomised 100 patients wit...

  3. Engineering posttranslational proofreading to discriminate nonstandard amino acids

    OpenAIRE

    Kunjapur, Aditya M.; Stork, Devon A.; Kuru, Erkin; Vargas-Rodriguez, Oscar; Landon, Matthieu; Söll, Dieter; Church, George M.

    2018-01-01

    Incorporation of nonstandard amino acids (nsAAs) leads to chemical diversification of proteins, which is an important tool for the investigation and engineering of biological processes. However, the aminoacyl-tRNA synthetases crucial for this process are polyspecific in regard to nsAAs and standard amino acids. Here, we develop a quality control system called “posttranslational proofreading” to more accurately and rapidly evaluate nsAA incorporation. We achieve this proofreading by hijacking ...

  4. [Detection of irregular anti-erythrocyte antibodies using the indirect antiglobulin test in a low-ionic-strength medium. Immunohematology Group of the French Blood Transfusion Society].

    Science.gov (United States)

    Mannessier, L; Roubinet, F

    1999-06-01

    The detection of irregular antibodies is usually performed with serum by the indirect antiglobulin test (IAT) with a polyspecific antiglobulin reagent. In a first study in 1996, we compared the results obtained with 3,264 blood samples of patients drawn with or without anticoagulant: no significant difference was observed among the 240 allo-antibodies detected and identified. In this paper we report the comparison of the results obtained by IAT on column of filtration with two kinds of reagents: polyspecific and anti-IgG antibodies. Respectively 2,927 (76 contained an antibody), and 643 (161 contained an antibody) sera of patients were tested with methods ID-Diamed and Ortho-Biovue. Titrations of 153 other antibodies were also performed with the two reagents. Results showed no significant difference using either polyspecific reagent or the anti-IgG antibodies. This study proves that it is possible to perform screening of irregular antibodies on uncoagulated blood samples. This possibility allows automation as blood typing and screening of irregular antibodies can be carried out with the same sample.

  5. Water-mediated interactions enable smooth substrate transport in a bacterial efflux pump.

    Science.gov (United States)

    Vargiu, Attilio Vittorio; Ramaswamy, Venkata Krishnan; Malvacio, Ivana; Malloci, Giuliano; Kleinekathöfer, Ulrich; Ruggerone, Paolo

    2018-04-01

    Efflux pumps of the Resistance-Nodulation-cell Division superfamily confer multi-drug resistance to Gram-negative bacteria. The most-studied polyspecific transporter belonging to this class is the inner-membrane trimeric antiporter AcrB of Escherichia coli. In previous studies, a functional rotation mechanism was proposed for its functioning, according to which the three monomers undergo concerted conformational changes facilitating the extrusion of substrates. However, the molecular determinants and the energetics of this mechanism still remain unknown, so its feasibility must be proven mechanistically. A computational protocol able to mimic the functional rotation mechanism in AcrB was developed. By using multi-bias molecular dynamics simulations we characterized the translocation of the substrate doxorubicin driven by conformational changes of the protein. In addition, we estimated for the first time the free energy profile associated to this process. We provided a molecular view of the process in agreement with experimental data. Moreover, we showed that the conformational changes occurring in AcrB enable the formation of a layer of structured waters on the internal surface of the transport channel. This water layer, in turn, allows for a fairly constant hydration of the substrate, facilitating its diffusion over a smooth free energy profile. Our findings reveal a new molecular mechanism of polyspecific transport whereby water contributes by screening potentially strong substrate-protein interactions. We provided a mechanistic understanding of a fundamental process related to multi-drug transport. Our results can help rationalizing the behavior of other polyspecific transporters and designing compounds avoiding extrusion or inhibitors of efflux pumps. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

  6. Anti-JMH identified in serum and in eluate from red cells of a JMH-negative man

    International Nuclear Information System (INIS)

    Whitsett, C.F.; Moulds, M.; Pierce, J.A.; Hare, V.

    1983-01-01

    Anti-JMH was identified in the serum of an 80-year-old JMH-negative man. Before transfusion, his direct antiglobulin test was weakly positive with polyspecific reagents, anti-C3 and anti-IgG. An eluate prepared from his red cells contained anti-JMH. Chromium-51-labeled JMH-positive cells which were weakly incompatible in vitro appeared to survive normally. Following transfusion with three JMH-positive units, the patient's hematocrit increased from 20.7 percent to 32.1 percent

  7. Thermodynamic secrets of multidrug resistance: A new take on transport mechanisms of secondary active antiporters.

    Science.gov (United States)

    Zhang, Xuejun C; Liu, Min; Lu, Guangyuan; Heng, Jie

    2018-03-01

    Multidrug resistance (MDR) presents a growing challenge to global public health. Drug extrusion transporters play a critical part in MDR; thus, their mechanisms of substrate recognition are being studied in great detail. In this work, we review common structural features of key transporters involved in MDR. Based on our membrane potential-driving hypothesis, we propose a general energy-coupling mechanism for secondary-active antiporters. This putative mechanism provides a common framework for understanding poly-specificity of most-if not all-MDR transporters. © 2017 The Protein Society.

  8. Impact of regional variation in Bothrops asper snake venom on the design of antivenoms: integrating antivenomics and neutralization approaches.

    Science.gov (United States)

    Gutiérrez, José María; Sanz, Libia; Flores-Díaz, Marietta; Figueroa, Lucía; Madrigal, Marvin; Herrera, María; Villalta, Mauren; León, Guillermo; Estrada, Ricardo; Borges, Adolfo; Alape-Girón, Alberto; Calvete, Juan J

    2010-01-01

    Intraspecific snake venom variations have implications in the preparation of venom pools for the generation of antivenoms. The impact of such variation in the cross-reactivity of antivenoms against Bothrops asper venom was assessed by comparing two commercial and four experimental antivenoms. All antivenoms showed similar immunorecognition pattern toward the venoms from adult and neonate specimens. They completely immunodepleted most P-III snake venom metalloproteinases (SVMPs), l-amino acid oxidases, serine proteinases, DC fragments, cysteine-rich secretory proteins (CRISPs), and C-type lectin-like proteins, and partially immunodepleted medium-sized disintegrins, phospholipases A(2) (PLA(2)s), some serine proteinases, and P-I SVMPs. Although all antivenoms abrogated the lethal, hemorrhagic, coagulant, proteinase, and PLA(2) venoms activities, monospecific experimental antivenoms were more effective than the polyspecific experimental antivenom. In addition, the commercial antivenoms, produced in horses subjected to repeated immunization cycles, showed higher neutralization than experimental polyspecific antivenom, produced by a single round of immunization. Overall, a conspicuous pattern of cross-neutralization was evident for all effects by all antivenoms, and monospecific antivenoms raised against venom from the Caribbean population were effective against venom from the Pacific population, indicating that geographic variations in venom proteomes of B. asper from Costa Rica do not result in overt variations in immunological cross-reactivity between antivenoms.

  9. Expansion of antibody reactivity in the cerebrospinal fluid of multiple sclerosis patients – follow-up and clinical implications

    Directory of Open Access Journals (Sweden)

    Reske Dirk

    2005-06-01

    Full Text Available Abstract Background An intrathecal polyspecific antibody response is a well known finding in multiple sclerosis. However, little is known about the evolution of intrathecal antibodies over time and their impact on the disease progress. Therefore, we focused in this study on the intrathecal polyspecific antibody response in multiple sclerosis. Methods Here we present a follow-up study of 70 patients with multiple sclerosis over 1 to 106 months. Serum and cerebrospinal fluid sample pairs were obtained from 1 to 5 consecutive lumbar punctures. CSF cell count, the IgG index, local IgG synthesis, oligoclonal bands and the antibody index for measles, rubella or varicella zoster were calculated. Results were analysed with regard to clinical characteristics of the patients. Results Once an intrathecal antibody response was established, it persisted. De novo antibody response against measles virus developed in 7% of the patients between the first and the second spinal tap. In two of seven patients where 5 consecutive CSF samples were available, the intrathecal antibody response expanded from one to three antigens. Furthermore, an intrathecal measles antibody production was associated with a rapid progression of the disease. Conclusion These data stress the importance of activated B cells for the disease process and the clinical outcome in multiple sclerosis.

  10. 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. Copyright © 2013 John Wiley & Sons, Ltd.

  11. REPLICATION TOOL AND METHOD OF PROVIDING A REPLICATION TOOL

    DEFF Research Database (Denmark)

    2016-01-01

    structured master surface (3a, 3b, 3c, 3d) having a lateral master pattern and a vertical master profile. The microscale structured master surface (3a, 3b, 3c, 3d) has been provided by localized pulsed laser treatment to generate microscale phase explosions. A method for producing a part with microscale...... protrusions. The microscale protrusions may be provided on a flange portion of a first part and are configured to act as energy directors when forming an ultrasonic joint with a cooperating flange portion of a second part....

  12. 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

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

    NARCIS (Netherlands)

    Veerhuis, Robert; Boshuizen, Ronald S.; Morbin, Michela; Mazzoleni, Giulia; Hoozemans, Jeroen J. M.; Langedijk, Johannes P. M.; Tagliavini, Fabrizio; Langeveld, Jan P. M.; Eikelenboom, Piet

    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-Straussier-Scheinker disease and scrapie-infected mouse brain. Biological

  14. The role of complement in the acquired immune response

    DEFF Research Database (Denmark)

    Nielsen, C H; Fischer, E M; Leslie, R G

    2000-01-01

    to specific T cells; the activation of a CD21/CD19 complex-mediated signalling pathway in B cells, which provides a stimulus synergistic to that induced by antigen interaction with the B-cell receptor (BCR); and promotion of the interaction between B cells and FDC, where C3d-bearing immune complexes...

  15. Potential pitfalls in the anorectal region during CT colonography: A ...

    African Journals Online (AJOL)

    2017-02-28

    Feb 28, 2017 ... FIGURE 9: (a) 3D endoluminal view showing artefacts (black arrows) obscuring visualisation of the rectum; (b) 2D axial of the same patient shows streak artefacts limiting visualisation of colon (red arrow). This is a typical example of artefacts caused by hip prostheses; (c) 3D view shows 'black hole' artefact.

  16. 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-dep...

  17. Comparison of Isocentric C-Arm 3-Dimensional Navigation and Conventional Fluoroscopy for Percutaneous Retrograde Screwing for Anterior Column Fracture of Acetabulum

    Science.gov (United States)

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

    2016-01-01

    Abstract 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. PMID:26765448

  18. 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.

  19. 15 CFR 4.34 - Specific exemptions.

    Science.gov (United States)

    2010-01-01

    ...—COMMERCE/DEPT-14; and (ii) The foregoing are exempted from 5 U.S.C. 552a (c)(3), (d), (e)(1), (e)(4)(G), (H... Censuses—COMMERCE/ CENSUS-5; (E) Population Census Personal Service Records for 1900 and All Subsequent... Midshipman Personnel Files—COMMERCE/MA-18; (D) USMMA Non-Appropriated fund Employees—COMMERCE/MA-19; (E...

  20. 77 FR 23173 - Privacy Act of 1974: Implementation

    Science.gov (United States)

    2012-04-18

    ... UMRA analysis is required. This proposed rule would not impose federal mandates on any state, local, or... subsections (c)(3); (d)(1), (2), (3) and (4); and (e)(1): (1) Air Intelligence Program (Justice/DEA-001) (2... pursuant to 5 U.S.C. 552a(j)(2), (k)(1), and (k)(2): Air Intelligence Program (Justice/DEA-001...

  1. Comparative Study of C-arms for Intraoperative 3-dimensional Imaging and Navigation in Minimally Invasive Spine Surgery Part I: Applicability and Image Quality.

    Science.gov (United States)

    Klingler, Jan-Helge; Sircar, Ronen; Scheiwe, Christian; Kogias, Evangelos; Volz, Florian; Krüger, Marie T; Hubbe, Ulrich

    2017-07-01

    This was a retrospective analysis. This study compares 2 different 3-dimensional (3D) C-arm devices for intraoperative imaging and navigation with regard to clinical applicability and image quality. Minimally invasive spine surgery requires intraoperative imaging techniques to adequately visualize the unexposed spine. For this purpose, mobile 3D C-arms became available along with the evolution of intraoperative navigation techniques. The C-arm devices Siremobil Iso-C 3D (Siemens) and Vision FD Vario 3D (Ziehm) perform an automated orbital rotation around the patient acquiring a 3D image set out of multiple successive fluoroscopic images. We report on technical specifications of the C-arms and our daily experience regarding clinical applicability. Furthermore, 5 spine surgeons evaluated blinded triplanar planes of 40 cervical, thoracic, and lumbar 3D scans that were obtained during routine surgery regarding usability for navigation. We assessed the delineation of cortical bone, artifacts, and overall image quality using a 0-10 numeric rating scale. The Siremobil Iso-C 3D requires 128 seconds for its 190-degree scanning arc with equidistant isocenter. The Vision FD Vario 3D performs an elliptical scanning arc and completes its 135-degree scan in 64 seconds; furthermore, it features a flat panel detector and fully digital imaging. The smaller dimensions of the Vision FD Vario 3D made it easier to maneuver in the operating room compared with the more bulky Siremobil Iso-C 3D. With respect to image quality in cervical 3D scans, the Siremobil Iso-C 3D reached significantly higher scores in all categories. The Vision FD Vario 3D revealed less artifacts in lumbar 3D scans. The Siremobil Iso-C 3D provides high-quality 3D scans in slender spine regions (eg, cervical spine), whereas the Vision FD Vario 3D appears to have advantages in the lumbar spine. Further evolution and novel devices are needed to optimize image quality and handling.

  2. Arterial Blood Pressure Induces Transient C4b-Binding Protein in Human Saphenous Vein Grafts.

    Science.gov (United States)

    Kupreishvili, Koba; Meischl, Christof; Vonk, Alexander B A; Stooker, Wim; Eijsman, Leon; Blom, Anna M; Quax, Paul H A; van Hinsbergh, Victor W M; Niessen, Hans W M; Krijnen, Paul A J

    2017-05-01

    Complement is an important mediator in arterial blood pressure-induced vein graft failure. Previously, we noted activation of cell protective mechanisms in human saphenous veins too. Here we have analyzed whether C4b-binding protein (C4bp), an endogenous complement inhibitor, is present in the vein wall. Human saphenous vein segments obtained from patients undergoing coronary artery bypass grafting (n = 55) were perfused in vitro at arterial blood pressure with either autologous blood for 1, 2, 4, or 6 hr or with autologous blood supplemented with reactive oxygen species scavenger N-acetylcysteine. The segments were subsequently analyzed quantitatively for presence of C4bp and complement activation product C3d using immunohistochemistry. Perfusion induced deposition of C3d and C4bp within the media of the vessel wall, which increased reproducibly and significantly over a period of 4 hr up to 3.8% for C3d and 81% for C4bp of the total vessel area. Remarkably after 6 hr of perfusion, the C3d-positive area decreased significantly to 1.3% and the C4bp-positive area to 19% of the total area of the vein. The areas positive for both C4bp and C3d were increased in the presence of N-acetylcysteine. Exposure to arterial blood pressure leads to a transient presence of C4bp in the vein wall. This may be part of a cell-protective mechanism to counteract arterial blood pressure-induced cellular stress and inflammation in grafted veins. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Discovering sequence motifs in quantitative and qualitative pepetide data

    DEFF Research Database (Denmark)

    Andreatta, Massimo

    the number of experimental tests needed to identify new epitopes. Taken as a whole, this thesis provides a valuable series of algorithms and tools for the analysis of peptide data, both from the point of view of characterization of sequence motifs and the prediction of protein-peptide interactions....... and interpret such data. The first paper in this thesis presents a new, publicly available method based on artificial neural networks that allows custom analysis of quantitative peptide data. The online NNAlign web-server provides a simple yet powerful tool for the discovery of sequence motifs in large...... with the presence of multiple motifs, due to the experimental setup or the actual poly-specificity of the receptor, in peptide data. A new algorithm, based on Gibbs sampling, identifies multiple specificities by performing two tasks simultaneously: alignment and clustering of peptide data. The method, available...

  4. The foraging kinetics of ground ant communities in different mexican coffee agroecosystems.

    Science.gov (United States)

    Nestel, D; Dickschen, F

    1990-08-01

    Foraging efficiency was studied by measuring the rate of tuna fish bait discovery by ants in unshaded and two types of shaded coffee systems. We also investigated the effect of weed biomass upon ant foraging efficiency. We found that the rate of discovery was faster in the coffee system with no shade than in systems with shade trees. The rate of discovery in the two types of shade systems (monospecific and polyspecific shade) was similar. Differences in the foraging rate between systems seem to be related to the composition of the ground ant community in each of the systems, and to cumulative factors such as plant diversity, microclimate and interspecific competition. No correlation was found between weed biomass and ant foraging efficiency. The results of this study support the idea of manipulating agroecosystem plant and structural diversity in order to enhance pest regulation by ants.

  5. [Value of positive auto controls in the gel centrifugation method].

    Science.gov (United States)

    Eichler, H; Kretschmer, V

    1994-01-01

    We studied 97 samples of patients being positive in the autocontrol of the indirect antiglobulin test (IAT) in the gel system (DiaMed). In 83.2%, retesting with monospecific anti-IgG serum gave also positive results, due to a specific phenomenon caused, for example, by drug-specific antibodies (AB), warm auto-AB or allo-AB. In contrast, only 52.9% of the samples retested by the standard tube technique with polyspecific antiglobulin serum reacted positive. Only in 6 patients slightly increased cold agglutinins could be detected. None of the investigated patients showed any clinical or laboratory signs of hemolysis except one with pernicious anemia. We conclude that positive results of the autocontrol in the gel IAT should be confirmed by an additional DAT in the tube technique. If this second test shows a negative result, transfusions can take place without any restrictions.

  6. Improved Prediction of Bovine Leucocyte Antigens (BoLA) Presented Ligands by Use of Mass-Spectrometry-Determined Ligand and in Vitro Binding Data

    DEFF Research Database (Denmark)

    Nielsen, Morten; Connelley, Tim; Ternette, Nicola

    2018-01-01

    of the data. We here outline a general pipeline for dealing with this challenge and accurately annotate ligands to the relevant MHC-I molecule they were eluted from by use of GibbsClustering and binding motif information inferred from in silico models. We illustrate the approach here in the context of MHC......, and predictors of peptide-MHC interactions constitute an attractive alternative. Recently, an increasing amount of MHC presented peptides identified by mass spectrometry (MS ligands) has been published. Handling and interpretation of MS ligand data is, in general, challenging due to the polyspecificity nature......-I molecules (BoLA) of cattle. Next, we demonstrate how such annotated BoLA MS ligand data can readily be integrated with in vitro binding affinity data in a prediction model with very high and unprecedented performance for identification of BoLA-I restricted T-cell epitopes. The prediction model is freely...

  7. Cumulative autoimmunity: T cell clones recognizing several self-epitopes exhibit enhanced pathogenicity

    Directory of Open Access Journals (Sweden)

    Roland S. LIBLAU

    2011-10-01

    Full Text Available T cell receptor (TCR recognition is intrinsically polyspecific. In the field of autoimmunity, recognition of both self- and microbial peptides by a single TCR has led to the concept of molecular mimicry. However, findings made by our group and others clearly demonstrate that a given TCR can also recognize multiple distinct self-peptides. Based on our data we postulate that recognition of several self-peptides is an important parameter governing the pathogenicity of an autoreactive T cell, and refer to this function as ‘cumulative autoimmunity’. The mechanisms of such increased pathogenicity, and the implications of cumulative autoimmunity regarding the pathophysiology of T cell-mediated autoimmune diseases will be discussed.

  8. 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.

  9. 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...

  10. The value of intraoperative three dimensional fluoroscopy in anterior decompressive surgery of the cervical spine.

    Science.gov (United States)

    Baldauf, J; Müller, J-U; Fleck, S; Hinz, P; Chiriac, A; Schroeder, H W S

    2008-02-01

    Intraoperative use of the mobile Siremobil Iso-C3D C-arm (Siemens AG, Medical Solutions, Erlangen) considerably improves the information available during cervical spine surgery. We report our experiences with the Iso-C3D fluoroscopic unit during anterior decompressive surgery of the cervical spine. We used the mobile Siremobil Iso-C3D C-arm during decompressive cervical spine surgery. The study included 25 patients (22 males, 3 females) with degenerative cervical stenosis. Mean age was 55.9 years (42-73 years). Eighteen patients were surgically treated for one-level, six for two-level and one for three-level disease. Intraoperative 3D imaging was performed to evaluate the extent of bony decompression and to assist correct positioning of the cages when the surgeon believed that sufficient decompression had been achieved. Visualization of the extent of bone removal was good in all patients. In 3 patients, insufficient bony decompression with persisting dorsal osteophytic spurs was noticed on sagittal and axial images. In these patients, surgery had to be continued. Successful decompression was proved thereafter by a second scan. The quality of the images of the cervical spine was sufficient, although slightly inferior to that of a CT scan. The Siremobil Iso-C3D provides intraoperative 3D images of bony structures of the cervical spine. Although the imagine quality is inferior to that of a CT, in our series surgical revisions could be avoided in 12.5% of the patients on the basis of these intraoperative images of incomplete bony decompression. This means a reduction of additional costs which would arise with surgical revision.

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

    OpenAIRE

    Rose, M. L.; Habeshaw, J. A.; Kennedy, R.; 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 ...

  12. African Journal of Neurological Sciences 2010 - Vol. 29, No 2 http ...

    African Journals Online (AJOL)

    voie publique, dont le mécanisme n'a pu être précisé. L'examen clinique avait retrouvé une cervicalgie avec contracture des muscles para-vertébraux cervicaux sans signes neurologiques déficitaires. La radiographie du rachis cervical avaient objectivé une fracture bipédiculaire de C2 avec luxation C2-C3 d'environ 4 mm.

  13. Granulocyte enzymes and complement after an anaphylactoid reaction to coronary angiography

    Energy Technology Data Exchange (ETDEWEB)

    Rasmussen, Finn (Odense University Hospital (Denmark). Department of Diagnostic Radiology); Antonsen, Steen (Odense University Hospital (Denmark). Department of Clinical Chemistry); Georgsen, Joergen (State University Hospital, Copenhagen (Denmark). Department of Clinical Immunology)

    An anaphylactoid reaction following angiography with ioxaglate in a 59-year-old man implied generalized pruritis, angioedema, bronchospasm and hypotension. Leucocytosis and an increased number of neutrophils were observed from 90 min to 8 h after the reaction. Elevated values of the neutrophil specific enzymes elastase and lactoferrin were demonstrated . The concentrations of C3d and CH50 did not change which indicate that no complement activation took place. (author). 32 refs.; 1 fig.

  14. Infantile Cytomegalovirus-Associated Severe Warm Autoimmune Hemolytic Anemia: A Case Report

    OpenAIRE

    Khalifeh, Hassan K.; Mourad, Youmna M.; Chamoun, Cynthia T.

    2017-01-01

    Autoimmune hemolytic anemia is a rare hematologic entity in children. Etiologies are mainly viruses or bacteria. We describe here a case of severe warm autoimmune hemolytic anemia (IgG- and C3d-positive direct antiglobulin test) in an immunocompetent 6-month-old infant with acute Cytomegalovirus infection that responded well to corticotherapy and intraveneous immunoglobulins without using blood component transfusion. This case demonstrates the importance of recognizing CMV in infantile Autoim...

  15. Proceedings of the Japan - U.S. Conference on Composite Materials (6th) Held in Orlando, Florida on June 22-24, 1992

    Science.gov (United States)

    1993-03-01

    set free in all direction. (4) Solver : ABAQUS (5) Element : For the twisted cord; an element of C3D8 (8 node, linear displacement brick) is used, while...carbon is a high-strength refractory composite material which has excellent specific strength at very high temperatures. Therefore, it is a prime...conventional refractory lined heat treat furnace. Treatments investigated were twenty four hours of exposure in oxidizing environments at temperatures of

  16. Three-dimensional Radar Imaging of a Building

    Science.gov (United States)

    2012-12-01

    CFAR ) detector. We discuss methods of 3-D image visualization and interpretation of the results and point the way to possible future improvements. 15...13 Figure 6. CFAR detector sliding windows for point-like targets, showing (a) 2-D and (b) 3-D version... CFAR detection of walls, showing (a) 2-D version (line detector), (b) 3-D version for the airborne case (line detector), and (c) 3-D version for the

  17. 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 Use...

  18. STRATIFICATION IN WASTE STABILIZATION PONDS I: EFFECTS ...

    African Journals Online (AJOL)

    NIJOTECH

    within the pond. Hence thermal stratification resulted in the variation of BOD values within the vertical water column with the maximum value of 1149.5mg/l at the bottom and a mini mum value of 450mg/l at the surface layers as shown in Figures 3c, 3d and 5 to 10. Chemical Oxygen Demand (COD). The vertical distribution of ...

  19. Swept blade influence on aerodynamic performance of steam ...

    Indian Academy of Sciences (India)

    ZI-MING FENG

    2018-04-12

    Apr 12, 2018 ... iments with air and water for fundamental turbulent shear flows, including homogeneous shear ... wide range of wall-bounded and free shear flows. 2.3 Geometric model 3 of blade .... Computation grid: (a) grid of leading edge part; (b) grid of trailing edge part; (c) 3D grids. SЕdhanЕ (2018) 43:56. Page 3 of ...

  20. Five new triterpene bisglycosides with acyclic side chains from the rhizomes of Cimicifuga foetida L.

    Science.gov (United States)

    Lu, Lu; Chen, Jian-Chao; Song, He-Jiao; Li, Yan; Nian, Yin; Qiu, Ming-Hua

    2010-05-01

    Five new triterpene bisglycosides, foetidinosides A (1), B (2), C (3), D (4) and E (5), including three of the cycloartane type, one of its derivative, and one of the lanostane type were isolated from the rhizomes of Cimicifuga foetida. Their structures were elucidated on the basis of spectroscopic data and chemical evidence. They were the first bisglycosides with acyclic side chains which were different from the typical triterpenes with side chains epoxidized with ring D in Cimicifuga species.

  1. Download this PDF file

    African Journals Online (AJOL)

    DELL

    surface analysis was also done using 3-D profilometry technique and optical microscopy in order to determine .... Thermal conductivity. 16.2 W/m K at 100 oC. Thermal expansion. 17.2 x 10-6/K at 100 oC. 3-D surface parameter Ra. 213 nm. ( )a. Fig. 1 (a) 3-D optical profile (b) optical micrograph of 304L stainless steel.

  2. Structural Acoustic Physics Based Modeling of Curved Composite Shells

    Science.gov (United States)

    2017-09-19

    various geometries and materials. This can help drive future research on composite material applications and enhance design methods for future Navy...both the plate and the water is 0.15 inch. The plate elements are eight-node, linear , brick stress/displacement continuum elements (C3D8R) while the...water elements are eight-node, linear , brick acoustic continuum elements (AC3D8). The analyses of the flat plate model were completed using Abaqus

  3. [Intraoperative three-dimensional navigation for pedicle screw placement].

    Science.gov (United States)

    Grützner, P A; Beutler, T; Wendl, K; von Recum, J; Wentzensen, A; Nolte, L-P

    2004-10-01

    The mobile SIREMOBIL Iso-C(3D) C-arm (Siemens, Erlangen, Germany) is the first device permitting intraoperative, three-dimensional representation of bone structures. A high-resolution, isotropic 3D data cube in the isocenter with sides of approximately 12 cm is calculated simultaneously. The SIREMOBIL Iso-C(3D) is linked to the navigation system. This makes it possible to transfer the generated 3D data directly to the linked navigation system without the need for surgeon-dependent registration. In this prospective clinical trial, we evaluated the accuracy of pedicle screw placement using this device. In 61 patients, a total of 302 pedicle screws were placed. Only in five cases (1.7%) were misplacements of > or =2 mm shown in postoperative control CT. The average fluoroscopy time was 1.28+/-0.56 min, and the average operative duration was 103.26+/-23.3 min. There were no postoperative neurological complications in any of the 30 patients. From these data, we conclude that Iso-C(3D) navigation is a very accurate method for the placement of pedicle screws.

  4. 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. Copyright © 2011. Published by Elsevier Ltd.

  5. 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). Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

    Gantner, Melisa Edith; Di Ianni, Mauricio Emiliano; Ruiz, María Esperanza; Bruno-Blanch, Luis E.

    2013-01-01

    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. PMID:23984415

  7. Preclinical assessment of the neutralizing capacity of antivenoms produced in six Latin American countries against medically-relevant Bothrops snake venoms.

    Science.gov (United States)

    Segura, A; Castillo, M C; Núñez, V; Yarlequé, A; Gonçalves, L R C; Villalta, M; Bonilla, C; Herrera, M; Vargas, M; Fernández, M; Yano, M Y; Araújo, H P; Boller, M A A; León, P; Tintaya, B; Sano-Martins, I S; Gómez, A; Fernández, G P; Geoghegan, P; Higashi, H G; León, G; Gutiérrez, J M

    2010-11-01

    Species of the genus Bothrops induce the vast majority of snakebite envenomings in Latin America. A preclinical study was performed in the context of a regional network of public laboratories involved in the production, quality control and development of antivenoms in Latin America. The ability of seven polyspecific antivenoms, produced in Argentina, Brazil, Peru, Bolivia, Colombia and Costa Rica, to neutralize lethal, hemorrhagic, coagulant, defibrinogenating and myotoxic activities of the venoms of Bothrops neuwiedi (diporus) (Argentina), Bothrops jararaca (Brazil), B. neuwiedi (mattogrossensis) (Bolivia), Bothrops atrox (Peru and Colombia) and Bothrops asper (Costa Rica) was assessed using standard laboratory tests. Despite differences in the venom mixtures used in the immunization of animals for the production of these antivenoms, a pattern of extensive cross-neutralization was observed between these antivenoms and all the venoms tested, with quantitative differences in the values of effective doses. This study reveals the capacity of these antivenoms to neutralize, in preclinical tests, homologous and heterologous Bothrops venoms in Central and South America, and also highlight quantitative differences in the values of Median Effective Doses (ED50s) between the various antivenoms. (c) 2010 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. B1 Cell IgE Impedes Mast Cell-Mediated Enhancement of Parasite Expulsion through B2 IgE Blockade.

    Science.gov (United States)

    Martin, Rebecca K; Damle, Sheela R; Valentine, Yolander A; Zellner, Matthew P; James, Briana N; Lownik, Joseph C; Luker, Andrea J; Davis, Elijah H; DeMeules, Martha M; Khandjian, Laura M; Finkelman, Fred D; Urban, Joseph F; Conrad, Daniel H

    2018-02-13

    Helminth infection is known for generating large amounts of poly-specific IgE. Here we demonstrate that innate-like B1 cells are responsible for this IgE production during infection with the nematode parasites Nippostrongylus brasiliensis and Heligmosomoides polygyrus bakeri. In vitro analysis of B1 cell immunoglobulin class switch recombination to IgE demonstrated a requirement for anti-CD40 and IL-4 that was further enhanced when IL-5 was added or when the B1 source was helminth infected mice. An IL-25-induced upregulation of IgE in B1 cells was also demonstrated. In T cell-reconstituted RAG1 -/- mice, N. brasiliensis clearance was enhanced with the addition of B2 cells in an IgE-dependent manner. This enhanced clearance was impeded by reconstitution with IgE sufficient B1 cells. Mucosal mast cells mediated the B2 cell enhancement of clearance in the absence of B1 cells. The data support B1 cell IgE secretion as a regulatory response exploited by the helminth. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  12. Spizaetus hawk-eagles as predators of arboreal colobines.

    Science.gov (United States)

    Fam, S D; Nijman, V

    2011-04-01

    The predation pressure put on primates by diurnal birds of prey differs greatly between continents. Africa and South America have specialist raptors (e.g. crowned hawk-eagle Stephanoaetus coronatus and harpy eagle Harpia harpyja) whereas in Asia the only such specialist's (Philippine eagle Pithecophaga jefferyi) distribution is largely allopatric with primates. The almost universal absence of polyspecific groups in Asia (common in Africa and South America) may indicate reduced predation pressure. As such there is almost no information on predation pressures on primates in Asia by raptors. Here we report successful predation of a juvenile banded langur Presbytis femoralis (~2 kg) by a changeable hawk-eagle Spizaetus cirrhatus. The troop that was attacked displayed no signs of being alarmed, and no calls were made before the event. We argue that in insular Southeast Asia, especially, large Spizaetus hawk-eagles (~2 kg) are significant predators of arboreal colobines. Using data on the relative size of sympatric Spizaetus hawk-eagles and colobines we make predictions on where geographically we can expect the highest predation pressure (Thai-Malay Peninsula) and which colobines are least (Nasalis larvatus, Trachypithecus auratus, P. thomasi) and most (P. femoralis, T. cristatus) affected.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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.

  15. 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

  16. Exploring the venom of the forest cobra snake: Toxicovenomics and antivenom profiling of Naja melanoleuca

    DEFF Research Database (Denmark)

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

    2017-01-01

    A toxicovenomic analysis of the venom of the forest cobra, N. melanoleuca, was performed, revealing the presence of a total of 52 proteins by proteomics analysis. The most abundant proteins belong to the three-finger toxins (3FTx) (57.1 wt%), which includes post-synaptically acting α-neurotoxins.......A toxicovenomic analysis of the venom of the forest cobra, N. melanoleuca, was performed, revealing the presence of a total of 52 proteins by proteomics analysis. The most abundant proteins belong to the three-finger toxins (3FTx) (57.1 wt%), which includes post-synaptically acting α......% of venom proteins. A toxicity screening of the fractions, using the mouse lethality test, identified toxicity in RP-HPLC peaks 3, 4, 5 and 8, all of them containing α-neurotoxins of the 3FTx family, whereas the rest of the fractions did not show toxicity at a dose of 0.53 mg/kg. Three polyspecific...... antivenoms manufactured in South Africa and India were tested for their immunoreactivity against crude venom and fractions of N. melanoleuca. Overall, antivenoms immunorecognized all fractions in the venom, the South African antivenom showing a higher titer against the neurotoxin-containing fractions...

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  19. Common spectrum of polypeptides occurs in secretion granule membranes of different exocrine glands

    International Nuclear Information System (INIS)

    Cameron, R.S.; Cameron, P.L.; Castle, J.D.

    1986-01-01

    A highly purified membrane preparation from rat parotid secretion granules has been used as a comparative probe to examine the extent of compositional overlap in granule membranes of three other exocrine secretory tissues - pancreatic, lacrimal, and submandibular - from several standpoints. First, indirect immunofluorescent studies using a polyclonal polyspecific anti-parotid granule membrane antiserum has indicated a selective staining of granule membrane profiles in all acinar cells of all tissues. Second, highly purified granule membrane subfractions have been isolated from each exocrine tissue; comparative two-dimensional (isoelectric focusing; SDS) PAGE of radioiodinated granule membranes has identified 10-15 polypeptides of identical pI and apparent molecular mass. These species are likely to be integral membrane components since they are not extracted by either saponin-sodium sulfate or sodium carbonate (pH 11.5) treatments, and they do not have counterparts in the granule content. Finally, the identity among selected parotid and pancreatic radioiodinated granule membrane polypeptides has been documented using two-dimensional peptide mapping of chymotryptic and tryptic digests. These findings clearly indicate that exocrine secretory granules, irrespective of the nature of stored secretion, comprise a type of vesicular carrier with a common (and probably refined) membrane composition. Conceivably, the polypeptides identified carry out general functions related to exocrine secretion

  20. Zinc-induced Self-association of Complement C3b and Factor H

    Science.gov (United States)

    Nan, Ruodan; Tetchner, Stuart; Rodriguez, Elizabeth; Pao, Po-Jung; Gor, Jayesh; Lengyel, Imre; Perkins, Stephen J.

    2013-01-01

    The sub-retinal pigment epithelial deposits that are a hallmark of age-related macular degeneration contain both C3b and millimolar levels of zinc. C3 is the central protein of complement, whereas C3u is formed by the spontaneous hydrolysis of the thioester bridge in C3. During activation, C3 is cleaved to form active C3b, then C3b is inactivated by Factor I and Factor H to form the C3c and C3d fragments. The interaction of zinc with C3 was quantified using analytical ultracentrifugation and x-ray scattering. C3, C3u, and C3b associated strongly in >100 μm zinc, whereas C3c and C3d showed weak association. With zinc, C3 forms soluble oligomers, whereas C3u and C3b precipitate. We conclude that the C3, C3u, and C3b association with zinc depended on the relative positions of C3d and C3c in each protein. Computational predictions showed that putative weak zinc binding sites with different capacities exist in all five proteins, in agreement with experiments. Factor H forms large oligomers in >10 μm zinc. In contrast to C3b or Factor H alone, the solubility of the central C3b-Factor H complex was much reduced at 60 μm zinc and even more so at >100 μm zinc. The removal of the C3b-Factor H complex by zinc explains the reduced C3u/C3b inactivation rates by zinc. Zinc-induced precipitation may contribute to the initial development of sub-retinal pigment epithelial deposits in the retina as well as reducing the progression to advanced age-related macular degeneration in higher risk patients. PMID:23661701

  1. An open source software tool to assign the material properties of bone for ABAQUS finite element simulations.

    Science.gov (United States)

    Pegg, Elise C; Gill, Harinderjit S

    2016-09-06

    A new software tool to assign the material properties of bone to an ABAQUS finite element mesh was created and compared with Bonemat, a similar tool originally designed to work with Ansys finite element models. Our software tool (py_bonemat_abaqus) was written in Python, which is the chosen scripting language for ABAQUS. The purpose of this study was to compare the software packages in terms of the material assignment calculation and processing speed. Three element types were compared (linear hexahedral (C3D8), linear tetrahedral (C3D4) and quadratic tetrahedral elements (C3D10)), both individually and as part of a mesh. Comparisons were made using a CT scan of a hemi-pelvis as a test case. A small difference, of -0.05kPa on average, was found between Bonemat version 3.1 (the current version) and our Python package. Errors were found in the previous release of Bonemat (version 3.0 downloaded from www.biomedtown.org) during calculation of the quadratic tetrahedron Jacobian, and conversion of the apparent density to modulus when integrating over the Young׳s modulus field. These issues caused up to 2GPa error in the modulus assignment. For these reasons, we recommend users upgrade to the most recent release of Bonemat. Processing speeds were assessed for the three different element types. Our Python package took significantly longer (110s on average) to perform the calculations compared with the Bonemat software (10s). Nevertheless, the workflow advantages of the package and added functionality makes 'py_bonemat_abaqus' a useful tool for ABAQUS users. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Isobenzofuranones from the aerial parts of Leontopodium leontopodioides (Wild.) Beauv.

    Science.gov (United States)

    Zhang, Yi; Yang, Yuling; Ruan, Jingya; Chen, Qiu; Li, Jian; Guo, Yuanqiang; Han, Lifeng; Wang, Tao

    2018-01-01

    A phytochemical investigation to obtain new triglyceride (TG) accumulation inhibitors resulted in the isolation of six new isobenzofuranones, leontopodiols A (1), B (2), leontopodiosides C (3), D (4), E (5), F (6), together with three known ones (7-9) from the aerial parts of Leontopodium leontopodioides (Willd.) Beauv. The structures of these isolates were identified by routine NMR experiments, optical rotation determination, electronic circular dichroism (ECD) calculation, along with chemical reaction. Moreover, compounds 1, 2, 5, and 7-9 displayed TG accumulation inhibitory effects on HepG2 cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Complement-mediated solubilization of immune complexes. Solubilization inhibition and complement factor levels in SLE patients

    DEFF Research Database (Denmark)

    Baatrup, Gunnar; Petersen, Ivan; Kappelgaard, E

    1984-01-01

    Thirty-two of 36 serum samples from 19 SLE patients showed reduced capacity to mediate complement-dependent solubilization of immune complexes (IC). SLE patients with nephritis exerted the lowest complement-mediated solubilization capacity (CMSC) whereas sera from patients with inactive disease...... no medical treatment and the lowest inhibition by sera from patients with inactive disease. There was a significant negative correlation between CMSC and CMSC inhibition (r = -0.67, P less than 0.001). Sera with low concentrations of C1q, C3, factor B or high C3d levels showed markedly reduced CMSC values...

  4. 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.

  5. 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)

  6. Synthesis of thienyl analogues of PCBM and investigation of morphology of mixtures in P3HT

    Directory of Open Access Journals (Sweden)

    2008-09-01

    Full Text Available Novel [6,6]-phenyl-C61-butyric acid methyl ester (PCBM analogues containing benzo[b]thiophene (3a, 3b and thieno[3,2-b]thiophene (3c, 3d were synthesized and characterized. The morphology of the thin films prepared from the mixtures of these methanofullerenes with regioregular poly(3-hexylthiophene (P3HT was investigated by AFM measurement and UV-Vis absorption spectroscopy. A solubility test of these methanofullerenes was performed by using dichloromethane as a solvent. es-TThCBM (3d exhibited 1.4 times greater solubility in dichloromethane than PCBM.

  7. A Novel Multiscale Design of Interfaces for Polymeric Composites and Bonded Joints using Additive Manufacturing

    Science.gov (United States)

    2016-09-13

    existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding...the edges in the x2−x3 plane and the interfaces between the layers. Eight noded linear hexahedral elements (C3D8 in ABAQUS notation) are used to mesh...script A pythonTM script is written that reads the ABAQUS input file and writes the multi-point con- straints. Working procedure of the pythonTM

  8. Robotic technique improves entry point alignment for intramedullary nailing of femur fractures compared to the conventional technique: a cadaveric study.

    Science.gov (United States)

    Suero, Eduardo M; Westphal, Ralf; Citak, Musa; Hawi, Nael; Liodakis, Emmanouil; Krettek, Christian; Stuebig, Timo

    2017-08-11

    We aimed to test whether a robotic technique would offer more accurate access to the proximal femoral medullary cavity for insertion of an intramedullary nail compared to the conventional manual technique. The medullary cavity of ten femur specimens was accessed in a conventional fashion using fluoroscopic control. In ten additional femur specimens, ISO-C 3D scans were obtained and a computer program calculated the ideal location of the cavity opening based on the trajectory of the medullary canal. In both techniques, the surgeon opened the cavity using a drill and inserted a radiopaque tube that matched the diameter of the cavity. The mean difference in angle between the proximal opening and the medullary canal in the shaft of the femur was calculated for both groups. Robotic cavity opening was more accurate than the manual technique, with a mean difference in trajectory between the proximal opening and the shaft canal of 2.0° (95% CI 0.6°-3.5°) compared to a mean difference of 4.3° (95% CI 2.11°-6.48°) using the manual technique (P = 0.0218). The robotic technique was more accurate than the manual procedure for identifying the optimal location for opening the medullary canal for insertion of an intramedullary nail. Additional advantages may include a reduction in total radiation exposure, as only one ISO-C 3D scan is needed, as opposed to multiple radiographs when using the manual technique.

  9. View-invariant gait recognition method by three-dimensional convolutional neural network

    Science.gov (United States)

    Xing, Weiwei; Li, Ying; Zhang, Shunli

    2018-01-01

    Gait as an important biometric feature can identify a human at a long distance. View change is one of the most challenging factors for gait recognition. To address the cross view issues in gait recognition, we propose a view-invariant gait recognition method by three-dimensional (3-D) convolutional neural network. First, 3-D convolutional neural network (3DCNN) is introduced to learn view-invariant feature, which can capture the spatial information and temporal information simultaneously on normalized silhouette sequences. Second, a network training method based on cross-domain transfer learning is proposed to solve the problem of the limited gait training samples. We choose the C3D as the basic model, which is pretrained on the Sports-1M and then fine-tune C3D model to adapt gait recognition. In the recognition stage, we use the fine-tuned model to extract gait features and use Euclidean distance to measure the similarity of gait sequences. Sufficient experiments are carried out on the CASIA-B dataset and the experimental results demonstrate that our method outperforms many other methods.

  10. Ceftriaxone-induced hemolytic anemia in a child successfully managed with intravenous immunoglobulin.

    Science.gov (United States)

    Vehapoğlu, Aysel; Göknar, Nilüfer; Tuna, Rümeysa; Çakır, Fatma Betül

    2016-01-01

    Drug-induced hemolytic anemia is an immune-mediated phenomenon that leads to the destruction of red blood cells. Here, we present a case of life-threatening ceftriaxone-induced hemolytic anemia (CIHA) in a previously healthy 3-year-old girl. We also reviewed the literature to summarize the clinical features and treatment of hemolytic anemia. Acute hemolysis is a rare side effect of ceftriaxone therapy associated with high mortality. Our patient had a sudden loss of consciousness with macroscopic hematuria and her hemoglobin dropped from 10.2 to 2.2 g/dl over 4 hours, indicating that the patient had life-threatening hemolysis after an intravascular dose of ceftriaxone who had previously been treated with ceftriaxone in intramuscular form for six days. CIHA is associated with a positive direct antiglobulin test, revealing the presence of IgG in all cases and C3d in most cases. Our patient's direct antiglobulin test was positive for IgG (3+) and for C3d (4+). The case was managed successfully with supportive measures and intravenous immunoglobulin therapy. Ceftriaxone is used very frequently in children; an early diagnosis and proper treatment of hemolytic anemia are essential to improve the patient outcome. The pathophysiological mechanism is the same as for non-drug autoimmune hemolytic anemia. However, there is still no consensus treatment for CIHA. Intravenous immunoglobulin can be used in clinical emergencies, such as our case, or in refractory cases.

  11. Executive Summary of Ares V: Lunar Capabilities Concept Review Through Phase A-Cycle 3

    Science.gov (United States)

    Holladay, J. B.; Baggett, K. E.; Feldman, S. M.

    2011-01-01

    This Technical Memorandum (TM) was generated as an overall Ares V summary from the Lunar Capabilities Concept Review (LCCR) through Phase A-Cycle 3 (PA-C3) with the intent that it may be coupled with separately published appendices for a more detailed, integrated narrative. The Ares V has evolved from the initial point of departure (POD) 51.00.48 LCCR configuration to the current candidate POD, PA-C3D, and the family of vehicles concept that contains vehicles PA-C3A through H. The logical progression from concept to POD vehicles is summarized in this TM and captures the trade space and performance of each. The family-of-vehicles concept was assessed during PA-C3 and offered flexibility in the path forward with the ability to add options deemed appropriate. A description of each trade space is given in addition to a summary of each Ares V element. The Ares V contributions to a Mars campaign are also highlighted with the goal of introducing Ares V capabilities within the trade space. The assessment of the Ares V vehicle as it pertains to Mars missions remained locked to the architecture presented in Mars Design Reference Authorization 5.0 using the PA-C3D vehicle configuration to assess Mars transfer vehicle options, in-space EDS capabilities, docking adaptor and propellant transfer assessments, and lunar and Mars synergistic potential.

  12. Iron-tellurium-selenium mixed oxide catalysts for the selective oxidation of propylene to acrolein

    International Nuclear Information System (INIS)

    Patel, B.M.; Price, G.L.

    1990-01-01

    This paper reports on iron-tellurium-selenium mixed oxide catalysts prepared by coprecipitation from aqueous solution investigated for the propylene to acrolein reaction in the temperature range 543-773 K. Infrared spectroscopy, electron dispersive X-ray analysis, X-ray diffraction, and isotopic tracer techniques have also been employed to characterize this catalytic system. Properties of the Fe-Te-Se mixed oxide catalysts have been compared with Fe-Te mixed oxides in an effort to deduce the functionality of Se. The selenium in the Fe-Te-Se-O catalyst has been found to be the hydrocarbon activating site. The activation energies for the acrolein and carbon dioxide formation are 71 and 54 kJ/mol, respectively. Reactions carried out with 18 O 2 have shown lattice oxygen to be primarily responsible for the formation of both acrolein and carbon dioxide. The initial and rate-determining step for acrolein formation is hydrogen abstraction as determined by an isotope effect associated with the C 3 D 6 reaction. No isotope effect is observed for carbon dioxide formation from C 3 D 6 suggesting that CO 2 is formed by parallel, not consecutive, oxidation of propylene

  13. Helminth infections in faecal samples of Apennine wolf (Canis lupus italicus) and Marsican brown bear (Ursus arctos marsicanus) in two protected national parks of central Italy

    Science.gov (United States)

    Paoletti, Barbara; Iorio, Raffaella; Traversa, Donato; Di Francesco, Cristina E; Gentile, Leonardo; Angelucci, Simone; Amicucci, Cristina; Bartolini, Roberto; Marangi, Marianna; Di Cesare, Angela

    This article reports the results of a copromicroscopic and molecular investigation carried out on faecal samples of wolves (n=37) and brown bears (n=80) collected in two protected national parks of central Italy (Abruzzo Region). Twenty-three (62.2%) samples from wolves were positive for parasite eggs. Eight (34.78%) samples scored positive for single infections, i.e. E. aerophilus (21.74%), Ancylostoma/Uncinaria (4.34%), Trichuris vulpis (4.34%), T. canis (4.34%). Polyspecific infections were found in 15 samples (65.21%), these being the most frequent association: E. aerophilus and Ancylostoma/Uncinaria. Thirty-seven (46.25%) out of the 80 faecal samples from bears were positive for parasite eggs. Fourteen (37.83%) samples were positive for B. transfuga, and six (16.21%) of them also contained Ancylostoma/Uncinaria, one (2.7%) E. aerophilus and one (2.7%) both E. aerophilus and Ancylostoma/Uncinaria. Of the other samples, 19 (51.35%) were positive for Ancylostoma/Uncinaria, two (5.4%) for E. aerophilus and two (5.4%) for both. Molecular analysis found the roundworm and capillariid eggs found in wolves and bear samples to be Toxocara canis, Baylisascaris transfuga and Eucoleus aerophilus (syn. Capillaria aerophila). Considering the high prevalence of zoonotic intestinal helminths detected in this study, it is important to improve the knowledge and awareness of the general public and park operators regarding the potential health risk associated with infections in wildlife.

  14. 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.

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

    Science.gov (United States)

    Arora, Satyam; Doda, Veena; Maria, Arti; Kotwal, Urvershi; Goyal, Saurabh

    2015-01-01

    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. Ophiophagus hannah Venom: Proteome, Components Bound by Naja kaouthia Antivenin and Neutralization by N. kaouthia Neurotoxin-Specific Human ScFv

    Directory of Open Access Journals (Sweden)

    Witchuda Danpaiboon

    2014-05-01

    Full Text Available Venomous snakebites are an important health problem in tropical and subtropical countries. King cobra (Ophiophagus hannah is the largest venomous snake found in South and Southeast Asia. In this study, the O. hannah venom proteome and the venom components cross-reactive to N. kaouthia monospecific antivenin were studied. O. hannah venom consisted of 14 different protein families, including three finger toxins, phospholipases, cysteine-rich secretory proteins, cobra venom factor, muscarinic toxin, L-amino acid oxidase, hypothetical proteins, low cysteine protein, phosphodiesterase, proteases, vespryn toxin, Kunitz, growth factor activators and others (coagulation factor, endonuclease, 5’-nucleotidase. N. kaouthia antivenin recognized several functionally different O. hannah venom proteins and mediated paratherapeutic efficacy by rescuing the O. hannah envenomed mice from lethality. An engineered human ScFv specific to N. kaouthia long neurotoxin (NkLN-HuScFv cross-neutralized the O. hannah venom and extricated the O. hannah envenomed mice from death in a dose escalation manner. Homology modeling and molecular docking revealed that NkLN-HuScFv interacted with residues in loops 2 and 3 of the neurotoxins of both snake species, which are important for neuronal acetylcholine receptor binding. The data of this study are useful for snakebite treatment when and where the polyspecific antivenin is not available. Because the supply of horse-derived antivenin is limited and the preparation may cause some adverse effects in recipients, a cocktail of recombinant human ScFvs for various toxic venom components shared by different venomous snakes, exemplified by the in vitro produced NkLN-HuScFv in this study, should contribute to a possible future route for an improved alternative to the antivenins.

  17. 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.

  18. Ipomoelin, a jacalin-related lectin with a compact tetrameric association and versatile carbohydrate binding properties regulated by its N terminus.

    Science.gov (United States)

    Chang, Wei-Chieh; Liu, Kai-Lun; Hsu, Fang-Ciao; Jeng, Shih-Tong; Cheng, Yi-Sheng

    2012-01-01

    Many proteins are induced in the plant defense response to biotic stress or mechanical wounding. One group is lectins. Ipomoelin (IPO) is one of the wound-inducible proteins of sweet potato (Ipomoea batatas cv. Tainung 57) and is a Jacalin-related lectin (JRL). In this study, we resolved the crystal structures of IPO in its apo form and in complex with carbohydrates such as methyl α-D-mannopyranoside (Me-Man), methyl α-D-glucopyranoside (Me-Glc), and methyl α-D-galactopyranoside (Me-Gal) in different space groups. The packing diagrams indicated that IPO might represent a compact tetrameric association in the JRL family. The protomer of IPO showed a canonical β-prism fold with 12 strands of β-sheets but with 2 additional short β-strands at the N terminus. A truncated IPO (ΔN10IPO) by removing the 2 short β-strands of the N terminus was used to reveal its role in a tetrameric association. Gel filtration chromatography confirmed IPO as a tetrameric form in solution. Isothermal titration calorimetry determined the binding constants (K(A)) of IPO and ΔN10IPO against various carbohydrates. IPO could bind to Me-Man, Me-Glc, and Me-Gal with similar binding constants. In contrast, ΔN10IPO showed high binding ability to Me-Man and Me-Glc but could not bind to Me-Gal. Our structural and functional analysis of IPO revealed that its compact tetrameric association and carbohydrate binding polyspecificity could be regulated by the 2 additional N-terminal β-strands. The versatile carbohydrate binding properties of IPO might play a role in plant defense.

  19. Ipomoelin, a Jacalin-Related Lectin with a Compact Tetrameric Association and Versatile Carbohydrate Binding Properties Regulated by Its N Terminus

    Science.gov (United States)

    Chang, Wei-Chieh; Liu, Kai-Lun; Hsu, Fang-Ciao; Jeng, Shih-Tong; Cheng, Yi-Sheng

    2012-01-01

    Many proteins are induced in the plant defense response to biotic stress or mechanical wounding. One group is lectins. Ipomoelin (IPO) is one of the wound-inducible proteins of sweet potato (Ipomoea batatas cv. Tainung 57) and is a Jacalin-related lectin (JRL). In this study, we resolved the crystal structures of IPO in its apo form and in complex with carbohydrates such as methyl α-D-mannopyranoside (Me-Man), methyl α-D-glucopyranoside (Me-Glc), and methyl α-D-galactopyranoside (Me-Gal) in different space groups. The packing diagrams indicated that IPO might represent a compact tetrameric association in the JRL family. The protomer of IPO showed a canonical β-prism fold with 12 strands of β-sheets but with 2 additional short β-strands at the N terminus. A truncated IPO (ΔN10IPO) by removing the 2 short β-strands of the N terminus was used to reveal its role in a tetrameric association. Gel filtration chromatography confirmed IPO as a tetrameric form in solution. Isothermal titration calorimetry determined the binding constants (KA) of IPO and ΔN10IPO against various carbohydrates. IPO could bind to Me-Man, Me-Glc, and Me-Gal with similar binding constants. In contrast, ΔN10IPO showed high binding ability to Me-Man and Me-Glc but could not bind to Me-Gal. Our structural and functional analysis of IPO revealed that its compact tetrameric association and carbohydrate binding polyspecificity could be regulated by the 2 additional N-terminal β-strands. The versatile carbohydrate binding properties of IPO might play a role in plant defense. PMID:22808208

  20. 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. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  1. High-Density Peptide Microarray Analysis of IgG Autoantibody Reactivities in Serum and Cerebrospinal Fluid of Multiple Sclerosis Patients*

    Science.gov (United States)

    Hecker, Michael; Fitzner, Brit; Wendt, Matthias; Lorenz, Peter; Flechtner, Kristin; Steinbeck, Felix; Schröder, Ina; Thiesen, Hans-Jürgen; Zettl, Uwe Klaus

    2016-01-01

    Intrathecal immunoglobulin G (IgG) synthesis and oligoclonal IgG bands in cerebrospinal fluid (CSF) are hallmarks of multiple sclerosis (MS), but the antigen specificities remain enigmatic. Our study is the first investigating the autoantibody repertoire in paired serum and CSF samples from patients with relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and other neurological diseases by the use of high-density peptide microarrays. Protein sequences of 45 presumed MS autoantigens (e.g. MOG, MBP, and MAG) were represented on the microarrays by overlapping 15mer peptides. IgG reactivities were screened against a total of 3991 peptides, including also selected viral epitopes. The measured antibody reactivities were highly individual but correlated for matched serum and CSF samples. We found 54 peptides to be recognized significantly more often by serum or CSF antibodies from MS patients compared with controls (p values <0.05). The results for RRMS and PPMS clearly overlapped. However, PPMS patients presented a broader peptide-antibody signature. The highest signals were detected for a peptide mapping to a region of the Epstein-Barr virus protein EBNA1 (amino acids 392–411), which is homologous to the N-terminal part of human crystallin alpha-B. Our data confirmed several known MS-associated antigens and epitopes, and they delivered additional potential linear epitopes, which await further validation. The peripheral and intrathecal humoral immune response in MS is polyspecific and includes antibodies that are also found in serum of patients with other diseases. Further studies are required to assess the pathogenic relevance of autoreactive and anti-EBNA1 antibodies as well as their combinatorial value as biomarkers for MS. PMID:26831522

  2. High-Density Peptide Microarray Analysis of IgG Autoantibody Reactivities in Serum and Cerebrospinal Fluid of Multiple Sclerosis Patients.

    Science.gov (United States)

    Hecker, Michael; Fitzner, Brit; Wendt, Matthias; Lorenz, Peter; Flechtner, Kristin; Steinbeck, Felix; Schröder, Ina; Thiesen, Hans-Jürgen; Zettl, Uwe Klaus

    2016-04-01

    Intrathecal immunoglobulin G (IgG) synthesis and oligoclonal IgG bands in cerebrospinal fluid (CSF) are hallmarks of multiple sclerosis (MS), but the antigen specificities remain enigmatic. Our study is the first investigating the autoantibody repertoire in paired serum and CSF samples from patients with relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and other neurological diseases by the use of high-density peptide microarrays. Protein sequences of 45 presumed MS autoantigens (e.g.MOG, MBP, and MAG) were represented on the microarrays by overlapping 15mer peptides. IgG reactivities were screened against a total of 3991 peptides, including also selected viral epitopes. The measured antibody reactivities were highly individual but correlated for matched serum and CSF samples. We found 54 peptides to be recognized significantly more often by serum or CSF antibodies from MS patients compared with controls (pvalues <0.05). The results for RRMS and PPMS clearly overlapped. However, PPMS patients presented a broader peptide-antibody signature. The highest signals were detected for a peptide mapping to a region of the Epstein-Barr virus protein EBNA1 (amino acids 392-411), which is homologous to the N-terminal part of human crystallin alpha-B. Our data confirmed several known MS-associated antigens and epitopes, and they delivered additional potential linear epitopes, which await further validation. The peripheral and intrathecal humoral immune response in MS is polyspecific and includes antibodies that are also found in serum of patients with other diseases. Further studies are required to assess the pathogenic relevance of autoreactive and anti-EBNA1 antibodies as well as their combinatorial value as biomarkers for MS. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Single-Domain Antibodies and the Promise of Modular Targeting in Cancer Imaging and Treatment

    Directory of Open Access Journals (Sweden)

    María Elena Iezzi

    2018-02-01

    Full Text Available Monoclonal antibodies and their fragments have significantly changed the outcome of cancer in the clinic, effectively inhibiting tumor cell proliferation, triggering antibody-dependent immune effector cell activation and complement mediated cell death. Along with a continued expansion in number, diversity, and complexity of validated tumor targets there is an increasing focus on engineering recombinant antibody fragments for lead development. Single-domain antibodies (sdAbs, in particular those engineered from the variable heavy-chain fragment (VHH gene found in Camelidae heavy-chain antibodies (or IgG2 and IgG3, are the smallest fragments that retain the full antigen-binding capacity of the antibody with advantageous properties as drugs. For similar reasons, growing attention is being paid to the yet smaller variable heavy chain new antigen receptor (VNAR fragments found in Squalidae. sdAbs have been selected, mostly from immune VHH libraries, to inhibit or modulate enzyme activity, bind soluble factors, internalize cell membrane receptors, or block cytoplasmic targets. This succinct review is a compilation of recent data documenting the application of engineered, recombinant sdAb in the clinic as epitope recognition “modules” to build monomeric, dimeric and multimeric ligands that target, tag and stall solid tumor growth in vivo. Size, affinity, specificity, and the development profile of sdAbs drugs are seemingly consistent with desirable clinical efficacy and safety requirements. But the hepatotoxicity of the tetrameric anti-DR5-VHH drug in patients with pre-existing anti-drug antibodies halted the phase I clinical trial and called for a thorough pre-screening of the immune and poly-specific reactivities of the sdAb leads.

  4. Ophiophagus hannah Venom: Proteome, Components Bound by Naja kaouthia Antivenin and Neutralization by N. kaouthia Neurotoxin-Specific Human ScFv

    Science.gov (United States)

    Danpaiboon, Witchuda; Reamtong, Onrapak; Sookrung, Nitat; Seesuay, Watee; Sakolvaree, Yuwaporn; Thanongsaksrikul, Jeeraphong; Dong-din-on, Fonthip; Srimanote, Potjanee; Thueng-in, Kanyarat; Chaicumpa, Wanpen

    2014-01-01

    Venomous snakebites are an important health problem in tropical and subtropical countries. King cobra (Ophiophagus hannah) is the largest venomous snake found in South and Southeast Asia. In this study, the O. hannah venom proteome and the venom components cross-reactive to N. kaouthia monospecific antivenin were studied. O. hannah venom consisted of 14 different protein families, including three finger toxins, phospholipases, cysteine-rich secretory proteins, cobra venom factor, muscarinic toxin, L-amino acid oxidase, hypothetical proteins, low cysteine protein, phosphodiesterase, proteases, vespryn toxin, Kunitz, growth factor activators and others (coagulation factor, endonuclease, 5’-nucleotidase). N. kaouthia antivenin recognized several functionally different O. hannah venom proteins and mediated paratherapeutic efficacy by rescuing the O. hannah envenomed mice from lethality. An engineered human ScFv specific to N. kaouthia long neurotoxin (NkLN-HuScFv) cross-neutralized the O. hannah venom and extricated the O. hannah envenomed mice from death in a dose escalation manner. Homology modeling and molecular docking revealed that NkLN-HuScFv interacted with residues in loops 2 and 3 of the neurotoxins of both snake species, which are important for neuronal acetylcholine receptor binding. The data of this study are useful for snakebite treatment when and where the polyspecific antivenin is not available. Because the supply of horse-derived antivenin is limited and the preparation may cause some adverse effects in recipients, a cocktail of recombinant human ScFvs for various toxic venom components shared by different venomous snakes, exemplified by the in vitro produced NkLN-HuScFv in this study, should contribute to a possible future route for an improved alternative to the antivenins. PMID:24828754

  5. Cell-penetrating, guanidinium-rich molecular transporters for overcoming efflux-mediated multidrug resistance.

    Science.gov (United States)

    Vargas, Jessica R; Stanzl, Erika Geihe; Teng, Nelson N H; Wender, Paul A

    2014-08-04

    Multidrug resistance (MDR) is a major cause of chemotherapy failure in the clinic. Drugs that were once effective against naïve disease subsequently prove ineffective against recurrent disease, which often exhibits an MDR phenotype. MDR can be attributed to many factors; often dominating among these is the ability of a cell to suppress or block drug entry through upregulation of membrane-bound drug efflux pumps. Efflux pumps exhibit polyspecificity, recognizing and exporting many different types of drugs, especially those whose lipophilic nature contributes to residence in the membrane. We have developed a general strategy to overcome efflux-based resistance. This strategy involves conjugating a known drug that succumbs to efflux-mediated resistance to a cell-penetrating molecular transporter, specifically, the cell-penetrating peptide (CPP), d-octaarginine. The resultant conjugates are discrete single entities (not particle mixtures) and highly water-soluble. They rapidly enter cells, are not substrates for efflux pumps, and release the free drug only after cellular entry at a rate controlled by linker design and favored by target cell chemistry. This general strategy can be applied to many classes of drugs and allows for an exceptionally rapid advance to clinical testing, especially of drugs that succumb to resistance. The efficacy of this strategy has been successfully demonstrated with Taxol in cellular and animal models of resistant cancer and with ex vivo samples from patients with ovarian cancer. Next generation efforts in this area will involve the extension of this strategy to other chemotherapeutics and other MDR-susceptible diseases.

  6. Identification and characterization of B-cell epitopes of 3FTx and PLA(2) toxins from Micrurus corallinus snake venom.

    Science.gov (United States)

    Castro, K L; Duarte, C G; Ramos, H R; Machado de Avila, R A; Schneider, F S; Oliveira, D; Freitas, C F; Kalapothakis, E; Ho, P L; Chávez-Olortegui, C

    2015-01-01

    The main goal of this work was to develop a strategy to identify B-cell epitopes on four different three finger toxins (3FTX) and one phospholipase A2 (PLA2) from Micrurus corallinus snake venom. 3FTx and PLA2 are highly abundant components in Elapidic venoms and are the major responsibles for the toxicity observed in envenomation by coral snakes. Overlapping peptides from the sequence of each toxin were prepared by SPOT method and three different anti-elapidic sera were used to map the epitopes. After immunogenicity analysis of the spot-reactive peptides by EPITOPIA, a computational method, nine sequences from the five toxins were chemically synthesized and antigenically and immunogenically characterized. All the peptides were used together as immunogens in rabbits, delivered with Freund's adjuvant for a first cycle of immunization and Montanide in the second. A good antibody response against individual synthetic peptides and M. corallinus venom was achieved. Anti-peptide IgGs were also cross-reactive against Micrurus frontalis and Micrurus lemniscatus crude venoms. In addition, anti-peptide IgGs inhibits the lethal and phospholipasic activities of M. corallinus crude venom. Our results provide a rational basis to the identification of neutralizing epitopes on coral snake toxins and show that their corresponding synthetic peptides could improve the generation of immuno-therapeutics. The use of synthetic peptide for immunization is a reasonable approach, since it enables poly-specificity, low risk of toxic effects and large scale production. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Identification of B cell recognized linear epitopes in a snake venom serine proteinase from the central American bushmaster Lachesis stenophrys.

    Science.gov (United States)

    Madrigal, M; Alape-Girón, A; Barboza-Arguedas, E; Aguilar-Ulloa, W; Flores-Díaz, M

    2017-12-15

    Snake venom serine proteinases are toxins that perturb hemostasis acting on proteins from the blood coagulation cascade, the fibrinolytic or the kallikrein-kinin system. Despite the relevance of these enzymes in envenomations by viper bites, the characterization of the antibody response to these toxins at the molecular level has not been previously addressed. In this work surface-located B cell recognized linear epitopes from a Lachesis stenophrys venom serine proteinase (UniProt accession number Q072L7) were predicted using an artificial neuronal network at the ABCpred server, the corresponding peptides were synthesized and their immunoreactivity was analyzed against a panel of experimental and therapeutic antivenoms. A molecular model of the L. stenophrys enzyme was built using as a template the structure of the D. acutus Dav-PA serine proteinase (Q9I8X1), which displays the highest degree of sequence similarity to the L. stenophrys enzyme among proteins of known 3D structure, and the surface-located epitopes were identified in the protein model using iCn3D. A total of 13 peptides corresponding to the surface exposed predicted epitopes from L. stenophrys serine proteinase were synthesized and, their reactivity with a rabbit antiserum against the recombinant enzyme and a panel of antivenoms was evaluated by a capture ELISA. Some of the epitopes recognized by monospecific and polyspecific antivenoms comprise sequences overlapping motifs conserved in viper venom serine proteinases. The identification and characterization of relevant epitopes recognized by B cells in snake venom toxins may provide valuable information for the preparation of immunogens that help in the production of improved therapeutic antivenoms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. 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.

  9. 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.

  10. 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.

  11. Passenger Lymphocyte Syndrome After Simultaneous Pancreas-Kidney Transplantation: A Case Report of an Unusual Cause of Alloimmune Hemolytic Anemia.

    Science.gov (United States)

    Hurtarte-Sandoval, A R; Navarro-Cabello, M D; Álvarez-Rivas, M A; Robles-López, A I; Salmerón-Rodríguez, M D; Agüera-Morales, M L; Rodríguez-Benot, A; Aljama-García, P

    2015-11-01

    Passenger lymphocyte syndrome (PLS) is a disease in which the donor's lymphocytes produce antibodies to the red blood cell antigens of the recipient, causing alloimmune hemolysis. We report the case of a 39-year-old woman with stage V chronic kidney disease on hemodialysis secondary to poorly controlled diabetes mellitus type 1. She received a simultaneous pancreas-kidney transplant from a cadaver donor. The donor was A- and the recipient was A+ without initial complications with normal renal and pancreatic function, and her hemoglobin (Hb) level was 10.2 g/dL at discharge. Four weeks later she was admitted with acute pyelonephritis of the renal graft, with a Hb level of 7.5 g/dL, creatinine level of 0.7 mg/dL, and glucose level of 80 mg/dL. The study of anemia showed direct polyspecific direct Coombs weakly positive (w/+), presenting 2 alloantibodies against the Rh system: anti-D, anti-E. We increased Prednisone dose to 1 mg/kg/d and then decreased it in a pattern. Eight days after discharge, without transfusion, her Hb level was 9.9 g/dL and then it normalized. PLS is a very rare condition and should be suspected in the first few weeks after transplantation. In our case anemia was probably due to a residual population of Rh-negative donor cells in the transplanted pancreas-kidney received. It is usually a sudden onset of hemolytic anemia in patients with a solid organ transplant and different Rh or ABO lower incompatibility. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Comparative Study of C-Arms for Intraoperative 3-dimensional Imaging and Navigation in Minimally Invasive Spine Surgery Part II: Radiation Exposure.

    Science.gov (United States)

    Klingler, Jan-Helge; Sircar, Ronen; Scheiwe, Christian; Kogias, Evangelos; Krüger, Marie T; Scholz, Christoph; Hubbe, Ulrich

    2017-07-01

    A radiation exposure study in vitro. This study aimed to compare the radiation exposure of 2 different 3-dimensional (3D) C-arm devices on an anthropomorphic phantom. Minimally invasive pedicle screw placement requires intraoperative imaging techniques for visualization of the unexposed spine. Mobile 3D C-arms compose a 3D image data set out of multiple successive fluoroscopic images. We compared the 3D C-arm devices Siremobil Iso-C 3D (Siemens Sector Healthcare, Erlangen, Germany) and Vision FD Vario 3D (Ziehm Imaging, Nuremberg, Germany) regarding their radiation exposure. For this purpose, dosimeters were attached on an anthropomorphic phantom at various sites (eye lenses, thyroid gland, female, and male gonads). With each C-arm, 10 automated 3D scans as well as 400 fluoroscopic images were performed on the cervical and lumbar spine, respectively. The Vision FD Vario 3D generally causes higher radiation exposures than the Siremobil Iso-C 3D. Significantly higher radiation exposures were assessed at the eye lenses performing cervical (294.1 vs. 84.6 μSv) and lumbar 3D scans (22.5 vs. 11.2 μSv) as well as at the thyroid gland performing cervical 3D scans (4405.2 vs. 2761.9 μSv). Moreover, the Vision FD Vario 3D caused significantly higher radiation exposure at the eye lenses for standard cervical fluoroscopic images (3.2 vs. 0.4 μSv). 3D C-arms facilitate minimally invasive and accurate pedicle screw placement by providing 3D image datasets for intraoperative 3D imaging and navigation. However, the hereby potentially increased radiation exposure has to be considered. In particular, the Vision FD Vario 3D appears to generally evoke higher radiation exposures than the Siremobil Iso-C 3D. Well-indicated application of ionizing radiation and compliance with radiation protection principles remain mandatory to keep radiation exposure to patient and staff as low as reasonably achievable.

  13. Glucose and glycerol concentrations and their tracer enrichment measurements using liquid chromatography tandem mass spectrometry

    DEFF Research Database (Denmark)

    Bornø, Andreas; Foged, Lene; van Hall, Gerrit

    2014-01-01

    The present study describes a new liquid chromatography tandem mass spectrometry method for high-throughput quantification of glucose and glycerol in human plasma using stable isotopically labeled internal standards and is suitable for simultaneous measurements of glucose and glycerol enrichments...... in connection to in vivo metabolic studies investigating glucose turnover and lipolytic rate. Moreover, in order to keep up with this new fast analysis, simple derivatization procedures have been developed. Prior to analysis, glucose and glycerol were derivatized using benzoyl chloride in order to form...... benzoylated derivatives via new simplified fast procedures. For glucose, two internal standards were evaluated, [U-(13) C(6)]glucose and [U-(13) C(6), D(7)]glucose, and for glycerol, [U-(13) C(3), D(8)]glycerol was used. The method was validated by means of calibration curves, quality control samples...

  14. Interactions of opsonized immune complexes with whole blood cells: binding to erythrocytes restricts complex uptake by leucocyte populations

    DEFF Research Database (Denmark)

    Nielsen, C H; Svehag, S E; Marquart, H V

    1994-01-01

    The binding of opsonized, fluorescein-labelled bovine serum albumin (BSA)/rabbit anti-BSA complexes (IC) to washed human whole blood cells and isolated leucocytes in the presence of autologous serum was investigated by flow cytometry. In the presence of erythrocytes (E), the IC-binding to granulo......The binding of opsonized, fluorescein-labelled bovine serum albumin (BSA)/rabbit anti-BSA complexes (IC) to washed human whole blood cells and isolated leucocytes in the presence of autologous serum was investigated by flow cytometry. In the presence of erythrocytes (E), the IC...... binding, the main contributors being B cells. E initially inhibited and then later enhanced the IC binding to lymphocytes, suggesting that E promote B cell uptake of C3d,g-covered IC via CR2. Our findings, that E can restrict the IC uptake by circulating leucocytes, and that an IC-induced degranulation...

  15. 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.

  16. Laser induced sonofusion: A new road toward thermonuclear reactions

    Directory of Open Access Journals (Sweden)

    Rasoul Sadighi-Bonabi

    2016-03-01

    Full Text Available The Possibility of the laser assisted sonofusion is studied via single bubble sonoluminescence (SBSL in Deuterated acetone (C3D6O using quasi-adiabatic and hydro-chemical simulations at the ambient temperatures of 0 and −28.5 °C. The interior temperature of the produced bubbles in Deuterated acetone is 1.6 × 106 K in hydro-chemical model and it is reached up to 1.9 × 106 K in the laser induced SBSL bubbles. Under these circumstances, temperature up to 107 K can be produced in the center of the bubble in which the thermonuclear D-D fusion reactions are promising under the controlled conditions.

  17. 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.

  18. Parvovirus B19 induced lupus-like syndrome with nephritis.

    Science.gov (United States)

    Georges, Elodie; Rihova, Zuzana; Cmejla, Radek; Decleire, Pierre-Yves; Langen, Corinne

    2016-12-01

    We report a case of a 65-year-old man who developed an acute illness with fever, arthralgia and nephritic syndrome. Antinuclear antibodies were slightly positive and complement levels were low. Renal biopsy showed exudative diffuse proliferative endocapillary glomerulonephritis with diffuse immunoglobulin (IgG, IgA, IgM) and complement deposition (C3d, C4d, C1q) on immunofluorescence. The patient was first treated with corticosteroids and mycophenolate mofetil for suspected lupus with WHO class IV glomerulonephritis. The diagnosis was questioned and a diagnosis of parvovirus B19-associated nephritis was made based on elevation of serum IgM antibodies for parvovirus B19 and detection of parvovirus B19 DNA on renal biopsy. The immunosuppressive treatment was stopped and progressive spontaneous regression of clinical and laboratory abnormalities was observed. We conclude that human parvovirus B19 infection should be considered as a cause of lupus-like symptomatology and acute glomerulonephritis.

  19. Final Technical Report on Office of Naval Research Contract Number N00014-77-C-0354.

    Science.gov (United States)

    1987-10-23

    pp. 4651-4662, 1983. Lcgeckis, R., and J.M. Bane: Comparison of the TIROS -N Satellite and Aircraft Measurements of Gulf Stream Surface Tempcratures...in a ’. Con tin uously Stratified Western Boundary Current Univ. North Carolina Report No CM-SO-I, 77 pp., 1980. ,,,-. Bane, I.M. and D.A. Brooks: The...arretit the~ C3d nioras deiitl r t a arcoe ul StrearNv I II tIg. It’ rc i c rI 111,111’,i l 1 utkits 11 O~ 1 Al this P)ontI if)I title. Ile cleAr -,t

  20. Full-length genomic analysis of korean porcine sapelovirus strains

    DEFF Research Database (Denmark)

    Son, Kyu-Yeol; Kim, Deok-Song; Kwon, Joseph

    2014-01-01

    the typical picornavirus genome organization; 5'untranslated region (UTR)-L-VP4-VP2-VP3-VP1-2A-2B-2C-3A-3B-3C-3D-3'UTR. Three distinct cis-active RNA elements, the internal ribosome entry site (IRES) in the 5'UTR, a cis-replication element (CRE) in the 2C coding region and 3'UTR were identified...... and their structures were predicted. Interestingly, the structural features of the CRE and 3'UTR were different between PSV strains. The availability of these first complete genome sequences for PSV strains will facilitate future investigations of the molecular pathogenesis and evolutionary characteristics of PSV....

  1. Synthesis and antibacterial activity of some new 3-hydroxy-2-naphthoic acid hydrazide derivatives for dyeing polyester fabrics

    Directory of Open Access Journals (Sweden)

    Abd El-Galil M. Khalil

    2016-03-01

    Full Text Available Dibenzobarallene was used as a key intermediate for the synthesis of 2-(3-hydroxy-2-naphthoyl-3,4,4a,5,10,10a-hexahydro-1H-5,10-benzenobenzo[g]phthalazine-1,4-dione (2. The previous compound was coupled with the appropriate diazonium chloride to give the corresponding 4-arylazo-2-naphthol derivatives 3a–l. Also, nitration, nitrosation and bromination of compound 2 afforded the corresponding nitro, nitroso and bromo derivatives 4–6, respectively. The synthesized compounds were established and evaluated as antibacterial agents. The results showed clearly that compounds 2, 3a, 3c, 3d, 3g, 3i, 4, 5 and 6 exhibited interesting high activities compared with reference drugs. Also, these compounds were applied to polyester as disperse dyes in which their color measurement and fastness properties were evaluated.

  2. Microwave-Assisted Synthesis of Some 1,3,4-Oxadiazole Derivatives and Evaluation of Their Antibacterial and Antifungal Activity

    Directory of Open Access Journals (Sweden)

    Deepak Swarnkar

    2014-01-01

    Full Text Available A series of substituted 1,3,4-oxadiazole derivatives (3a–f and (6a–f have been synthesized from diphenylacetic acid hydrazide under microwave irradiation in various reaction conditions. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, and 1H NMR. These targeted compounds have been tested for their antibacterial and antifungal activities compared to ampicillin and griseofulvin as standard drug. Compounds 3a, 3e, 3f, 6c, 6d, 6e, and 6d exhibited the maximum antibacterial activities while 3b, 3c, 3d, 3e, 6a, 6d, and 6e exhibited the maximum antifungal activities.

  3. The role of complement in the acquired immune response

    DEFF Research Database (Denmark)

    Nielsen, C H; Fischer, E M; Leslie, R G

    2000-01-01

    Studies over the past three decades have clearly established a central role for complement in the promotion of a humoral immune response. The primary function of complement, in this regard, is to opsonize antigen or immune complexes for uptake by complement receptor type 2 (CR2, CD21) expressed...... on B cells, follicular dendritic cells (FDC) and some T cells. A variety of mechanisms appear to be involved in complement-mediated promotion of the humoral response. These include: enhancement of antigen (Ag) uptake and processing by both Ag-specific and non-specific B cells for presentation...... to specific T cells; the activation of a CD21/CD19 complex-mediated signalling pathway in B cells, which provides a stimulus synergistic to that induced by antigen interaction with the B-cell receptor (BCR); and promotion of the interaction between B cells and FDC, where C3d-bearing immune complexes...

  4. Amino Acid Conjugated Anthraquinones from the Marine-Derived Fungus Penicillium sp. SCSIO sof101.

    Science.gov (United States)

    Luo, Minghe; Cui, Zhaomeng; Huang, Hongbo; Song, Xianqin; Sun, Aijun; Dang, Yongjun; Lu, Laichun; Ju, Jianhua

    2017-05-26

    Emodacidamides A-H (1-8), natural products featuring anthraquinone-amino acid conjugates, have been isolated from a marine-derived fungus, Penicillium sp. SCSIO sof101, together with known anthraquinones 9 and 10. The planar structures of 1-8 were elucidated using a combination of NMR spectroscopy and mass spectrometry. The absolute configurations of the amino acid residues were confirmed using Marfey's method and chiral-phase HPLC analyses. Additionally, isolates were evaluated for possible immunomodulatory and cytotoxic activities. Emodacidamides A (1), C (3), D (4), and E (5) inhibited interleukin-2 secretion from Jurkat cells with IC 50 values of 4.1, 5.1, 12, and 5.4 μM, respectively.

  5. Synthesis and biological evaluation of novel quinazoline-sulfonamides as anti-cancer agents.

    Science.gov (United States)

    Poudapally, Suresh; Battu, Shankar; Velatooru, Loka Reddy; Bethu, Murali Satyanarayana; Janapala, Venkateswara Rao; Sharma, Somesh; Sen, Subhabrata; Pottabathini, Narender; Iska, Vijaya Bhaskara Reddy; Katangoor, Vidya

    2017-05-01

    A robust economic approach to N-(quinazoline-4-yl)sulfonamides was developed and synthesized different aryl, hetero aryl, alkyl and cyclopropyl sulfonamides in excellent yields. All the compounds were evaluated for cytotoxic affinity to SKOV3, DU145, THP1, U937, and COLO205 cell lines. Interesting to find that the bulkiness of substituent at C-2 position of quinazoline forces the molecule to flip around in order to bind in the active site, when compared to the binding preference of previously known quinazoline compounds. Among the 21 compounds synthesized 2b, 2d, 2e, 2h, 2i, 3c, 3d, 3f, 3g and 3h found to be active on all the cell lines tested with IC 50 values <10µg/mL. Performed docking simulations to understand the binding preference of various C-2 substituted quinazoline sulfonamides. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. 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

    with an NCAM ligand, the C3d peptide. NCAM-mediated ERK phosphorylation depended on activation of the fibroblast growth factor receptor (FGFR), Src-family kinases, MEK (MAP and ERK kinase) and G(0)/G(i)-proteins, whereas NCAM-mediated CREB phosphorylation depended on the activity of Src-family kinases and MEK...... 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...

  7. High Reynolds Number Wave Force Investigation in a Wave Flume.

    Science.gov (United States)

    1985-03-01

    RESULTS 43 6.0 CONCLUSIONS 45 7.0 REFERENCES 49 8.0 ACKNOWLEDGEMENTS 51 9.0 TABLES 53 10.0 FIGURES 93 11.0 APPENDIX A" 11.1 Druck Pressure Transducer...adjoining test cylinder by 0.7 mm, which had a negligible influence on the resulting measurements. After the Druck pressure transducers were installed and...dC C 3d 4 ;88dC 38dC CI8 cninfl"nV0to .t" o ,t in cv d-. ,0 en w . nC M..r nin - -0 - I!- I!- V! - -i !V L4JN C; .0 d C0000000 40000008 o .6 C

  8. The role of complement in the acquired immune response

    DEFF Research Database (Denmark)

    Nielsen, C H; Fischer, E M; Leslie, R G

    2000-01-01

    on B cells, follicular dendritic cells (FDC) and some T cells. A variety of mechanisms appear to be involved in complement-mediated promotion of the humoral response. These include: enhancement of antigen (Ag) uptake and processing by both Ag-specific and non-specific B cells for presentation...... to specific T cells; the activation of a CD21/CD19 complex-mediated signalling pathway in B cells, which provides a stimulus synergistic to that induced by antigen interaction with the B-cell receptor (BCR); and promotion of the interaction between B cells and FDC, where C3d-bearing immune complexes......Studies over the past three decades have clearly established a central role for complement in the promotion of a humoral immune response. The primary function of complement, in this regard, is to opsonize antigen or immune complexes for uptake by complement receptor type 2 (CR2, CD21) expressed...

  9. Intraoperative cone-beam CT for image-guided tibial plateau fracture reduction.

    Science.gov (United States)

    Khoury, A; Siewerdsen, J H; Whyne, C M; Daly, M J; Kreder, H J; Moseley, D J; Jaffray, D A

    2007-07-01

    A mobile isocentric C-arm was modified in our laboratory in collaboration with Siemens Medical Solutions to include a large-area flat-panel detector providing multi-mode fluoroscopy and cone-beam CT (CBCT) imaging. This technology is an important advance over existing intraoperative imaging (e.g., Iso-C(3D)), offering superior image quality, increased field of view, higher spatial resolution, and soft-tissue visibility. The aim of this study was to assess the system's performance and image quality in tibial plateau (TP) fracture reconstruction. Three TP fractures were simulated in fresh-frozen cadaveric knees through combined axial loading and lateral impact. The fractures were reduced through a lateral approach and assessed by fluoroscopy. The reconstruction was then assessed using CBCT. If necessary, further reduction and localization of remaining displaced bone fragments was performed using CBCT images for guidance. CBCT image quality was assessed with respect to projection speed, dose and filtering technique. CBCT imaging provided exquisite visualization of articular details, subtle fragment detection and localization, and confirmation of reduction and implant placement. After fluoroscopic images indicated successful initial reduction, CBCT imaging revealed areas of malalignment and displaced fragments. CBCT facilitated fragment localization and improved anatomic reduction. CBCT image noise increased gradually with reduced dose, but little difference in images resulted from increased projections. High-resolution reconstruction provided better delineation of plateau depressions. This study demonstrated a clear advantage of intraoperative CBCT over 2D fluoroscopy and Iso-C(3D) in TP fracture fixation. CBCT imaging provided benefits in fracture type diagnosis, localization of fracture fragments, and intraoperative 3D confirmation of anatomic reduction.

  10. [Positive Distribution Rate of Coombs Test in Patients with Clinical Anemia and Blood Transfusion and Its Effect on Clinical Blood Transfusion].

    Science.gov (United States)

    Wu, Gang; Duan, Yu-Han

    2018-02-01

    To study the positive distribution rate of Coombs test in patients with clinical anemia and blood transfusion, and its effect on clinical blood transfusion. Seventy patients with hemoglobin level in the normal range were enrolled into control group, while 130 patients with anemia or blood transfusion who' s hemoglobin level was lower comfirmed by micro-column gel antihuman globin detection card and 70 surgical patients with anemia or blood transfusion who' s hemoglobin level was lower comfirmed by micro-column gel anti-human globin card were enrolled into anemia or blood transfusion (A or BT) group. And coomb' s test performed for all the patients, in which the positive patients in Department of Internal Medicine need to be re-typed. Among 70 surgical patients with anemia or blood transfusion, 14 cases were directly detected to be anti-human globine positive with detection rate 20%; among 130 internal medicine patients with anemia or blood transfusion, 54 cases were directly detected to be anti-human globine positive with detection rate 41.4%. Among 270 cases, the highest positive rate (66.7%) was observed in patients with 50-59 g/L of hemoglobin. According to type test, the samples of 54 patients with anemia in Department of Internal Medicine, who were directly selected to be anti-human globin positive, could be divided into anti-C3d(7 cases, accounting for 13.0%), anti-IgG(12 cases accounting for, 22.2%) and anti-C3d+anti-IgG(35 cases, accounting for 64.8%), while according to diseases, the anti-human globin positive ratio was high in tumor cancer, hephropathy and gastroenteropathy patients, and patients in intensive care unit, moreover the blood transfusion frequency of these patients was higher than that of patients with anti-human globin negative(Pblood transfusion, so as to ensure the effectiveness of blood transfusion.

  11. 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.

  12. New insights into childhood autoimmune hemolytic anemia: a French national observational study of 265 children

    Science.gov (United States)

    Aladjidi, Nathalie; Leverger, Guy; Leblanc, Thierry; Picat, Marie Quitterie; Michel, Gérard; Bertrand, Yves; Bader-Meunier, Brigitte; Robert, Alain; Nelken, Brigitte; Gandemer, Virginie; Savel, Hélène; Stephan, Jean Louis; Fouyssac, Fanny; Jeanpetit, Julien; Thomas, Caroline; Rohrlich, Pierre; Baruchel, André; Fischer, Alain; Chêne, Geneviève; Perel, Y.

    2011-01-01

    Background Autoimmune hemolytic anemia is a rare condition in children. Little is known about its initial presentation and the subsequent progression of the disease. Design and Methods Since 2004, a national observational study has been aiming to thoroughly describe cases and identify prognostic factors. Patients from all French hematologic pediatric units have been included if they had a hemoglobin concentration less than 11 g/dL, a positive direct antiglobulin test and hemolysis. Evans’ syndrome was defined by the association of autoimmune hemolytic anemia and immunological thrombocytopenic purpura. Data from patients’ medical records were registered from birth to last follow-up. Autoimmune hemolytic anemia was classified as primary or secondary. Remission criteria, qualifying the status of anemia at last follow-up, were used with the aim of identifying a subgroup with a favorable prognosis in continuous complete remission. Results The first 265 patients had a median age of 3.8 years at diagnosis. In 74% of cases the direct antiglobulin test was IgG/IgG+C3d. Consanguinity was reported in 8% of cases and first degree familial immunological diseases in 15% of cases. Evans’ syndrome was diagnosed in 37% of cases. Autoimmune hemolytic anemia was post-infectious in 10%, immunological in 53% and primary in 37% of cases. After a median follow-up of 3 years, 4% of children had died, 28% were still treatment-dependent and 39% were in continuous complete remission. In multivariate analysis, IgG and IgG+C3d direct antiglobulin tests were associated with a lower rate of survival with continuous complete remission (adjusted hazard ratio, 0.43; 95% confidence interval, 0.21–0.86). Conclusions This nationwide French cohort is the largest reported study of childhood autoimmune hemolytic anemia. The rarity of this condition is confirmed. Subgroups with genetic predisposition and underlying immune disorders were identified. PMID:21228033

  13. Red blood cell Thomsen-Friedenreich antigen expression and galectin-3 plasma concentrations in Streptococcus pneumoniae-associated hemolytic uremic syndrome and hemolytic anemia.

    Science.gov (United States)

    Burin des Roziers, Nicolas; Chadebech, Philippe; Bodivit, Gwellaouen; Guinchard, Emmanuelle; Bruneel, Arnaud; Dupré, Thierry; Chevret, Laurent; Jugie, Myriam; Gallon, Philippe; Bierling, Philippe; Noizat-Pirenne, France

    2015-06-01

    Pneumococcal hemolytic uremic syndrome (P-HUS) is a rare but severe complication of invasive pneumococcal disease (IPD) in young children. Consensual biologic diagnosis criteria are currently lacking. A prospective study was conducted on 10 children with culture-confirmed IPD. Five presented with full-blown P-HUS, three had an incomplete form with hemolytic anemia and mild or no uremia (P-HA), and two had neither HUS nor HA. Thomsen-Friedenreich (T), Th, and Tk cryptantigens and sialic acid expression were determined on red blood cells (RBCs) with peanut (PNA), Glycine soja (SBA), Bandeiraea simplicifolia II, and Maackia amurensis lectins. Plasma concentrations of the major endogenous T-antigen-binding protein, galectin-3 (Gal-3), were analyzed. We found that RBCs strongly reacted with PNA and SBA lectins in all P-HUS and P-HA patients. Three P-HUS and three P-HA patients showed also concomitant Tk activation. Direct antiglobulin test (DAT) was positive in three P-HUS (one with anti-C3d and two with anti-IgG) and two P-HA patients (one with anti-C3d and one with anti-IgG). RBCs derived from the two uncomplicated IPD patients reacted with PNA but not with SBA lectin. Gal-3 plasma concentrations were increased in all P-HUS patients. The results indicate high levels of neuraminidase activity and desialylation in both P-HUS and P-HA patients. T-antigen activation is more sensitive than DAT for P-HUS diagnosis. Combining PNA and SBA lectins is needed to improve the specificity of T-antigen activation. High concentrations of Gal-3 in P-HUS patients suggest that Gal-3 may contribute to the pathogenesis of P-HUS. © 2014 AABB.

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

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    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.

  15. Endogenous C1-inhibitor production and expression in the heart after acute myocardial infarction.

    Science.gov (United States)

    Emmens, Reindert W; Baylan, Umit; Juffermans, Lynda J M; Karia, Rashmi V; Ylstra, Bauke; Wouters, Diana; Zeerleder, Sacha; Simsek, Suat; van Ham, Marieke; Niessen, Hans W M; Krijnen, Paul A J

    2016-01-01

    Complement activation contributes significantly to inflammation-related damage in the heart after acute myocardial infarction. Knowledge on factors that regulate postinfraction complement activation is incomplete however. In this study, we investigated whether endogenous C1-inhibitor, a well-known inhibitor of complement activation, is expressed in the heart after acute myocardial infarction. C1-inhibitor and complement activation products C3d and C4d were analyzed immunohistochemically in the hearts of patients who died at different time intervals after acute myocardial infarction (n=28) and of control patients (n=8). To determine putative local C1-inhibitor production, cardiac transcript levels of the C1-inhibitor-encoding gene serping1 were determined in rats after induction of acute myocardial infarction (microarray). Additionally, C1-inhibitor expression was analyzed (fluorescence microscopy) in human endothelial cells and rat cardiomyoblasts in vitro. C1-inhibitor was found predominantly in and on jeopardized cardiomyocytes in necrotic infarct cores between 12h and 5days old. C1-inhibitor protein expression coincided in time and colocalized with C3d and C4d. In the rat heart, serping1 transcript levels were increased from 2h up until 7days after acute myocardial infarction. Both endothelial cells and cardiomyoblasts showed increased intracellular expression of C1-inhibitor in response to ischemia in vitro (n=4). These observations suggest that endogenous C1-inhibitor is likely involved in the regulation of complement activity in the myocardium following acute myocardial infarction. Observations in rat and in vitro suggest that C1-inhibitor is produced locally in the heart after acute myocardial infarction. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Direct determination of atom and radical concentrations in thermal reactions of hydrocarbons and other gases. Progress report, December 1, 1981-December 31, 1982

    International Nuclear Information System (INIS)

    Skinner, G.B.; Rao, V.S.; Wood, D.R.

    1983-01-01

    This is the seventh annual progress report on this project. During the period covered by the first six reports (June 1976 through December 1980) a shock tube and optical systems to measure H, D and O atom concentrations were built and fully characterized. The performance of our microwave discharge lamps were defined by numerous high-resolution spectroscopic profiles, while empirical calibrations were also made for all three of the above species. H, D and O atom concentrations were measured in gas mixtures containing H 2 , D 2 , O 2 , CD 4 , C 2 H 6 , C 2 D 6 , C 3 H 8 and C 3 D 8 in various proportions, and rate constants of several elementary reactions were deduced from the data. During the period covered by this report (December 1, 1981 to December 31, 1982) we have made kinetic modelling calculations to correlate H, D and O atom concentrations measured in shock-heated mixtures of C 2 H 6 -O 2 -Ar, C 2 D 6 -O 2 -Ar, C 3 H 8 -O 2 -Ar and C 3 D 8 -O 2 -Ar. These computations are difficult because there are several reactions for which rate constants are not known, so that it is necessary to do many calculations to completely optimize the results. Consequently, work is still going on with these calculations. We have completed an extensive series of measurements of H and D atom concentrations in pyrolysis experiments of benzene, toluene and neopentane and deuterium analogs, that have led to rate constants for the initial dissociation of these compounds, and for the reaction of H atoms with benzene and toluene

  17. The MRZ reaction as a highly specific marker of multiple sclerosis: re-evaluation and structured review of the literature.

    Science.gov (United States)

    Jarius, S; Eichhorn, P; Franciotta, D; Petereit, H F; Akman-Demir, G; Wick, M; Wildemann, B

    2017-03-01

    It has long been known that the majority of patients with multiple sclerosis (MS) display an intrathecal, polyspecific humoral immune response to a broad panel of neurotropic viruses. This response has measles virus, rubella virus and varicella zoster virus as its most frequent constituents and is thus referred to as the MRZ reaction (MRZR). Re-evaluation of the specificity of MRZR as a marker of MS. Structured review of the existing English-, German- and Spanish-language literature on MRZR testing, with evaluation of MRZR in a cohort of 43 unselected patients with MS and other neurological diseases as a proof of principle. A positive MRZ reaction, defined as a positive intrathecal response to at least two of the three viral agents, was found in 78% of MS patients but only in 3% of the controls (p < 0.00001), corresponding to specificity of 97%. Median antibody index values were significantly lower in non-MS patients (measles, p < 0.0001; rubella, p < 0.006; varicella zoster, p < 0.02). The 30 identified original studies on MRZR reported results from 1478 individual MRZR tests. A positive MRZR was reported for 458/724 (63.3%) tests in patients with MS but only for 19/754 (2.5%) tests in control patients (p < 0.000001), corresponding to cumulative specificity of 97.5% (CI 95% 96-98.4), cumulative sensitivity of 63.3% (CI 95% 59.6-66.8) (or 67.4% [CI 95% 63.5-71.1] in the adult MS subgroup), a positive likelihood ratio of 25.1 (CI 95% 16-39.3) and a negative likelihood ratio of 0.38 (CI 95% 0.34-0.41). Of particular note, MRZR was absent in 52/53 (98.1%) patients with neuromyelitis optica or MOG-IgG-positive encephalomyelitis, two important differential diagnoses of MS. MRZR is the most specific laboratory marker of MS reported to date. If present, MRZR substantially increases the likelihood of the diagnosis of MS. Prospective and systematic studies on the diagnostic and prognostic impact of MRZR testing are highly warranted.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

    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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Imunocitoma IgA: A propósito de um caso clínico Immunocytoma IgA: Case report

    Directory of Open Access Journals (Sweden)

    Bebiana Conde

    2009-01-01

    Full Text Available O imunocitoma é um linfoma não Hodgkin (LNHde células B, com evolução habitualmente indolente. Representa aproximadamente 1 -3% dos LNH e atinge habitualmente adultos com mais de 50 anos, podendo manifestar-se por adenomegalias, hepatomegalia, esplenomegalia e linfocitose em 15 a 30% dos casos. Raramente tem envolvimento pulmonar. Com frequência ocorrendo picos monoclonais de imunoglobulinas, sericos, frequentemente IgM e raramente IgA. Como exemplo desta patologia apresentamos o caso clinico de um doente do sexo masculino, 52 anos, com clinica de infecções respiratórias bacterianas de repetição, com necessidade de internamentos sucessivos, cuja investigação identificou um imunocitoma IgA, estádio IV. Assumindo-se o diagnóstico de um linfoma indolente, decidiu-se iniciar terapêutica profiláctica com imunoglobulinas humanas poliespecÍficas, tendo havido diminuição das infecçoes respiratórias. Posteriormente, a evidência de progressão do linfoma condicionou o inicio de poliquimioterapia, com o esquema ciclofosfamida, vincristina, prednisolona (CVP e rituximabR, tendo-se alcançado uma resposta parcial, que se manteve durante dois anos.Immunocytoma is a non-Hodgkin’s indolent evolution B cell lymphoma. It accounts for approximately 1-3% of non-Hodgkin's limphomas and usually onsets in adults aged over 50 years old. It manifests as lymphadenopathy, splenomegaly, hepatomegaly and lymphcytosis in 15 -30% of cases and is rarely seen with pulmonary involvement. Monocloncal peaks of serum immunoglobulin often occur. These are IgM and rarely IgA. We present as an example a male patient aged 52 years old, with recurrent respiratory infections. Clinical work -up identified an immunocytoma IgA stage IV. Diagnosing an indolent lymphoma, we prophylactic polyspecific human immunoglobulin to treat the respiratory infection. Evidence of lymphoma progression leads us to prescribe combined cyclophosphamide (C, vincristine (V, prednisone (P

  3. Effects of lipopolysaccharide on the expression of plasma membrane monoamine transporter (PMAT) at the blood-brain barrier and its implications to the transport of neurotoxins.

    Science.gov (United States)

    Wu, Kuo-Chen; Lu, Ya-Hsuan; Peng, Yi-Hsuan; Hsu, Lih-Ching; Lin, Chun-Jung

    2015-12-01

    Plasma membrane monoamine transporter (PMAT) is a polyspecific organic cation transporter that is highly expressed in the central nervous system. This study aimed to investigate the effect of lipopolysaccharide on PMAT expression at the blood-brain barrier and the interaction between PMAT and neurotoxins. As a result, PMAT mRNA was identified in brain microvessels (BMVs), brain microvascular endothelial cells (BMECs), astrocytes, and pericytes isolated from C57BL/6 mice and/or Wistar rats using RT-qPCR. The immunofluorescence staining confirmed the expression of PMAT protein in BMVs and striatum of C57BL/6 mice. Western blotting demonstrated its localization at the luminal and abluminal sides of BMECs. In C57BL/6 mice, PMAT protein was significantly increased in BMVs 24 h after an intraperitoneal injection of 3 mg/kg lipopolysaccharide. Lipopolysaccharide treatment also significantly increased PMAT expression in cerebral cortex and the striatum in a time-dependent manner, as well as the brain-to-plasma ratio of 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1-benzyl-TIQ). In isolated cells, lipopolysaccharide treatment significantly increased PMAT mRNA in brain astrocytes and the BMECs co-cultured with astrocytes. In addition to 1-methyl-4-phenylpyridinium, the kinetic study indicated that both 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 1-benzyl-TIQ are substrates of human PMAT. These findings suggest that inflammation can change PMAT expression at the blood-brain barrier, which may affect PMAT-mediated transport of neurotoxins. We demonstrated the expression of plasma membrane monoamine transporter (PMAT; mRNA or protein) at several subunits of the blood-brain barrier. Lipopolysaccharide treatment can significantly increase the expression of PMAT in vivo (in brain microvessels, cerebral cortex, and the striatum of C57BL/6 mice) and in vitro (in brain astrocytes and brain microvascular endothelial cells co-cultured with astrocytes). Lipopolysaccharide treatment

  4. 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.

    Science.gov (United States)

    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

  5. Human milk sIgA molecules contain various combinations of different antigen-binding sites resulting in a multiple binding specificity of antibodies and enzymatic activities of abzymes.

    Directory of Open Access Journals (Sweden)

    Sergey E Sedykh

    explanation of the phenomenon of polyspecificity and cross-reactivity of Abs.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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

    Directory of Open Access Journals (Sweden)

    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

  8. Strain-specific Plasmodium falciparum multifunctional CD4(+) T cell cytokine expression in Malian children immunized with the FMP2.1/AS02A vaccine candidate.

    Science.gov (United States)

    Graves, Shawna F; Kouriba, Bourema; Diarra, Issa; Daou, Modibo; Niangaly, Amadou; Coulibaly, Drissa; Keita, Yamoussa; Laurens, Matthew B; Berry, Andrea A; Vekemans, Johan; Ripley Ballou, W; Lanar, David E; Dutta, Sheetij; Gray Heppner, D; Soisson, Lorraine; Diggs, Carter L; Thera, Mahamadou A; Doumbo, Ogobara K; Plowe, Christopher V; Sztein, Marcelo B; Lyke, Kirsten E

    2016-05-17

    Based on Plasmodium falciparum (Pf) apical membrane antigen 1 (AMA1) from strain 3D7, the malaria vaccine candidate FMP2.1/AS02A showed strain-specific efficacy in a Phase 2 clinical trial in 400 Malian children randomized to 3 doses of the AMA1 vaccine candidate or control rabies vaccine on days 0, 30 and 60. A subset of 10 Pf(-) (i.e., no clinical malaria episodes) AMA1 recipients, 11 Pf(+) (clinical malaria episodes with parasites with 3D7 or Fab9-type AMA1 cluster 1 loop [c1L]) AMA1 recipients, and 10 controls were randomly chosen for analysis. Peripheral blood mononuclear cells (PBMCs) isolated on days 0, 90 and 150 were stimulated with full-length 3D7 AMA1 and c1L from strains 3D7 (c3D7) and Fab9 (cFab9). Production of IFN-γ, TNF-α, IL-2, and/or IL-17A was analyzed by flow cytometry. Among AMA1 recipients, 18/21 evaluable samples stimulated with AMA1 demonstrated increased IFN-γ, TNF-α, and IL-2 derived from CD4(+) T cells by day 150 compared to 0/10 in the control group (pvaccines, CD4(+) cells expressing both TNF-α and IL-2 were increased in Pf(-) children compared to Pf(+) children. When PBMCs were stimulated with c3D7 and cFab9 separately, 4/18 AMA1 recipients with an AMA1-specific CD4(+) response had a significant response to one or both c1L. This suggests that recognition of the AMA1 antigen is not dependent upon c1L alone. In summary, AMA1-specific T cell responses were notably increased in children immunized with an AMA1-based vaccine candidate. The role of CD4(+)TNF-α(+)IL-2(+)-expressing T cells in vaccine-induced strain-specific protection against clinical malaria requires further exploration. Clinicaltrials.gov Identifier: NCT00460525. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Quality assessment and shelf life modeling of pulsed electric field pretreated osmodehydrofrozen kiwifruit slices

    Directory of Open Access Journals (Sweden)

    Efimia Dermesonlouoglou

    2018-04-01

    Full Text Available The objective of this workwas to investigate the potential use of pulsed electric field (PEF in combination with osmotic dehydration (OD as a pre-freezing step and to evaluate the effect on quality characteristics and shelf life of frozen kiwifruit. Peeled kiwifruit was subjected to PEF (1.8 kV/cm, sliced and treated in OD-solution [containing glycerol, maltodextrin, trehalose, ascorbic acid, calcium chloride, citric acid, sodium chloride; 1/5 (wfruit/wsolution] for 30 and 60 min at 35 °C. Combined, PEF only and OD only treated samples as well as nontreated and blanched (80 °C, 60 s samples were frozen and stored at constant (-5, -10, -15, -25 °C and dynamic temperature conditions (-18 °C-3 d, -8 °C-2.5 d, -15 °C-3 d. Quality of frozen samples was evaluated by means of drip loss, colour, texture, vitamin C and sensory evaluation (1-9 scale; and shelf life (SL was calculated. Nontreated and blanched samples presented high drip loss and tissue softening (instrumentally measured as Fmax decrease. The tissue integrity was well retained in all osmotically pretreated samples. PEF pretreatment caused increase of fruit whiteness (increase of L value and yellowness (a and/or b value increase; SL calculation was based on colour change. All OD samples had high vitamin content (24.6 mg/100 g fresh material compared to 138-154 mg/100 g osmodehydrated material; PEF led to 93% (of the initial vitamin retention; blanched samples showed the lowest retention (86.9% of the initial (criteria for SL calculation. OD and combined PEF-OD treatment increased the shelf life of frozen kiwifruit (up to 3 times; based on sensorial criteria. The developed kinetic models for colour change, vitamin loss, and sensory quality deterioration were validated at dynamic temperature conditions. PEF pretreated OD (at significantly shorter time, 30 min compared to 60 min kiwifruits retained optimum quality and sensory characteristics. PEF and OD could be used as a preprocessing

  10. [Building an effective nonlinear three-dimensional finite-element model of human thoracolumbar spine].

    Science.gov (United States)

    Zeng, Zhi-Li; Cheng, Li-Ming; Zhu, Rui; Wang, Jian-Jie; Yu, Yan

    2011-08-23

    To build an effective nonlinear three-dimensional finite-element (FE) model of T(11)-L(3) segments for a further biomechanical study of thoracolumbar spine. The CT (computed tomography) scan images of healthy adult T(11)-L(3) 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 (CL) was modeled with 3-node shell element. All surrounding ligaments were represented by envelope 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 T(11)-L(3) 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. In this study, a 3-dimensional, 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 results of FEM

  11. Accuracy of Linear Measurements in Stitched Versus Non-Stitched Cone Beam Computed Tomography Images

    International Nuclear Information System (INIS)

    Srimawong, P.; Krisanachinda, A.; Chindasombatjaroen, J.

    2012-01-01

    Cone beam computed tomography images are useful in clinical dentistry. Linear measurements are necessary for accurate treatment planning.Therefore, the accuracy of linear measurements on CBCT images is needed to be verified. Current program called stitching program in Kodak 9000C 3D systems automatically combines up to three localized volumes to construct larger images with small voxel size.The purpose of this study was to assess the accuracy of linear measurements from stitched and non-stitched CBCT images in comparison to direct measurements.This study was performed in 10 human dry mandibles. Gutta-percha rods were marked at reference points to obtain 10 vertical and horizontal distances. Direct measurements by digital caliper were served as gold standard. All distances on CBCT images obtained by using and not using stitching program were measured, and compared with direct measurements.The intraclass correlation coefficients (ICC) were calculated.The ICC of direct measurements were 0.998 to 1.000.The ICC of intraobserver of both non-stitched CBCT images and stitched CBCT images were 1.000 indicated strong agreement made by a single observer.The intermethod ICC between direct measurements vs non-stitched CBCT images and direct measurements vs stitched CBCT images ranged from 0.972 to 1.000 and 0.967 to 0.998, respectively. No statistically significant differences between direct measurements and stitched CBCT images or non-stitched CBCT images (P > 0.05). The results showed that linear measurements on non-stitched and stitched CBCT images were highly accurate with no statistical difference compared to direct measurements. The ICC values in non-stitched and stitched CBCT images and direct measurements of vertical distances were slightly higher than those of horizontal distances. This indicated that the measurements in vertical orientation were more accurate than those in horizontal orientation. However, the differences were not statistically significant. Stitching

  12. 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.

  13. Facial symmetry in unilateral cleft lip and palate following alar base augmentation with bone graft: a three-dimensional assessment.

    Science.gov (United States)

    Devlin, Mark F; Ray, Arup; Raine, Peter; Bowman, Adrian; Ayoub, Ashraf F

    2007-07-01

    The aim of this study was to assess the outcome of bone grafting using a corticocancellous block of iliac crest to reconstruct the support for the deformed, volume-deficient alar base in treated patients with unilateral cleft lip and palate (UCLP). The main outcome being measured was nasal symmetry. This was a prospective study using a noninvasive three-dimensional stereophotogrammetry system (C3D) to assess the position of the alar base. Images were captured immediately preoperatively and at 6 months following the augmentation of the alar base with a block of bone graft. These images were used to calculate facial symmetry scores and were compared using a two sample Student's t test to assess the efficacy of the surgical method in reducing facial/nasal asymmetry. This investigation was conducted on 18 patients with one patient failing to attend for follow-up. The results for 17 patients are presented. Facial symmetry scores improved significantly following the insertion of the bone graft at the deficient alar base (p=0.005). 3D stereophotogrammetry is a noninvasive, accurate, and archiveable method of assessing facial form and surgical change. Nasal symmetry can be quantified and measured reliably with this tool. Bone grafting to the alar base region of treated UCLP patients with volume deficiency produces improvement in nasal symmetry.

  14. 4Cin: A computational pipeline for 3D genome modeling and virtual Hi-C analyses from 4C data.

    Science.gov (United States)

    Irastorza-Azcarate, Ibai; Acemel, Rafael D; Tena, Juan J; Maeso, Ignacio; Gómez-Skarmeta, José Luis; Devos, Damien P

    2018-03-01

    The use of 3C-based methods has revealed the importance of the 3D organization of the chromatin for key aspects of genome biology. However, the different caveats of the variants of 3C techniques have limited their scope and the range of scientific fields that could benefit from these approaches. To address these limitations, we present 4Cin, a method to generate 3D models and derive virtual Hi-C (vHi-C) heat maps of genomic loci based on 4C-seq or any kind of 4C-seq-like data, such as those derived from NG Capture-C. 3D genome organization is determined by integrative consideration of the spatial distances derived from as few as four 4C-seq experiments. The 3D models obtained from 4C-seq data, together with their associated vHi-C maps, allow the inference of all chromosomal contacts within a given genomic region, facilitating the identification of Topological Associating Domains (TAD) boundaries. Thus, 4Cin offers a much cheaper, accessible and versatile alternative to other available techniques while providing a comprehensive 3D topological profiling. By studying TAD modifications in genomic structural variants associated to disease phenotypes and performing cross-species evolutionary comparisons of 3D chromatin structures in a quantitative manner, we demonstrate the broad potential and novel range of applications of our method.

  15. Characteristic of the immunological state of Chernobyl accident clean-up workers in a late period after the accident

    International Nuclear Information System (INIS)

    Kurjane, N.; Zvagule, T.; Curbakova, E.; Bruvere, R.; Romanova, T.; Sitova, O; Hagina, E.; Socnevs, A.

    2001-01-01

    No differences in the number of immunologically competent cells and other immunological variables were found among the clean-up workers, depending on the time they were in Chernobyl. However, a statistically significant reduction in the number of CD3+, CD4+, CD16+ and CD19+, decrease in the levels of IgG and suppression of APH and the phagocytic activity of neutrophils with a simultaneous increase in the levels of IgA and C3d was found in all clean-up workers when compared to controls. In a small group of clean-up workers, the levels of some plasma cytokines were detected. A statistically significant increase in IL-6 levels was found in the clean-up workers when compared to controls. The irradiation received by the Chernobyl accident clean-up workers was large enough to cause disturbances in the function of cells and organ systems through immune system disorders with a resultant weakening of the body response and adaptation mechanisms. (authors)

  16. N-arylmethylideneaminophthalimide: Design, synthesis and evaluation as analgesic and anti-inflammatory agents.

    Science.gov (United States)

    Banarouei, Nasimossadat; Davood, Asghar; Shafaroodi, Hamed; Saeedi, Ghazaleh; Shafiee, Abbas

    2018-04-23

    N-aryl derivatives of phthalimide and 4-nitro phthalimide have demonstrated cyclooxygenase inhibitory activity. Also they possess an excellent analgesic and anti-inflammatory activity. In this work, a new series of N-arylmethylideneamino derivatives of phthalimide and 4-nitro phthalimide were designed and synthesized. The designed compounds were synthesized by condensation of the appropriate aldehyde and N-aminophthalimide in ethanol at room temperature at PH around 3. Their analgesic and anti-inflammatory activity were evaluated by acetic acid-induced pain test and carrageenan-induced paw edema test in mice and rats, respectively. The details of the synthesis and chemical characterization of the analogs are described. In vivo screening showed compounds 3a, 3b, 3f and 3h were the most potent analgesic compounds. In addition compounds 3a, 3c, 3d, 3e and 3j indicated comparable anti-inflammatory activity to indomethacin as reference drug. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. 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.

  18. 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)

  19. A comparative analysis of the uncertainty of astigmatism-{mu}PTV, stereo-{mu}PIV, and {mu}PIV

    Energy Technology Data Exchange (ETDEWEB)

    Cierpka, C.; Rossi, M.; Segura, R.; Kaehler, C.J. [Universitaet der Bundeswehr Muenchen, Institute of Fluid Mechanics and Aerodynamics, Neubiberg (Germany); Mastrangelo, F. [Department of Mechanics, Torino (Italy)

    2012-03-15

    Astigmatism or wavefront deformation, microscopic particle tracking velocimetry (A-{mu}PTV) (Chen et al. in Exp Fluids 47:849-863, 2009; Cierpka et al. in Meas Sci Technol 21:045401, 2010b) is a method to determine the complete 3D3C velocity field in micro-fluidic devices with a single camera. By using an intrinsic calibration procedure that enables a robust and precise calibration on the basis of the measured data itself (Cierpka et al. in Meas Sci Technol 22:015401, doi:10.1088/0957-0233/22/1/015401, 2011), accurate results without errors due to spatial averaging or bias due to the depth of correlation can be obtained. This method takes all image aberrations into account, allows for the use of the whole CCD sensor, and is easy to apply without expert knowledge. In this paper, a comparative study is presented to assess the uncertainties of two state-of-the-art methods for 3C3D velocity field measurements in microscopic flows: stereoscopic micro-particle image velocimetry (S-{mu}PIV) and astigmatism micro-particle tracking velocimetry (A-{mu}PTV). First, the main parameters affecting all methods' measurement uncertainty are identified, described, and quantified. Second, the test case of the flow over a backward-facing step is analyzed using all methods. For comparison, standard 2D2C {mu}PIV measurements and numerical flow simulations are shown as well. Advantages and disadvantages of both methods are discussed. (orig.)

  20. Stochastic electrodynamics and its relation to quantum theory

    International Nuclear Information System (INIS)

    Peterson, P.R.

    1977-01-01

    A classical hidden variable theory is investigated which is based on a classical fluctuating electromagnetic background radiation field persisting even at the absolute zero of temperature. It has a Lorentz invariant average spectral energy density [rho 0 (ω)] d/sub ω/ = ω 2 /π 2 c 3 dω 1 / 2 dirac constantω erg cm -3 where dirac constant is Planck's constant divided by 2π, ω the frequency and c the speed of light. This model is tested against several excepted theories. A quantum mechanical application of the ground state model is the development of a semiclassical radiation theory where the atomic system is quantized and the radiation fields are strictly classical. The procedure adopted, which is different from all previous methods, is that of time dependent perturbation theory with a stochastic classical ground state. This allows a direct comparison with quantum electrodynamic first and second-order absorption, emission and scattering formulas. It is found that the semiclassical method gives the correct spontaneous terms only by introducing a very plausible physical postulate. This postulate is a result of the model being phase insensitive and is related to the effect of radiation reaction forces. Finally, the semiclassical perturbation theory is applied to the Lamb shift. It is shown that this model can account for second-order virtual processes only with the addition of a postulate which forbids virtual absorption. The major classical application of the ground state is a discussion of blackbody radiation theory

  1. Success of anti-CD20 monoclonal antibody treatment for severe autoimmune hemolytic anemia caused by warm-reactive immunoglobulin A, immunoglobulin G, and immunoglobulin M autoantibodies in a child: a case report.

    Science.gov (United States)

    Ajmi, Houda; Mabrouk, Sameh; Hassayoun, Saida; Regaieg, Haifa; Tfifha, Minyar; Jalel, Chemli; Skouri, Hadef; Zouari, Noura; Abroug, Saoussan

    2017-11-14

    Autoimmune hemolytic anemia is rare in children. First-line therapies for this disease consist of corticosteroids and intravenously administered immunoglobulin that are effective in most patients. However, a small proportion of cases (5 to 10%) is refractory to these therapies and may represent a medical emergency, especially when hemolysis is due to warm immunoglobulin M. Recently, reports of the use of rituximab in adult autoimmune diseases have shown promising results. In children, there are few studies on the use of rituximab in the treatment for autoimmune hemolytic anemia, especially on its long-term efficacy and adverse effects. Here, we report the case of a 10-year-old Tunisian girl with refractory acute autoimmune hemolytic anemia caused by warm-reactive immunoglobulin A, immunoglobulin G, immunoglobulin M, and C3d autoantibodies. First-line treatments using corticosteroids and intravenously administered immunoglobulin were ineffective in controlling her severe disease. On the other hand, she was successfully treated with rituximab. In fact, her hemolytic anemia improved rapidly and no adverse effects were observed. The case that we report in this paper shows that rituximab could be an alternative therapeutic option in severe acute autoimmune hemolytic anemia with profound hemolysis refractory to conventional treatment. Moreover, it may preclude the use of plasmapheresis in such an urgent situation with a sustained remission.

  2. Design and synthesis of γ-butyrolactone derivatives as potential spermicidal agents.

    Science.gov (United States)

    Pandey, Rishi Ranjan; Srivastava, Akansha; Pachauri, Shakti Deep; Khandelwal, Kiran; Naqvi, Arshi; Malasoni, Richa; Kushwaha, Bhavana; Kumar, Lokesh; Maikhuri, Jagdamba Prasad; Pandey, Garima; Paliwal, Sarvesh; Gupta, Gopal; Dwivedi, Anil Kumar

    2014-08-15

    A series of γ-butyrolactone derivatives has been designed and synthesized from commercially available 2-acetyl butyrolactone (3-acetyldihydrofuran-2(3H)-one, 1) by aminoalkylating its active methylene followed by condensation with different aldehydes. Compounds having amino group were further converted to their respective tartrate salts and were evaluated for spermicidal activity against human sperm in vitro. Compounds showing appreciable spermicidal activity at ⩽0.5% [3c, 4d (0.5%); 2c, 3d (0.1%); 2d, 4c (0.05%)] were tested for safety studies against human cervical (HeLa) cell line. These compounds were found safer than, Nonoxynol-9. One of the two most active compounds was also found to be the safest (IC50=961 μg/ml; 4c), while the second compound exhibited lower safety against HeLa (IC50=269 μg/ml; 2d). The compound 4c significantly reduced the number of free thiols on human sperm. All the compounds were inactive against Trichomonas vaginalis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Mechanisms of Host-Pathogen Protein Complex Formation and Bacterial Immune Evasion of Streptococcus suis Protein Fhb.

    Science.gov (United States)

    Li, Xueqin; Liu, Peng; Gan, Shuzhen; Zhang, Chunmao; Zheng, Yuling; Jiang, Yongqiang; Yuan, Yuan

    2016-08-12

    Streptococcus suis serotype 2 (S. suis 2)-induced sepsis and meningitis are often accompanied by bacteremia. The evasion of polymorphonuclear leukocyte-mediated phagocytic clearance is central to the establishment of bacteremia caused by S. suis 2 and is facilitated by the ability of factor H (FH)-binding protein (Fhb) to bind FH on the bacterial surface, thereby impeding alternative pathway complement activation and phagocytic clearance. Here, C3b/C3d was found to bind to Fhb, along with FH, forming a large immune complex. The formation of this immune complex was mediated by domain II of Fhb via electrostatic and hydrophobic interactions, which, to our knowledge, is a new type of interaction. Interestingly, Fhb was found to be associated with the cell envelope and also present in the culture supernatant, where secreted Fhb inhibited complement activation via interactions with domain II, thereby enhancing antiphagocytic clearance by polymorphonuclear leukocytes. Thus, Fhb is a multifunctional bacterial protein, which binds host complement component C3 as well as FH and interferes with innate immune recognition in a secret protein manner. S. suis 2 therefore appears to have developed a new strategy to combat host innate immunity and enhance survival in host blood. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Mechanisms of Host-Pathogen Protein Complex Formation and Bacterial Immune Evasion of Streptococcus suis Protein Fhb*

    Science.gov (United States)

    Li, Xueqin; Liu, Peng; Gan, Shuzhen; Zhang, Chunmao; Zheng, Yuling; Jiang, Yongqiang; Yuan, Yuan

    2016-01-01

    Streptococcus suis serotype 2 (S. suis 2)-induced sepsis and meningitis are often accompanied by bacteremia. The evasion of polymorphonuclear leukocyte-mediated phagocytic clearance is central to the establishment of bacteremia caused by S. suis 2 and is facilitated by the ability of factor H (FH)-binding protein (Fhb) to bind FH on the bacterial surface, thereby impeding alternative pathway complement activation and phagocytic clearance. Here, C3b/C3d was found to bind to Fhb, along with FH, forming a large immune complex. The formation of this immune complex was mediated by domain II of Fhb via electrostatic and hydrophobic interactions, which, to our knowledge, is a new type of interaction. Interestingly, Fhb was found to be associated with the cell envelope and also present in the culture supernatant, where secreted Fhb inhibited complement activation via interactions with domain II, thereby enhancing antiphagocytic clearance by polymorphonuclear leukocytes. Thus, Fhb is a multifunctional bacterial protein, which binds host complement component C3 as well as FH and interferes with innate immune recognition in a secret protein manner. S. suis 2 therefore appears to have developed a new strategy to combat host innate immunity and enhance survival in host blood. PMID:27342778

  5. Registered report: Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs.

    Science.gov (United States)

    Phelps, Mitch; Coss, Chris; Wang, Hongyan; Cook, Matthew

    2016-03-01

    The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Registered Report describes the proposed replication plan of key experiments from "Coding-Independent Regulation of the Tumor Suppressor PTEN by Competing Endogenous 'mRNAs' by Tay and colleagues, published in Cell in 2011 (Tay et al., 2011). The experiments to be replicated are those reported in Figures 3C, 3D, 3G, 3H, 5A and 5B, and in Supplemental Figures 3A and B. Tay and colleagues proposed a new regulatory mechanism based on competing endogenous RNAs (ceRNAs), which regulate target genes by competitive binding of shared microRNAs. They test their model by identifying and confirming ceRNAs that target PTEN. In Figure 3A and B, they report that perturbing expression of putative PTEN ceRNAs affects expression of PTEN. This effect is dependent on functional microRNA machinery (Figure 3G and H), and affects the pathway downstream of PTEN itself (Figures 5A and B). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published by eLife.

  6. Virtual Exploration of the Ring Systems Chemical Universe.

    Science.gov (United States)

    Visini, Ricardo; Arús-Pous, Josep; Awale, Mahendra; Reymond, Jean-Louis

    2017-11-27

    Here, we explore the chemical space of all virtually possible organic molecules focusing on ring systems, which represent the cyclic cores of organic molecules obtained by removing all acyclic bonds and converting all remaining atoms to carbon. This approach circumvents the combinatorial explosion encountered when enumerating the molecules themselves. We report the chemical universe database GDB4c containing 916 130 ring systems up to four saturated or aromatic rings and maximum ring size of 14 atoms and GDB4c3D containing the corresponding 6 555 929 stereoisomers. Almost all (98.6%) of these ring systems are unknown and represent chiral 3D-shaped macrocycles containing small rings and quaternary centers reminiscent of polycyclic natural products. We envision that GDB4c can serve to select new ring systems from which to design analogs of such natural products. The database is available for download at www.gdb.unibe.ch together with interactive visualization and search tools as a resource for molecular design.

  7. Magnetic resonance imaging in the assessment of urologic disease: an all-in-one approach

    Energy Technology Data Exchange (ETDEWEB)

    Verswijvel, G.A.; Oyen, R.H.; Vaninbrouckx, J.; Bosmans, H.; Marchal, G. [University Hospital, Leuven (Belgium). Dept. of Radiology; Van Poppel, H.P.; Goethuys, H. [Catholic University of Leuven (Belgium). Dept. of Urology; Maes, B. [Catholic University of Leuven (Belgium). Dept. of Nephrology

    2000-10-01

    The aim of this study was to evaluate an ''all-in-one'' MR procedure to examine the kidneys, the renal vascular supply and renal perfusion, and the urinary tract. In 64 patients (58 with urologic disease and 6 healthy volunteers), MR was performed including: (a) T1- and T2-weighted imaging; (b) 3D contrast-enhanced MR angiography (MRA), including the renal arteries, renal veins, as well as renal perfusion; and (c) 3D contrast-enhanced MR urography (MRU) in the coronal and sagittal plane. For the latter, low- and high-resolution images were compared. Prior to gadolinium injection, 0.1 mg/kg body weight of furosemide was administered intravenously. The results were compared with correlative imaging modalities (ultrasonography, intravenous urography, CT), ureterorenoscopy and/or surgical-pathologic findings. Visualization of the renal parenchyma, the vascular supply, and the collecting system was adequate in all cases, both in nondilated and in dilated systems and irrespective of the renal function. One infiltrating urothelial cancer was missed; there was one false-positive urothelial malignancy. Different MR techniques can be combined to establish an all-in-one imaging modality in the assessment of diseases which affect the kidneys and urinary tracts. Continuous refinement of the applied MR techniques and further improvements in spatial resolution is needed to expand the actual imaging possibilities and to create new tracts and challenges in the MR evaluation of urologic disease. (orig.)

  8. Autoantibodies to vimentin cause accelerated rejection of cardiac allografts.

    Science.gov (United States)

    Mahesh, Balakrishnan; Leong, Hon-Sing; McCormack, Ann; Sarathchandra, Padmini; Holder, Angela; Rose, Marlene L

    2007-04-01

    Autoimmune responses to vimentin occur after solid organ transplantation, but their pathogenic effects are unclear. The aim of these studies was to investigate the effects of vimentin preimmunization on allogeneic and isografted hearts in a murine transplant model. Immunization of C57BL/6 mice with murine vimentin in complete Freund's adjuvant resulted in anti-vimentin antibodies and vimentin-reactive Th-1 cells. Transplantation of 129/sv hearts into vimentin-immunized C57BL/6 recipients resulted in accelerated rejection (8.4 +/- 1.5 days; n = 18), compared with hen egg lysozyme-immunized C57BL/6 (13.3 +/- 2.2 days; n = 10; P rejection, shown by the fact that vimentin-immunized B-cell-deficient IgH6 mice did not show accelerated rejection of 129/sv allografts, but rejection was restored by adoptive transfer of serum containing anti-vimentin antibodies. Eluates from donor hearts placed in vimentin/complete Freund's adjuvant recipients contained anti-vimentin antibodies, shown by Western blotting. Confocal imaging of rejected hearts de-monstrated presence of vimentin and C3d on apoptosed leukocytes, endothelial cells, and platelet/leukocyte conjugates. These results demonstrate that autoantibodies to vimentin, in conjunction with the alloimmune response, have a pathogenic role in allograft rejection.

  9. 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.

  10. The plasma focus as a compact accelerator/plasma-target system

    International Nuclear Information System (INIS)

    Brzosko, J.S.; Nardi, V.

    1988-01-01

    It is well known that high energy beams of D + ions (HEB, say, with E > 1 MeV) are ejected from the pinch region of a plasma focus discharge in D 2 during the pinch disruption state. In the same experiments, information on confined HEB in the pinch magnetic field - where they contribute to D-D fusion reactions - can be obtained with some difficulty. The yield of those reactions is in fact relatively insensitive to the confined HEB population. Intensity and other properties of confined HEB's can be obtained from other nuclear reactions if the plasma focus chamber is filled with a mixture, e.g., of D 2 and N 2 or of D 2 and C 3 D 8 with an atomic ratio, r, of heavy nuclei as large as r = 0.15/1. The authors report results from a plasma focus of an advanced design (APF, say, in which field distortion elements are introduced in the interelectrode gap) with a capacitor bank energy of W=7 kJ at V o =17 kV and a total filling gas pressure rho=3-6 Torr

  11. CFA-1: the first chiral metal-organic framework containing Kuratowski-type secondary building units.

    Science.gov (United States)

    Schmieder, Phillip; Denysenko, Dmytro; Grzywa, Maciej; Baumgärtner, Benjamin; Senkovska, Irena; Kaskel, Stefan; Sastre, German; van Wüllen, Leo; Volkmer, Dirk

    2013-08-14

    The novel homochiral metal-organic framework CFA-1 (Coordination Framework Augsburg-1), [Zn5(OAc)4(bibta)3], containing the achiral linker {H2-bibta = 1H,1'H-5,5'-bibenzo[d][1,2,3]triazole}, has been synthesised. The reaction of H2-bibta and Zn(OAc)2·2H2O in N-methylformamide (NMF) (90 °C, 3 d) yields CFA-1 as trigonal prismatic single crystals. CFA-1 serves as a convenient precursor for the synthesis of isostructural frameworks with redox-active metal centres, which is demonstrated by the postsynthetic exchange of Zn(2+) by Co(2+) ions. The framework is robust to solvent removal and has been structurally characterized by synchrotron single-crystal X-ray diffraction and solid state NMR measurements ((13)C MAS- and (1)H MAS-NMR at 10 kHz). Results from MAS-NMR and IR spectroscopy studies are corroborated by cluster and periodic DFT calculations performed on CFA-1 cluster fragments.

  12. 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.

  13. 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.

  14. Simulation and experiment of thermal energy management with phase change material for ageing LiFePO4 power battery

    International Nuclear Information System (INIS)

    Rao Zhonghao; Wang Shuangfeng; Zhang Guoqing

    2011-01-01

    Highlights: → We study the thermal energy management performance of ageing LiFePO 4 power battery. → 3-D modules of single cell and battery pack are formulated according to the experimental results. → Thermal resistance in the battery cell leaded to an inevitable temperature difference. → It is necessary to improve the thermal conductivity and lower the melting point of phase change material. → Thermal conductivity of phase change material and battery exist an effective proportion. - Abstract: Thermal energy management performance of ageing commercial rectangular LiFePO 4 power batteries using phase change material (PCM) and thermal behavior related to thermal conductivity between the PCM and the cell are discussed in this paper. The heat sources are simplified according to the experimental results of the cells discharged at 35 A (∼5 C). 3-D modules of a single cell and battery pack are formulated, respectively. The results show that the thermal resistance in the cell leads to an inevitable temperature difference. It is necessary to improve the thermal conductivity and to lower the melting point of the PCM for heat transfer enhancement. The PCM with a melting point lower than 45 deg. C will be more effective for heat dissipation, with a desired maximum temperature below 50 deg. C. The temperature difference in the whole unit before PCM melting will be decreased significantly. In addition, a proper k PCM :k c is necessary for a well designed battery thermal energy management system.

  15. Impacts of trace carbon on the microstructure of as-sintered biomedical Ti-15Mo alloy and reassessment of the maximum carbon limit.

    Science.gov (United States)

    Yan, M; Qian, M; Kong, C; Dargusch, M S

    2014-02-01

    The formation of grain boundary (GB) brittle carbides with a complex three-dimensional (3-D) morphology can be detrimental to both the fatigue properties and corrosion resistance of a biomedical titanium alloy. A detailed microscopic study has been performed on an as-sintered biomedical Ti-15Mo (in wt.%) alloy containing 0.032 wt.% C. A noticeable presence of a carbon-enriched phase has been observed along the GB, although the carbon content is well below the maximum carbon limit of 0.1 wt.% specified by ASTM Standard F2066. Transmission electron microscopy (TEM) identified that the carbon-enriched phase is face-centred cubic Ti2C. 3-D tomography reconstruction revealed that the Ti2C structure has morphology similar to primary α-Ti. Nanoindentation confirmed the high hardness and high Young's modulus of the GB Ti2C phase. To avoid GB carbide formation in Ti-15Mo, the carbon content should be limited to 0.006 wt.% by Thermo-Calc predictions. Similar analyses and characterization of the carbide formation in biomedical unalloyed Ti, Ti-6Al-4V and Ti-16Nb have also been performed. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  16. 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

  17. Solvothermal synthesis and high optical performance of three-dimensional sea-urchin-like TiO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Yi, E-mail: zhouyihn@163.com; Wang, Yutang; Li, Mengyao; Li, Xuzhi; Yi, Qin; Deng, Pan; Wu, Hongyan

    2015-06-15

    Graphical abstract: I–V characteristics of different TiO{sub 2} microspheres based DSSCs (a) 3D sphere-like, (b) 3D flower-like, (c) 3D sea-urchin-like. - Highlights: • 3D sea-urchin-like TiO{sub 2} was synthesized by solvothermal method. • The effects of preparation parameters on the microstructure of the microspheres were investigated. • The photoelectric properties of 3D sea-urchin-like TiO{sub 2} were studied upon DSSCs. • The PCE of the 3D sea-urchin-like TiO{sub 2} was higher than that of other morphologies. - Abstract: Three-dimensional (3D) sea-urchin-like TiO{sub 2} microspheres were successfully synthesised by solvothermal method. The effects of preparation parameters including reaction temperature, concentration and mass fraction of precursor, and solvent volume on the microstructure of the microspheres were investigated. Results of scanning electron microscopy showed that the preparation parameters played a critical role in the morphology of 3D sea-urchin-like TiO{sub 2}. In addition, when the sea-urchin-like TiO{sub 2} nanostructures were used as the dye-sensitized solar cells (DSSCs) anode, the power-conversion efficiency was higher than that of other morphologies, which was due to the special 3D hierarchical nanostructure, large specific surface area, and enhanced absorption of UV–vis of the TiO{sub 2} nanostructures.

  18. Motion database of disguised and non-disguised team handball penalty throws by novice and expert performers

    Directory of Open Access Journals (Sweden)

    Fabian Helm

    2017-12-01

    Full Text Available This article describes the motion database for a large sample (n = 2400 of 7-m penalty throws in team handball that includes 1600 disguised throws. Throws were performed by both novice (n = 5 and expert (n = 5 penalty takers. The article reports the methods and materials used to capture the motion data. The database itself is accessible for download via JLU Web Server and provides all raw files in a three-dimensional motion data format (.c3d. Additional information is given on the marker placement of the penalty taker, goalkeeper, and ball together with details on the skill level and/or playing history of the expert group. The database was first used by Helm et al. (2017 [1] to investigate the kinematic patterns of disguised movements. Results of this analysis are reported and discussed in their article “Kinematic patterns underlying disguised movements: Spatial and temporal dissimilarity compared to genuine movement patterns” (doi:10.1016/j.humov.2017.05.010 [1]. Keywords: Motion capture data, Disguise, Expertise

  19. Cell and tissue tropism of enterovirus 71 and other enteroviruses infections.

    Science.gov (United States)

    Lin, Jing-Yi; Shih, Shin-Ru

    2014-03-07

    Enterovirus 71 (EV71) is a member of Picornaviridae that causes mild and self-limiting hand, foot, and mouth disease (HFMD). However, EV71 infections can progress to polio-like paralysis, neurogenic pulmonary edema, and fatal encephalitis in infants and young children. Large EV71 outbreaks have been reported in Taiwan, China, Japan, Malaysia, Singapore, and Australia. This virus is considered a critical emerging public health threat. EV71 is an important crucial neurotropic enterovirus for which there is currently no effective antiviral drug or vaccine. The mechanism by which EV71 causes severe central nervous system complications remains unclear. The interaction between the virus and the host is vital for viral replication, virulence, and pathogenicity. SCARB2 or PSGL-1 receptor binding is the first step in the development of viral infections, and viral factors (e.g., 5' UTR, VP1, 3C, 3D, 3' UTR), host factors and environments (e.g., ITAFs, type I IFN) are also involved in viral infections. The tissue tropism and pathogenesis of viruses are determined by a combination of several factors. This review article provides a summary of host and virus factors affecting cell and tissue tropism and the pathogenesis of enteroviruses.

  20. Cytotoxicity effects of alkoxy

    Directory of Open Access Journals (Sweden)

    Wan M. Khairul

    2017-05-01

    Full Text Available In this study, the effort was to design and synthesize five new members of alkoxy substituted thiourea derivatives (3a–3e featuring general formula of A-ArC(ONHC(SNHAr-D in which A represents the methoxy group and D as –OCnH2n+1 (alkoxyl group, where n = 6,7,8,9, and 10 have been successfully designed, prepared, characterized, and evaluated for anti-amoebic activities. They were spectroscopically characterized by 1H and 13C Nuclear Magnetic Resonance (NMR, Fourier Transform Infrared (FT-IR spectroscopy, and Ultraviolet–visible (UV–vis spectroscopy analysis. In turn, they were used to investigate the cytotoxicity effect on Acanthamoeba sp. at their IC50 values and membrane permeability. Compounds 3a and 3b revealed to have good activity towards Acanthamoeba sp. compared to other compounds of 3c, 3d, and 3e. The observation under fluorescence microscopy by AOPI (Acridine-orange/Propidium iodide staining indicated that treated amoeba cells by 3a–3e show loss of their membrane permeability.

  1. Venomics of Bungarus caeruleus (Indian krait): Comparable venom profiles, variable immunoreactivities among specimens from Sri Lanka, India and Pakistan.

    Science.gov (United States)

    Oh, Angeline Mei Feng; Tan, Choo Hock; Ariaranee, Gnanathasan Christeine; Quraishi, Naeem; Tan, Nget Hong

    2017-07-05

    The Indian krait (Bungarus caeruleus) is one of the "Big Four" venomous snakes widely distributed in South Asia. The present venomic study reveals that its venom (Sri Lankan origin) is predominated by phospholipases A 2 (64.5% of total proteins), in which at least 4.6% are presynaptically-acting β-bungarotoxin A-chains. Three-finger toxins (19.0%) are the second most abundant, comprising 15.6% κ-neurotoxins, the potent postsynaptically-acting long neurotoxins. Comparative chromatography showed that venom samples from Sri Lanka, India and Pakistan did not exhibit significant variation. These venoms exhibited high immunoreactivity toward VINS Indian Polyvalent Antivenom (VPAV). The Pakistani krait venom, however, had a relatively lower degree of binding, consistent with its moderate neutralization by VPAV (potency=0.3mg venom neutralized per ml antivenom) while the Sri Lankan and Indian venoms were more effectively neutralized (potency of 0.44 mg/ml and 0.48 mg/ml, respectively). Importantly, VPAV was able to neutralize the Sri Lankan and Indian venoms to a comparable extent, supporting its use in Sri Lanka especially in the current situation where Sri Lanka-specific antivenom is unavailable against this species. The findings also indicate that the Pakistani B. caeruleus venom is immunologically less comparable and should be incorporated in the production of a pan-regional, polyspecific antivenom. The Indian krait or blue krait, Bungarus caeruleus, is a highly venomous snake that contributes to the snakebite envenoming problem in South Asia. This is a less aggressive snake species but its accidental bite can cause rapid and severe neurotoxicity, in which the patient may succumb to paralysis, respiratory failure and death within a short frame of time. The proteomic analysis of its venom (sourced from Sri Lanka) unveils its content that well correlates to its envenoming pathophysiology, driven primarily by the abundant presynaptic and postsynaptic neurotoxins (

  2. Exploring the venom of the forest cobra snake: Toxicovenomics and antivenom profiling of Naja melanoleuca.

    Science.gov (United States)

    Lauridsen, Line P; Laustsen, Andreas H; Lomonte, Bruno; Gutiérrez, José María

    2017-01-06

    A toxicovenomic analysis of the venom of the forest cobra, N. melanoleuca, was performed, revealing the presence of a total of 52 proteins by proteomics analysis. The most abundant proteins belong to the three-finger toxins (3FTx) (57.1wt%), which includes post-synaptically acting α-neurotoxins. Phospholipases A 2 (PLA 2 ) were the second most abundant group of proteins (12.9wt%), followed by metalloproteinases (SVMPs) (9.7wt%), cysteine-rich secretory proteins (CRISPs) (7.6wt%), and Kunitz-type serine proteinase inhibitors (3.8wt%). A number of additional protein families comprised each <3wt% of venom proteins. A toxicity screening of the fractions, using the mouse lethality test, identified toxicity in RP-HPLC peaks 3, 4, 5 and 8, all of them containing α-neurotoxins of the 3FTx family, whereas the rest of the fractions did not show toxicity at a dose of 0.53mg/kg. Three polyspecific antivenoms manufactured in South Africa and India were tested for their immunoreactivity against crude venom and fractions of N. melanoleuca. Overall, antivenoms immunorecognized all fractions in the venom, the South African antivenom showing a higher titer against the neurotoxin-containing fractions. This toxicovenomic study identified the 3FTx group of α-neurotoxins in the venom of N. melanoleuca as the relevant targets to be neutralized. A toxicovenomic analysis of the venom of the forest cobra, also known as black cobra, Naja melanoleuca, was performed. Envenomings by this elapid species are characterized by a progressive descending paralysis which starts with palpebral ptosis and, in severe cases, ends up with respiratory arrest and death. A total of 52 different proteins were identified in this venom. The most abundant protein family was the three-finger toxin (3FTx) family, which comprises almost 57.1wt% of the venom, followed by phospholipases A 2 (PLA 2 ) (12.9wt%). In addition, several other protein families were identified in a much lower percentage in the venom. A

  3. 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

  4. 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

  5. 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

  6. 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

  7. Structural and mutational studies on an aldo-keto reductase AKR5C3 from Gluconobacter oxydans

    Science.gov (United States)

    Liu, Xu; Wang, Chao; Zhang, Lujia; Yao, Zhiqiang; Cui, Dongbing; Wu, Liang; Lin, Jinping; Yuan, Yu-Ren Adam; Wei, Dongzhi

    2014-01-01

    An aldo-keto reductase AKR5C3 from Gluconobacter oxydans (designated as Gox0644) is a useful enzyme with various substrates, including aldehydes, diacetyl, keto esters, and α-ketocarbonyl compounds. The crystal structures of AKR5C3 in apoform in complex with NADPH and the D53A mutant (AKR5C3-D53A) in complex with NADPH are presented herein. Structure comparison and site-directed mutagenesis combined with biochemical kinetics analysis reveal that the conserved Asp53 in the AKR5C3 catalytic tetrad has a crucial role in securing active pocket conformation. The gain-of-function Asp53 to Ala mutation triggers conformational changes on the Trp30 and Trp191 side chains, improving NADPH affinity to AKR5C3, which helps increase catalytic efficiency. The highly conserved Trp30 and Trp191 residues interact with the nicotinamide moiety of NADPH and help form the NADPH-binding pocket. The AKR5C3-W30A and AKR5C3-W191Y mutants show decreased activities, confirming that both residues facilitate catalysis. Residue Trp191 is in the loop structure, and the AKR5C3-W191Y mutant does not react with benzaldehyde, which might also determine substrate recognition. Arg192, which is involved in the substrate binding, is another important residue. The introduction of R192G increases substrate-binding affinity by improving hydrophobicity in the substrate-binding pocket. These results not only supplement the AKRs superfamily with crystal structures but also provide useful information for understanding the catalytic properties of AKR5C3 and guiding further engineering of this enzyme. PMID:25131535

  8. 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. © 2015 American Heart Association, Inc.

  9. Approaches towards DNA Vaccination against a Skin Ciliate Parasite in Fish

    Science.gov (United States)

    von Gersdorff Jørgensen, Louise; Sigh, Jens; Kania, Per Walter; Holten-Andersen, Lars; Buchmann, Kurt; Clark, Theodore; Rasmussen, Jesper Skou; Einer-Jensen, Katja; Lorenzen, Niels

    2012-01-01

    Rainbow trout (Oncorhynchus mykiss) were immunized with plasmid DNA vaccine constructs encoding selected antigens from the parasite Ichthyophthirius multifiliis. Two immobilization antigens (I-ags) and one cysteine protease were tested as genetic vaccine antigen candidates. Antigenicity was evaluated by immunostaining of transfected fish cells using I-ag specific mono- and polyclonal antibodies. I. multifiliis specific antibody production, regulation of immune-relevant genes and/or protection in terms of parasite burden or mortality was measured to evaluate the induced immune response in vaccinated fish. Apart from intramuscular injection, needle free injection and gene gun delivery were tested as alternative administration techniques. For the I-ags the complement protein fragment C3d and the termini of the viral haemorrhagic septicaemia virus glyco(G)protein (VHSV G) were tested as opsonisation and cellular localisation mediators, respectively, while the full length viral G protein was tested as molecular adjuvant. Expression of I-ags in transfected fish cells was demonstrated for several constructs and by immunohistochemistry it was possible to detect expression of a secreted form of the Iag52B in the muscle cells of injected fish. Up-regulations of mRNA coding for IgM, MHC I, MHC II and TCR β, respectively, were observed in muscle tissue at the injection site in selected trials. In the spleen up-regulations were found for IFN-γ and IL-10. The highest up-regulations were seen following co-administration of I-ag and cysteine protease plasmid constructs. This correlated with a slight elevation of an I. multifiliis specific antibody response. However, in spite of detectable antigen expression and immune reactions, none of the tested vaccination strategies provided significant protection. This might suggest an insufficiency of DNA vaccination alone to trigger protective mechanisms against I. multifiliis or that other or additional parasite antigens are required for

  10. Radioimmunoassay of milk progesterone to monitor reproductive performance in smallholder dairy herds in Indonesia

    International Nuclear Information System (INIS)

    Mahaputra, L.; Hariadi, M.; Hardjopranjoto, S.

    1990-01-01

    Studies involving 260 Friesian cows from three different locations were conducted to monitor the reproductive performance in small dairy herds in Indonesia by using milk progesterone RIA. In the first study 90 post-partum cows at three locations (Surabaya, Grati and Puspo) were used to investigate post-partum ovarian function. The highest incidence of cows not showing oestrus up to 80 days post-partum, with progesterone profiles less than 0.75 ng/mL, was found in Puspo (63.3%), compared with 10% in Surabaya and 20% in Grati. The incidence of cows with silent heat and oestrus without ovulation was 13.3 and 3.3% in Surabaya, 16.7 and 6.7% in Grati, and 23.3 and 0% in Puspo. There was no significant difference (P>0.05) between the lengths of oestrous cycles at the three different locations. In the second study, using 120 cows for investigating confirmation of oestrus at AI, 69.7% of cows inseminated during the follicular phase had become pregnant, compared with 16.1% of cows inseminated during the luteal phase. The incidence of long luteal phases which included embryonic death was 13.4%. The accuracy of pregnancy diagnosis based on progesterone concentrations at day 22 was 77% and was lower than that at day 29 (88%). In the third study, cows in Subgroups 3A and 3B had cystic ovaries and were treated with prostaglandin F 2α by either intramuscular (3A) or intrauterine (3B) routes. Pregnancy rates were 50 and 40%, respectively. Cows in Subgroups 3C, 3D and 3E had inactive ovaries and were treated with intravaginal application of MPA sponges (3C), PRID (3D) or PRID followed by LH injection (3E). The pregnancy rates were 30, 40 and 60%, respectively. (author). 10 refs, 6 tabs

  11. Fe XVII X-RAY LINE RATIOS FOR ACCURATE ASTROPHYSICAL PLASMA DIAGNOSTICS

    International Nuclear Information System (INIS)

    Gillaspy, J. D.; Tedesco, L.; Tan, J. N.; Pomeroy, J. M.; Lin, T.; Brickhouse, N.; Chen, G.-X.; Silver, E.; Laming, J. M.

    2011-01-01

    New laboratory measurements using an electron beam ion trap and an X-ray microcalorimeter are presented for the n = 3 to n = 2 Fe XVII emission lines in the 15-17 A range, along with new theoretical predictions for a variety of electron energy distributions. This work improves upon our earlier work on these lines by providing measurements at more electron-impact energies (seven values from 846 to 1185 eV), performing an in situ determination of the X-ray window transmission, taking steps to minimize the ion impurity concentrations, correcting the electron energies for space charge shifts, and estimating the residual electron energy uncertainties. The results for the 3C/3D and 3s/3C line ratios are generally in agreement with the closest theory to within 10%, and in agreement with previous measurements from an independent group to within 20%. Better consistency between the two experimental groups is obtained at the lowest electron energies by using theory to interpolate, taking into account the significantly different electron energy distributions. Evidence for resonance collision effects in the spectra is discussed. Renormalized values for the absolute cross sections of the 3C and 3D lines are obtained by combining previously published results and shown to be in agreement with the predictions of converged R-matrix theory. This work establishes consistency between results from independent laboratories and improves the reliability of these lines for astrophysical diagnostics. Factors that should be taken into account for accurate diagnostics are discussed, including electron energy distribution, polarization, absorption/scattering, and line blends.

  12. The flow field in a high aspect ratio cooling duct with and without one heated wall

    Science.gov (United States)

    Rochlitz, Henrik; Scholz, Peter; Fuchs, Thomas

    2015-12-01

    The flow in a high aspect ratio generic cooling duct is described for different Reynolds numbers and for adiabatic as well as non-adiabatic conditions. The Reynolds number is varied in a range from 39,000 to 111,000. The generic cooling duct facility allows for applying a constant temperature on the duct's lower wall, and it ensures having well-defined boundary conditions. The high-quality, optical noninvasive measurement methods, namely Particle Image Velocimetry (2C2D-PIV, i.e., two velocity components in a plane), Stereo Particle Image Velocimetry (3C2D-PIV, i.e., three velocity components in a plane) and Volumetric Particle Tracking Velocimetry (3C3D-PTV, i.e., three velocity components in a volume), are used to characterize the flow in detail. Pressure transducers are installed for measuring the pressure losses. The repeatability and the validity of the data are discussed in detail. For that purpose, modifications in the test facility and in the experimental setup as well as comparisons between the different measurement methods are given. A focus lies on the average velocity distribution and on the turbulent statistics. The longitudinal velocity profile is analyzed in detail for Reynolds number variations. Secondary flows are identified with velocities of two orders of magnitude smaller than the longitudinal velocity. Reynolds stress distributions are given for several different cases. The Reynolds number dependency of overline{u'^2} and overline{v'^2} is shown, and a comparison between the adiabatic and the heated case is given. overline{u'^2} changes significantly when the lower wall heat flux is applied, whereas overline{v'^2} and overline{u'v'} almost stay constant.

  13. Antimicrobial activities of the methanol extract and compounds from the twigs of Dorstenia mannii (Moraceae).

    Science.gov (United States)

    Mbaveng, Armelle T; Kuete, Victor; Ngameni, Bathelemy; Beng, Veronique P; Ngadjui, Bonaventure T; Meyer, Jacobus J Marion; Lall, Namrita

    2012-06-29

    Dorstenia mannii (Moraceae) is a medicinal herb used traditionally for the treatment of many diseases. In the present study, the methanol extract of D. mannii and nine of its isolated compounds, namely dorsmanin A (1), B (2), C (3), D (4), E (6), F (7), G (8) dorsmanin I (9) and 6,8-diprenyleriodictyol (5), were tested for their antimicrobial activities against yeast, Mycobacteria and Gram-negative bacteria. The microplate alamar blue assay (MABA) and the broth microdilution method were used to determine the minimal inhibitory concentration (MIC) and minimal microbicidal concentration (MMC) of the above extract and compounds on a panel of bacterial species. The results of the MIC determinations demonstrated that the methanol extract as well as compounds 3 and 8 were able to prevent the growth of all the fourteen studied microorganisms within the concentration range of 4 to 1024 μg/ml. The lowest MIC value for the methanol extract (64 μg/ml) was obtained on Candida albicans. The lowest value for individual compounds (4 μg/ml) was recorded with compounds 3 on Pseudomonas aeruginosa PA01 and 7 on Eschericia coli ATCC strain. The MIC values recorded with compounds 3 on P. aeruginosa PA01, 6 on C. albicans,7 on P. aeruginosa PA01 and K. pneumoniae ATCC strain and C. albicans,and 8 on P. aeruginosa PA01, PA124, P. stuartii, M. tuberculosis MTCS1 were lower than or equal to those of the reference drugs. MMC values not greater than 1024 μg/ml were recorded on all studied microorganisms with compounds 3 and 8. The overall results of the present investigation provided evidence that the crude extract of D. mannii as well as some of its compounds such compounds 3 and 8 could be a potential source of natural antimicrobial products.

  14. Genome analysis of two type 6 echovirus (E6) strains recovered from sewage specimens in Greece in 2006.

    Science.gov (United States)

    Kyriakopoulou, Zaharoula; Pliaka, Vaia; Tsakogiannis, Dimitris; Ruether, Irina G A; Komiotis, Dimitris; Gartzonika, Constantina; Levidiotou-Stefanou, Stamatina; Markoulatos, Panayotis

    2012-04-01

    Echovirus 6 (E6) is one of the main enteroviral serotypes that was isolated from cases of aseptic meningitis and encephalitis during the last years in Greece. Two E6 (LR51A5 and LR61G3) were isolated from the sewage treatment plant unit in Larissa, Greece, in May 2006, 1 year before their characterization from aseptic meningitis cases. The two isolates were initially found to be intra-serotypic recombinants in the genomic region VP1, a finding that initiated a full genome sequence analysis. In the present study, nucleotide, amino acid, and phylogenetic analyses for all genomic regions were conducted. For the detection of recombination events, Simplot and bootscan analyses were carried out. The continuous phylogenetic relationship in 2C-3D genomic region of strains LR51A5 and LR61G3 with E30 isolated in France in 2002-2005 indicated that the two strains were recombinants. SimPlot and Bootscan analyses confirmed that LR51A5 and LR61G3 carry an inter-serotypic recombination in the 2C genomic region. The present study provide evidence that recombination events occurred in the regions VP1 (intraserotypic) and non-capsid (interserotypic) during the evolution of LR51A5 and LR61G3, supporting the statement that the genomes of circulating enteroviruses are a mosaic of genomic regions of viral strains of the same or different serotypes. In conclusion, full genome sequence analysis of circulating enteroviral strains is a prerequisite to understand the complexity of enterovirus evolution.

  15. 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)

  16. Staphylococcus aureus SdrE captures complement factor H's C-terminus via a novel 'close, dock, lock and latch' mechanism for complement evasion.

    Science.gov (United States)

    Zhang, Yingjie; Wu, Minhao; Hang, Tianrong; Wang, Chengliang; Yang, Ye; Pan, Weimin; Zang, Jianye; Zhang, Min; Zhang, Xuan

    2017-05-04

    Complement factor H (CFH) is a soluble complement regulatory protein essential for the down-regulation of the alternative pathway on interaction with specific markers on the host cell surface. It recognizes the complement component 3b (C3b) and 3d (C3d) fragments in addition to self cell markers (i.e. glycosaminoglycans, sialic acid) to distinguish host cells that deserve protection from pathogens that should be eliminated. The Staphylococcus aureus surface protein serine-aspartate repeat protein E (SdrE) was previously reported to bind human CFH as an immune-evasion tactic. However, the molecular mechanism underlying SdrE-CFH-mediated immune evasion remains unknown. In the present study, we identified a novel region at CFH's C-terminus (CFH 1206-1226 ), which binds SdrE N2 and N3 domains (SdrE N2N3 ) with high affinity, and determined the crystal structures of apo-SdrE N2N3 and the SdrE N2N3 -CFH 1206-1226 complex. Comparison of the structure of the CFH-SdrE complex with other CFH structures reveals that CFH's C-terminal tail flips from the main body to insert into the ligand-binding groove of SdrE. In addition, SdrE N2N3 adopts a 'close' state in the absence of CFH, which undergoes a large conformational change on CFH binding, suggesting a novel 'close, dock, lock and latch' (CDLL) mechanism for SdrE to recognize its ligand. Our findings imply that SdrE functions as a 'clamp' to capture CFH's C-terminal tail via a unique CDLL mechanism and sequesters CFH on the surface of S. aureus for complement evasion. © 2017 The Author(s).

  17. Staphylococcus aureus SdrE captures complement factor H's C-terminus via a novel ‘close, dock, lock and latch' mechanism for complement evasion

    Science.gov (United States)

    Zhang, Yingjie; Wu, Minhao; Hang, Tianrong; Wang, Chengliang; Yang, Ye; Pan, Weimin; Zang, Jianye

    2017-01-01

    Complement factor H (CFH) is a soluble complement regulatory protein essential for the down-regulation of the alternative pathway on interaction with specific markers on the host cell surface. It recognizes the complement component 3b (C3b) and 3d (C3d) fragments in addition to self cell markers (i.e. glycosaminoglycans, sialic acid) to distinguish host cells that deserve protection from pathogens that should be eliminated. The Staphylococcus aureus surface protein serine–aspartate repeat protein E (SdrE) was previously reported to bind human CFH as an immune-evasion tactic. However, the molecular mechanism underlying SdrE–CFH-mediated immune evasion remains unknown. In the present study, we identified a novel region at CFH's C-terminus (CFH1206–1226), which binds SdrE N2 and N3 domains (SdrEN2N3) with high affinity, and determined the crystal structures of apo-SdrEN2N3 and the SdrEN2N3–CFH1206–1226 complex. Comparison of the structure of the CFH–SdrE complex with other CFH structures reveals that CFH's C-terminal tail flips from the main body to insert into the ligand-binding groove of SdrE. In addition, SdrEN2N3 adopts a ‘close’ state in the absence of CFH, which undergoes a large conformational change on CFH binding, suggesting a novel ‘close, dock, lock and latch' (CDLL) mechanism for SdrE to recognize its ligand. Our findings imply that SdrE functions as a ‘clamp' to capture CFH's C-terminal tail via a unique CDLL mechanism and sequesters CFH on the surface of S. aureus for complement evasion. PMID:28258151

  18. Taguchi design optimization of machining parameters on the CNC end milling process of halloysite nanotube with aluminium reinforced epoxy matrix (HNT/Al/Ep hybrid composite

    Directory of Open Access Journals (Sweden)

    J.S. Pang

    2014-08-01

    Full Text Available This paper introduces the application of Taguchi optimization methodology in optimizing the cutting parameters of end-milling process for machining the halloysite nanotubes (HNTs with aluminium reinforced epoxy hybrid composite material under dry condition. The machining parameters which are chosen to be evaluated in this study are the depth of cut (d, cutting speed (S and feed rate (f. While, the response factors to be measured are the surface roughness of the machined composite surface and the cutting force. An orthogonal array of the Taguchi method was set-up and used to analyse the effect of the milling parameters on the surface roughness and cutting force. The result from this study shows that the application of the Taguchi method can determine the best combination of machining parameters that can provide the optimal machining response conditions which are the lowest surface roughness and lowest cutting force value. For the best surface finish, A1–B3–C3 (d = 0.4 mm, S = 1500 rpm, f = 60 mmpm is found to be the optimized combination of levels for all the three control factors from the analysis. Meanwhile, the optimized combination of levels for all the three control factors from the analysis which provides the lowest cutting force was found to be A2–B2–C2 (d = 0.6 mm, S = 1000 rpm, f = 40 mmpm.

  19. PERSPECTIVES OF INTERNET-IMPLEMENTATION OF OCEANOGRAPHIC INFORMATION SYSTEMS

    Directory of Open Access Journals (Sweden)

    V. V. Dolotov

    2017-01-01

    Full Text Available The article considers new version of the Internet implementation of the interactive information system “Crimea Coasts” based on the use of the Javascript in conjunction with the open library Leaflet and vector formats for the oceanographic data presentation. The first current system version includes a complete set of materials of published earlier monograph “The Current State of the Crimean Seashores”, implemented as interactive maps. In contrast to the printed version, interactive maps allow one to obtain data about the length of individual coast sections, the areas of coastal objects, and other characteristic data. It is expected that further system development will be performed with the wide using of modern vector graphics technologies, such as GeoDjango, C3- D3, Dojo and other add-ons over Javascript modules. The main attention will be given to the operational presentation of the results of nature observations and the assessment of the dynamics of the Crimea coastal zone as a whole. Variants of this approach have now been implemented on the basis of data on the measurement of the position of the coastline of the north-west Crimea coast. In addition, the system has reserved sections both for the basics and results of the implementation of a previously developed algorithm of the beaches cadastral assessment, including their recreational areas, the economic evaluation of recreational resources, as well as the results of a complex interdisciplinary monitoring of the ecological status of the Sevastopol Bay since 1998, including the geoinformation cartographic representation of the region elements. The monitoring results allow one to realize the visualization of the spatial distributions for the hydrological, hydrochemical and hydrobiological characteristics of the bay marine environment in a user-specified digital format, as well as to perform vertical distributions and some calculations. It is planned to put the final materials on the

  20. Hydrogen--deuterium exchange in saturated hydrocarbons on α-chromia catalyst

    International Nuclear Information System (INIS)

    Kalman, J.; Guczi, L.

    1977-01-01

    The kinetics of hydrogen--deuterium exchange in methane, ethane, and propane have been studied with unsupported α-chromia as catalyst in the temperature range of 598 to 688 0 K. The apparent activation energies for methane, ethane, and propane are 88, 130, and 84 kJ mol -1 , respectively, similar to those found on chromia gel. The order of reaction with respect to hydrocarbons and deuterium has been determined as also having the kinetic isotope effect. The main initial products are CH 3 D and CD 4 with methane, C 2 H 4 D 2 and C 2 D 6 with ethane, and C 3 H 7 D and C 3 D 8 with propane. A change in product distribution as a function of temperature, conversion, aging, and oxygen--deuterium treatment has been observed. In agreement with the kinetic data and the effect of oxygen, Cr 3+ has been assumed as the active species of the chromia catalyst, whereas Cr 2+ is an inactive site on the surface. There is no direct proof that chromium ion in a valence state higher than 3+ plays an important role in the exchange reaction. It was established that dual Cr 3+ -- Cr 3+ sites are responsible for the formation of ethane-d 2 . After a long deuterium treatment the number of dual sites is decreased, the effect being revealed in the decreased rate of exchange and the small amount of ethane-d 2 . On the contrary, the formation of methane-d 4 is interpreted by the formation of Cr = C bonds by analogy with homogeneous complexes. In the case of propane, the exchange reaction can be adequately interpreted by a π-allyl mechanism

  1. Mechanism of Lipid Binding of Human Apolipoprotein E3 by Hydrogen/Deuterium Exchange/Mass Spectrometry and Fluorescence Polarization.

    Science.gov (United States)

    Fabilane, Charina S; Nguyen, Patricia N; Hernandez, Roy V; Nirudodhi, Sasidhar; Duong, Mai; Maier, Claudia S; Narayanaswami, Vasanthy

    2016-01-01

    Human apolipoprotein E3 (apoE3) is an exchangeable apolipoprotein that plays a critical role in maintaining plasma cholesterol/triglyceride homeostasis. The C-terminal (CT) domain of apoE3 (residues 201-299) is composed of amphipathic α-helices C1: W210-S223, C2: V236-E266, and C3: D271-W276, which play a dominant role in mediating high-affinity lipid binding. The objective is to understand the accessibility of the CT domain at the sub-domain level and the mechanistic details regarding lipid-binding interaction. Hydrogen-deuterium exchange coupled to mass spectrometry (HDX/MS) of recombinant wild type (WT) apoE(201-299), chemical-induced unfolding monitored as changes in fluorescence polarization (FP) of labeled apoE(201-299) bearing a probe at specified sites, and lipid binding studies were carried out. HDX/MS revealed that residues towards the C-terminal end of the domain display significantly lower %D uptake compared to those towards the center, suggesting extensive protein-protein interaction in this segment. Functional assays showed that locking apoE(201-299) in an inter-molecular disulfide-bonded state at position 209, 223, 255, or 277 significantly decreases its ability to interact with lipids, especially when tethered towards the ends; this could be restored by reduction. Unfolding studies indicate that the C-terminal end offers less resistance to unfolding compared to the central portion of the domain. Taken together, our data suggest that two dimers of CT domain are juxtaposed around helix C3 leading to apoE3 tetramerization, and that dissociation to monomeric units is a required step in lipid binding, with helix C3 likely seeking stability via lipid interaction prior to helices C1 or C2.

  2. Enhancement of the uptake and cytotoxic activity of doxorubicin in cancer cells by novel cRGD-semipeptide-anchoring liposomes.

    Science.gov (United States)

    Battistini, Lucia; Burreddu, Paola; Sartori, Andrea; Arosio, Daniela; Manzoni, Leonardo; Paduano, Luigi; D'Errico, Gerardino; Sala, Roberto; Reia, Laura; Bonomini, Sabrina; Rassu, Gloria; Zanardi, Franca

    2014-07-07

    Novel liposemipeptides hanging cyclic azabicycloalkane-RGD or aminoproline-RGD terminals were synthesized and incorporated into liposomal nanoparticles cAba/cAmpRGD-LNP5 3C/3D. Liposomes with similar composition and lacking semipeptide conjugates were constructed for comparison (LNP, 3A), and physical encapsulation of the anticancer doxorubicin drug in both targeted and untargeted liposomes was accomplished. Microstructural analysis performed by dynamic light scattering (DLS), small-angle neutron scattering (SANS), and electron paramagnetic resonance (EPR) revealed that the conjugated nanoparticles presented an average size of 80 nm and were constituted by 5 nm thick unilamellar liposome bilayer. Flow cytometry and fluorescent microscopy studies showed that 3C-DOXO and 3D-DOXO efficiently delivered the drug into the nuclei of both quiescent and proliferating cells even in a high serum concentration environment. The uptake of doxorubicin when carried by liposomes was faster than that of the free drug, and 30 min incubation was sufficient to load cell nuclei with doxorubicin. Targeted liposomes significantly induced cell death of human breast adenocarcinoma MCF7 cells (IC50 = 144 nM, 3C-DOXO; IC50 = 274 nM, 3D-DOXO), about 2- to 6-fold more potent than free doxorubicin or 3A-DOXO controls (IC50 = 527 and 854 nM, respectively). These results suggest that cAba/cAmpRGD liposomal nanoparticles hold promise for the rapid and efficient delivery of chemotherapeutic agents to αVβ3-expressing tumor cells.

  3. Estimation of solar radiation over Turkey using artificial neural network and satellite data

    International Nuclear Information System (INIS)

    Senkal, Ozan; Kuleli, Tuncay

    2009-01-01

    This study introduces artificial neural networks (ANNs) for the estimation of solar radiation in Turkey (26-45 E and 36-42 N). Resilient propagation (RP), Scale conjugate gradient (SCG) learning algorithms and logistic sigmoid transfer function were used in the network. In order to train the neural network, meteorological data for the period from August 1997 to December 1997 for 12 cities (Antalya, Artvin, Edirne, Kayseri, Kuetahya, Van, Adana, Ankara, Istanbul, Samsun, Izmir, Diyarbakir) spread over Turkey were used as training (nine stations) and testing (three stations) data. Meteorological and geographical data (latitude, longitude, altitude, month, mean diffuse radiation and mean beam radiation) are used in the input layer of the network. Solar radiation is the output. However, solar radiation has been estimated as monthly mean daily sum by using Meteosat-6 satellite C3 D data in the visible range over 12 cities in Turkey. Digital counts of satellite data were converted into radiances and these are used to calculate the albedos. Using the albedo, the cloud cover index of each pixel was constructed. Diffuse and direct component of horizontal irradiation were calculated as a function of optical air mass, turbidity factor and Rayleigh optical thickness for clear-sky. Using the relation between clear-sky index and cloud cover index, the solar irradiance for any pixel is calculated for Physical method. RMS between the estimated and ground values for monthly mean daily sum with ANN and Physical method values have been found as 2.32 MJ m -2 (54 W/m 2 ) and 2.75 MJ m -2 (64 W/m 2 ) (training cities), 3.94 MJ m -2 (91 W/m 2 ) and 5.37 MJ m -2 (125 W/m 2 ) (testing cities), respectively

  4. Search for structures, potential energy surfaces, and stabilities of planar BnP(n = 1 ∼ 7).

    Science.gov (United States)

    Shi, Rongwei; Shao, Jingling; Wang, Cheng; Zhu, Xiaolei; Lu, Xiaohua

    2011-05-01

    We have systematically explored and investigated the geometrical structures, stability, growth pattern, bonding character, and potential energy surface (PES) of the possible isomers of each cluster for planar B(n)P (n = 1 ∼ 7) at the CCSD(T)/6-311+;G(d)//B3LYP/6-311+G(d) level. A large number of planar structures for the possible isomers of B(n)P (n = 1 ∼ 7) and transition states are located. Isomers 1a ∼ 7a of B(n)P are the lowest-energy structures and 2a, 4a, as well as 6a are more stable than their neighbors. For the lowest-energy structures (1a ∼ 7a) of B(n)P, P atom lies at the apex and tends to form two B-P bonds with boron atoms. They exhibit planar zigzag growth feature or approximately spherical-like growth pattern. Results from molecular orbital analysis demonstrate that the formation of the delocalized π MOs and the σ-radial and σ-tangential MOs plays a critical role in stabilizing the structures of lowest-energy isomers (2a ∼ 7a) of B(n)P. Importantly, isomers 3a, 3c, 3d, 4a, 4b, 5b, and 5c of B(n)P are stable both thermodynamically and kinetically at the CCSD(T)/6-311+G(d)// B3LYP/6-311+G(d) level and detectable in laboratory, which is valuable for further experimental studies of B(n)P.

  5. Warm autoimmune hemolytic anemia: experience from a single referral center in Mexico City.

    Science.gov (United States)

    Alonso, Hernandez-Company; Manuel, Anguiano-Alvarez Victor; Amir, Carmona Gonzalez Carlos; Sergio, Rodriguez-Rodriguez; Allan, Pomerantz; Xavier, Lopez-Karpovitch; Juventina, Tuna-Aguilar Elena

    2017-03-01

    Autoimmune hemolytic anemia (AIHA) is characterized by an autoimmune-mediated destruction of red blood cells. Warm AIHA (wAIHA) represents 60% of AIHA cases and is associated with the positive detection of IgG and C3d in the direct antiglobulin test (DAT). This study aimed to assess the clinical and laboratorial differences between primary and secondary wAIHA patients from a referral center in Mexico City. All patients diagnosed with wAIHA in our institution from January 1992 to December 2015 were included and received corticosteroids as the first-line treatment. We analyzed the response to the first-line treatment, relapse-free survival, and time to splenectomy. Eighty-nine patients were included. Secondary wAIHA represented 55.1% of the cases. At diagnosis, secondary wAIHA patients showed a DAT mixed pattern more frequently than primary wAIHA patients (36.7 vs. 17.5%, P <0.001). In the survival analysis, patients with secondary wAIHA had a lower time to response (18 vs. 37 days, P =0.05), median disease-free survival (28.51 vs. 50.95 weeks, P =0.018), and time to splenectomy (43.5 vs. 61 wks, P =0.029) than those with primary wAIHA. Due to economic constraints, rituximab was considered as the third-line treatment in only two patients. Secondary wAIHA may benefit from a longer low-dose steroid maintenance period mainly due to its shorter time to relapse and time to splenectomy than primary wAIHA.

  6. Duodenal epithelial transport in functional dyspepsia: Role of serotonin.

    Science.gov (United States)

    Witte, Anne-Barbara; D'Amato, Mauro; Poulsen, Steen Seier; Laurent, Agneta; Knuhtsen, Svend; Bindslev, Niels; Hansen, Mark Berner; Schmidt, Peter Thelin

    2013-05-15

    To investigate functional duodenal abnormalities in functional dyspepsia (FD) and the role of serotonin (5-hydroxytryptamine, 5-HT) in mucosal ion transport and signalling. Duodenal mucosal biopsies were obtained from 15 patients with FD and 18 healthy controls. Immunohistochemistry was used to study the number of 5-HT-containing cells and real-time polymerase chain reaction for expression of 5-HT receptors 1A, 1B, 2A, 2B, 3A, 3B, 3C, 3D, 3E, 4 and 7, as well as expression of the serotonin re-uptake transporter (SERT) gene SLC6A4 and tryptophan hydroxylase 1 (TPH1). Biopsies were mounted in Ussing chambers for evaluation of basal and 5-HT-stimulated short-circuit current (SCC). Conductance was lower in FD [42.4 ± 4.7 mS/cm(2) (n = 15) vs 62.5 ± 4.5 mS/cm(2) (n = 18), P = 0.005]. 5-HT induced a dose dependent rise in SCC in both FD (n = 8) and controls (n = 9), the rise was lower in FD (P power field was the same [34.4 ± 8.4 in FD (n = 15) and 30.4 ± 3.7 in controls (n = 18), P = 0.647]. The following genes were highly expressed: 5-HT receptor HTR3E, HTR4, HTR7, SERT gene (SLC6A4) and TPH1. Differences in expression levels were observed for HTR3E (higher expression in FD, P = 0.008), HTR7 (lower expression in FD, P = 0.027), SLC6A4 (higher expression in FD, P = 0.033) and TPH1 (lower expression in FD, P = 0.031). Duodenal ion transport in response to exogenous 5-HT is abnormal in FD patients and associated with high expression of the HTR3E receptor and the serotonin transporter.

  7. Synthesis, fungicidal activity, and structure-activity relationship of 2-oxo- and 2-hydroxycycloalkylsulfonamides.

    Science.gov (United States)

    Li, Xing-Hai; Wu, De-Cai; Qi, Zhi-Qiu; Li, Xiu-Wei; Gu, Zu-Min; Wei, Song-Hong; Zhang, Yang; Wang, Ying-Zi; Ji, Ming-Shan

    2010-11-10

    To explore new potential fungicides, a series of novel compounds, including 11 2-oxocycloalkylsulfonamide (3) and 21 2-hydroxycycloalkylsulfonamide (4) derivatives, were synthesized and their structures were confirmed by (1)H nuclear magnetic resonance (NMR), infrared (IR), and elemental analysis. The results of the bioassay showed that the compounds 3 and 4 possessed excellent fungicidal activity against Botrytis cinerea Pers. both in vitro and in vivo. The fungicidal activity of the compounds with 7- or 8-membered rings is better than those with 5-, 6-, or 12-membered rings. According to the results of the mycelium growth rate test, the EC50 values of the compounds 3C, 4C, 3D, and 4D were 0.80, 0.85, 1.22, and 1.09 μg/mL, respectively, and similar to or better than commercial fungicide procymidone. The bioassay results of spore germination indicated that most of the compounds exhibited obvious inhibitory effects against B. cinerea and the inhibition rates of 2-oxocycloalkylsulfonamides were higher than 2-hydroxycycloalkylsulfonamides, among them. The EC50 values of compounds 3A, 3B17, 3E, and 4A were 4.21, 4.21 3.24, and 5.29 μg/mL, respectively. Those compounds containing 5- or 6-membered rings showed better activity than those containing 7-, 8-, or 12-membered rings. Furthermore, the results of the pot culture test showed that almost all of the compounds had effective control activity in vivo and 2-hydroxycycloalkylsulfonamides were obviously superior to 2-oxocycloalkylsulfonamides. The compounds 3E, 4C and 4D presented higher control efficacy than procymidone and pyrimethanil against gray mold disease on cucumber plants.

  8. 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

  9. Murine complement deficiency ameliorates acute cigarette smoke-induced nasal damage.

    Science.gov (United States)

    Davis, Kara S; Casey, Sarah E; Mulligan, Jennifer K; Mulligan, Ryan M; Schlosser, Rodney J; Atkinson, Carl

    2010-07-01

    Exposure to cigarette smoke is a risk factor for chronic rhinosinusitis. Current literature confirms complement fragments are activated in human nasal mucosa. The mechanism(s) responsible for this activation is unclear. We investigated the effects of cigarette smoke on nasal mucosa in vitro and via a model of cigarette smoke exposure by using animals deficient in complement components. Prospective, controlled animal and in vitro human cell line study. University laboratory. Human respiratory epithelial cells were exposed to five, 10, and 20 percent cigarette smoke extract (CSE) in vitro in the presence or absence of human serum. Complement activation was assessed by enzyme-linked immunosorbent assay and immunofluorescent techniques. Complement-deficient (C3(-/-), n = 6; factor B(-/-), n = 50) and sufficient mice (wild type, n = 10) were exposed to the smoke of four cigarettes per exposure for two exposures per day for three days. Mice were sacrificed 12 hours after the last exposure, and the nasal cavity was surgically removed. Histological characteristics were analyzed by the use of a subjective scale and quantitative image analysis scoring systems. In vitro analysis of respiratory cell cultures demonstrated that exposure of serum to CSE resulted in complement activation. Furthermore, immunofluorescent staining for C3d could only be demonstrated in CSE-exposed cultures. In vivo analysis demonstrated that complement deficiency, either C3 or factor B deficiency, resulted in a significant reduction in histological evidence of damage as compared with wild-type control mice (wild type vs C3(-/-), P = 0.02; wild type vs factor B(-/-), P = 0.07; no significant difference between C3(-/-) vs factor B(-/-)). These data demonstrate that cigarette smoke activates the complement system. Furthermore, complement deficiency protected against smoke-induced mucosal damage in this small series. 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by

  10. C1-esterase inhibitor protects against early vein graft remodeling under arterial blood pressure.

    Science.gov (United States)

    Krijnen, Paul A J; Kupreishvili, Koba; de Vries, Margreet R; Schepers, Abbey; Stooker, Wim; Vonk, Alexander B A; Eijsman, Leon; Van Hinsbergh, Victor W M; Zeerleder, Sacha; Wouters, Diana; van Ham, Marieke; Quax, Paul H A; Niessen, Hans W M

    2012-01-01

    Arterial pressure induced vein graft injury can result in endothelial loss, accelerated atherosclerosis and vein graft failure. Inflammation, including complement activation, is assumed to play a pivotal role herein. Here, we analyzed the effects of C1-esterase inhibitor (C1inh) on early vein graft remodeling. Human saphenous vein graft segments (n=8) were perfused in vitro with autologous blood either supplemented or not with purified human C1inh at arterial pressure for 6h. The vein segments and perfusion blood were analyzed for cell damage and complement activation. In addition, the effect of purified C1inh on vein graft remodeling was analyzed in vivo in atherosclerotic C57Bl6/ApoE3 Leiden mice, wherein donor caval veins were interpositioned in the common carotid artery. Application of C1inh in the in vitro perfusion model resulted in significantly higher blood levels and significantly more depositions of C1inh in the vein wall. This coincided with a significant reduction in endothelial loss and deposition of C3d and C4d in the vein wall, especially in the circular layer, compared to vein segments perfused without supplemented C1inh. Administration of purified C1inh significantly inhibited vein graft intimal thickening in vivo in atherosclerotic C57Bl6/ApoE3 Leiden mice, wherein donor caval veins were interpositioned in the common carotid artery. C1inh significantly protects against early vein graft remodeling, including loss of endothelium and intimal thickening. These data suggest that it may be worth considering its use in patients undergoing coronary artery bypass grafting. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  11. Discovery of novel biomarker candidates for liver fibrosis in hepatitis C patients: a preliminary study.

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    Bevin Gangadharan

    Full Text Available Liver biopsy is the reference standard for assessing liver fibrosis and no reliable non-invasive diagnostic approach is available to discriminate between the intermediate stages of fibrosis. Therefore suitable serological biomarkers of liver fibrosis are urgently needed. We used proteomics to identify novel fibrosis biomarkers in hepatitis C patients with different degrees of liver fibrosis.Proteins in plasma samples from healthy control individuals and patients with hepatitis C virus (HCV induced cirrhosis were analysed using a proteomics technique: two dimensional gel electrophoresis (2-DE. This technique separated the proteins in plasma samples of control and cirrhotic patients and by visualizing the separated proteins we were able to identify proteins which were increasing or decreasing in hepatic cirrhosis. Identified markers were validated across all Ishak fibrosis stages and compared to the markers used in FibroTest, Enhanced Liver Fibrosis (ELF test, Hepascore and FIBROSpect by Western blotting. Forty four candidate biomarkers for hepatic fibrosis were identified of which 20 were novel biomarkers of liver fibrosis. Western blot validation of all candidate markers using plasma samples from patients across all Ishak fibrosis scores showed that the markers which changed with increasing fibrosis most consistently included lipid transfer inhibitor protein, complement C3d, corticosteroid-binding globulin, apolipoprotein J and apolipoprotein L1. These five novel fibrosis markers which are secreted in blood showed a promising consistent change with increasing fibrosis stage when compared to the markers used for the FibroTest, ELF test, Hepascore and FIBROSpect. These markers will be further validated using a large clinical cohort.This study identifies 20 novel fibrosis biomarker candidates. The proteins identified may help to assess hepatic fibrosis and eliminate the need for invasive liver biopsies.

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

    Directory of Open Access Journals (Sweden)

    Mary C Peavey

    Full Text Available 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

  13. New structure-activity relationship studies in a series of N,N-bis(cyclohexanol)amine aryl esters as potent reversers of P-glycoprotein-mediated multidrug resistance (MDR).

    Science.gov (United States)

    Orlandi, Francesca; Coronnello, Marcella; Bellucci, Cristina; Dei, Silvia; Guandalini, Luca; Manetti, Dina; Martelli, Cecilia; Romanelli, Maria Novella; Scapecchi, Serena; Salerno, Milena; Menif, Hayette; Bello, Ivan; Mini, Enrico; Teodori, Elisabetta

    2013-01-15

    As a continuation of previous research on a new series of potent and efficacious P-gp-dependent multidrug resistant (MDR) reversers with a N,N-bis(cyclohexanol)amine scaffold, we have designed and synthesized several analogs by modulation of the two aromatic moieties linked through ester functions to the N,N-bis(cyclohexanol)amine, aiming to optimize activity and to extend structure-activity relationships (SAR) within the series. This scaffold, when esterified with two different aromatic carboxylic acids, gives origin to four geometric isomers (cis/trans, trans/trans, cis/cis and trans/cis). The new compounds were tested on doxorubicin-resistant erythroleukemia K562 cells (K562/DOX) in the pirarubicin uptake assay. Most of them resulted in being potent modulators of the extrusion pump P-gp, showing potency values ([I](0.5)) in the submicromolar and nanomolar range. Of these, compounds 2b, 2c, 3d, 5a-d and 6d, showed excellent efficacy with a α(max) close to 1. Selected compounds (2d, 3a, 3b, 5a-d) were further studied to evaluate their doxorubicin cytotoxicity potentiation (RF) on doxorubicin-resistant erythroleukemia K562 cells and were found able to enhance significantly doxorubicin cytotoxicity on K562/DOX cells. The results of both pirarubicin uptake and the cytotoxicity assay, indicate that the new compounds of the series are potent P-gp-mediated MDR reversers. They present a structure with a mix of flexible and rigid moieties, a property that seems critical to allow the molecules to choose the most productive of the several binding modes possible in the transporter recognition site. In particular, compounds 5c and 5d, similar to the already reported analogous isomers 1c and 1d,(29) are potent and efficacious modulators of P-gp-dependent MDR and may be promising leads for the development of MDR-reversal drugs. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. The value of different imaging methods on classification in displaced proximal humeral fractures

    International Nuclear Information System (INIS)

    Cai Jingyu; Zhu Qingsheng

    2004-01-01

    Objective: To investigate the influence of common X-ray, two-dimensional computed tomography (2D-CT), spiral computed tomography (SCT), and three-dimensional (3-D) reconstruction on the classification in displaced proximal humeral fractures. Methods: Three groups were divided on the basis of various imaging methods, including group A (common X-ray), group B (common X-ray and 2D-CT), and group C (3-D reconstruction of SCT and 2D-SCT). 46 cases of displaced proximal humeral fractures were classified with Neer system. The true rate of fracture classification by use of three methods was compared with each other, and clinical significance of SCT and 3-D reconstruction was evaluated. Results: Based on operation, 46 cases of displaced proximal humeral fractures in group A included 26 cases of Neer two-part fractures, 13 cases of three-part fractures, and 7 cases of four-part fractures. The true cases of common X-ray were 22 in Neer two-part fractures and 8 in three and four-part fractures, there was significant difference between Neer two-part fractures and Neer three and four-part fractures (P<0.05); 18 cases of proximal humeral fractures in group B included 3 cases of Neer two-part fractures, 9 cases of three-part fractures, and 6 cases of four-part fractures. The true cases of common X-ray and 2D-CT were 7 in Neer three and four-part fractures. 10 cases of proximal humeral fractures in group C included 1 case of Neer two-part fracture, 5 cases of three-part fractures, and 4 cases of four-part fractures. The true cases of 3-D reconstruction, MPR of SCT, and 2D-SCT were 8 in Neer three and four-part fractures. With regard to the true cases of the classification in Neer three and four-part fractures, there was significant difference in three groups and between group A and group C (P<0.05). All SCT and 3-D reconstruction played an important role in the treatment of proximal humeral fractures. Conclusion: Series of good quality X-ray examinations were the first imaging

  15. Untangling the methane chemistry in interstellar and solar system ices toward ionizing radiation: a combined infrared and reflectron time-of-flight analysis.

    Science.gov (United States)

    Abplanalp, Matthew J; Jones, Brant M; Kaiser, Ralf I

    2018-02-21

    Pure methane (CH 4 /CD 4 ) ices were exposed to three ionizing radiation sources at 5.5 K under ultrahigh vacuum conditions to compare the complex hydrocarbon spectrum produced across several interstellar environments. These irradiation sources consisted of energetic electrons to simulate secondary electrons formed in the track of galactic cosmic rays (GCRs), Lyman α (10.2 eV; 121.6 nm) photons simulated the internal VUV field in a dense cloud, and broadband (112.7-169.8 nm; 11.0-7.3 eV) photons which mimic the interstellar ultra-violet field. The in situ chemical evolution of the ices was monitored via Fourier transform infrared spectroscopy (FTIR) and during heating via mass spectrometry utilizing a quadrupole mass spectrometer with an electron impact ionization source (EI-QMS) and a reflectron time-of-flight mass spectrometer with a photoionization source (PI-ReTOF-MS). The FTIR analysis detected six small hydrocarbon products from the three different irradiation sources: propane [C 3 H 8 (C 3 D 8 )], ethane [C 2 H 6 (C 2 D 6 )], the ethyl radical [C 2 H 5 (C 2 D 5 )], ethylene [C 2 H 4 (C 2 D 4 )], acetylene [C 2 H 2 (C 2 D 2 )], and the methyl radical [CH 3 (CD 3 )]. The sensitive PI-ReTOF-MS analysis identified a complex array of products with different products being detected between experiments with general formulae: C n H 2n+2 (n = 4-8), C n H 2n (n = 3-9), C n H 2n-2 (n = 3-9), C n H 2n-4 (n = 4-9), and C n H 2n-6 (n = 6-7) from electron irradiation and C n H 2n+2 (n = 4-8), C n H 2n (n = 3-10), C n H 2n-2 (n = 3-11), C n H 2n-4 (n = 4-11), C n H 2n-6 (n = 5-11), and C n H 2n-8 (n = 6-11) from broadband photolysis and Lyman α photolysis. These experiments show that even the simplest hydrocarbon can produce important complex hydrocarbons such as C 3 H 4 and C 4 H 6 isomers. Distinct isomers from these groups have been shown to be important reactants in the synthesis of polycyclic aromatic hydrocarbons like indene (C 9 H 8 ) and naphthalene (C 10 H 8

  16. Developing and implementing a high precision setup system

    Science.gov (United States)

    Peng, Lee-Cheng

    The demand for high-precision radiotherapy (HPRT) was first implemented in stereotactic radiosurgery using a rigid, invasive stereotactic head frame. Fractionated stereotactic radiotherapy (SRT) with a frameless device was developed along a growing interest in sophisticated treatment with a tight margin and high-dose gradient. This dissertation establishes the complete management for HPRT in the process of frameless SRT, including image-guided localization, immobilization, and dose evaluation. The most ideal and precise positioning system can allow for ease of relocation, real-time patient movement assessment, high accuracy, and no additional dose in daily use. A new image-guided stereotactic positioning system (IGSPS), the Align RT3C 3D surface camera system (ART, VisionRT), which combines 3D surface images and uses a real-time tracking technique, was developed to ensure accurate positioning at the first place. The uncertainties of current optical tracking system, which causes patient discomfort due to additional bite plates using the dental impression technique and external markers, are found. The accuracy and feasibility of ART is validated by comparisons with the optical tracking and cone-beam computed tomography (CBCT) systems. Additionally, an effective daily quality assurance (QA) program for the linear accelerator and multiple IGSPSs is the most important factor to ensure system performance in daily use. Currently, systematic errors from the phantom variety and long measurement time caused by switching phantoms were discovered. We investigated the use of a commercially available daily QA device to improve the efficiency and thoroughness. Reasonable action level has been established by considering dosimetric relevance and clinic flow. As for intricate treatments, the effect of dose deviation caused by setup errors remains uncertain on tumor coverage and toxicity on OARs. The lack of adequate dosimetric simulations based on the true treatment coordinates from

  17. 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

  18. 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.

  19. Natural IgM antibodies that bind neoepitopes exposed as a result of spinal cord injury , drive secondary injury by activating complement.

    Science.gov (United States)

    Narang, Aarti; Qiao, Fei; Atkinson, Carl; Zhu, Hong; Yang, Xiaofeng; Kulik, Liudmila; Holers, V Michael; Tomlinson, Stephen

    2017-06-19

    Natural IgM antibodies (Abs) function as innate immune sensors of injury via recognition of neoepitopes expressed on damaged cells, although how this recognition systems function following spinal cord injury (SCI) exposes various neoepitopes and their precise nature remains largely unknown. Here, we investigated the role of two natural IgM monoclonal Abs (mAbs), B4 and C2, that recognize post-ischemic neoepitopes following ischemia and reperfusion in other tissues. Identification of post-SCI expressed neoepitopes was examined using previously characterized monoclonal Abs (B4 and C2 mAbs). The role of post-SCI neoepitopes and their recognition by natural IgM Abs in propagating secondary injury was examined in Ab-deficient Rag1-/- or wild type C57BL/6 mice using Ab reconstitution experiments and neoepitope-targeted therapeutic studies, respectively. Administration of B4 or C2 mAb following murine SCI increased lesion size and worsened functional outcome in otherwise protected Ab-deficient Rag1-/- mice. Injury correlated with colocalized deposition of IgM and C3d in injured spinal cords from both mAb reconstituted Rag1-/- mice and untreated wild-type mice. Depletion of peritoneal B1 B cells, a source of natural Abs, reduced circulating levels of IgM with B4 (annexin-IV) and C2 (subset of phospholipids) reactivity, reduced IgM and complement deposition in the spinal cord, and protected against SCI. We therefore investigated whether the B4 neoepitope represents a therapeutic target for complement inhibition. B4-Crry, a fusion protein consisting of a single-chain Ab derived from B4 mAb, linked to the complement inhibitor Crry, significantly protected against SCI. B4-Crry exhibited a dual function in that it inhibited both the binding of pathogenic IgM and blocked complement activation in the spinal cord. This study identifies important neoepitopes expressed within the spinal cord after injury. These neoepitopes are recognized by clonally specific natural IgM Abs that

  20. 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

  1. Duodenal epithelial transport in functional dyspepsia: Role of serotonin

    Science.gov (United States)

    Witte, Anne-Barbara; D’Amato, Mauro; Poulsen, Steen Seier; Laurent, Agneta; Knuhtsen, Svend; Bindslev, Niels; Hansen, Mark Berner; Schmidt, Peter Thelin

    2013-01-01

    AIM: To investigate functional duodenal abnormalities in functional dyspepsia (FD) and the role of serotonin (5-hydroxytryptamine, 5-HT) in mucosal ion transport and signalling. METHODS: Duodenal mucosal biopsies were obtained from 15 patients with FD and 18 healthy controls. Immunohistochemistry was used to study the number of 5-HT-containing cells and real-time polymerase chain reaction for expression of 5-HT receptors 1A, 1B, 2A, 2B, 3A, 3B, 3C, 3D, 3E, 4 and 7, as well as expression of the serotonin re-uptake transporter (SERT) gene SLC6A4 and tryptophan hydroxylase 1 (TPH1). Biopsies were mounted in Ussing chambers for evaluation of basal and 5-HT-stimulated short-circuit current (SCC). RESULTS: Conductance was lower in FD [42.4 ± 4.7 mS/cm2 (n = 15) vs 62.5 ± 4.5 mS/cm2 (n = 18), P = 0.005]. 5-HT induced a dose dependent rise in SCC in both FD (n = 8) and controls (n = 9), the rise was lower in FD (P < 0.001). Mean number of 5-HT stained cells per high power field was the same [34.4 ± 8.4 in FD (n = 15) and 30.4 ± 3.7 in controls (n = 18), P = 0.647]. The following genes were highly expressed: 5-HT receptor HTR3E, HTR4, HTR7, SERT gene (SLC6A4) and TPH1. Differences in expression levels were observed for HTR3E (higher expression in FD, P = 0.008), HTR7 (lower expression in FD, P = 0.027), SLC6A4 (higher expression in FD, P = 0.033) and TPH1 (lower expression in FD, P = 0.031). CONCLUSION: Duodenal ion transport in response to exogenous 5-HT is abnormal in FD patients and associated with high expression of the HTR3E receptor and the serotonin transporter. PMID:23755368

  2. Liquid chromatography tandem mass spectrometry method for the estimation of lamotrigine in human plasma: Application to a pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Santosh Ghatol

    2013-04-01

    Full Text Available A reliable, selective and sensitive liquid chromatography tandem mass spectrometry method was developed and validated for the quantification of lamotrigine in human plasma using lamotrigine-13C3, d3 as an internal standard. Analyte and internal standard were extracted from human plasma by solid-phase extraction and detected in positive ion mode by tandem mass spectrometry with electrospray ionization (ESI interface. Chromatographic separation was performed on a Chromolith® SpeedROD; RP-18e column (50−4.6 mm i.d. using acetonitrile: 5±0.1 mM ammonium formate solution (90:10, v/v as the mobile phase at a flow rate of 0.500 mL/min. The calibration curves were linear over the range of 5.02–1226.47 ng/mL with the lower limit of quantitation validated at 5.02 ng/mL. The analytes were found stable in human plasma through three freeze (−20 °C-thaw (ice-cold water bath cycles and under storage on bench-top in ice-cold water bath for at least 6.8 h, and also in the mobile phase at 10 °C for at least 57 h. The method has shown good reproducibility, as the intra- and inter-day precisions were within 3.0%, while the accuracies were within ±6.0% of nominal values. The validated LC–MS/MS method was applied for the evaluation of pharmacokinetic and bioequivalence parameters of lamotrigine after an oral administration of 50 mg lamotrigine tablet to thirty-two healthy adult male volunteers. Keywords: Lamotrigine, Liquid chromatography/tandem mass spectrometry, Solid phase extraction, Pharmacokinetic study

  3. 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

  4. Time-Lapse Monitoring of an Engineering Scaled Excavation at Federal District, Brazil by Passive Ambient NoiseInterferometry

    Science.gov (United States)

    Cárdenas-Soto, M., Sr.; Hussain, Y.; Martinez-Carvajal, H., Sr.; Martino, S., Sr.; Rocha, M., Sr.

    2016-12-01

    Understanding the dynamics of stress relief mechanisms that lead to complete material collapse of unstable slopes is challenging. This research is focused on the novel use of Passive Ambient Noise Interferometry (PANI), a new technique that has revolutionized the seismology. In this technique the impulse response or Green function between two sensors is calculated by cross-correlation of the noise rescored at these stations. We applied PANI to monitor the deformational behavior of a prototype field experiment under semi controlled conditions for their use in landsliding early warning systems.The experimental setup consists of a 2 m engineering-scaled excavation,where induced failure was monitored by ambient vibrations propagating in tropical clayey deposits. The experimental setup consisted of dense network of 20 three components short period seismometers (Sercel L4C-3D) installed in three circular arrays with their distances from face of normal slope as 10, 20 and 30 meters, respectively.The frequency response of these seismometers is in range of 2-100 Hz. Recording was done in continuous mode at sampling rate of 1000 Hz with datalogger (RefTek DAS-130/3). Sensors were time synchronized by twenty 130 GPS/01. In this stage, the stress was applied on the one flank of this normal slope dug in the experimental field of University of Brasilia, by a hydraulic jack through a metallic plate. This incremental loading was kept on rising until the slope failure took place. This loading mechanism provided an opportunity to monitoring the changes in Rayleigh wave velocity before, during and after the complete failure. After initial processing, the green function (GF) or impulse response was calculated between each pair of sensors by cross correlation at time step of 4 second. All individual GFs, for entire monitoring period (30 minutes) were stacked to obtained a single reference GF. Stretching (dt/t) in waveform is calculated by subtracting individual GF from average GF, that

  5. 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

  6. 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.

  7. Reducing urban heat island effects to improve urban comfort and balance energy consumption in Bucharest (Romania)

    Science.gov (United States)

    Constantinescu, Dan; Ochinciuc, Cristina Victoria; Cheval, Sorin; Comşa, Ionuţ; Sîrodoev, Igor; Andone, Radu; Caracaş, Gabriela; Crăciun, Cerasella; Dumitrescu, Alexandru; Georgescu, Mihaela; Ianoş, Ioan; Merciu, Cristina; Moraru, Dan; Opriş, Ana; Paraschiv, Mirela; Raeţchi, Sonia; Saghin, Irina; Schvab, Andrei; Tătui-Văidianu, Nataşa

    2017-04-01

    In the recent decades, extreme temperature events and derived hazards are frequent and trigger noteworthy impacts in Romania, especially over the large urban areas. The cities produce significant disturbances of many elements of the regional climate, and generates adverse effects such as Urban Heat Islands (UHI). This presentation condenses the outputs of an ongoing research project (REDBHI) developed through (2013-2017) focused on developing a methodology for monitoring and forecasting indoor climate and energy challenges related to the intensity of UHI of Bucharest (Romania), based on relevant urban climate zones (UCZs). Multi-criteria correlations between the UHI and architectural, urban and landscape variables were determined, and the vulnerability of buildings expressed in the form of transfer function between indoor micro-climate and outdoor urban environment. The vulnerability of civil buildings was determined in relation with the potential for amplifying the thermal hazards intensity through the anthropogenic influence. The project REDBHI aims at developing innovative and original products, with direct applicability, which can be used in any urban settlement and have market potential with regards to energy design and consulting. The concrete innovative outcomes consist of a) localization of the Bucharest UCZs according to the UHI intensity, identifying reference buildings and sub-zones according to urban anthropic factors and landscape pattern; b) typology of representative buildings with regards to energy consumption and CO2 emitted as a result of building exploitation; c) 3D modelling of the reference buildings and of the thermal/energy reaction to severe climatic conditions d) empirical validation of the dynamic thermal/energy analysis; d) development of an pilot virtual studio capable to simulate climate alerts, analyse scenarios and suggest measures to mitigate the UHI effects, and disseminate the outcomes for educational purposes; e) compendium of

  8. Isostructural potassium and thallium salts of sterically crowded triazenes: a structural and computational study.

    Science.gov (United States)

    Lee, Hyui Sul; Hauber, Sven-Oliver; Vindus, Denis; Niemeyer, Mark

    2008-05-19

    Because of their similar cationic radii, potassium and thallium(I) compounds are usually regarded as closely related. Homologous molecular species containing either K(+) or Tl(+) are very rare, however. We have synthesized potassium and thallium salts MN3RR' derived from the biphenyl- or terphenyl-substituted triazenes Tph2N3H (1a), Dmp(Mph)N3H (1b), Dmp(Tph)N3H (1c), and (Me4Ter)2N3H (1d) (Dmp=2,6-Mes 2C6H3 with Mes=2,4,6-Me3C6H2; Me4Ter=2,6-(3,5-Me2C6H3)2C6H3; Mph=2-MesC6H4; Tph=2-TripC6H4 with Trip=2,4,6-(i)Pr3C6H2). The potassium complexes 2a- d were obtained in almost quantitative yield from the reaction of 1a- d with potassium metal in n-heptane. Metalation of 1a- d with TlOEt afforded the thallium triazenides 3a- d in high yields. All new compounds have been characterized by (1)H and (13)C NMR spectroscopy, elemental analysis, and X-ray crystallography and for selected species by melting point (not 3b), IR spectroscopy (2a, 2d, 3a, 3c, 3d), and mass spectrometry (2a, 3c). In the solid-state structures of monomeric 2a and 3a, quasi-monomeric 2b, 3b, 2c, and 3c, and dimeric 2d and 3d additional metal-eta (n)-pi-arene-interactions to the flanking arms of the biphenyl- and terphenyl groups in the triazenide ligands of decreasing hapticity n are observed. Remarkably, all homologous potassium and thallium complexes crystallize in isomorphous cells. For 2a and 3a, the nature of the M-N and M...C(arene) bonding was studied by density functional theory calculations.

  9. Quantification of the selective activation of C--H bonds in short chain alkanes: The reactivity of ethane, propane, isobutane, n-butane, and neopentane on Ir(111)

    International Nuclear Information System (INIS)

    Johnson, D.F.; Weinberg, W.H.

    1995-01-01

    The initial probabilities of precursor-mediated, dissociative chemisorption of the saturated hydrocarbons 13 C-labeled ethane, propane, isobutane, n-butane, and neopentane on the close-packed Ir(111) surface have been measured. The selective activation of primary (1 degree), secondary (2 degree), and tertiary (3 degree) C--H bonds has been quantified by examining the reactivities of the selectively deuterated isotopomers of propane, C 3 H 8 , CH 3 CD 2 CH 3 , and C 3 D 8 , and of isobutane, (CH 3 ) 3 CH, (CH 3 ) 3 CD, and (CD 3 ) 3 CH. With respect to the bottom of the physically adsorbed well for each hydrocarbon, the apparent C--H bond activation energies have been found to be 10.4±0.3 kcal/mol (ethane), 11.4±0.3 kcal/mol (propane), 11.5±0.3 kcal/mol (n-butane), 11.3±0.3 kcal/mol (i-butane), and 11.3±0.3 kcal/mol (neopentane). For all the alkanes examined, the ratios of the preexponential factors of the rate coefficients of reaction and desorption are 1x10 -2 . The C--D bond activation energies are higher than the corresponding C--H bond activation energies by 480 cal/mol (ethane), 630 cal/mol (propane), and 660 cal/mol (i-butane). By analyzing the primary kinetic isotope effects for the selectively deuterated isotopomers of propane and isobutane, the 2 degree C--H bond activation energy is found to be 310±160 cal/mol less than the 1 degree C--H bond activation energy on this surface, and similarly, 3 degree C--H bond cleavage is less by 80±70 cal/mol. The quantification of the branching ratios within the C--H bond activation channel for propane and isobutane on this surface shows that the formation of 1 degree-alkyl intermediates is, in general, favored over the formation of either 2 degree- or 3 degree-alkyl intermediates. (Abstract Truncated)

  10. 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.

  11. 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

  12. EXPRESSION OF CALCIUM-DEPENDENT PROTEIN KINASE (CDPK GENES IN VITIS AMURENSIS UNDER ABIOTIC STRESS CONDITIONS

    Directory of Open Access Journals (Sweden)

    Dubrovina A.S.

    2012-08-01

    CDPK genes (VaCDPK1a, 1e, 1d, 2a, 3a, 3b, 3c, 3d. We sequenced full cDNA sequences of the genes and analyzed their expression levels by real-time PCR and FAPP method, which has been recently developed by our research group. The prevalent CDPK transcript was VaCDPK3a under both non-stress and abiotic stress conditions. Under high-salt conditions, VaCDPK1d, 1e, 3b, and 3d transcripts were up-regulated. Under high mannitol conditions, expression of VaCPK1e and 3b was up-regulated, while expression of VaCDPK1d, 3c, and 3d was only slightly induced. Under water-deficit, expression of only VaCDPK3b and 3c genes was induced. Cold stress induced expression of VaCDPK2a and 3d genes; while hot stress induced expression of VaCDPK1a, 1d, 1e, 2a, 3a, and 3c genes. Taken together, the data show that the VaCDPK genes are transcriptionally regulated by osmotic, water-deficit, and temperature stresses. The differential expression of the VaCDPK genes during osmotic, water-deficit, and temperature stresses is suggestive of their involvement in the underlying signal transduction pathways.

  13. Origins of mass-dependent and mass-independent Ca isotope variations in meteoritic components and meteorites

    Science.gov (United States)

    Bermingham, K. R.; Gussone, N.; Mezger, K.; Krause, J.

    2018-04-01

    , C 3, D 1, D 2, D 3) possess the same 48/44Ca isotope composition as the standard within analytical uncertainty. These data indicate a heterogeneous distribution of 48Ca in the early solar nebula during formation of CAIs, AOAs, and chondrules. In a ε48/44Ca vs. δ44/40Ca plot, no strong correlation is evident which suggests that the thermal processing event which caused a heterogeneous distribution of ε48/44Ca in the solar nebula is unlikely to be directly related to the thermal processing event that caused coupled REE and Ca mass-dependent isotopic fractionation in meteoritic components.

  14. 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.

  15. Study of Absorption Characteristics of the Total Saponins from Radix Ilicis Pubescentis in an In Situ Single-Pass Intestinal Perfusion (SPIP Rat Model by Using Ultra Performance Liquid Chromatography (UPLC

    Directory of Open Access Journals (Sweden)

    Guojun Kuang

    2017-11-01

    Full Text Available In contrast to the extensively reported therapeutic activities, far less attention has been paid to the intestinal absorption of the total saponins from Radix Ilicis Pubescentis (in Chinese Mao-Dong-Qing, MDQ. This study aimed to investigate the intestinal absorption characteristics of ilexgenin A (C1, ilexsaponin A1 (C2, ilexsaponin B1 (C3, ilexsaponin B2 (C4, ilexsaponin B3 (DC1, and ilexoside O (DC2 when administrated with the total saponins from MDQ (MDQ-TS. An UPLC method for simultaneous determination of C1, C2, C3, C4, DC1, and DC2 in intestinal outflow perfusate was developed and validated. The absorption characteristics of MDQ-TS were investigated by evaluating the effects of intestinal segments, drug concentration, P-glycoprotein (P-gp inhibitor (verapomil, endocytosis inhibitor (amantadine and ethylene diamine tetraacetic acid (EDTA, tight junction modulator on the intestinal transportation of MDQ-TS by using a single-pass intestinal perfusion (SPIP rat model, and the influence of co-existing components on the intestinal transport of the six saponins was discussed. The results showed that effective apparent permeability (Papp of C1, C2, C3, C4, and DC2 administrated in MDQ-TS form had no segment-dependent changes at low and middle dosage levels. C1, C2, C3, D4, DC1, and DC2 administrated in MDQ-TS form all exhibited excellent transmembrane permeability with Papp > 0.12 × 10−2 cm·min−1. Meanwhile, Papp and effective absorption rate constant (Ka values for the most saponins showed concentration dependence and saturation characteristics. After combining with P-gp inhibitor of verapamil, Papp of C2, C3, and DC1 in MDQ-TS group was significantly increased up to about 2.3-fold, 1.4-fold, and 3.4-fold, respectively in comparison to that of non-verapamil added group. Verapamil was found to improve the absorption of C2, C3, and DC1, indicating the involvement of an active transport mechanism in the absorption process. Compared with the

  16. Intern Abstract for Spring 2016

    Science.gov (United States)

    Gibson, William

    2016-01-01

    The Human Interface Branch - EV3 - is evaluating Organic lighting-emitting diodes (OLEDs) as an upgrade for current displays on future spacecraft. OLEDs have many advantages over current displays. Conventional displays require constant backlighting which draws a lot of power, but with OLEDs they generate light themselves. OLEDs are lighter, and weight is always a concern with space launches. OLEDs also grant greater viewing angles. OLEDs have been in the commercial market for almost ten years now. What is not known is how they will perform in a space-like environment; specifically deep space far away from the Earth's magnetosphere. In this environment, the OLEDs can be expected to experience vacuum and galactic radiation. The intern's responsibility has been to prepare the OLED for a battery of tests. Unfortunately, it will not be ready for testing at the end of the internship. That being said much progress has been made: a) Developed procedures to safely disassemble the tablet. b) Inventoried and identified critical electronic components. c) 3D printed a testing apparatus. d) Wrote software in Python that will test the OLED screen while being radiated. e) Built circuits to restart the tablet and the test pattern, and ensure it doesn't fall asleep during radiation testing. f) Built enclosure that will house all of the electronics Also, the intern has been working on a way to take messages from a simulated Caution and Warnings system, process said messages into packets, send audio packets to a multicast address that audio boxes are listening to, and output spoken audio. Currently, Cautions and Warnings use a tone to alert crew members of a situation, and then crew members have to read through their checklists to determine what the tone means. In urgent situations, EV3 wants to deliver concise and specific alerts to the crew to facilitate any mitigation efforts on their part. Significant progress was made on this project: a) Open channel with the simulated Caution

  17. Omics-Based Approach Reveals Complement-Mediated Inflammation in Chronic Lymphocytic Inflammation With Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS

    Directory of Open Access Journals (Sweden)

    Morten Blaabjerg

    2018-04-01

    Full Text Available ObjectiveChronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS is a rare syndrome with relapsing brainstem/cerebellar symptoms. To examine the pathogenic processes and investigate potential biomarkers, we analyzed combined materials of brain and cerebrospinal fluid (CSF by comprehensive methodologies.Materials and methodsTo identify major pathways of perivascular inflammation in CLIPPERS, we first compared the CSF proteome (n = 5 to a neurodegenerative condition, Alzheimer’s disease (AD, n = 5. Activation of complement was confirmed by immunohistochemistry (IHC on CLIPPERS brain samples (n = 3 and by ELISA in the CSF. For potential biomarkers, we used biomarker arrays, and compared inflammatory and vessel-associated proteins in the CSF of CLIPPERS (n = 5 with another inflammatory relapsing CNS disease, multiple sclerosis (RMS, n = 9 and healthy subjects (HS, n = 7.ResultsTwo hundred and seven proteins in the CSF discriminated CLIPPERS from AD. The complement cascade, immunoglobulins, and matrix proteins were among the most frequently represented pathways. Pathway analysis of upstream regulators suggested the importance of vascular cell adhesion protein 1 (VCAM1, IFN-γ, interleukin (IL-1, and IL-10. Differential regulation of more than 10 complement proteins of the 3 complement pathways in the CSF pointed to the role of complement activation. IHC on brain samples confirmed the perivascular complement activation, i.e., deposition of C3bc, C3d, and the terminal C5b-9 complement complex that partially overlapped with accumulation of IgG in the vessel wall. Besides endothelial cell damage, reactivity to smooth muscle actin was lost in the walls of inflamed vessels, but the glia limitans was preserved. The semi-quantitative array indicated that increased level of IL-8/CXCL8 (p < 0.05, eotaxin/CCL11 (p < 0.01, and granulocyte colony-stimulating factor (p < 0.05 in

  18. 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