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Sample records for reject highly immunogenic

  1. High-testosterone men reject low ultimatum game offers.

    Science.gov (United States)

    Burnham, Terence C

    2007-09-22

    The ultimatum game is a simple negotiation with the interesting property that people frequently reject offers of 'free' money. These rejections contradict the standard view of economic rationality. This divergence between economic theory and human behaviour is important and has no broadly accepted cause. This study examines the relationship between ultimatum game rejections and testosterone. In a variety of species, testosterone is associated with male seeking dominance. If low ultimatum game offers are interpreted as challenges, then high-testosterone men may be more likely to reject such offers. In this experiment, men who reject low offers ($5 out of $40) have significantly higher testosterone levels than those who accept. In addition, high testosterone levels are associated with higher ultimatum game offers, but this second finding is not statistically significant.

  2. Comparison of Sociometrically High Visibility Rejected and Low Visibility Rejected Children on Teacher, Parent, and Self-Rating Measures.

    Science.gov (United States)

    Neighbor, Jonelle C.

    The study looked at differences between groups of children identified as high visibility rejected (HVR) and low visibility rejected (LVR) on a sociometric measure with 952 fourth, fifth, and sixth grade students. Questionnaires were analyzed to determine the number of positive and negative nominations from peers received by each child. HVR…

  3. Hyperbaric Oxygen Therapy as a Sole Agent Is Not Immunosuppressant in a Highly Immunogenic Mouse Model

    Directory of Open Access Journals (Sweden)

    Adam Gassas

    2011-01-01

    Full Text Available Background. Hyperbaric oxygen (HBO therapy, which is used for many conditions, may also have immunosuppressive effects and could be used for prevention or treatment of graft-versus-host disease (GvHD. If HBO is immunosuppressant, then we hypothesize that HBO therapy will delay the T-cell mediated skin graft rejection. Methods. C57/BL6 black-coated (H2B mice received skin graft from CBA (H2D white-coated mice. Mice were treated with either 19 session of 240 kpa oxygen or 29 session of 300 kpa oxygen, for 90 minutes. Mice were housed either 4 per cage or separately, to prevent friction and mechanical factors that may affect graft survival. Skin grafts were assessed daily. Results. There was no difference in length of graft survival between mice that received either regimens of HBO therapy and mice that did not receive HBO therapy. Conclusions. HBO therapy, as a sole agent, did not delay skin graft rejection in a highly immunogenic mouse model.

  4. Reverse osmosis membrane of high urea rejection properties. [water purification

    Science.gov (United States)

    Johnson, C. C.; Wydeven, T. J. (Inventor)

    1980-01-01

    Polymeric membranes suitable for use in reverse osmosis water purification because of their high urea and salt rejection properties are prepared by generating a plasma of an unsaturated hydrocarbon monomer and nitrogen gas from an electrical source. A polymeric membrane is formed by depositing a polymer of the unsaturated monomer from the plasma onto a substrate, so that nitrogen from the nitrogen gas is incorporated within the polymer in a chemically combined form.

  5. Anxious and angry rejection sensitivity, social withdrawal, and retribution in high and low ambiguous situations.

    Science.gov (United States)

    Zimmer-Gembeck, Melanie J; Nesdale, Drew

    2013-02-01

    Rejection sensitivity (RS) is a tendency to expect, perceive, and overreact to rejection. Our objective was to examine whether anxious and angry RS have specific associations with negative social reactions, and whether responses are intensified in situations of high rejection ambiguity. In two studies, youth (N = 464 and N = 371) reported their RS and anticipated responses to social scenarios. In Study 1, all scenarios portrayed overt rejection events. In Study 2, participants were randomly assigned to conditions portraying overt or ambiguous rejection. Greater rejection expectation was associated with more negative reactions to rejection. Moreover, as expected, anxiety about rejection was uniquely associated with withdrawal, and anger about rejection was uniquely associated with retribution (i.e., reactive aggression). In the second study, RS persons responded more negatively than others to both overt and high ambiguous rejections, but retribution was intensified among participants high in rejection expectation when rejection was ambiguous, and withdrawal was intensified among participants high in anxious RS in overt rejection situations. Consistent with the revised RS model, there are different patterns of emotions, cognitions, and behaviors in response to high and low ambiguous rejection events, which are heightened in youth sensitive to rejection. © 2012, Wiley Periodicals, Inc.

  6. High-testosterone men reject low ultimatum game offers

    OpenAIRE

    Burnham, Terence C

    2007-01-01

    The ultimatum game is a simple negotiation with the interesting property that people frequently reject offers of ‘free’ money. These rejections contradict the standard view of economic rationality. This divergence between economic theory and human behaviour is important and has no broadly accepted cause. This study examines the relationship between ultimatum game rejections and testosterone. In a variety of species, testosterone is associated with male seeking dominance. If low ultimatum game...

  7. High solute rejecting membranes for reverse osmosis: Polyetheramide hydrazide

    International Nuclear Information System (INIS)

    Bindal, R.C.; Ramachandhran, V.; Misra, B.M.; Ramani, M.P.S.

    1991-01-01

    Synthesis of benzhydrazide polymers and determination of reverse osmosis properties of their membranes were reported earlier. Their performance was not adequate for seawater desalination or for high radioactive decontamination factors (DF). The same hydrazide polymers modified by incorporation of additional monomers with ether linkages were synthesized by low temperature polycondensation of freshly prepared m-amino benzhydrazide, p-amino benzhydrazide, and 4,4'-diamino diphenyl ether, with isophthaloyl chloride and terephthaloyl chloride in dimethyl acetamide solvent. A series of film-forming polymers prepared by altering the molar ratios of the reacting monomers were characterized in terms of percent moisture regain, inherent viscosity, solubility parameters, and interfacial sorption characteristics. Asymmetric membranes prepared from these polymer samples were characterized in terms of the pure water permeability constant and the solute transport parameter, and were tested for their reverse osmosis performance. An optimum mole ratio of reaching monomers has been identified for the synthesis of polymer and the resulting membrane offered the best performance for reverse osmosis (salt rejection as high as 99.4% for 3.5% sodium chloride solution). The incorporation of aromatic ether linkages in the polyamide benzhydrazide polymeric chains appears to alter the polar and nonpolar character of the bulk polymer, and also the membrane solution interface characteristics, resulting in enhanced solute separation. These membranes appear to be potential candidates for single-stage seawater desalination and also for a variety of industrial effluent treatment applications for significantly high DF radioactive effluent treatment

  8. Induction of highly immunogenic variants of Lewis lung carcinoma tumor by ultraviolet irradiation

    International Nuclear Information System (INIS)

    Peppoloni, S.; Herberman, R.B.; Gorelik, E.

    1985-01-01

    This study was undertaken to determine whether in vitro treatment of Lewis lung carcinoma (3LL) cells with ultraviolet (UV) radiation could increase their immunogenicity. Tumor cells were irradiated with UV light from a germicidal lamp (254 nm; UV-C) at a dose of 720 J/sq m. After 2 weeks of culture, the surviving cell population was cloned by limiting dilution. Cell suspensions of each clone were injected intrafootpad in C57BL/6 mice at a dose of 2.5 X 10(5) cells per mouse. Eighty independent clones were tested. Fifty-one clones showed decreased tumorigenicity and failed to grow in 20 to 95% of immunocompetent mice, whereas they produced tumors in 100% of irradiated (550 R) and athymic nude mice. These clones were designated tum- (nontumorigenic) clones. In contrast, all 25 clones selected from the untreated parental 3LL induced progressively growing tumors in 100% of the mice. After two courses of UV treatment, the uncloned 3LL population was rejected in 45% of inoculated mice. Mice rejecting an inoculum of a tum- clone were completely resistant to subsequent challenge with higher doses of the same or unrelated tum- clones. This resistance was fully expressed even after irradiation of immune mice with 550 R. Mice immune to a tum- clone also were able to prevent the growth of various tum+ clones or untreated 3LL tumor cells. When tum- and tum+ clone cells were simultaneously inoculated intrafootpad in opposite legs, rejection of tum- clone resulted also in the prevention of the growth of tum+ clone. Spleen cells of immune mice caused rapid elimination of radiolabeled 3LL tumor cells from the place of their inoculation (intrafootpad) and prevented tumor growth

  9. High pre-transplant soluble CD30 levels are predictive of the grade of rejection.

    Science.gov (United States)

    Rajakariar, Ravindra; Jivanji, Naina; Varagunam, Mira; Rafiq, Mohammad; Gupta, Arun; Sheaff, Michael; Sinnott, Paul; Yaqoob, M M

    2005-08-01

    In renal transplantation, serum soluble CD30 (sCD30) levels in graft recipients are associated with increased rejection and graft loss. We investigated whether pre-transplant sCD30 concentrations are predictive of the grade of rejection. Pre-transplant sera of 51 patients with tubulointerstitial rejection (TIR), 16 patients with vascular rejection (VR) and an age-matched control group of 41 patients with no rejection (NR) were analyzed for sCD30. The transplant biopsies were immunostained for C4d. The median sCD30 level was significantly elevated in the group with VR (248 Units (U)/mL, range: 92-802) when compared with TIR (103 U/mL, range: 36-309, psCD30 levels compared to NR. Based on C4d staining, a TH2 driven process, the median sCD30 levels were significantly raised in C4d+ patients compared with C4d- group (177 U/mL vs. 120 U/mL, psCD30 levels measured at time of transplantation correlate with the grade of rejection. High pre-transplant levels are associated with antibody-mediated rejection which carries a poorer prognosis. sCD30 could be another tool to assess immunological risk prior to transplantation and enable a patient centered approach to immunosuppression.

  10. High serum soluble CD30 does not predict acute rejection in liver transplant patients.

    Science.gov (United States)

    Matinlauri, I; Höckerstedt, K; Isoniemi, H

    2006-12-01

    Increased pre- and posttransplantation values of soluble CD30 (sCD30) have been shown to be associated with acute kidney transplant rejection. We sought to study whether high sCD30 could predict rejection early after liver transplantation. The study population included 54 consecutive liver transplant patients, whose samples were collected before liver transplantation and at discharge, which was at a mean time of 3 weeks after transplantation. During the first 6 months posttransplantation, 22 patients experienced an acute rejection episode. Serum sCD30 concentrations were measured by an enzyme-linked immunoassay; changes in serum sCD30 levels posttransplantation were also expressed as relative values compared with pretransplantation results. Liver patients before transplantation displayed higher serum sCD30 values compared with healthy controls: mean values +/- SD were 93 +/- 58 IU/mL vs 17 +/- 8 IU/mL, respectively. At 3 weeks after transplantation the mean sCD30 concentration in liver transplant patients decreased to 59 +/- 42 IU/mL (P = .005). The mean pretransplantation serum sCD30 value was slightly lower among rejecting vs nonrejecting patients: 78 +/- 43 IU/mL vs 104 +/- 65 IU/mL (P = NS). Posttransplantation values in both groups decreased significantly: 47 +/- 34 IU/mL in patients with rejection (P = .014) vs 69 +/- 45 IU/mL in patients without rejection (P = .012). The relative value at 3 weeks posttransplantation decreased slightly more among patients with vs without rejection (70% vs 88%; NS). No correlation was found between serum sCD30 and anti-HLA class I antibodies or crossmatch positivity. In conclusion, neither pre- nor posttransplantation sCD30 levels were associated with acute rejection in liver transplant patients.

  11. Timing information and pileup rejection for the High Granularity Calorimeter

    CERN Document Server

    MONET, Geoffrey

    2015-01-01

    The Large Hadron Collider (LHC) at CERN is the world’s largest and most energetic hadron collider. The first run of the LHC (March 2010 - December 2012) has led to several measurements and discoveries, amongst which the Higgs boson candidate. In order to further increase its discovery potential beyond 2020 a leap in luminosity, by a factor of 10, is needed. It is what we call High Luminosity LHC (HL-LHC). Increase the total number of collision would provide more accurate measurements of new particles and enable observation of rare processes that occur below the current sensitivity level. The increase in luminosity will be achieved at the cost of an increase in pileup, i.e. the number of simultaneous collisions. Not only the LHC machine will be upgraded but also the detectors, namely CMS . To cope with this high pileup environment and reconstruct physics objects such as electrons, photons, jets and taus, High Granularity Calorimeter is being proposed as a substitute of the current endcap calorimeters of CMS...

  12. High pathogenicity and strong immunogenicity of a Chinese isolate of Eimeria magna Pérard, 1925.

    Science.gov (United States)

    Tao, Geru; Wang, Yunzhou; Li, Chao; Gu, Xiaolong; Cui, Ping; Fang, Sufang; Suo, Xun; Liu, Xianyong

    2017-06-01

    Coccidia infection of rabbits with one or several species of parasites of the genus Eimeria causes coccidiosis, a disease leading to huge economic losses in the rabbit industry. Eimeria magna, one of the causal agents of rabbit coccidiosis, was characterized as mildly pathogenic and moderately immunogenic in previous studies. In this study, we identified a Chinese isolate of E. magna by testing its biological features (oocyst morphology and size, prepatent time) and sequencing its internal transcribed spacer 1 (ITS-1) DNA fragment. This isolate is highly pathogenic; infection of rabbits with only 1×10 2 oocysts caused a 55% reduction in weight gain in 14days. In addition, immunization with 1×10 2 oocysts prevented body weight loss against re-infection with 5×10 4 oocysts, indicating the high immunogenicity of this isolate. Our study described the distinctive phenotype of the Chinese isolate of E. magna and contributed to the research of geographic variation of rabbit coccidia. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Computationally optimized deimmunization libraries yield highly mutated enzymes with low immunogenicity and enhanced activity.

    Science.gov (United States)

    Salvat, Regina S; Verma, Deeptak; Parker, Andrew S; Kirsch, Jack R; Brooks, Seth A; Bailey-Kellogg, Chris; Griswold, Karl E

    2017-06-27

    Therapeutic proteins of wide-ranging function hold great promise for treating disease, but immune surveillance of these macromolecules can drive an antidrug immune response that compromises efficacy and even undermines safety. To eliminate widespread T-cell epitopes in any biotherapeutic and thereby mitigate this key source of detrimental immune recognition, we developed a Pareto optimal deimmunization library design algorithm that optimizes protein libraries to account for the simultaneous effects of combinations of mutations on both molecular function and epitope content. Active variants identified by high-throughput screening are thus inherently likely to be deimmunized. Functional screening of an optimized 10-site library (1,536 variants) of P99 β-lactamase (P99βL), a component of ADEPT cancer therapies, revealed that the population possessed high overall fitness, and comprehensive analysis of peptide-MHC II immunoreactivity showed the population possessed lower average immunogenic potential than the wild-type enzyme. Although similar functional screening of an optimized 30-site library (2.15 × 10 9 variants) revealed reduced population-wide fitness, numerous individual variants were found to have activity and stability better than the wild type despite bearing 13 or more deimmunizing mutations per enzyme. The immunogenic potential of one highly active and stable 14-mutation variant was assessed further using ex vivo cellular immunoassays, and the variant was found to silence T-cell activation in seven of the eight blood donors who responded strongly to wild-type P99βL. In summary, our multiobjective library-design process readily identified large and mutually compatible sets of epitope-deleting mutations and produced highly active but aggressively deimmunized constructs in only one round of library screening.

  14. Experimental high-frequency ultrasound can detect graft rejection after small bowel transplantation.

    Science.gov (United States)

    Yang, R; Liu, Q; Wu, E X; Pescovitz, M D; Collins, M H; Kopecky, K K; Grosfeld, J L

    1994-02-01

    Early diagnosis of graft rejection after small bowel transplantation (SBT) can allow prompt institution of vigorous immunosuppressive therapy, with resultant reversal of the rejection process. The current method for graft monitoring is random mucosal biopsy from a stomal site or through an endoscope. However, because early rejection often has a patchy distribution, it could be missed by random biopsy. We hypothesized that the pathological process of rejection would alter acoustic impedance of the tissue and thus change the ultrasonic patterns of the graft intestinal wall. If this hypothesis is correct, then high-frequency endoscopic ultrasound (US) could be used to monitor the entire transplanted bowel and guide the biopsy, with improved yields. This hypothesis was tested in a rat orthotopic SBT model. Sixty-two intestinal specimens (9 isografts, 12 allografts treated with cyclosporine A [CsA], 22 untreated allografts, and 19 intestines from normal rats) were collected for in vitro transluminal US imaging (30 MHz) and histopathologic study. The echo pattern of normal rat intestinal wall consisted of five echo layers that correlated spatially with the histological layers: the innermost hyperechoic layer 1, plus hypoechoic layer 2, corresponded to the mucosa; hyperechoic layer 3, the submucosa; anechoic layer 4, the muscularis propria; and hyperechoic layer 5, the serosa. The isografts and CsA-treated allografts were identical histologically and ultrasonically to normal intestine. However, the echo patterns of the untreated allografts had progressive loss of architectural stratification, with worsening rejection. The change began with patchy indistinctness and disruption of hyperechoic layers 1, 3 and 5, and progressed to total obliteration of the layers, with the intestinal wall becoming a nonstratified hypoechoic structure.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. High-sensitivity cardiac troponin I assay to screen for acute rejection in patients with heart transplant.

    Science.gov (United States)

    Patel, Parag C; Hill, Douglas A; Ayers, Colby R; Lavingia, Bhavna; Kaiser, Patricia; Dyer, Adrian K; Barnes, Aliessa P; Thibodeau, Jennifer T; Mishkin, Joseph D; Mammen, Pradeep P A; Markham, David W; Stastny, Peter; Ring, W Steves; de Lemos, James A; Drazner, Mark H

    2014-05-01

    A noninvasive biomarker that could accurately diagnose acute rejection (AR) in heart transplant recipients could obviate the need for surveillance endomyocardial biopsies. We assessed the performance metrics of a novel high-sensitivity cardiac troponin I (cTnI) assay for this purpose. Stored serum samples were retrospectively matched to endomyocardial biopsies in 98 cardiac transplant recipients, who survived ≥3 months after transplant. AR was defined as International Society for Heart and Lung Transplantation grade 2R or higher cellular rejection, acellular rejection, or allograft dysfunction of uncertain pathogenesis, leading to treatment for presumed rejection. cTnI was measured with a high-sensitivity assay (Abbott Diagnostics, Abbott Park, IL). Cross-sectional analyses determined the association of cTnI concentrations with rejection and International Society for Heart and Lung Transplantation grade and the performance metrics of cTnI for the detection of AR. Among 98 subjects, 37% had ≥1 rejection episode. cTnI was measured in 418 serum samples, including 35 paired to a rejection episode. cTnI concentrations were significantly higher in rejection versus nonrejection samples (median, 57.1 versus 10.2 ng/L; P<0.0001) and increased in a graded manner with higher biopsy scores (P(trend)<0.0001). The c-statistic to discriminate AR was 0.82 (95% confidence interval, 0.76-0.88). Using a cut point of 15 ng/L, sensitivity was 94%, specificity 60%, positive predictive value 18%, and negative predictive value 99%. A high-sensitivity cTnI assay seems useful to rule out AR in cardiac transplant recipients. If validated in prospective studies, a strategy of serial monitoring with a high-sensitivity cTnI assay may offer a low-cost noninvasive strategy for rejection surveillance. © 2014 American Heart Association, Inc.

  16. Highly immunogenic and fully synthetic peptide-carrier constructs targetting GnRH

    DEFF Research Database (Denmark)

    Beekman, N.J.C.M.; Schaaper, W.M.M.; Turkstra, J.A.

    1999-01-01

    To use peptides as synthetic vaccines, they have to be coupled to a carrier protein to make them more immunogenic. Coupling efficiency between a carrier protein and a peptide, however, is difficult to control with respect to loading density of the peptide, This makes these carrier proteins poorly...... for the induction of antibodies against GnRH and immunocastration of pigs....

  17. Fetal cardiac cine imaging using highly accelerated dynamic MRI with retrospective motion correction and outlier rejection.

    Science.gov (United States)

    van Amerom, Joshua F P; Lloyd, David F A; Price, Anthony N; Kuklisova Murgasova, Maria; Aljabar, Paul; Malik, Shaihan J; Lohezic, Maelene; Rutherford, Mary A; Pushparajah, Kuberan; Razavi, Reza; Hajnal, Joseph V

    2018-01-01

    Development of a MRI acquisition and reconstruction strategy to depict fetal cardiac anatomy in the presence of maternal and fetal motion. The proposed strategy involves i) acquisition and reconstruction of highly accelerated dynamic MRI, followed by image-based ii) cardiac synchronization, iii) motion correction, iv) outlier rejection, and finally v) cardiac cine reconstruction. Postprocessing entirely was automated, aside from a user-defined region of interest delineating the fetal heart. The method was evaluated in 30 mid- to late gestational age singleton pregnancies scanned without maternal breath-hold. The combination of complementary acquisition/reconstruction and correction/rejection steps in the pipeline served to improve the quality of the reconstructed 2D cine images, resulting in increased visibility of small, dynamic anatomical features. Artifact-free cine images successfully were produced in 36 of 39 acquired data sets; prolonged general fetal movements precluded processing of the remaining three data sets. The proposed method shows promise as a motion-tolerant framework to enable further detail in MRI studies of the fetal heart and great vessels. Processing data in image-space allowed for spatial and temporal operations to be applied to the fetal heart in isolation, separate from extraneous changes elsewhere in the field of view. Magn Reson Med 79:327-338, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

  18. Sendai High Court rejects residents' appeal to nullify gov't permit for Fukushima II-1

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    The Sendai High Court on March 20 rejected an appeal made by 33 residents in Naraha-cho, Fukushima Prefecture, to nullify the government permit for Tokyo Electric Power Co.'s plan to establish Fukushima II Nuclear Power Plant Unit 1 (1,100 MW, BWR) near their homes, upholding the Fukushima District Court's 1984 ruling that the government's examination is adequate to ensure safety of the Unit. The plaintiffs are considering taking the case to the Supreme Court. This is the first ruling on the safety of a nuclear power plant in Japan, after the Chernobyl accident in 1986. Unit 1 is currently in operation. Presiding Judge Yoshio Ishikawa approved almost entirely the government's arguments except that on the competence of the plaintiff. The judgement said that the 33 residents living within the radius of fifty and several kilometers from the reactor facilities have plaintiff competency, because if the safety of the reactor facilities could not be assured, the facilities could possibly present a grave danger to the lives and health of the residents. The ruling said that issuing the reactor installation permit was committed to the government's special technical discretion. (N.K.)

  19. Preventing Rejection

    Science.gov (United States)

    ... After the transplant Preventing rejection Post-transplant medications Types of immunosuppressants Switching immunosuppressants Side effects Other medications Generic and brand name drugs Post-transplant tests Infections and immunity Lifestyle changes Health concerns Back to work or ...

  20. A Large Size Chimeric Highly Immunogenic Peptide Presents Multistage Plasmodium Antigens as a Vaccine Candidate System against Malaria.

    Science.gov (United States)

    Lozano, José Manuel; Varela, Yahson; Silva, Yolanda; Ardila, Karen; Forero, Martha; Guasca, Laura; Guerrero, Yuly; Bermudez, Adriana; Alba, Patricia; Vanegas, Magnolia; Patarroyo, Manuel Elkin

    2017-11-01

    Rational strategies for obtaining malaria vaccine candidates should include not only a proper selection of target antigens for antibody stimulation, but also a versatile molecular design based on ordering the right pieces from the complex pathogen molecular puzzle towards more active and functional immunogens. Classical Plasmodium falciparum antigens regarded as vaccine candidates have been selected as model targets in this study. Among all possibilities we have chosen epitopes of Pf CSP, STARP; MSA1 and Pf 155/RESA from pre- and erythrocyte stages respectively for designing a large 82-residue chimeric immunogen. A number of options aimed at diminishing steric hindrance for synthetic procedures were assessed based on standard Fmoc chemistry such as building block orthogonal ligation; pseudo-proline and microwave-assisted procedures, therefore the large-chimeric target was produced, characterized and immunologically tested. Antigenicity and functional in vivo efficacy tests of the large-chimera formulations administered alone or as antigen mixtures have proven the stimulation of high antibody titers, showing strong correlation with protection and parasite clearance of vaccinated BALB/c mice after being lethally challenged with both P. berghei -ANKA and P. yoelii 17XL malaria strains. Besides, 3D structure features shown by the large-chimera encouraged as to propose using these rational designed large synthetic molecules as reliable vaccine candidate-presenting systems.

  1. A Large Size Chimeric Highly Immunogenic Peptide Presents Multistage Plasmodium Antigens as a Vaccine Candidate System against Malaria

    Directory of Open Access Journals (Sweden)

    José Manuel Lozano

    2017-11-01

    Full Text Available Rational strategies for obtaining malaria vaccine candidates should include not only a proper selection of target antigens for antibody stimulation, but also a versatile molecular design based on ordering the right pieces from the complex pathogen molecular puzzle towards more active and functional immunogens. Classical Plasmodium falciparum antigens regarded as vaccine candidates have been selected as model targets in this study. Among all possibilities we have chosen epitopes of PfCSP, STARP; MSA1 and Pf155/RESA from pre- and erythrocyte stages respectively for designing a large 82-residue chimeric immunogen. A number of options aimed at diminishing steric hindrance for synthetic procedures were assessed based on standard Fmoc chemistry such as building block orthogonal ligation; pseudo-proline and microwave-assisted procedures, therefore the large-chimeric target was produced, characterized and immunologically tested. Antigenicity and functional in vivo efficacy tests of the large-chimera formulations administered alone or as antigen mixtures have proven the stimulation of high antibody titers, showing strong correlation with protection and parasite clearance of vaccinated BALB/c mice after being lethally challenged with both P. berghei-ANKA and P. yoelii 17XL malaria strains. Besides, 3D structure features shown by the large-chimera encouraged as to propose using these rational designed large synthetic molecules as reliable vaccine candidate-presenting systems.

  2. Anti-alpha interferon immunization: safety and immunogenicity in asymptomatic HIV positive patients at high risk of disease progression.

    Science.gov (United States)

    Gringeri, A; Santagostino, E; Mannucci, P M; Siracusano, L; Marinoni, A; Criscuolo, M; Carcagno, M; Fall, L S; M'Bika, J P; Bizzini, B

    1995-05-01

    A randomized, placebo-controlled trial was designed to evaluate safety and immunogenicity of an anti-cytokine vaccine in high risk HIV-positive patients. This strategy was aimed to modulate the impaired cytokine regulation in AIDS. Twelve asymptomatic patients on antiretroviral therapy for at least 1 year and with CD4 cell counts between 100-300/mm3 were randomized to receive adjuvanted formol-inactivated interferon alpha-2a (IFN alpha) and continue the current antiretroviral treatment, whatever it was, or to receive the adjuvant alone and the current antiretroviral treatment. All patients received 4 i.m. injections monthly, followed by booster injections every 3 months. Clinical status, immunology and virology were monitored. Immune response to vaccination was evaluated in term of antibody detection (ELISA) and serum anti-IFN alpha neutralizing capacity. Only local discomfort and transient fever were reported. All vaccines except one showed increased levels of anti-IFN alpha Abs and developed serum IFN alpha neutralizing capacity. Viral load did not increase in vaccinees while it remained unchanged or even increased in placebo-treated patients. None of them showed HIV-related symptoms and all had their CD4 cell counts stabilized over 18 months, whereas 2 placebo-treated patients developed full-blow AIDS. In conclusion, anti-IFN alpha vaccine was safe and immunogenic. Stable clinical and immunological status over 18 months was observed in vaccinees coupled to increased serum IFN alpha neutralizing capacity.

  3. High throughput sequencing and proteomics to identify immunogenic proteins of a new pathogen: the dirty genome approach.

    Science.gov (United States)

    Greub, Gilbert; Kebbi-Beghdadi, Carole; Bertelli, Claire; Collyn, François; Riederer, Beat M; Yersin, Camille; Croxatto, Antony; Raoult, Didier

    2009-12-23

    With the availability of new generation sequencing technologies, bacterial genome projects have undergone a major boost. Still, chromosome completion needs a costly and time-consuming gap closure, especially when containing highly repetitive elements. However, incomplete genome data may be sufficiently informative to derive the pursued information. For emerging pathogens, i.e. newly identified pathogens, lack of release of genome data during gap closure stage is clearly medically counterproductive. We thus investigated the feasibility of a dirty genome approach, i.e. the release of unfinished genome sequences to develop serological diagnostic tools. We showed that almost the whole genome sequence of the emerging pathogen Parachlamydia acanthamoebae was retrieved even with relatively short reads from Genome Sequencer 20 and Solexa. The bacterial proteome was analyzed to select immunogenic proteins, which were then expressed and used to elaborate the first steps of an ELISA. This work constitutes the proof of principle for a dirty genome approach, i.e. the use of unfinished genome sequences of pathogenic bacteria, coupled with proteomics to rapidly identify new immunogenic proteins useful to develop in the future specific diagnostic tests such as ELISA, immunohistochemistry and direct antigen detection. Although applied here to an emerging pathogen, this combined dirty genome sequencing/proteomic approach may be used for any pathogen for which better diagnostics are needed. These genome sequences may also be very useful to develop DNA based diagnostic tests. All these diagnostic tools will allow further evaluations of the pathogenic potential of this obligate intracellular bacterium.

  4. Compact printed high rejection triple band-notch UWB antenna with multiple wireless applications

    Directory of Open Access Journals (Sweden)

    Manish Sharma

    2016-09-01

    Full Text Available In this paper, small printed urn-shape triple notch ultra-wideband (UWB monopole antenna with diverse wireless applications is presented. Notch bands include WiMAX (IEEE802.16 3.30–3.80 GHz, WLAN IEEE802.11a/h/j/n (5.15–5.35 GHz, 5.25–5.35 GHz, 5.47–5.725 GHz, 5.725–5.825 GHz, and X-band downlink satellite system (7.25–7.75 GHz and other multiple wireless services as close range radar (8–12 GHz in X-band & satellite communication (12–18 GHz in Ku-band. By including T-shape stub and etching two C-shaped slots on the radiating patch, triple band-notch function is obtained with measured high band rejection (VSWR = 16.54 at 3.60 GHz, VSWR = 22.35 at 5.64 GHz and VSWR = 6.38 at 7.64 GHz and covers a wide useable fractional bandwidth of 154.56% (2.49–19.41 GHz. In short the antenna offers triple band-notch UWB systems as a compact multifunctional antenna to reduce the number of antennas installed in wireless devices for accessing multiple wireless networks with wide radiation pattern.

  5. Approximation of rejective sampling inclusion probabilities and application to high order correlations

    NARCIS (Netherlands)

    Boistard, H.; Lopuhää, H.P.; Ruiz-Gazen, A.

    2012-01-01

    This paper is devoted to rejective sampling. We provide an expansion of joint inclusion probabilities of any order in terms of the inclusion probabilities of order one, extending previous results by Hájek (1964) and Hájek (1981) and making the remainder term more precise. Following Hájek (1981), the

  6. Single-shot, high-dose rabbit ATG for rejection prophylaxis after kidney transplantation

    NARCIS (Netherlands)

    R. Zietse (Bob); E.P.M. van Steenberge (E. P M); C.J. Hesse (Cees); L.B. Vaessen (L.); J.N.M. IJzermans (Jan); W. Weimar (Willem)

    1993-01-01

    textabstractWe studied the effects of a single intravenous injection of rabbit ATG (RIVM, Bilthoven, The Netherlands) in a dose of 8 mg/kg body weight administered 6 h after kidney transplantation on graft survival, rejection incidence, T-cell subsets, and cost-effectiveness. A total of 58 (37

  7. Practices for Identifying and Rejecting Hemolyzed Specimens Are Highly Variable in Clinical Laboratories.

    Science.gov (United States)

    Howanitz, Peter J; Lehman, Christopher M; Jones, Bruce A; Meier, Frederick A; Horowitz, Gary L

    2015-08-01

    Hemolysis is an important clinical laboratory quality attribute that influences result reliability. To determine hemolysis identification and rejection practices occurring in clinical laboratories. We used the College of American Pathologists Survey program to distribute a Q-Probes-type questionnaire about hemolysis practices to Chemistry Survey participants. Of 3495 participants sent the questionnaire, 846 (24%) responded. In 71% of 772 laboratories, the hemolysis rate was less than 3.0%, whereas in 5%, it was 6.0% or greater. A visual scale, an instrument scale, and combination of visual and instrument scales were used to identify hemolysis in 48%, 11%, and 41% of laboratories, respectively. A picture of the hemolysis level was used as an aid to technologists' visual interpretation of hemolysis levels in 40% of laboratories. In 7.0% of laboratories, all hemolyzed specimens were rejected; in 4% of laboratories, no hemolyzed specimens were rejected; and in 88% of laboratories, some specimens were rejected depending on hemolysis levels. Participants used 69 different terms to describe hemolysis scales, with 21 terms used in more than 10 laboratories. Slight and moderate were the terms used most commonly. Of 16 different cutoffs used to reject hemolyzed specimens, moderate was the most common, occurring in 30% of laboratories. For whole blood electrolyte measurements performed in 86 laboratories, 57% did not evaluate the presence of hemolysis, but for those that did, the most common practice in 21 laboratories (24%) was centrifuging and visually determining the presence of hemolysis in all specimens. Hemolysis practices vary widely. Standard assessment and consistent reporting are the first steps in reducing interlaboratory variability among results.

  8. Linear active disturbance rejection-based load frequency control concerning high penetration of wind energy

    International Nuclear Information System (INIS)

    Tang, Yanmei; Bai, Yan; Huang, Congzhi; Du, Bin

    2015-01-01

    Highlights: • A disturbance rejection solution to the load frequency control issue is proposed. • Several power systems with wind energy conversation system have been tested. • A tuning algorithm of the controller parameters was proposed. • The performance of the proposed approach is better than traditional controllers. - Abstract: A new grid load frequency control approach is proposed for the doubly fed induction generator based wind power plants. The load frequency control issue in a power system is undergoing fundamental changes due to the rapidly growing amount of wind energy conversation system, and concentrating on maintaining generation-load balance and disturbance rejection. The prominent feature of the linear active disturbance rejection control approach is that the total disturbance can be estimated and then eliminated in real time. And thus, it is a feasible solution to deal with the load frequency control issue. In this paper, the application of the linear active disturbance rejection control approach in the load frequency control issue for a complex power system with wind energy conversation system based on doubly fed induction generator is investigated. The load frequency control issue is formulated as a decentralized multi-objective optimization control problem, the solution to which is solved by the hybrid particle swarm optimization technique. To show the effectiveness of the proposed control scheme, the robust performance testing based on Monte-Carlo approach is carried out. The performance superiority of the system with the proposed linear active disturbance rejection control approach over that with the traditional proportional integral and fuzzy-proportional integral-based controllers is validated by the simulation results

  9. Pile-up Rejection in the High Granularity Time Detector for the High Luminosity LHC

    CERN Document Server

    McNulty, Paul

    2016-01-01

    The High Granularity Timing Detector, a proposed upgrade to the Liquid Argon Calorimeter during the transition to the High Luminosity LHC, will provide increased resolution in the time domain and offer an avenue for efficiently mitigating the expected increase in pile-up jets. This study analyzes how effectively current algorithms are using a signal jet peak calculation to disentangle desired information from other events. Two samples, one with only hard-scattering events and another that also included pile-up events, were used. A transverse momentum range of 30GeV to 70GeV and pseudo-rapidity range of 2.4 to 4.8 divided the sample to see how the HGTD performed when calculating the signal peak for each jet and how many cells had detections in and out of that peak for each sample.

  10. High conservation level of CD8(+) T cell immunogenic regions within an unusual H1N2 human influenza variant.

    Science.gov (United States)

    Komadina, Naomi; Quiñones-Parra, Sergio M; Kedzierska, Katherine; McCaw, James M; Kelso, Anne; Leder, Karin; McVernon, Jodie

    2016-10-01

    Current seasonal influenza vaccines require regular updates due to antigenic drift causing loss of effectiveness and therefore providing little or no protection against novel influenza A subtypes. Next generation vaccines capable of eliciting CD8(+) T cell (CTL) mediated cross-protective immunity may offer a long-term alternative strategy. However, measuring pre- and existing levels of CTL cross-protection in humans is confounded by differences in infection histories across individuals. During 2000-2003, H1N2 viruses circulated persistently in the human population for the first time and we hypothesized that the viral nucleoprotein (NP) contained novel CTL epitopes that may have contributed to the survival of the viruses. This study describes the immunogenic NP peptides of H1N1, H2N2, and H3N2 influenza viruses isolated from humans over the past century, 1918-2003, by comparing this historical dataset to reference NP peptides from H1N2 that circulated in humans during 2000-2003. Observed peptides sequences ranged from highly conserved (15%) to highly variable (12%), with variation unrelated to reported immunodominance. No unique NP peptides which were exclusive to the H1N2 viruses were noted. However, the virus had inherited the NP from a recently emerged H3N2 variant containing novel peptides, which may have assisted its persistence. Any advantage due to this novelty was subsequently lost with emergence of a newer H3N2 variant in 2003. Our approach has potential to provide insight into the population context in which influenza viruses emerge, and may help to inform immunogenic peptide selection for CTL-inducing influenza vaccines. J. Med. Virol. 88:1725-1732, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Recovery and recycling of uranium from rejected coated particles for compact high temperature reactors

    Energy Technology Data Exchange (ETDEWEB)

    Pai, Rajesh V., E-mail: pairajesh007@gmail.com [Fuel Chemistry Division, Bhabha Atomic Research Centre, Mumbai (India); Mollick, P.K. [Powder Metallurgy Division, Bhabha Atomic Research Centre, Mumbai (India); Kumar, Ashok [Fuel Chemistry Division, Bhabha Atomic Research Centre, Mumbai (India); Banerjee, J. [Radiometullurgy Division, Bhabha Atomic Research Centre, Mumbai (India); Radhakrishna, J. [Fuel Chemistry Division, Bhabha Atomic Research Centre, Mumbai (India); Chakravartty, J.K. [Powder Metallurgy Division, Bhabha Atomic Research Centre, Mumbai (India)

    2016-05-15

    UO{sub 2} microspheres prepared by internal gelation technique were coated with pyrolytic carbon and silicon carbide using CVD technique. The particles which were not meeting the specifications were rejected. The rejected/failed UO{sub 2} based coated particles prepared by CVD technique was used for oxidation and recovery and recycling. The oxidation behaviour of sintered UO{sub 2} microspheres coated with different layers of carbon and SiC was studied by thermal techniques to develop a method for recycling and recovery of uranium from the failed/rejected coated particles. It was observed that the complete removal of outer carbon from the spheres is difficult. The crushing of microspheres enabled easier accessibility of oxygen and oxidation of carbon and uranium at 800–1000 °C. With the optimized process of multiple crushing using die & plunger and sieving the broken coated layers, we could recycle around fifty percent of the UO{sub 2} microspheres which could be directly recoated. The rest of the particles were recycled using a wet recycling method. - Highlights: • The oxidation behaviour of coated particles was studied in air, O{sub 2} and moist O{sub 2}. • It was observed that coated layers cannot be completely removed by mere oxidation. • Complete recovery of uranium from the rejected coated particles has been carried out using a combination of dry and wet recovery scheme. • A crushing step prior to oxidation is needed for full recovery of uranium from the coated particles.

  12. Dicarbonyl Induced Structural Perturbations Make Histone H1 Highly Immunogenic and Generate an Auto-Immune Response in Cancer.

    Directory of Open Access Journals (Sweden)

    Abdul Rouf Mir

    Full Text Available Increased oxidative stress under hyperglycemic conditions, through the interaction of AGEs with RAGE receptors and via activation of interleukin mediated transcription signalling, has been reported in cancer. Proteins modifications are being explored for their roles in the development and progression of cancer and autoantibody response against them is gaining interest as a probe for early detection of the disease. This study has analysed the changes in histone H1 upon modification by methylglyoxal (MG and its implications in auto-immunopathogenesis of cancer. Modified histone showed modifications in the aromatic residues, changed tyrosine microenvironment, intermolecular cross linking and generation of AGEs. It showed masking of hydrophobic patches and a hypsochromic shift in the in ANS specific fluorescence. MG aggressively oxidized histone H1 leading to the accumulation of reactive carbonyls. Far UV CD measurements showed di-carbonyl induced enhancement of the alpha structure and the induction of beta sheet conformation; and thermal denaturation (Tm studies confirmed the thermal stability of the modified histone. FTIR analysis showed amide I band shift, generation of a carboxyethyl group and N-Cα vibrations in the modified histone. LCMS analysis confirmed the formation of Nε-(carboxyethyllysine and electron microscopic studies revealed the amorphous aggregate formation. The modified histone showed altered cooperative binding with DNA. Modified H1 induced high titre antibodies in rabbits and the IgG isolated form sera of rabbits immunized with modified H1 exhibited specific binding with its immunogen in Western Blot analysis. IgG isolated from the sera of patients with lung cancer, prostate cancer, breast cancer and cancer of head and neck region showed better recognition for neo-epitopes on the modified histone, reflecting the presence of circulating autoantibodies in cancer. Since reports suggest a link between AGE-RAGE axis and

  13. High throughput sequencing and proteomics to identify immunogenic proteins of a new pathogen: the dirty genome approach.

    Directory of Open Access Journals (Sweden)

    Gilbert Greub

    Full Text Available BACKGROUND: With the availability of new generation sequencing technologies, bacterial genome projects have undergone a major boost. Still, chromosome completion needs a costly and time-consuming gap closure, especially when containing highly repetitive elements. However, incomplete genome data may be sufficiently informative to derive the pursued information. For emerging pathogens, i.e. newly identified pathogens, lack of release of genome data during gap closure stage is clearly medically counterproductive. METHODS/PRINCIPAL FINDINGS: We thus investigated the feasibility of a dirty genome approach, i.e. the release of unfinished genome sequences to develop serological diagnostic tools. We showed that almost the whole genome sequence of the emerging pathogen Parachlamydia acanthamoebae was retrieved even with relatively short reads from Genome Sequencer 20 and Solexa. The bacterial proteome was analyzed to select immunogenic proteins, which were then expressed and used to elaborate the first steps of an ELISA. CONCLUSIONS/SIGNIFICANCE: This work constitutes the proof of principle for a dirty genome approach, i.e. the use of unfinished genome sequences of pathogenic bacteria, coupled with proteomics to rapidly identify new immunogenic proteins useful to develop in the future specific diagnostic tests such as ELISA, immunohistochemistry and direct antigen detection. Although applied here to an emerging pathogen, this combined dirty genome sequencing/proteomic approach may be used for any pathogen for which better diagnostics are needed. These genome sequences may also be very useful to develop DNA based diagnostic tests. All these diagnostic tools will allow further evaluations of the pathogenic potential of this obligate intracellular bacterium.

  14. Identification and rejection of pile-up jets at high pseudorapidity with the ATLAS detector

    Energy Technology Data Exchange (ETDEWEB)

    Aaboud, M. [Univ. Mohamed Premier et LPTPM, Oujda (Morocco). Faculte des Sciences; Aad, G. [CPPM, Aix-Marseille Univ. et CNRS/IN2P3, Marseille (France); Abbott, B. [Oklahoma Univ., Norman, OK (United States). Homer L. Dodge Dept. of Physics and Astronomy; Collaboration: ATLAS Collaboration; and others

    2017-09-15

    The rejection of forward jets originating from additional proton-proton interactions (pile-up) is crucial for a variety of physics analyses at the LHC, including Standard Model measurements and searches for physics beyond the Standard Model. The identification of such jets is challenging due to the lack of track and vertex information in the pseudorapidity range vertical stroke η vertical stroke > 2.5. This paper presents a novel strategy for forward pile-up jet tagging that exploits jet shapes and topological jet correlations in pile-up interactions. Measurements of the per-jet tagging efficiency are presented using a data set of 3.2 fb{sup -1} of proton-proton collisions at a centre-of-mass energy of 13 TeV collected with the ATLAS detector. The fraction of pile-up jets rejected in the range 2.5 < vertical stroke η vertical stroke < 4.5 is estimated in simulated events with an average of 22 interactions per bunch-crossing. It increases with jet transverse momentum and, for jets with transverse momentum between 20 and 50 GeV, it ranges between 49% and 67% with an efficiency of 85% for selecting hard-scatter jets. A case study is performed in Higgs boson production via the vector-boson fusion process, showing that these techniques mitigate the background growth due to additional proton-proton interactions, thus enhancing the reach for such signatures. (orig.)

  15. High dose of plasmid IL-15 inhibits immune responses in an influenza non-human primates immunogenicity model

    International Nuclear Information System (INIS)

    Yin Jiangmei; Dai Anlan; Laddy, Dominick J.; Yan Jian; Arango, Tatiana; Khan, Amir S.; Lewis, Mark G.; Andersen, Hanne; Kutzler, Michele A.; Draghia-Akli, Ruxandra; Weiner, David B.; Boyer, Jean D.

    2009-01-01

    Interleukin (IL)-15, is a cytokine that is important for the maintenance of long-lasting, high-avidity T cell response to invading pathogens and has, therefore, been used in vaccine and therapeutic platforms as an adjuvant. In addition to pure protein delivery, plasmids encoding the IL-15 gene have been utilized. However, it is critical to determine the appropriate dose to maximize the adjuvanting effects. We immunized rhesus macaques with different doses of IL-15 expressing plasmid in an influenza non-human primate immunogenicity model. We found that co-immunization of rhesus macaques with a Flu DNA-based vaccine and low doses of plasmid encoding macaque IL-15 enhanced the production of IFN-γ (0.5 mg) and the proliferation of CD4 + and CD8 + T cells, as well as T CM levels in proliferating CD8 + T cells (0.25 mg). Whereas, high doses of IL-15 (4 mg) decrease the production of IFN-γ and the proliferation of CD4 + and CD8 + T cells and T CM levels in the proliferating CD4 + and CD8 + T cells. In addition, the data of hemagglutination inhibition (HI) antibody titer suggest that although not significantly different, there appears to be a slight increase in antibodies at lower doses of IL-15. Importantly, however, the higher doses of IL-15 decrease the antibody levels significantly. This study demonstrates the importance of optimizing DNA-based cytokine adjuvants.

  16. The importance of handling high-value biologicals: Physico-chemical instability and immunogenicity of monoclonal antibodies.

    Science.gov (United States)

    Laptoš, Tomislav; Omersel, Jasna

    2018-04-01

    The present review specifies the various chemical and physical factors that can influence drug stability and immunogenicity, and the treatment outcomes of antibody biologicals. Although monoclonal antibodies (mAbs) are known to be more resistant to environmental changes compared with other proteins, the molecules themselves can be subjected to chemical and physical processes that promote their degradation and transformation into their specific amino-acid moieties. With increasing use of medicinal products that contain mAbs, and their self-administration by the patients, the issue of the correct manipulation of these drugs is of increasing importance. This review summarises the correct handling of mAb biologicals from the point of view of the pharmacist, clinical biochemist and patient, as is supported by relevant cases from the literature and our own data and experience. In particular, if there is a break in the cold chain, both healthcare professionals and patients need to be aware of the potential pharmacokinetics and pharmacodynamics alterations to these biologicals. Furthermore, any alterations in the protein structure can induce harmful immune reactions, including anaphylaxis and cytokine storms, or result in the production of neutralising or blocking Abs. Overall, considering also that treatment costs usually remain high, drug stability can have a tremendous effect on the clinical, humanistic and economic outcomes of such treatments.

  17. Expression of the multimeric and highly immunogenic Brucella spp. lumazine synthase fused to bovine rotavirus VP8d as a scaffold for antigen production in tobacco chloroplasts

    Directory of Open Access Journals (Sweden)

    Edgardo Federico Alfano

    2015-12-01

    Full Text Available Lumazine synthase from Brucella spp. (BLS is a highly immunogenic decameric protein which can accommodate foreign polypeptides or protein domains fused to its N-termini, markedly increasing their immunogenicity.The inner core domain (VP8d of VP8 spike protein from bovine rotavirus (BRV is responsible for viral adhesion to sialic acid residues and infection. It also displays neutralizing epitopes, making it a good candidate for vaccination.In this work, the BLS scaffold was assessed for the first time in plants for recombinant vaccine development by N-terminally fusing BLS to VP8d and expressing the resulting fusion (BLSVP8d in tobacco chloroplasts. Transplastomic plants were obtained and characterized by Southern, northern and western blot. BLSVP8d was highly expressed, representing 40% of total soluble protein (TSP (4.85 mg/g fresh tissue. BLSVP8d remained soluble and stable during all stages of plant development and even in lyophilized leaves stored at room temperature. Soluble protein extracts from fresh and lyophilized leaves were able to induce specific neutralizing IgY antibodies in a laying hen model. This work presents BLS as an interesting platform for highly immunogenic injectable, or even oral, subunit vaccines. Lyophilization of transplastomic leaves expressing stable antigenic fusions to BLS would further reduce costs and simplify downstream processing, purification and storage, allowing for more practical vaccines.

  18. Discrete-time nonlinear damping backstepping control with observers for rejection of low and high frequency disturbances

    Science.gov (United States)

    Kim, Wonhee; Chen, Xu; Lee, Youngwoo; Chung, Chung Choo; Tomizuka, Masayoshi

    2018-05-01

    A discrete-time backstepping control algorithm is proposed for reference tracking of systems affected by both broadband disturbances at low frequencies and narrow band disturbances at high frequencies. A discrete time DOB, which is constructed based on infinite impulse response filters is applied to compensate for narrow band disturbances at high frequencies. A discrete-time nonlinear damping backstepping controller with an augmented observer is proposed to track the desired output and to compensate for low frequency broadband disturbances along with a disturbance observer, for rejecting narrow band high frequency disturbances. This combination has the merit of simultaneously compensating both broadband disturbances at low frequencies and narrow band disturbances at high frequencies. The performance of the proposed method is validated via experiments.

  19. The Effect of Local Irradiation in Prevention and Reversal of Acute Rejection of Transplanted Kidney with High-dose Steroid Pulse

    International Nuclear Information System (INIS)

    Kim, I. H.; Ha, S. W.; Park, C. I.; Kim, S. T.

    1986-01-01

    From 1979 to 1984, 39 local allograft irradiations were given to 29 patients: 10 irradiations were administered for prevention and 29 for reversal of acute rejection of transplanted kidney. Three doses of 150 cGy every other day were combined with high-dose of methylprednisolone pulse (1 gm/day) for 3 days. For prevention of acute rejection, local irradiation was delivered on the days 1, 3, and 5 after the transplantation, and for reversal, irradiation started after the diagnosis of acute rejection. Eight out of 10 patients irradiated for prevention had acute allograft rejection, and, what is more, there was no surviving graft at 15 months after transplantation. Reversal of acute rejection was achieved in 71%. When the pre-irradiation level of serum creatinine was below 5.5 mg%, the reversal rate was 93%, but above 5.5 mg% the reversal rate was only 17% (p<0.01). Reirradiation after failure was not successful. Among 15 reversed patients, 7 (47%) had subsequent rejection (s). The functional graft survivals at 6 month, 1, 2, and 3 year were 70%, 65%, 54%, and 65%, respectively. Therapeutic irradiation resulted in better graft survival when serum creatinine was below 5.5 mg% (p<0.001) or when irradiation started within 15 days after the diagnosis of acute rejection (p<0.001)

  20. Time gating for energy selection and scatter rejection: High-energy pulsed neutron imaging at LANSCE

    Science.gov (United States)

    Swift, Alicia; Schirato, Richard; McKigney, Edward; Hunter, James; Temple, Brian

    2015-09-01

    The Los Alamos Neutron Science Center (LANSCE) is a linear accelerator in Los Alamos, New Mexico that accelerates a proton beam to 800 MeV, which then produces spallation neutron beams. Flight path FP15R uses a tungsten target to generate neutrons of energy ranging from several hundred keV to ~600 MeV. The beam structure has micropulses of sub-ns width and period of 1.784 ns, and macropulses of 625 μs width and frequency of either 50 Hz or 100 Hz. This corresponds to 347 micropulses per macropulse, or 1.74 x 104 micropulses per second when operating at 50 Hz. Using a very fast, cooled ICCD camera (Princeton Instruments PI-Max 4), gated images of various objects were obtained on FP15R in January 2015. Objects imaged included blocks of lead and borated polyethylene; a tungsten sphere; and a tungsten, polyethylene, and steel cylinder. Images were obtained in 36 min or less, with some in as little as 6 min. This is novel because the gate widths (some as narrow as 10 ns) were selected to reject scatter and other signal not of interest (e.g. the gamma flash that precedes the neutron pulse), which has not been demonstrated at energies above 14 MeV. This proof-of-principle experiment shows that time gating is possible above 14MeV and is useful for selecting neutron energy and reducing scatter, thus forming clearer images. Future work (simulation and experimental) is being undertaken to improve camera shielding and system design and to precisely determine optical properties of the imaging system.

  1. Highly immunogenic prime–boost DNA vaccination protects chickens against challenge with homologous and heterologous H5N1 virus

    Directory of Open Access Journals (Sweden)

    Anna Stachyra

    2014-01-01

    Full Text Available Highly pathogenic avian influenza viruses (HPAIVs cause huge economic losses in the poultry industry because of high mortality rate in infected flocks and trade restrictions. Protective antibodies, directed mainly against hemagglutinin (HA, are the primary means of protection against influenza outbreaks. A recombinant DNA vaccine based on the sequence of H5 HA from the H5N1/A/swan/Poland/305-135V08/2006 strain of HPAIV was prepared. Sequence manipulation included deletion of the proteolytic cleavage site to improve protein stability, codon usage optimization to improve translation and stability of RNA in host cells, and cloning into a commercially available vector to enable expression in animal cells. Naked plasmid DNA was complexed with a liposomal carrier and the immunization followed the prime–boost strategy. The immunogenic potential of the DNA vaccine was first proved in broilers in near-to-field conditions resembling a commercial farm. Next, the protective activity of the vaccine was confirmed in SPF layer-type chickens. Experimental infections (challenge experiments indicated that 100% of vaccinated chickens were protected against H5N1 of the same clade and that 70% of them were protected against H5N1 influenza virus of a different clade. Moreover, the DNA vaccine significantly limited (or even eliminated transmission of the virus to contact control chickens. Two intramuscular doses of DNA vaccine encoding H5 HA induced a strong protective response in immunized chicken. The effective protection lasted for a minimum 8 weeks after the second dose of the vaccine and was not limited to the homologous H5N1 virus. In addition, the vaccine reduced shedding of the virus.

  2. A detector module with highly efficient surface-alpha event rejection operated in CRESST-II Phase 2

    Energy Technology Data Exchange (ETDEWEB)

    Strauss, R. [Max-Planck-Institut fuer Physik, Munich (Germany); Technische Universitaet Muenchen, Physik-Department, Garching (Germany); Angloher, G.; Ferreiro, N.; Hauff, D.; Kiefer, M.; Petricca, F.; Proebst, F.; Reindl, F.; Seidel, W.; Stodolsky, L.; Tanzke, A.; Wuestrich, M. [Max-Planck-Institut fuer Physik, Munich (Germany); Bento, A. [Universidade de Coimbra, CIUC, Departamento de Fisica, Coimbra (Portugal); Bucci, C.; Canonica, L.; Gorla, P.; Schaeffner, K. [Laboratori Nazionali del Gran Sasso, INFN, Assergi (Italy); Erb, A. [Technische Universitaet Muenchen, Physik-Department, Garching (Germany); Walther-Meissner-Institut fuer Tieftemperaturforschung, Garching (Germany); Feilitzsch, F. von; Guetlein, A.; Lanfranchi, J.C.; Muenster, A.; Potzel, W.; Roth, S.; Schoenert, S.; Stanger, M.; Ulrich, A.; Wawoczny, S.; Willers, M.; Zoeller, A. [Technische Universitaet Muenchen, Physik-Department, Garching (Germany); Jochum, J.; Loebell, J.; Rottler, K.; Sailer, C.; Scholl, S.; Strandhagen, C.; Uffinger, M.; Usherov, I. [Eberhard-Karls-Universitaet Tuebingen, Physikalisches Institut, Tuebingen (Germany); Kluck, H. [Institut fuer Hochenergiephysik der Oesterreichischen Akademie der Wissenschaften, Wien (Austria); Vienna University of Technology, Atominstitut, Wien (Austria); Kraus, H. [University of Oxford, Department of Physics, Oxford (United Kingdom); Schieck, J. [Institut fuer Hochenergiephysik der Oesterreichischen Akademie der Wissenschaften, Wien (Austria); Sivers, M. von [Technische Universitaet Muenchen, Physik-Department, Garching (Germany); University of Bern, Albert Einstein Center for Fundamental Physics, Bern (Switzerland)

    2015-08-15

    The cryogenic dark matter experiment CRESSTII aims at the direct detection of WIMPs via elastic scattering off nuclei in scintillating CaWO{sub 4} crystals. We present a new, highly improved, detector design installed in the current run of CRESST-II Phase 2 with an efficient active rejection of surface-alpha backgrounds. Using CaWO{sub 4} sticks instead of metal clamps to hold the target crystal, a detector housing with fully-scintillating inner surface could be realized. The presented detector (TUM40) provides an excellent threshold of ∝0.60 keV and a resolution of σ ∼ 0.090 keV (at 2.60 keV).With significantly reduced background levels, TUM40 sets stringent limits on the spin-independent WIMP nucleon scattering cross section and probes a new region of parameter space for WIMP masses below 3GeV/c{sup 2}. In this paper, we discuss the novel detector design and the surface-alpha event rejection in detail. (orig.)

  3. Identification of immunogenic HLA-B7 "Achilles' heel" epitopes within highly conserved regions of HIV

    DEFF Research Database (Denmark)

    De Groot, Anne S; Rivera, Daniel S; McMurry, Julie A

    2008-01-01

    Genetic polymorphisms in class I human leukocyte antigen molecules (HLA) have been shown to determine susceptibility to HIV infection as well as the rate of progression to AIDS. In particular, the HLA-B7 supertype has been shown to be associated with high viral loads and rapid progression to dise...

  4. New immunogenic form for vasopressin: production of high-affinity antiserum and RIA for plasmatic AVP

    International Nuclear Information System (INIS)

    Rougon-Rappuzi, G.; Delaage, M.A.; Conte-Devolx, B.; Millet, Y.

    1977-01-01

    A highly sensitive and specific radioimmunoassay (RIA) for arginine-vasopressin (AVP) was developped and applied to the measurement of AVP in human plasma. High-affinity antivasopressin antibodies with limited association constant heterogeneity have been induced by immunizing rabbits with Lysine-vasopressine (LVP) coupled to a human immunoglobulin (IgA). Replacing air drying of acetone-petroleum ether extracts by lyophilisation increased significantly the yields of AVP. Equilibrium dialysis was used for separating bound and free antigen, thus reducing the total time required for the assay to 48 hours. Only 1 ml of plasma was required for routine determinations due to a sensitivity threshold better than 0.5 pg/ml. Plasma AVP levels of normal subjects and of patients with inappropriate ADH secretion (SIADH) were determined during different hydratation states and following nicotin of ethanol infusions. (orig.) [de

  5. Identification and rejection of pile-up jets at high pseudorapidity with the ATLAS detector

    Czech Academy of Sciences Publication Activity Database

    Aaboud, M.; Aad, G.; Abbott, B.; Chudoba, Jiří; Hejbal, Jiří; Hladík, Ondřej; Jakoubek, Tomáš; Kepka, Oldřich; Kroll, Jiří; Kupčo, Alexander; Kůs, Vlastimil; Lokajíček, Miloš; Lysák, Roman; Marčišovský, Michal; Mikeštíková, Marcela; Němeček, Stanislav; Penc, Ondřej; Šícho, Petr; Staroba, Pavel; Svatoš, Michal; Taševský, Marek

    2017-01-01

    Roč. 77, č. 9 (2017), s. 1-32, č. článku 580. ISSN 1434-6044 Institutional support: RVO:68378271 Keywords : ATLAS * CERN LHC Coll * new physics * topological * background * signature * tracks * data analysis method * experimental results * 13000 GeV-cms Subject RIV: BF - Elementary Particles and High Energy Physics OBOR OECD: Particles and field physics Impact factor: 5.331, year: 2016

  6. Experimental test of the background rejection, through imaging capability, of a highly segmented AGATA germanium detector

    International Nuclear Information System (INIS)

    Doncel, M.; Recchia, F.; Quintana, B.; Gadea, A.; Farnea, E.

    2010-01-01

    The development of highly segmented germanium detectors as well as the algorithms to identify the position of the interaction within the crystal opens the possibility to locate the γ-ray source using Compton imaging algorithms. While the Compton-suppression shield, coupled to the germanium detector in conventional arrays, works also as an active filter against the γ rays originated outside the target, the new generation of position sensitive γ-ray detector arrays has to fully rely on tracking capabilities for this purpose. In specific experimental conditions, as the ones foreseen at radioactive beam facilities, the ability to discriminate background radiation improves the sensitivity of the gamma spectrometer. In this work we present the results of a measurement performed at the Laboratori Nazionali di Legnaro (LNL) aiming the evaluation of the AGATA detector capabilities to discriminate the origin of the γ rays on an event-by-event basis. It will be shown that, exploiting the Compton scattering formula, it is possible to track back γ rays coming from different positions, assigning them to specific emitting locations. These imaging capabilities are quantified for a single crystal AGATA detector.

  7. Heterologous prime-boost vaccination with DNA and MVA vaccines, expressing HIV-1 subtype C mosaic Gag virus-like particles, is highly immunogenic in mice.

    Directory of Open Access Journals (Sweden)

    Ros Chapman

    Full Text Available In an effort to make affordable vaccines suitable for the regions most affected by HIV-1, we have constructed stable vaccines that express an HIV-1 subtype C mosaic Gag immunogen (BCG-GagM, MVA-GagM and DNA-GagM. Mosaic immunogens have been designed to address the tremendous diversity of this virus. Here we have shown that GagM buds from cells infected and transfected with MVA-GagM and DNA-GagM respectively and forms virus-like particles. Previously we showed that a BCG-GagM prime MVA-GagM boost generated strong cellular immune responses in mice. In this study immune responses to the DNA-GagM and MVA-GagM vaccines were evaluated in homologous and heterologous prime-boost vaccinations. The DNA homologous prime boost vaccination elicited predominantly CD8+ T cells while the homologous MVA vaccination induced predominantly CD4+ T cells. A heterologous DNA-GagM prime MVA-GagM boost induced strong, more balanced Gag CD8+ and CD4+ T cell responses and that were predominantly of an effector memory phenotype. The immunogenicity of the mosaic Gag (GagM was compared to a naturally occurring subtype C Gag (GagN using a DNA homologous vaccination regimen. DNA-GagN expresses a natural Gag with a sequence that was closest to the consensus sequence of subtype C viruses sampled in South Africa. DNA-GagM homologous vaccination induced cumulative HIV-1 Gag-specific IFN-γ ELISPOT responses that were 6.5-fold higher than those induced by the DNA-GagN vaccination. Similarly, DNA-GagM vaccination generated 7-fold higher levels of cytokine-positive CD8+ T cells than DNA-GagN, indicating that this subtype C mosaic Gag elicits far more potent immune responses than a consensus-type Gag. Cells transfected and infected with DNA-GagM and MVA-GagM respectively, expressed high levels of GagM and produced budding virus-like particles. Our data indicates that a heterologous prime boost regimen using DNA and MVA vaccines expressing HIV-1 subtype C mosaic Gag is highly

  8. Lung allograft rejection in the rat. I. Accelerated rejection caused by graft lymphocytes

    International Nuclear Information System (INIS)

    Prop, J.; Nieuwenhuis, P.; Wildevuur, C.R.

    1985-01-01

    To find out to what extent rejection of lungs differs from that of other organs, functional rejection of lung allografts was studied in five combinations of inbred rat strains. Rejection could be monitored accurately by perfusion scintigraphy, and equally well by chest roentgenography. The rejection of lung grafts was found to proceed remarkably fast, when compared with heart grafts, in combinations with strong RT1-incompatibilities. This accelerated rejection pattern could be converted into rejection at a normal pace by pretreatment of the donor with 10 Gy roentgen irradiation one day before transplantation. Donor pretreatment depleted the lung graft's bronchus-associated lymphoid tissue (BALT) of lymphocytes. When grafts were depleted of all other passenger cells as well--by retransplantation from a cyclosporine-treated intermediate host--they showed an even more reduced immunogenicity, probably because of the loss of donor-type dendritic cells. These results indicate that lymphocytes from the BALT of lung grafts are capable of accelerating the rejection response

  9. Observational demonstration of a high image rejection SIS mixer receiver using a new waveguide filter at 230 GHz

    Science.gov (United States)

    Hasegawa, Yutaka; Asayama, Shinichiro; Harada, Ryohei; Tokuda, Kazuki; Kimura, Kimihiro; Ogawa, Hideo; Onishi, Toshikazu

    2017-12-01

    A new sideband separation method was developed for use in millimeter-/submillimeter-band radio receivers using a novel waveguide frequency separation filter (FSF), which consists of two branch line hybrid couplers and two waveguide high-pass filters. The FSF was designed to allow the radio frequency (RF) signal to pass through to an output port when the frequency is higher than a certain value (225 GHz), and to reflect the RF signal back to another output port when the frequency is lower. The FSF is connected to two double sideband superconductor-insulator-superconductor (SIS) mixers, and an image rejection ratio (IRR) is determined by the FSF characteristics. With this new sideband separation method, we can achieve good and stable IRR without the balancing two SIS mixers such as is necessary for conventional sideband-separating SIS mixers. To demonstrate the applicability of this method, we designed and developed an FSF for simultaneous observations of the J = 2-1 rotational transition lines of three CO isotopes (12CO, 13CO, and C18O): the 12CO line is in the upper sideband and the others are in the lower sideband with an intermediate-frequency range of 4-8 GHz at the radio frequency of 220/230 GHz. This FSF was then installed in the receiver system of the 1.85 m radio telescope of Osaka Prefecture University, and was used during the 2014 observation season. The observation results indicate that the IRR of the proposed receiver is 25 dB or higher for the 12CO line, and no significant fluctuation larger than 1 dB in the IRR was observed throughout the season. These results demonstrate the practical utility of the FSF receiver for observations like extensive molecular cloud surveys in specified lines with a fixed frequency setting.

  10. Highly-Immunogenic Virally-Vectored T-cell Vaccines Cannot Overcome Subversion of the T-cell Response by HCV during Chronic Infection

    Directory of Open Access Journals (Sweden)

    Leo Swadling

    2016-08-01

    Full Text Available An effective therapeutic vaccine for the treatment of chronic hepatitis C virus (HCV infection, as an adjunct to newly developed directly-acting antivirals (DAA, or for the prevention of reinfection, would significantly reduce the global burden of disease associated with chronic HCV infection. A recombinant chimpanzee adenoviral (ChAd3 vector and a modified vaccinia Ankara (MVA, encoding the non-structural proteins of HCV (NSmut, used in a heterologous prime/boost regimen induced multi-specific, high-magnitude, durable HCV-specific CD4+ and CD8+ T-cell responses in healthy volunteers, and was more immunogenic than a heterologous Ad regimen. We now assess the immunogenicity of this vaccine regimen in HCV infected patients (including patients with a low viral load suppressed with interferon/ribavirin therapy, determine T-cell cross-reactivity to endogenous virus, and compare immunogenicity with that observed previously in both healthy volunteers and in HCV infected patients vaccinated with the heterologous Ad regimen. Vaccination of HCV infected patients with ChAd3-NSmut/MVA-NSmut was well tolerated. Vaccine-induced HCV-specific T-cell responses were detected in 8/12 patients; however, CD4+ T-cell responses were rarely detected, and the overall magnitude of HCV-specific T-cell responses was markedly reduced when compared to vaccinated healthy volunteers. Furthermore, HCV-specific cells had a distinct partially-functional phenotype (lower expression of activation markers, granzyme B, and TNFα production, weaker in vitro proliferation, and higher Tim3 expression, with comparable Tbet and Eomes expression compared to healthy volunteers. Robust anti-vector T-cells and antibodies were induced, showing that there is no global defect in immunity. The level of viremia at the time of vaccination did not correlate with the magnitude of the vaccine-induced T-cell response. Full-length, next-generation sequencing of the circulating virus demonstrated that T

  11. The type IV pilin of Burkholderia mallei is highly immunogenic but fails to protect against lethal aerosol challenge in a murine model.

    Science.gov (United States)

    Fernandes, Paula J; Guo, Qin; Waag, David M; Donnenberg, Michael S

    2007-06-01

    Burkholderia mallei is the cause of glanders and a proven biological weapon. We identified and purified the type IV pilin protein of this organism to study its potential as a subunit vaccine. We found that purified pilin was highly immunogenic. Furthermore, mice infected via sublethal aerosol challenge developed significant increases in titers of antibody against the pilin, suggesting that it is expressed in vivo. Nevertheless, we found no evidence that high-titer antipilin antisera provided passive protection against a sublethal or lethal aerosol challenge and no evidence of protection afforded by active immunization with purified pilin. These results contrast with the utility of type IV pilin subunit vaccines against other infectious diseases and highlight the need for further efforts to identify protective responses against this pathogen.

  12. Canine parvovirus VP2 protein expressed in silkworm pupae self-assembles into virus-like particles with high immunogenicity.

    Directory of Open Access Journals (Sweden)

    Hao Feng

    Full Text Available The VP2 structural protein of parvovirus can produce virus-like particles (VLPs by a self-assembly process in vitro, making VLPs attractive vaccine candidates. In this study, the VP2 protein of canine parvovirus (CPV was expressed using a baculovirus expression system and assembled into parvovirus-like particles in insect cells and pupae. Electron micrographs of VLPs showed that they were very similar in size and morphology when compared to the wild-type parvovirus. The immunogenicity of the VLPs was investigated in mice and dogs. Mice immunized intramuscularly with purified VLPs, in the absence of an adjuvant, elicited CD4(+ and CD8(+ T cell responses and were able to elicit a neutralizing antibody response against CPV, while the oral administration of raw homogenates containing VLPs to the dogs resulted in a systemic immune response and long-lasting immunity. These results demonstrate that the CPV-VLPs stimulate both cellular and humoral immune responses, and so CPV-VLPs may be a promising candidate vaccine for the prevention of CPV-associated disease.

  13. Canine parvovirus VP2 protein expressed in silkworm pupae self-assembles into virus-like particles with high immunogenicity.

    Science.gov (United States)

    Feng, Hao; Hu, Gui-qiu; Wang, Hua-lei; Liang, Meng; Liang, Hongru; Guo, He; Zhao, Pingsen; Yang, Yu-jiao; Zheng, Xue-xing; Zhang, Zhi-fang; Zhao, Yong-kun; Gao, Yu-wei; Yang, Song-tao; Xia, Xian-zhu

    2014-01-01

    The VP2 structural protein of parvovirus can produce virus-like particles (VLPs) by a self-assembly process in vitro, making VLPs attractive vaccine candidates. In this study, the VP2 protein of canine parvovirus (CPV) was expressed using a baculovirus expression system and assembled into parvovirus-like particles in insect cells and pupae. Electron micrographs of VLPs showed that they were very similar in size and morphology when compared to the wild-type parvovirus. The immunogenicity of the VLPs was investigated in mice and dogs. Mice immunized intramuscularly with purified VLPs, in the absence of an adjuvant, elicited CD4(+) and CD8(+) T cell responses and were able to elicit a neutralizing antibody response against CPV, while the oral administration of raw homogenates containing VLPs to the dogs resulted in a systemic immune response and long-lasting immunity. These results demonstrate that the CPV-VLPs stimulate both cellular and humoral immune responses, and so CPV-VLPs may be a promising candidate vaccine for the prevention of CPV-associated disease.

  14. Low Bioavailability and High Immunogenicity of a New Brand of E. coli l-Asparaginase with Active Host Contaminating Proteins

    Directory of Open Access Journals (Sweden)

    Priscila Pini Zenatti

    2018-04-01

    Full Text Available The drug l-asparaginase is a cornerstone in the treatment of acute lymphoblastic leukemia (ALL. The native E. coli l-asparaginase used in Brazil until recently has been manufactured by Medac/Kyowa. Then a decision was taken by the Ministry of Health in 2017 to supply the National Health System with a cheaper alternative l-asparaginase manufactured by Beijing SL Pharmaceutical, called Leuginase®. As opposed to Medac, the asparaginase that has been in use in Brazil under the trade name of Aginasa®, it was not possible to find a single entry with the terms Leuginase in the Pubmed repository. The apparent lack of clinical studies and the scarcity of safety information provided to the hospitals by the drug distributor created a debate among Brazilian pediatric oncologists about issues of safety and efficacy that culminated eventually in a court decision to halt the distribution of the new drug all over the country. Boldrini Children's Center, a non-profit pediatric oncohematology hospital, has conducted its own evaluation of Leuginase®. Mass spectrometry analyses found at least 12 different contaminating host-cell proteins (HCP in Leuginase®. The presence of two HCP (beta-lactamase and malate dehydrogenase was confirmed by orthogonal methodologies. The relative number of HCP peptides ranged from 19 to 37% of the total peptides identified by mass spectrometry. In vivo studies in mice injected with Leuginase® revealed a 3 times lower plasma bioavailability and the development of higher antibody titres against l-asparaginase in comparison to Aginasa®-injected animals. The decision to buy a new drug based on its price alone is not safe. Developing countries are especially vulnerable to cheaper alternatives that lack solid quality assurance. Keywords: l-Asparaginase, Host contaminant proteins, Mass spectrometry, Bioavailability, Immunogenicity

  15. Enhancing poxvirus vectors vaccine immunogenicity.

    Science.gov (United States)

    García-Arriaza, Juan; Esteban, Mariano

    2014-01-01

    Attenuated recombinant poxvirus vectors expressing heterologous antigens from pathogens are currently at various stages in clinical trials with the aim to establish their efficacy. This is because these vectors have shown excellent safety profiles, significant immunogenicity against foreign expressed antigens and are able to induce protective immune responses. In view of the limited efficacy triggered by some poxvirus strains used in clinical trials (i.e, ALVAC in the RV144 phase III clinical trial for HIV), and of the restrictive replication capacity of the highly attenuated vectors like MVA and NYVAC, there is a consensus that further improvements of these vectors should be pursuit. In this review we considered several strategies that are currently being implemented, as well as new approaches, to improve the immunogenicity of the poxvirus vectors. This includes heterologous prime/boost protocols, use of co-stimulatory molecules, deletion of viral immunomodulatory genes still present in the poxvirus genome, enhancing virus promoter strength, enhancing vector replication capacity, optimizing expression of foreign heterologous sequences, and the combined use of adjuvants. An optimized poxvirus vector triggering long-lasting immunity with a high protective efficacy against a selective disease should be sought.

  16. Preemptive scheduling with rejection

    NARCIS (Netherlands)

    Hoogeveen, H.; Skutella, M.; Woeginger, Gerhard

    2003-01-01

    We consider the problem of preemptively scheduling a set of n jobs on m (identical, uniformly related, or unrelated) parallel machines. The scheduler may reject a subset of the jobs and thereby incur job-dependent penalties for each rejected job, and he must construct a schedule for the remaining

  17. Preemptive scheduling with rejection

    NARCIS (Netherlands)

    Hoogeveen, J.A.; Skutella, M.; Woeginger, G.J.; Paterson, M.

    2000-01-01

    We consider the problem of preemptively scheduling a set of n jobs on m (identical, uniformly related, or unrelated) parallel machines. The scheduler may reject a subset of the jobs and thereby incur job-dependent penalties for each rejected job, and he must construct a schedule for the remaining

  18. Immunogenicity of autoantigens

    Directory of Open Access Journals (Sweden)

    Keller Andreas

    2011-07-01

    Full Text Available Abstract Background Autoantibodies against self-antigens have been associated not only with autoimmune diseases, but also with cancer and are even found in healthy individuals. The mechanism causing the autoantibody response remains elusive for the majority of the immunogenic antigens. To deepen the understanding of autoantibody responses, we ask whether natural-occurring, autoimmunity-associated and tumor-associated antigens have structural or biological features related to the immune response. To this end, we have carried out the most comprehensive in-silicio study of different groups of autoantigens including large antigen sets identified by our groups combined with publicly available antigen sets. Results We found evidence for an enrichment of genes with a larger exon length increasing the probability of the occurrence of potential immunogenic features such as mutations, SNPs, immunogenic sequence patterns and structural epitopes, or alternative splicing events. While SNPs seem to play a more central role in autoimmunity, somatic mutations seem to be stronger enriched in tumor-associated antigens. In addition, antigens of autoimmune diseases are different from other antigen sets in that they appear preferentially secreted, have frequently an extracellular location, and they are enriched in pathways associated with the immune system. Furthermore, for autoantibodies in general, we found enrichment of sequence-based properties including coiled-coils motifs, ELR motifs, and Zinc finger DNA-binding motifs. Moreover, we found enrichment of proteins binding to proteins or nucleic acids including RNA and enrichment of proteins that are part of ribosome or spliceosome. Both, homologies to proteins of other species and an enrichment of ancient protein domains indicate that immunogenic proteins are evolutionary conserved and that mimicry might play a central role. Conclusions Our results provide evidence that proteins which i are evolutionary conserved

  19. Chimeric human parainfluenza virus bearing the Ebola virus glycoprotein as the sole surface protein is immunogenic and highly protective against Ebola virus challenge

    International Nuclear Information System (INIS)

    Bukreyev, Alexander; Marzi, Andrea; Feldmann, Friederike; Zhang Liqun; Yang Lijuan; Ward, Jerrold M.; Dorward, David W.; Pickles, Raymond J.; Murphy, Brian R.; Feldmann, Heinz; Collins, Peter L.

    2009-01-01

    We generated a new live-attenuated vaccine against Ebola virus (EBOV) based on a chimeric virus HPIV3/ΔF-HN/EboGP that contains the EBOV glycoprotein (GP) as the sole transmembrane envelope protein combined with the internal proteins of human parainfluenza virus type 3 (HPIV3). Electron microscopy analysis of the virus particles showed that they have an envelope and surface spikes resembling those of EBOV and a particle size and shape resembling those of HPIV3. When HPIV3/ΔF-HN/EboGP was inoculated via apical surface of an in vitro model of human ciliated airway epithelium, the virus was released from the apical surface; when applied to basolateral surface, the virus infected basolateral cells but did not spread through the tissue. Following intranasal (IN) inoculation of guinea pigs, scattered infected cells were detected in the lungs by immunohistochemistry, but infectious HPIV3/ΔF-HN/EboGP could not be recovered from the lungs, blood, or other tissues. Despite the attenuation, the virus was highly immunogenic, and a single IN dose completely protected the animals against a highly lethal intraperitoneal challenge of guinea pig-adapted EBOV

  20. High-level immunogenicity is achieved vaccine with adjuvanted pandemic H1N1(2009) and improved with booster dosing in a randomized trial of HIV-infected adults.

    Science.gov (United States)

    Cooper, Curtis; Klein, Marina; Walmsley, Sharon; Haase, David; MacKinnon-Cameron, Donna; Marty, Kimberley; Li, Yan; Smith, Bruce; Halperin, Scott; Law, Barb; Scheifele, David

    2012-01-01

    More severe influenza disease and poor vaccine immunogenicity in HIV-infected patients necessitate improved immunization strategies to maximize vaccine efficacy. A phase III, randomized trial was conducted at 4 Canadian sites. Two dosing strategies (standard dose vs standard dose plus booster on day 21) were assessed in HIV patients aged 20 to 59 years during the H1N1(2009) pandemic. A single antigen, inactivated split adjuvanted (AS03(A)) influenza vaccine (Arepanrix) was utilized. Serum hemagglutination inhibition (HAI) titres were assessed at days 21 and 42 and at month 6. 150 participants received at least one injection. Baseline parameters were similar between groups: 83% male, 85% on HAART, median CD4 = 519 cells/mm(3), 84% with HIV RNA < 50 copies/mL. At day 21, seroprotection (HAI ≥1:40) was achieved in 80% (95% CI, 70-89) of participants. Seroconversion occurred in 74% (63-85). Seroprotection and seroconversion were further improved in those randomized to booster dosing: day 42, 94% (85-98) versus 73% (60-83) (P < .01) and 86% (75-93) versus 66% (5-77) (P = .01). Seroprotec-tion was retained in 40% (28-54) of recipients at month 6 with trends toward greater retention of immunity in booster recipients. High-level immunogenicity was achieved with a single dose of this adjuvanted vaccine. Immunogenicity was further improved with booster dosing. Use of this adjuvanted vaccine and booster represent an important approach to increasing immunogenicity in this vaccine hypo-responsive population.

  1. The kSORT assay to detect renal transplant patients at high risk for acute rejection: results of the multicenter AART study.

    Directory of Open Access Journals (Sweden)

    Silke Roedder

    2014-11-01

    Full Text Available Development of noninvasive molecular assays to improve disease diagnosis and patient monitoring is a critical need. In renal transplantation, acute rejection (AR increases the risk for chronic graft injury and failure. Noninvasive diagnostic assays to improve current late and nonspecific diagnosis of rejection are needed. We sought to develop a test using a simple blood gene expression assay to detect patients at high risk for AR.We developed a novel correlation-based algorithm by step-wise analysis of gene expression data in 558 blood samples from 436 renal transplant patients collected across eight transplant centers in the US, Mexico, and Spain between 5 February 2005 and 15 December 2012 in the Assessment of Acute Rejection in Renal Transplantation (AART study. Gene expression was assessed by quantitative real-time PCR (QPCR in one center. A 17-gene set--the Kidney Solid Organ Response Test (kSORT--was selected in 143 samples for AR classification using discriminant analysis (area under the receiver operating characteristic curve [AUC] = 0.94; 95% CI 0.91-0.98, validated in 124 independent samples (AUC = 0.95; 95% CI 0.88-1.0 and evaluated for AR prediction in 191 serial samples, where it predicted AR up to 3 mo prior to detection by the current gold standard (biopsy. A novel reference-based algorithm (using 13 12-gene models was developed in 100 independent samples to provide a numerical AR risk score, to classify patients as high risk versus low risk for AR. kSORT was able to detect AR in blood independent of age, time post-transplantation, and sample source without additional data normalization; AUC = 0.93 (95% CI 0.86-0.99. Further validation of kSORT is planned in prospective clinical observational and interventional trials.The kSORT blood QPCR assay is a noninvasive tool to detect high risk of AR of renal transplants. Please see later in the article for the Editors' Summary.

  2. Immunogenicity and safety of high-dose trivalent inactivated influenza vaccine compared to standard-dose vaccine in children and young adults with cancer or HIV infection.

    Science.gov (United States)

    Hakim, Hana; Allison, Kim J; Van de Velde, Lee-Ann; Tang, Li; Sun, Yilun; Flynn, Patricia M; McCullers, Jonathan A

    2016-06-08

    Approaches to improve the immune response of immunocompromised patients to influenza vaccination are needed. Children and young adults (3-21 years) with cancer or HIV infection were randomized to receive 2 doses of high-dose (HD) trivalent influenza vaccine (TIV) or of standard-dose (SD) TIV. Hemagglutination inhibition (HAI) antibody titers were measured against H1, H3, and B antigens after each dose and 9 months later. Seroconversion was defined as ≥4-fold rise in HAI titer comparing pre- and post-vaccine sera. Seroprotection was defined as a post-vaccine HAI titer ≥1:40. Reactogenicity events (RE) were solicited using a structured questionnaire 7 and 14 days after each dose of vaccine, and adverse events by medical record review for 21 days after each dose of vaccine. Eighty-five participants were enrolled in the study; 27 with leukemia, 17 with solid tumor (ST), and 41 with HIV. Recipients of HD TIV had significantly greater fold increase in HAI titers to B antigen in leukemia group and to H1 antigen in ST group compared to SD TIV recipients. This increase was not documented in HIV group. There were no differences in seroconversion or seroprotection between HD TIV and SD TIV in all groups. There was no difference in the percentage of solicited RE in recipients of HD TIV (54% after dose 1 and 38% after dose 2) compared to SD TIV (40% after dose 1 and 20% after dose 2, p=0.27 and 0.09 after dose 1 and 2, respectively). HD TIV was more immunogenic than SD TIV in children and young adults with leukemia or ST, but not with HIV. HD TIV was safe and well-tolerated in children and young adults with leukemia, ST, or HIV. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Tandem truncated rotavirus VP8* subunit protein with T cell epitope as non-replicating parenteral vaccine is highly immunogenic.

    Science.gov (United States)

    Wen, Xiaobo; Cao, Dianjun; Jones, Ronald W; Hoshino, Yasutaka; Yuan, Lijuan

    2015-01-01

    The two currently available live oral rotavirus vaccines, Rotarix(®) and RotaTeq(®), are highly efficacious in the developed countries. However, the efficacy of such vaccines in resource deprived countries in Africa and Southeast Asia is low. We reported previously that a bacterially-expressed rotavirus P2-P[8] ΔVP8* subunit vaccine candidate administered intramuscularly elicited high-titers of neutralizing antibodies in guinea pigs and mice and significantly shortened the duration of diarrhea in neonatal gnotobiotic pigs upon oral challenge with virulent human rotavirus Wa strain. To further improve its vaccine potential and provide wider coverage against rotavirus strains of global and regional epidemiologic importance, we constructed 2 tandem recombinant VP8* proteins, P2-P[8] ΔVP8*-P[8] ΔVP8* and P2-P[8] ΔVP8*-P[6] ΔVP8* based on Escherichia coli expression system. The two resulting recombinant tandem proteins were highly soluble and P2-P[8] ΔVP8*-P[8] ΔVP8* was generated with high yield. Moreover, guinea pigs immunized intramuscularly by 3 doses of the P2-P[8] ΔVP8*-P[8] ΔVP8* or P2-P[8] ΔVP8*-P[6] ΔVP8* vaccine with aluminum phosphate adjuvant developed high titers of homotypic and heterotypic neutralizing antibodies against human rotaviruses bearing G1-G4, G8, G9 and G12 with P[8], P[4] or P[6] combination. The results suggest that these 2 subunit vaccines in monovalent or bivalent formulation can provide antigenic coverage to almost all the rotavirus G (VP7) types and major P (VP4) types of global as well as regional epidemiologic importance.

  4. An experimental study on inhibiting graft rejection following high-risk penetrating keratoplasty by CD25 siRNA nanocarrier in rats

    Directory of Open Access Journals (Sweden)

    Yun-jie SHI

    2015-06-01

    Full Text Available Objective To investigate the effects of CD25 siRNA nanoparticles against immune rejection and prolongation of corneal graft survival time after high-risk corneal grafting in rats. Methods Orthotopic corneal transplantation was performed in SD rats with alkali burned corneas to mimic high-risk rat models. Donor cornea (Wistar rats was grafted into the right cornea of SD recipients on day 14 after alkali burn. The grafted rats were randomly divided into control group (Group A, EntransterTM-control CD25siRNA instillation treatment (Group B, EntransterTM-CD25siRNA instillation treatment (Group C and EntransterTM-CD25siRNA twice instillation treatment (Group D, first administration at 2-hour post-surgery and second on day 7 post-surgery. The recipient eyes were examined using a slit lamp microscope. Then, the mean survival time and rejection index (RI were calculated. The morphologies of grafts were microscopically examined with HE staining, and TEM. CD25 expression after operation was determined by quantitative RT-PCR and immunohistochemistry. Results The survival curves of transplanted cornea showed that the mean survival time in rats of groups C and D was significantly longer than that in groups A and B (P<0.05. No significant difference was found in survival time between group A and group B, and the same between group C and group D. The grafts in groups A and B showed obvious edema and thickening, with irregular arrangement of collagen fibers and infiltration of a large amount of inflammatory cells. Immunohistochemical results showed that expression of CD25 was found in the corneal epithelium, stroma and endothelium in all rats, and higher CD25 expression was observed in groups A and B. Transmission electron microscopy revealed that the degree of stromal fibroblast apoptosis and necrosis in corneal graft was obviously lower in groups C and D than that of groups A and B, with a significant statistical difference. The expression of CD25 m

  5. Immunogenicity and safety of a novel monovalent high-dose inactivated poliovirus type 2 vaccine in infants: a comparative, observer-blind, randomised, controlled trial.

    Science.gov (United States)

    Sáez-Llorens, Xavier; Clemens, Ralf; Leroux-Roels, Geert; Jimeno, José; Clemens, Sue Ann Costa; Weldon, William C; Oberste, M Steven; Molina, Natanael; Bandyopadhyay, Ananda S

    2016-03-01

    Following the proposed worldwide switch from trivalent oral poliovirus vaccine (tOPV) to bivalent types 1 and 3 OPV (bOPV) in 2016, inactivated poliovirus vaccine (IPV) will be the only source of protection against poliovirus type 2. With most countries opting for one dose of IPV in routine immunisation schedules during this transition because of cost and manufacturing constraints, optimisation of protection against all poliovirus types will be a priority of the global eradication programme. We assessed the immunogenicity and safety of a novel monovalent high-dose inactivated poliovirus type 2 vaccine (mIPV2HD) in infants. This observer-blind, comparative, randomised controlled trial was done in a single centre in Panama. We enrolled healthy infants who had not received any previous vaccination against poliovirus. Infants were randomly assigned (1:1) by computer-generated randomisation sequence to receive a single dose of either mIPV2HD or standard trivalent IPV given concurrently with a third dose of bOPV at 14 weeks of age. At 18 weeks, all infants were challenged with one dose of monovalent type 2 OPV (mOPV2). Primary endpoints were seroconversion and median antibody titres to type 2 poliovirus 4 weeks after vaccination with mIPV2HD or IPV; and safety (as determined by the proportion and nature of serious adverse events and important medical events for 8 weeks after vaccination). The primary immunogenicity analyses included all participants for whom a post-vaccination blood sample was available. All randomised participants were included in the safety analyses. This trial is registered with ClinicalTrials.gov, number NCT02111135. Between April 14 and May 9, 2014, 233 children were enrolled and randomly assigned to receive mIPV2HD (117 infants) or IPV (116 infants). 4 weeks after vaccination with mIPV2HD or IPV, seroconversion to poliovirus type 2 was recorded in 107 (93·0%, 95% CI 86·8-96·9) of 115 infants in the mIPV2HD group compared with 86 (74·8%, 65·8

  6. [Immunogenicity of biosimilars].

    Science.gov (United States)

    van Aerts, L A G J M; Franken, A A M; Leufkens, H G M

    2016-01-01

    Biosimilars of more complex recombinant protein drugs, such as monoclonal antibodies and fusion proteins, are entering the market. The manufacturer should demonstrate that its product does not show any relevant differences in terms of quality characteristics, biological activity, safety and efficacy compared to the reference product, as outlined in EMA guidelines. This should be established with an extensive comparability exercise. One aspect that is subject to particular scrutiny is the immunogenicity of the biosimilar and the reference medicinal product. For three cases, one etanercept and two infliximab biosimilars, we describe how data are assessed and an opinion is reached by authorities. Not in all cases unanimity exists whether all remaining uncertainties on biosimilarity have been resolved satisfactorily before marketing authorisation. The Dutch Medicines Evaluation Board therefore emphasises that even after marketing authorisation, biosimilars and other biologicals should be properly monitored.

  7. Immunogenicity of a low-passage, high-titer modified live canine parvovirus vaccine in pups with maternally derived antibodies.

    Science.gov (United States)

    Hoare, C M; DeBouck, P; Wiseman, A

    1997-02-01

    The study evaluated the ability of a low-passage, high-titer modified live canine parvovirus (CPV) vaccine to produce seroconversion in pups with maternally derived hemagglutination inhibition (HI) titers ranging from attenuated and therefore more infective than conventional modified live CPV strains in order to overcome relatively greater levels of maternally derived antibodies, the principal cause of CPV vaccine failures in pups. To assess vaccine performance under field conditions, healthy pups presented at five private veterinary clinics were used as test animals. A single dose of vaccine was given to 59 pups at 12 weeks of age (Group A). To accommodate the protocol of clinics where earlier CPV vaccination was practiced, 87 other pups were vaccinated with two doses, the first at 8-10 weeks of age, and the second at 12 weeks of age (Group B). Geometric mean HI titers were measured for blood samples obtained at the time of vaccination and at 14 weeks of age. Seroconversion was considered to have occurred if pups developed a fourfold or greater increase in HI titer to a level > or = 64. Of the 59 pups in Group A, 100% seroconverted following the single vaccine dose at 12 weeks of age. Of the 87 Group B pups, 82 (94.3%) seroconverted following either of the two vaccine doses. A geometric mean HI titer of 4828 was measured for Group A, and a geometric mean HI titer of 2028 was measured for Group B. An overall seroconversion rate of 96.5% was achieved in pups with maternally derived HI titers < or = 256.

  8. SagE induces highly effective protective immunity against Streptococcus iniae mainly through an immunogenic domain in the extracellular region.

    Science.gov (United States)

    Sun, Yun; Sun, Li; Xing, Ming-qing; Liu, Chun-sheng; Hu, Yong-hua

    2013-11-12

    Streptococcus iniae is a Gram-positive bacterium and a severe pathogen of a wide range of farmed fish. S. iniae possesses a virulence-associated streptolysin S cluster composed of several components, one of which is SagE. SagE a transmembrane protein with one major extracellular region named ECR. This study aimed to develop a SagE-based DNA candidate vaccine against streptococcosis and examine the immunoprotective mechanism of the vaccine. We constructed a DNA vaccine, pSagE, based on the sagE gene and examined its immunological property in a Japanese flounder (Paralichthys olivaceus) model. The results showed that at 7 days post-vaccination, expression of SagE at transcription and translation levels was detected in the tissues of the vaccinated fish. After challenge with S. iniae at one and two months post-vaccination, pSagE-vaccinated fish exhibited relative percent survival (RPS) of 95% and 88% respectively. Immunological analysis showed that (i) pSagE significantly upregulated the expression of a wide range of immune genes, (ii) pSagE induced the production of specific serum antibodies that bound whole-cell S. iniae, and (iii) treatment of S. iniae with pSagE-induced antibodies blocked bacterial invasion of host cells. To localize the immunoprotective domain of SagE, the ECR-expressing DNA vaccine pSagEECR was constructed. Immunization analysis showed that flounder vaccinated with pSagEECR exhibited a RPS of 68%, and that pSagEECR induced serum antibody production and immune gene expression in a manner similar to, though to lower magnitudes than, those induced by pSagE. We in this study developed a DNA vaccine, pSagE, which induces highly protective immunity against S. iniae. The protective effect of pSagE is probably due to its ability to elicit systemic immune response, in particular that of the humoral branch, which leads to production of specific serum antibodies that impair bacterial infection. These results add insights to the immunoprotective mechanism

  9. "Science" Rejects Postmodernism.

    Science.gov (United States)

    St. Pierre, Elizabeth Adams

    2002-01-01

    The National Research Council report, "Scientific Research in Education," claims to present an inclusive view of sciences in responding to federal attempts to legislate educational research. This article asserts that it narrowly defines science as positivism and methodology as quantitative, rejecting postmodernism and omitting other theories. Uses…

  10. Identification of immunogenic hot spots within plum pox potyvirus capsid protein for efficient antigen presentation.

    Science.gov (United States)

    Fernández-Fernández, M Rosario; Martínez-Torrecuadrada, Jorge L; Roncal, Fernando; Domínguez, Elvira; García, Juan Antonio

    2002-12-01

    PEPSCAN analysis has been used to characterize the immunogenic regions of the capsid protein (CP) in virions of plum pox potyvirus (PPV). In addition to the well-known highly immunogenic N- and C-terminal domains of CP, regions within the core domain of the protein have also shown high immunogenicity. Moreover, the N terminus of CP is not homogeneously immunogenic, alternatively showing regions frequently recognized by antibodies and others that are not recognized at all. These results have helped us to design efficient antigen presentation vectors based on PPV. As predicted by PEPSCAN analysis, a small displacement of the insertion site in a previously constructed vector, PPV-gamma, turned the derived chimeras into efficient immunogens. Vectors expressing foreign peptides at different positions within a highly immunogenic region (amino acids 43 to 52) in the N-terminal domain of CP were the most effective at inducing specific antibody responses against the foreign sequence.

  11. ‘Healthy’ identities? : Revisiting rejection-identification and rejection-disidentification models among voluntary and forced immigrants

    NARCIS (Netherlands)

    Bobowik, Magdalena; Martinovic, Borja; Basabe, Nekane; Barsties, Lisa S.; Wachter, Gusta

    2017-01-01

    Rejection-identification and rejection-disidentification models propose that low-status groups identify with their in-group and disidentify with a high-status out-group in response to rejection by the latter. Our research tests these two models simultaneously among multiple groups of foreign-born

  12. C4d-negative antibody-mediated rejection with high anti-angiotensin II type I receptor antibodies in absence of donor-specific antibodies.

    Science.gov (United States)

    Fuss, Alexander; Hope, Christopher M; Deayton, Susan; Bennett, Greg Donald; Holdsworth, Rhonda; Carroll, Robert P; Coates, P Toby H

    2015-07-01

    Acute antibody-mediated rejection can occur in absence of circulating donor-specific antibodies. Agonistic antibodies targeting the anti-angiotensin II type 1 receptor (anti-AT1 R) are emerging as important non-human leucocyte antigen (HLA) antibodies. Elevated levels of anti-angiotensin II receptor antibodies were first observed in kidney transplant recipients with malignant hypertension and allograft rejection. They have now been studied in three separate kidney transplant populations and associate to frequency of rejection, severity of rejection and graft failure. We report 11 cases of biopsy-proven, Complement 4 fragment d (C4d)-negative, acute rejection occurring without circulating donor-specific anti-HLA antibodies. In eight cases, anti-angiotensin receptor antibodies were retrospectively examined. The remaining three subjects were identified from our centre's newly instituted routine anti-angiotensin receptor antibody screening. All subjects fulfilled Banff 2013 criteria for antibody-mediated rejection and all responded to anti-rejection therapy, which included plasma exchange and angiotensin receptor blocker therapy. These cases support the routine assessment of anti-AT1 R antibodies in kidney transplant recipients to identify subjects at risk. Further studies will need to determine optimal assessment protocol and the effectiveness of pre-emptive treatment with angiotensin receptor blockers. © 2015 Asian Pacific Society of Nephrology.

  13. Thin film CdTe based neutron detectors with high thermal neutron efficiency and gamma rejection for security applications

    Energy Technology Data Exchange (ETDEWEB)

    Smith, L.; Murphy, J.W. [Materials Science and Engineering, University of Texas at Dallas, Richardson, TX 75080 (United States); Kim, J. [Korean Research Institute of Standards and Science, Daejeon 305-600 (Korea, Republic of); Rozhdestvenskyy, S.; Mejia, I. [Materials Science and Engineering, University of Texas at Dallas, Richardson, TX 75080 (United States); Park, H. [Korean Research Institute of Standards and Science, Daejeon 305-600 (Korea, Republic of); Allee, D.R. [Flexible Display Center, Arizona State University, Phoenix, AZ 85284 (United States); Quevedo-Lopez, M. [Materials Science and Engineering, University of Texas at Dallas, Richardson, TX 75080 (United States); Gnade, B., E-mail: beg031000@utdallas.edu [Materials Science and Engineering, University of Texas at Dallas, Richardson, TX 75080 (United States)

    2016-12-01

    Solid-state neutron detectors offer an alternative to {sup 3}He based detectors, but suffer from limited neutron efficiencies that make their use in security applications impractical. Solid-state neutron detectors based on single crystal silicon also have relatively high gamma-ray efficiencies that lead to false positives. Thin film polycrystalline CdTe based detectors require less complex processing with significantly lower gamma-ray efficiencies. Advanced geometries can also be implemented to achieve high thermal neutron efficiencies competitive with silicon based technology. This study evaluates these strategies by simulation and experimentation and demonstrates an approach to achieve >10% intrinsic efficiency with <10{sup −6} gamma-ray efficiency.

  14. Action against Kruemmel rejected

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    In its verdict dated September 2nd, 1976 - 10 A 211/74 -, the administrative court of Schleswig-Holstein at Schleswig has rejected with costs the action of a plaintiff resident in Hessen concerning the contestation of the 2nd partial licence for the erection of a nuclear power station at Kruemmel near Hamburg. The verdict is not subject to appeal. Furthermore, the administrative court of Schleswig-Holstein at Schleswig, in its verdict dated September 2nd, 1976 - 10 A 214/74 - has rejected with costs the actions of eight plaintiffs living in Hamburg and surroundings, concerning the contestation of the 1st, 2nd and 3rd partial licence for the erection of a nuclear power station at Kruemmel near Hamburg. An appeal against this verdict has been lodged at the higher administrative court at Lueneburg. The main gounds for the two judgments are given in full text. (orig./HP) [de

  15. Direct label-free electrical immunodetection of transplant rejection protein biomarker in physiological buffer using floating gate AlGaN/GaN high electron mobility transistors.

    Science.gov (United States)

    Tulip, Fahmida S; Eteshola, Edward; Desai, Suchita; Mostafa, Salwa; Roopa, Subramanian; Evans, Boyd; Islam, Syed Kamrul

    2014-06-01

    Monokine induced by interferon gamma (MIG/CXCL9) is used as an immune biomarker for early monitoring of transplant or allograft rejection. This paper demonstrates a direct electrical, label-free detection method of recombinant human MIG with anti-MIG IgG molecules in physiologically relevant buffer environment. The sensor platform used is a biologically modified GaN-based high electron mobility transistor (HEMT) device. Biomolecular recognition capability was provided by using high affinity anti-MIG monoclonal antibody to form molecular affinity interface receptors on short N-hydroxysuccinimide-ester functionalized disulphide (DSP) self-assembled monolayers (SAMs) on the gold sensing gate of the HEMT device. A floating gate configuration has been adopted to eliminate the influences of external gate voltage. Preliminary test results with the proposed chemically treated GaN HEMT biosensor show that MIG can be detected for a wide range of concentration varying from 5 ng/mL to 500 ng/mL.

  16. Factors Predicting Risk for Antibody-mediated Rejection and Graft Loss in Highly Human Leukocyte Antigen Sensitized Patients Transplanted After Desensitization.

    Science.gov (United States)

    Vo, Ashley A; Sinha, Aditi; Haas, Mark; Choi, Jua; Mirocha, James; Kahwaji, Joseph; Peng, Alice; Villicana, Rafael; Jordan, Stanley C

    2015-07-01

    Desensitization with intravenous immunoglobulin and rituximab (I+R) significantly improves transplant rates in highly sensitized patients, but antibody-mediated rejection (ABMR) remains a concern. Between July 2006 and December 2012, 226 highly sensitized patients received transplants after desensitization. Most received alemtuzumab induction and standard immunosuppression. Two groups were examined: ABMR (n = 181) and ABMR (n = 45, 20%). Risk factors for ABMR, pathology, and outcomes were assessed. Significant risks for ABMR included previous transplants and pregnancies as sensitizing events, donor-specific antibody (DSA) relative intensity scores greater than 17, presence of both class I and II DSAs at transplant and time on waitlist. The ABMR showed a significant benefit for graft survival and glomerular filtration rate at 5 years (P desensitized with I+R who remain ABMR have long-term graft and patient survival. The ABMR patients have significantly reduced graft survival and glomerular filtration rate at 5 years, especially TMA. Severe ABMR episodes benefit from treatment with PLEX + Eculizumab. The DSA-relative intensity scores at transplant was a strong predictor of ABMR. Donor-specific antibody avoidance and reduction strategies before transplantation are critical to avoiding ABMR and improving long-term outcomes.

  17. Understanding Rejection between First-and-Second-Grade Elementary Students through Reasons Expressed by Rejecters.

    Science.gov (United States)

    García Bacete, Francisco J; Carrero Planes, Virginia E; Marande Perrin, Ghislaine; Musitu Ochoa, Gonzalo

    2017-01-01

    Objective: The aim of this research was to obtain the views of young children regarding their reasons for rejecting a peer. Method: To achieve this goal, we conducted a qualitative study in the context of theory building research using an analysis methodology based on Grounded Theory. The collected information was extracted through semi-structured individual interviews from a sample of 853 children aged 6 from 13 urban public schools in Spain. Results: The children provided 3,009 rejection nominations and 2,934 reasons for disliking the rejected peers. Seven reason categories emerged from the analysis. Four categories refer to behaviors of the rejected children that have a cost for individual peers or peer group such as: direct aggression, disturbance of wellbeing, problematic social and school behaviors and dominance behaviors. A further two categories refer to the identities arising from the preferences and choices of rejected and rejecter children and their peers: personal identity expressed through preferences and disliking, and social identity expressed through outgroup prejudices. The "no-behavior or no-choice" reasons were covered by one category, unfamiliarity. In addition, three context categories were found indicating the participants (interpersonal-group), the impact (low-high), and the subjectivity (subjective-objective) of the reason. Conclusion: This study provides researchers and practitioners with a comprehensive taxonomy of reasons for rejection that contributes to enrich the theoretical knowledge and improve interventions for preventing and reducing peer rejection.

  18. Simulation of hydrodynamic effects of salt rejection due to permafrost. Hydrogeological numerical model of density-driven mixing, at a regional scale, due to a high salinity pulse

    International Nuclear Information System (INIS)

    Vidstrand, Patrik; Svensson, Urban; Follin, Sven

    2006-10-01

    The main objective of this study is to support the safety assessment of the investigated candidate sites concerning hydrogeological and hydrogeochemical issues related to permafrost. However, a more specific objective of the study is to improve the assessment of processes in relation to permafrost scenarios. The model is based on a mathematical model that includes Darcy velocities, mass conservation, matrix diffusion, and salinity distribution. Gravitational effects are thus fully accounted for. A regional groundwater flow model (POM v1.1, Simpevarp) was used as basis for the simulations. The main results of the model include salinity distributions in time. The general conclusion is that density-driven mixing processes are contained within more permeable deformation zones and that these processes are fast as compared with preliminary permafrost growth rates. The results of the simulation suggest that a repository volume in the rock mass in-between the deterministic deformation zones, approximately 150 m below the permafrost will not experience a high salinity situation due to the salt rejection process

  19. Disparate rates of acute rejection and donor-specific antibodies among high-immunologic risk renal transplant subgroups receiving antithymocyte globulin induction.

    Science.gov (United States)

    Patel, Samir J; Suki, Wadi N; Loucks-DeVos, Jennifer; Graviss, Edward A; Nguyen, Duc T; Knight, Richard J; Kuten, Samantha A; Moore, Linda W; Teeter, Larry D; Gaber, Lillian W; Gaber, A Osama

    2016-08-01

    Lymphocyte-depleting induction lowers acute rejection (AR) rates among high-immunologic risk (HIR) renal transplant recipients, including African Americans (AAs), retransplants, and the sensitized. It is unclear whether different HIR subgroups experience similarly low rates of AR. We aimed to describe the incidence of AR and de novo donor-specific antibody (dnDSA) among HIR recipients categorized by age, race, or donor type. All received antithymocyte globulin (ATG) induction and triple maintenance immunosuppression. A total of 464 HIR recipients from 2007 to 2014 were reviewed. AR and dnDSA rates at 1 year for the entire population were 14% and 27%, respectively. AR ranged from 6.7% among living donor (LD) recipients to 30% in younger AA deceased donor (DD) recipients. De novo donor-specific antibody at 1 year ranged from 7% in older non-AA LD recipients to 32% in AAs. AA race remained as an independent risk factor for AR among DD recipients and for dnDSA among all HIR recipients. Development of both AR and dnDSA within the first year was associated with a 54% graft survival at 5 years and was an independent risk factor for graft loss. Despite utilization of recommended immunosuppression for HIR recipients, substantial disparities exist among subgroups, warranting further consideration of individualized immunosuppression in certain HIR subgroups. © 2016 Steunstichting ESOT.

  20. Percutaneous implantation of the CoreValve aortic valve prosthesis in patients at high risk or rejected for surgical valve replacement: Clinical evaluation and feasibility of the procedure in the first 30 patients in the AMC-UvA

    NARCIS (Netherlands)

    Baan, J.; Yong, Z. Y.; Koch, K. T.; Henriques, J. P. S.; Bouma, B. J.; de Hert, S. G.; van der Meulen, J.; Tijssen, J. G. P.; Piek, J. J.; de Mol, B. A. J. M.

    2010-01-01

    Objective. To report the feasibility, safety and efficacy of percutaneous aortic valve implantation (PAVI) with the CoreValve self-expanding aortic valve bioprosthesis in elderly patients with aortic valve stenosis who are rejected for surgery or have a high surgical risk.Methods. PAVI using the

  1. Modeling rejection immunity

    Directory of Open Access Journals (Sweden)

    Gaetano Andrea De

    2012-05-01

    Full Text Available Abstract Background Transplantation is often the only way to treat a number of diseases leading to organ failure. To overcome rejection towards the transplanted organ (graft, immunosuppression therapies are used, which have considerable side-effects and expose patients to opportunistic infections. The development of a model to complement the physician’s experience in specifying therapeutic regimens is therefore desirable. The present work proposes an Ordinary Differential Equations model accounting for immune cell proliferation in response to the sudden entry of graft antigens, through different activation mechanisms. The model considers the effect of a single immunosuppressive medication (e.g. cyclosporine, subject to first-order linear kinetics and acting by modifying, in a saturable concentration-dependent fashion, the proliferation coefficient. The latter has been determined experimentally. All other model parameter values have been set so as to reproduce reported state variable time-courses, and to maintain consistency with one another and with the experimentally derived proliferation coefficient. Results The proposed model substantially simplifies the chain of events potentially leading to organ rejection. It is however able to simulate quantitatively the time course of graft-related antigen and competent immunoreactive cell populations, showing the long-term alternative outcomes of rejection, tolerance or tolerance at a reduced functional tissue mass. In particular, the model shows that it may be difficult to attain tolerance at full tissue mass with acceptably low doses of a single immunosuppressant, in accord with clinical experience. Conclusions The introduced model is mathematically consistent with known physiology and can reproduce variations in immune status and allograft survival after transplantation. The model can be adapted to represent different therapeutic schemes and may offer useful indications for the optimization of

  2. High variation of individual soluble serum CD30 levels of pre-transplantation patients: sCD30 a feasible marker for prediction of kidney allograft rejection?

    Science.gov (United States)

    Altermann, Wolfgang; Schlaf, Gerald; Rothhoff, Anita; Seliger, Barbara

    2007-10-01

    Previous studies have suggested that the pre-transplant levels of the soluble CD30 molecule (sCD30) represent a non-invasive tool which can be used as a biomarker for the prediction of kidney allograft rejections. In order to evaluate the feasibility of sCD30 for pre-transplantation monitoring the sera of potential kidney recipients (n = 652) were collected four times in a 3 months interval. Serum from healthy blood donors (n = 203) served as controls. The sCD30 concentrations of all samples were determined using a commercially available ELISA. This strategy allowed the detection of possible variations of individual sCD30 levels over time. Heterogeneous sCD30 concentrations were found in the samples obtained from individual putative kidney transplant recipients when quarterly measured over 1 year. Total 95% of serum samples obtained from healthy controls exhibited sCD30 values 30 U/ml). Total 524 patients (80.4%) constantly exhibited serum concentrations of sCD30 values >100 U/ml was significantly lower than that previously reported. The high degree of variation does not allow the stratification of patients into high and low immunological risk groups based on a single sCD30 value > 100 U/ml. Due to the heterogeneity of sCD30 levels during time course and the high values of SD, its implementation as a pre-transplant marker cannot be justified to generate special provisions for the organ allocation to patients with single sCD30 values > 100 U/ml.

  3. Mosaic HIV envelope immunogenic polypeptides

    Science.gov (United States)

    Korber, Bette T. M.; Gnanakaran, S.; Perkins, Simon; Sodroski, Joseph; Haynes, Barton

    2018-01-02

    Disclosed herein are mosaic HIV envelope (Env) polypeptides that can elicit an immune response to HIV (such as cytotoxic T cell (CTL), helper T cell, and/or humoral responses). Also disclosed are sets of the disclosed mosaic Env polypeptides, which include two or more (for example, three) of the polypeptides. Also disclosed herein are methods for treating or inhibiting HIV in a subject including administering one or more of the disclosed immunogenic polypeptides or compositions to a subject infected with HIV or at risk of HIV infection. In some embodiments, the methods include inducing an immune response to HIV in a subject comprising administering to the subject at least one (such as two, three, or more) of the immunogenic polypeptides or at least one (such as two, three, or more) nucleic acids encoding at least one of the immunogenic polypeptides disclosed herein.

  4. Performance of n-γ pulse-shape discrimination with simple pile-up rejection at high γ-ray count rates

    International Nuclear Information System (INIS)

    Okuda, T.; Yamazaki, H.; Kawabata, M.; Kasagi, J.; Harada, H.

    1999-01-01

    The performance of n-γ pulse-shape discrimination for a liquid scintillation detector has been investigated for γ-ray count rates up to 50 kcps. A method in which the ratio of the total to partial charge in the anode pulse is directly measured has shown much improved quality of the pulse-shape discrimination when pile-up events are rejected; it can discriminate neutron events of 50 cps from γ-ray events of 29 kcps. The method with simple pile-up rejection has the advantage that only general purpose electronics are required

  5. Image rejects in general direct digital radiography

    International Nuclear Information System (INIS)

    Hofmann, Bjørn; Rosanowsky, Tine Blomberg; Jensen, Camilla; Wah, Kenneth Hong Ching

    2015-01-01

    The number of rejected images is an indicator of image quality and unnecessary imaging at a radiology department. Image reject analysis was frequent in the film era, but comparably few and small studies have been published after converting to digital radiography. One reason may be a belief that rejects have been eliminated with digitalization. To measure the extension of deleted images in direct digital radiography (DR), in order to assess the rates of rejects and unnecessary imaging and to analyze reasons for deletions, in order to improve the radiological services. All exposed images at two direct digital laboratories at a hospital in Norway were reviewed in January 2014. Type of examination, number of exposed images, and number of deleted images were registered. Each deleted image was analyzed separately and the reason for deleting the image was recorded. Out of 5417 exposed images, 596 were deleted, giving a deletion rate of 11%. A total of 51.3% were deleted due to positioning errors and 31.0% due to error in centering. The examinations with the highest percentage of deleted images were the knee, hip, and ankle, 20.6%, 18.5%, and 13.8% respectively. The reject rate is at least as high as the deletion rate and is comparable with previous film-based imaging systems. The reasons for rejection are quite different in digital systems. This falsifies the hypothesis that digitalization would eliminates rejects. A deleted image does not contribute to diagnostics, and therefore is an unnecessary image. Hence, the high rates of deleted images have implications for management, training, education, as well as for quality

  6. Image rejects in general direct digital radiography.

    Science.gov (United States)

    Hofmann, Bjørn; Rosanowsky, Tine Blomberg; Jensen, Camilla; Wah, Kenneth Hong Ching

    2015-10-01

    The number of rejected images is an indicator of image quality and unnecessary imaging at a radiology department. Image reject analysis was frequent in the film era, but comparably few and small studies have been published after converting to digital radiography. One reason may be a belief that rejects have been eliminated with digitalization. To measure the extension of deleted images in direct digital radiography (DR), in order to assess the rates of rejects and unnecessary imaging and to analyze reasons for deletions, in order to improve the radiological services. All exposed images at two direct digital laboratories at a hospital in Norway were reviewed in January 2014. Type of examination, number of exposed images, and number of deleted images were registered. Each deleted image was analyzed separately and the reason for deleting the image was recorded. Out of 5417 exposed images, 596 were deleted, giving a deletion rate of 11%. A total of 51.3% were deleted due to positioning errors and 31.0% due to error in centering. The examinations with the highest percentage of deleted images were the knee, hip, and ankle, 20.6%, 18.5%, and 13.8% respectively. The reject rate is at least as high as the deletion rate and is comparable with previous film-based imaging systems. The reasons for rejection are quite different in digital systems. This falsifies the hypothesis that digitalization would eliminates rejects. A deleted image does not contribute to diagnostics, and therefore is an unnecessary image. Hence, the high rates of deleted images have implications for management, training, education, as well as for quality.

  7. Mucosal immunogenicity of plant lectins in mice

    Science.gov (United States)

    Lavelle, E C; Grant, G; Pusztai, A; Pfüller, U; O’Hagan, D T

    2000-01-01

    The mucosal immunogenicity of a number of plant lectins with different sugar specificities was investigated in mice. Following intranasal (i.n.) or oral administration, the systemic and mucosal antibody responses elicited were compared with those induced by a potent mucosal immunogen (cholera toxin; CT) and a poorly immunogenic protein (ovalbumin; OVA). After three oral or i.n. doses of CT, high levels of specific serum antibodies were measured and specific IgA was detected in the serum, saliva, vaginal wash, nasal wash and gut wash of mice. Immunization with OVA elicited low titres of serum IgG but specific IgA was not detected in mucosal secretions. Both oral and i.n. delivery of all five plant lectins investigated [Viscum album (mistletoe lectin 1; ML‐1), Lycospersicum esculentum (tomato lectin; LEA), Phaseolus vulgaris (PHA), Triticum vulgaris (wheat germ agglutinin (WGA), Ulex europaeus I (UEA‐1)] stimulated the production of specific serum IgG and IgA antibody after three i.n. or oral doses. Immunization with ML‐1 induced high titres of serum IgG and IgA in addition to specific IgA in mucosal secretions. The response to orally delivered ML‐1 was comparable to that induced by CT, although a 10‐fold higher dose was administered. Immunization with LEA also induced high titres of serum IgG, particularly after i.n. delivery. Low specific IgA titres were also detected to LEA in mucosal secretions. Responses to PHA, WGA and UEA‐1 were measured at a relatively low level in the serum, and little or no specific mucosal IgA was detected. PMID:10651938

  8. Immunogenicity and safety of high-dose hepatitis B vaccine among drug users: A randomized, open-labeled, blank-controlled trial.

    Science.gov (United States)

    Feng, Yongliang; Shi, Jing; Gao, Linying; Yao, Tian; Feng, Dan; Luo, Dan; Li, Zhansheng; Zhang, Yawei; Wang, Fuzhen; Cui, Fuqiang; Li, Li; Liang, Xiaofeng; Wang, Suping

    2017-06-03

    Due to the low uptake, adherence, and completion of vaccination among drug users, and their compromised immune responses to hepatitis B vaccination, the current practice of hepatitis B vaccination may not provide optimal protection. The aim of this study was to evaluate the immunogenicity and safety of 60 µg and 20 µg hepatitis B vaccines among drug users. A randomized, open-labeled, blank-controlled trial was conducted among drug users at 2 drug rehabilitation centers in China. The eligible participants were drug users who were serologically negative for the hepatitis B surface antigen (HBsAg) and the hepatitis B surface antibody (anti-HBs). Participants were randomized in a ratio of 1:1:1 to receive 20 µg (IM20 group) or 60 µg (IM60 group) of hepatitis B vaccine or blank control at months 0, 1, and 6, and followed at months 6, 7, and 12. Seroconversion rates of 94.7% and 92.6% were observed in IM20 and IM60 groups at month 7, and correspondingly decreased to 89.5% and 91.7% respectively at month 12. The IM60 group showed significantly higher geometric mean concentrations (GMCs) of anti-HBs (2022.5 and 676.7 mIU mL-1) than the IM20 group did (909.6 and 470.5 mIU mL-1) at months 7 and 12 (P B vaccines showed good immunogenicity among the drug users.

  9. Immunogenicity and Clinical Efficacy of Influenza Vaccination In Pregnancy

    Directory of Open Access Journals (Sweden)

    Alexander W Kay

    2015-06-01

    Full Text Available Pregnant women are at high risk from influenza due to disproportionate morbidity, mortality, and adverse pregnancy outcomes following infection. As such, they are classified as a high priority group for vaccination. However, changes in the maternal immune system required to accommodate the allogeneic fetus may alter the immunogenicity of influenza vaccines. A large number of studies have evaluated the safety of the influenza vaccine. Here, we will review available studies on the immunogenicity and efficacy of the influenza vaccine during pregnancy, focusing on both humoral and cellular immunity.

  10. Novel Non-Histocompatibility Antigen Mismatched Variants Improve the Ability to Predict Antibody-Mediated Rejection Risk in Kidney Transplant

    Directory of Open Access Journals (Sweden)

    Silvia Pineda

    2017-12-01

    Full Text Available Transplant rejection is the critical clinical end-point limiting indefinite survival after histocompatibility antigen (HLA mismatched organ transplantation. The predominant cause of late graft loss is antibody-mediated rejection (AMR, a process whereby injury to the organ is caused by donor-specific antibodies, which bind to HLA and non-HLA (nHLA antigens. AMR is incompletely diagnosed as donor/recipient (D/R matching is only limited to the HLA locus and critical nHLA immunogenic antigens remain to be identified. We have developed an integrative computational approach leveraging D/R exome sequencing and gene expression to predict clinical post-transplant outcome. We performed a rigorous statistical analysis of 28 highly annotated D/R kidney transplant pairs with biopsy-confirmed clinical outcomes of rejection [either AMR or T-cell-mediated rejection (CMR] and no-rejection (NoRej, identifying a significantly higher number of mismatched nHLA variants in AMR (ANOVA—p-value = 0.02. Using Fisher’s exact test, we identified 123 variants associated mainly with risk of AMR (p-value < 0.001. In addition, we applied a machine-learning technique to circumvent the issue of statistical power and we found a subset of 65 variants using random forest, that are predictive of post-tx AMR showing a very low error rate. These variants are functionally relevant to the rejection process in the kidney and AMR as they relate to genes and/or expression quantitative trait loci (eQTLs that are enriched in genes expressed in kidney and vascular endothelium and underlie the immunobiology of graft rejection. In addition to current D/R HLA mismatch evaluation, additional mismatch nHLA D/R variants will enhance the stratification of post-tx AMR risk even before engraftment of the organ. This innovative study design is applicable in all solid organ transplants, where the impact of mitigating AMR on graft survival may be greater, with considerable benefits on

  11. Rejection Sensitivity Moderates the Impact of Rejection on Self-Concept Clarity

    Science.gov (United States)

    Ayduk, Özlem; Gyurak, Anett; Luerssen, Anna

    2014-01-01

    Self-concept clarity (SCC) refers to the extent to which self-knowledge is clearly and confidently defined, internally consistent, and temporally stable. Research shows that SCC can be undermined by failures in valued goal domains. Because preventing rejection is an important self-relevant goal for people high in rejection sensitivity (RS), it is hypothesized here that failures to attain this goal would cause them to experience diminished SCC. Study 1, an experimental study, showed that high-RS people’s SCC was undermined following rejection but not following an aversive experience unrelated to rejection. Study 2, a daily diary study of couples in relationships, used occurrence of partner conflicts to operationalize rejection. Replicating the findings in Study 1, having a conflict on any given diary day predicted a greater reduction in the SCC of high- compared to low-RS people on the following day. The implications for understanding the conditions under which rejection negatively affects the self-concept are discussed. PMID:19713567

  12. Immunogenic and non-immunogenic hyperthyroidism - a comparison

    International Nuclear Information System (INIS)

    Pohl, M.; Emrich, D.

    1993-01-01

    In a retrospective study 161 hyperthyroid patients without treatment were divided into 74 with immunogenic hyperthyroidism (IMH) and 87 with non-immunogenic hypethyroidism (NIMH). The frequency of complaints and the mean hormone concentrations were significantly higher in IMH and the median thyroid volume was significantly smaller. Diffusely reduced sonographic echos were observed in only 50% of patients with IMH compared to 5% of those with NIMH. Homogenous distribution of 99m Tc in the thyroid was observed scintigraphically in 95% of patients with IMH and in only 3% of those with NIMH. Although the median of global thyroid uptake of 99m Tc was significantly higher in IMH there was a broad overlap between the two groups. The mean hormone production is higher in IMH than in NIMH. In order to separate IMH and NIMH, several criteria have to be employed which differ concerning their diagnostic significance. (orig.) [de

  13. Immunostimulatory CpG-oligonucleotides induce functional high affinity IL-2 receptors on B-CLL cells: costimulation with IL-2 results in a highly immunogenic phenotype.

    Science.gov (United States)

    Decker, T; Schneller, F; Kronschnabl, M; Dechow, T; Lipford, G B; Wagner, H; Peschel, C

    2000-05-01

    CpG-oligodeoxynucleotides (CpG-ODN) have been shown to induce proliferation, cytokine production, and surface molecule regulation in normal and malignant human B cells. In the present study, we investigated the potential of CpG-ODN to induce functional high-affinity receptors in leukemic and normal B cells and the effects of costimulation with IL-2 on proliferation, cytokine secretion, and surface molecule regulation. Highly purified B cells from B-CLL patients and normal controls were stimulated with CpG-ODN with or without IL-2. Expression of CD25 was determined using FACS, and the presence of high-affinity IL-2 receptors was determined by scatchard analysis. Costimulatory effects of IL-2 and CpG-ODN were investigated using proliferation assays, ELISA (IL-6, TNF-alpha), and FACS analysis (CD80, CD86 expression). Reactivity of autologous and allogeneic T cells toward activated B-CLL cells was determined in mixed lymphocyte reactions and Interferon-gamma Elispot assays. The CpG-ODN DSP30 caused a significantly stronger induction of the IL-2 receptor alpha chain in malignant as compared with normal B cells (p = 0.03). This resulted in the expression of functional high-affinity IL-2 receptors in B-CLL cells, but fewer numbers of receptors with less affinity were expressed in normal B cells. Although addition of IL-2 to CpG-ODN-stimulated cells augmented proliferation in both normal B cells and B-CLL cells, no costimulatory effect on cytokine production or surface molecule expression could be observed in normal B cells. In contrast, TNF-alpha and IL-6 production was increased in B-CLL cells, and the expression of CD80 and CD86 was further enhanced when IL-2 was used as a costimulus. Autologous and allogeneic immune recognition of B-CLL cells stimulated with CpG-ODN and IL-2 was increased compared with B-CLL cells stimulated with CpG-ODN alone. Stimulation of B-CLL cells with CpG-ODN and IL-2 might be an attractive strategy for potential immunotherapies for B

  14. Salk's HIV immunogen: an immune-based therapy in human trials since 1988.

    Science.gov (United States)

    Jonas Salk, the developer of the first polio vaccine, has created a therapeutic vaccine for HIV which helps the immune system fight disease progression. Salk uses inactivated HIV-1 virus combined with Incomplete Freund's Adjuvant (IFA) in the vaccine preparation. The resulting HIV-1 immunogen was first studied in 1987, and since then, 235 seropositive individuals have received inoculations without serious adverse effects. Data from the first 25 subjects indicate that immunization with the HIV-1 immunogen results in improvement of cell-mediated response against the virus, a slower increase in the amount of virus present, and a reduced rate of clinical progression. Subsequent studies also show that higher doses of immunogen may produce stronger cell-mediated responses and high HIV-DTH (delayed-type hypersensitivity responsiveness immunogen) is associated with better outcome. Additional trials of HIV-1 immunogen are awaiting Food and Drug Administration approval.

  15. Ferrite grade iron oxides from ore rejects

    Indian Academy of Sciences (India)

    Iron oxyhydroxides and hydroxides were synthesized from chemically beneficiated high SiO2/Al2O3 low-grade iron ore (57.49% Fe2O3) rejects and heated to get iron oxides of 96–99.73% purity. The infrared band positions, isothermal weight loss and thermogravimetric and chemical analysis established the chemical ...

  16. Radionuclide diagnosis of allograft rejection

    International Nuclear Information System (INIS)

    George, E.A.

    1982-01-01

    Interaction with one or more anatomical and physiopathological characteristics of the rejecting renal allograft is suggested by those radioagents utilized specifically for the diagnosis of allograft rejection. Rejection, the most common cause of declining allograft function, is frequently mimicked clinically or masked by other immediate or long term post transplant complications. Understanding of the anatomical pathological features and kinetics of rejection and their modification by immunosuppressive maintenance and therapy are important for the proper clinical utilization of these radioagents. Furthermore, in selecting these radionuclides, one has to consider the comparative availability, preparatory and procedural simplicity, acquisition and display techniques and the possibility of timely report. The clinical utilities of radiofibrinogen, /sup 99m/Tc sulfur colloid and 67 Ga in the diagnosis of allograft rejection have been evaluated to a variable extent in the past. The potential usefulness of the recently developed preparations of 111 In labeled autologous leukocytes and platelets are presently under investigation

  17. A dermatologist guide to immunogenicity

    Directory of Open Access Journals (Sweden)

    Collin M. Blattner, DO

    2016-09-01

    Full Text Available Dermatologists should be aware that autoantibody formation may occur after the initiation of biologic therapy. This phenomenon has been referred to as immunogenicity and biologic fatigue. Because of this, patients may experience loss of clinical efficacy to a particular drug. To combat this phenomenon, low-dose immunomodulators may be used in hopes of preventing autoantibodies. We review the current literature and provide a basic treatment algorithm for patients with moderate to severe psoriasis.

  18. Immunogenic and non-immunogenic hyperthyroidism - a comparison. Immunogene und nichtimmunogene Hyperthyreose - ein Vergleich

    Energy Technology Data Exchange (ETDEWEB)

    Pohl, M. (Abt. Nuklearmedizin in Zentrum Radiologie, Georg-August-Univ., Goettingen (Germany)); Emrich, D. (Abt. Nuklearmedizin in Zentrum Radiologie, Georg-August-Univ., Goettingen (Germany))

    1993-08-01

    In a retrospective study 161 hyperthyroid patients without treatment were divided into 74 with immunogenic hyperthyroidism (IMH) and 87 with non-immunogenic hypethyroidism (NIMH). The frequency of complaints and the mean hormone concentrations were significantly higher in IMH and the median thyroid volume was significantly smaller. Diffusely reduced sonographic echos were observed in only 50% of patients with IMH compared to 5% of those with NIMH. Homogenous distribution of [sup 99m]Tc in the thyroid was observed scintigraphically in 95% of patients with IMH and in only 3% of those with NIMH. Although the median of global thyroid uptake of [sup 99m]Tc was significantly higher in IMH there was a broad overlap between the two groups. The mean hormone production is higher in IMH than in NIMH. In order to separate IMH and NIMH, several criteria have to be employed which differ concerning their diagnostic significance. (orig.)

  19. Relapse rate following antithyroid drug therapy of immunogenic and non-immunogenic hyperthyroidism

    International Nuclear Information System (INIS)

    Voth, E.; Dickmann, N.; Schicha, H.; Emrich, D.

    1990-01-01

    Data of 196 patients treated for hyperthyroidism exclusively with anthyroid drugs were analyzed retrospectively concerning the relapse rate within a follow-up period of four years. Patients were subdivided for primary or recurrent disease, and for immunogenic or non-immunogenic hyperthyroidism, respectively. In immunogenic as well as in non-immunogenic hyperthyroidism, the relapse rate was significantly lower for patients with primary disease (35% and 52%, respectively) compared to those with recurrent hyperthyroidism (82%, p [de

  20. Rejection Sensitivity, Jealousy, and the Relationship to Interpersonal Aggression.

    Science.gov (United States)

    Murphy, Anna M; Russell, Gemma

    2018-07-01

    The development and maintenance of interpersonal relationships lead individuals to risk rejection in the pursuit of acceptance. Some individuals are predisposed to experience a hypersensitivity to rejection that is hypothesized to be related to jealous and aggressive reactions within interpersonal relationships. The current study used convenience sampling to recruit 247 young adults to evaluate the relationship between rejection sensitivity, jealousy, and aggression. A mediation model was used to test three hypotheses: Higher scores of rejection sensitivity would be positively correlated to higher scores of aggression (Hypothesis 1); higher scores of rejection sensitivity would be positively correlated to higher scores of jealousy (Hypothesis 2); jealousy would mediate the relationship between rejection sensitivity and aggression (Hypothesis 3). Study results suggest a tendency for individuals with high rejection sensitivity to experience higher levels of jealousy, and subsequently have a greater propensity for aggression, than individuals with low rejection sensitivity. Future research that substantiates a link between hypersensitivity to rejection, jealousy, and aggression may provide an avenue for prevention, education, or intervention in reducing aggression within interpersonal relationships.

  1. Systemically administered DNA and fowlpox recombinants expressing four vaccinia virus genes although immunogenic do not protect mice against the highly pathogenic IHD-J vaccinia strain.

    Science.gov (United States)

    Bissa, Massimiliano; Pacchioni, Sole Maria; Zanotto, Carlo; De Giuli Morghen, Carlo; Illiano, Elena; Granucci, Francesca; Zanoni, Ivan; Broggi, Achille; Radaelli, Antonia

    2013-12-26

    The first-generation smallpox vaccine was based on live vaccinia virus (VV) and it successfully eradicated the disease worldwide. Therefore, it was not administered any more after 1980, as smallpox no longer existed as a natural infection. However, emerging threats by terrorist organisations has prompted new programmes for second-generation vaccine development based on attenuated VV strains, which have been shown to cause rare but serious adverse events in immunocompromised patients. Considering the closely related animal poxviruses that might also be used as bioweapons, and the increasing number of unvaccinated young people and AIDS-affected immunocompromised subjects, a safer and more effective smallpox vaccine is still required. New avipoxvirus-based vectors should improve the safety of conventional vaccines, and protect from newly emerging zoonotic orthopoxvirus diseases and from the threat of deliberate release of variola or monkeypox virus in a bioterrorist attack. In this study, DNA and fowlpox recombinants expressing the L1R, A27L, A33R and B5R genes were constructed and evaluated in a pre-clinical trial in mouse, following six prime/boost immunisation regimens, to compare their immunogenicity and protective efficacy against a challenge with the lethal VV IHD-J strain. Although higher numbers of VV-specific IFNγ-producing T lymphocytes were observed in the protected mice, the cytotoxic T-lymphocyte response and the presence of neutralising antibodies did not always correlate with protection. In spite of previous successful results in mice, rabbits and monkeys, where SIV/HIV transgenes were expressed by the fowlpox vector, the immune response elicited by these recombinants was low, and most of the mice were not protected. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Local graft irradiation in renal transplant rejection

    International Nuclear Information System (INIS)

    Kawamura, Masashi; Kataoka, Masaaki; Itoh, Hisao

    1990-01-01

    From 1977 to 1988, of 142 renal transplantations, seven recipients (4.9%) received local graft irradiation following rejective reaction refractory to antirejection medical managements. Concurrent with the administration of pulsed high dose methylprednisolone and other antirejection medical managements, the graft was irradiated with a total dose of 6.0 Gy-150 cGy per fraction every other day at the midplane of the graft using two opposing portals of 4MX Linac. The fields were defined by palpation and echography. All patients had improvements in serum creatinine on the 10th day after beginning the irradiation. Four patients with peripheral lymphocytosis during the irradiation combined with pulsed high dose methylprednisolone improved in renal functions. On the other hand, out of 3 patients with lymphcytopenic changes, in two the transplanted graft was removed due to deteriorations, and the other patient is currently suffering from chronic rejection. Local graft irradiation can be useful in maintaining a rejective graft and reversing its functions in some patients whose rejective reaction failed to respond to the antirejection medical managements. (author)

  3. Is the bitter rejection response always adaptive?

    Science.gov (United States)

    Glendinning, J I

    1994-12-01

    The bitter rejection response consists of a suite of withdrawal reflexes and negative affective responses. It is generally assumed to have evolved as a way to facilitate avoidance of foods that are poisonous because they usually taste bitter to humans. Using previously published studies, the present paper examines the relationship between bitterness and toxicity in mammals, and then assesses the ecological costs and benefits of the bitter rejection response in carnivorous, omnivorous, and herbivorous (grazing and browsing) mammals. If the bitter rejection response accurately predicts the potential toxicity of foods, then one would expect the threshold for the response to be lower for highly toxic compounds than for nontoxic compounds. The data revealed no such relationship. Bitter taste thresholds varied independently of toxicity thresholds, indicating that the bitter rejection response is just as likely to be elicited by a harmless bitter food as it is by a harmful one. Thus, it is not necessarily in an animal's best interest to have an extremely high or low bitter threshold. Based on this observation, it was hypothesized that the adaptiveness of the bitter rejection response depends upon the relative occurrence of bitter and potentially toxic compounds in an animal's diet. Animals with a relatively high occurrence of bitter and potentially toxic compounds in their diet (e.g., browsing herbivores) were predicted to have evolved a high bitter taste threshold and tolerance to dietary poisons. Such an adaptation would be necessary because a browser cannot "afford" to reject all foods that are bitter and potentially toxic without unduly restricting its dietary options. At the other extreme, animals that rarely encounter bitter and potentially toxic compounds in their diet (e.g., carnivores) were predicted to have evolved a low bitter threshold. Carnivores could "afford" to utilize such a stringent rejection mechanism because foods containing bitter and potentially

  4. Corneal allograft rejection: Risk factors, diagnosis, prevention, and treatment

    Directory of Open Access Journals (Sweden)

    Dua Harminder

    1999-01-01

    Full Text Available Recent advances in corneal graft technology, including donor tissue retrieval, storage and surgical techniques, have greatly improved the clinical outcome of corneal grafts. Despite these advances, immune mediated corneal graft rejection remains the single most important cause of corneal graft failure. Several host factors have been identified as conferring a "high risk" status to the host. These include: more than two quadrant vascularisation, with associated lymphatics, which augment the afferent and efferent arc of the immune response; herpes simplex keratitis; uveitis; silicone oil keratopathy; previous failed (rejected grafts; "hot eyes"; young recipient age; and multiple surgical procedures at the time of grafting. Large grafts, by virtue of being closer to the host limbus, with its complement of vessels and antigen-presenting Langerhans cells, also are more susceptible to rejection. The diagnosis of graft rejection is entirely clinical and in its early stages the clinical signs could be subtle. Graft rejection is largely mediated by the major histocompatibility antigens, minor antigens and perhaps blood group ABO antigens and some cornea-specific antigens. Just as rejection is mediated by active immune mediated events, the lack of rejection (tolerance is also sustained by active immune regulatory mechanisms. The anterior chamber associated immune deviation (ACAID and probably, conjunctiva associated lymphoid tissue (CALT induced mucosal tolerance, besides others, play an important role. Although graft rejection can lead to graft failure, most rejections can be readily controlled if appropriate management is commenced at the proper time. Topical steroids are the mainstay of graft rejection management. In the high-risk situations however, systemic steroids, and other immunosuppressive drugs such as cyclosporin and tacrolimus (FK506 are of proven benefit, both for treatment and prevention of rejection.

  5. HIV-DNA Given with or without Intradermal Electroporation Is Safe and Highly Immunogenic in Healthy Swedish HIV-1 DNA/MVA Vaccinees: A Phase I Randomized Trial.

    Directory of Open Access Journals (Sweden)

    Charlotta Nilsson

    Full Text Available We compared safety and immunogenicity of intradermal (ID vaccination with and without electroporation (EP in a phase I randomized placebo-controlled trial of an HIV-DNA prime HIV-MVA boost vaccine in healthy Swedish volunteers.HIV-DNA plasmids encoding HIV-1 genes gp160 subtypes A, B and C; Rev B; Gag A and B and RTmut B were given ID at weeks 0, 6 and 12 in a dose of 0.6 mg. Twenty-five volunteers received vaccine using a needle-free device (ZetaJet with (n=16 or without (n=9 ID EP (Dermavax. Five volunteers were placebo recipients. Boosting with recombinant MVA-CMDR expressing HIV-1 Env, Gag, Pol of CRF01_AE (HIV-MVA or placebo was performed at weeks 24 and 40. Nine of the vaccinees received a subtype C CN54 gp140 protein boost together with HIV-MVA.The ID/EP delivery was very well tolerated. After three HIV-DNA immunizations, no statistically significant difference was seen in the IFN-γ ELISpot response rate to Gag between HIV-DNA ID/EP recipients (5/15, 33% and HIV-DNA ID recipients (1/7, 14%, p=0.6158. The first HIV-MVA or HIV-MVA+gp140 vaccination increased the IFN-γ ELISpot response rate to 18/19 (95%. CD4+ and/or CD8+ T cell responses to Gag or Env were demonstrable in 94% of vaccinees. A balanced CD4+ and CD8+ T cell response was noted, with 78% and 71% responders, respectively. IFN-γ and IL-2 dominated the CD4+ T cell response to Gag and Env. The CD8+ response to Gag was broader with expression of IFN-γ, IL-2, MIP-1β and/or CD107. No differences were seen between DNA vaccine groups. Binding antibodies were induced after the second HIV-MVA+/-gp140 in 93% of vaccinees to subtype C Env, with the highest titers among EP/gp140 recipients.Intradermal electroporation of HIV-DNA was well tolerated. Strong cell- and antibody-mediated immune responses were elicited by the HIV-DNA prime and HIV-MVA boosting regimen, with or without intradermal electroporation use.International Standard Randomised Controlled Trial Number (ISRCTN 60284968.

  6. HIV-DNA Given with or without Intradermal Electroporation Is Safe and Highly Immunogenic in Healthy Swedish HIV-1 DNA/MVA Vaccinees: A Phase I Randomized Trial.

    Science.gov (United States)

    Nilsson, Charlotta; Hejdeman, Bo; Godoy-Ramirez, Karina; Tecleab, Teghesti; Scarlatti, Gabriella; Bråve, Andreas; Earl, Patricia L; Stout, Richard R; Robb, Merlin L; Shattock, Robin J; Biberfeld, Gunnel; Sandström, Eric; Wahren, Britta

    2015-01-01

    We compared safety and immunogenicity of intradermal (ID) vaccination with and without electroporation (EP) in a phase I randomized placebo-controlled trial of an HIV-DNA prime HIV-MVA boost vaccine in healthy Swedish volunteers. HIV-DNA plasmids encoding HIV-1 genes gp160 subtypes A, B and C; Rev B; Gag A and B and RTmut B were given ID at weeks 0, 6 and 12 in a dose of 0.6 mg. Twenty-five volunteers received vaccine using a needle-free device (ZetaJet) with (n=16) or without (n=9) ID EP (Dermavax). Five volunteers were placebo recipients. Boosting with recombinant MVA-CMDR expressing HIV-1 Env, Gag, Pol of CRF01_AE (HIV-MVA) or placebo was performed at weeks 24 and 40. Nine of the vaccinees received a subtype C CN54 gp140 protein boost together with HIV-MVA. The ID/EP delivery was very well tolerated. After three HIV-DNA immunizations, no statistically significant difference was seen in the IFN-γ ELISpot response rate to Gag between HIV-DNA ID/EP recipients (5/15, 33%) and HIV-DNA ID recipients (1/7, 14%, p=0.6158). The first HIV-MVA or HIV-MVA+gp140 vaccination increased the IFN-γ ELISpot response rate to 18/19 (95%). CD4+ and/or CD8+ T cell responses to Gag or Env were demonstrable in 94% of vaccinees. A balanced CD4+ and CD8+ T cell response was noted, with 78% and 71% responders, respectively. IFN-γ and IL-2 dominated the CD4+ T cell response to Gag and Env. The CD8+ response to Gag was broader with expression of IFN-γ, IL-2, MIP-1β and/or CD107. No differences were seen between DNA vaccine groups. Binding antibodies were induced after the second HIV-MVA+/-gp140 in 93% of vaccinees to subtype C Env, with the highest titers among EP/gp140 recipients. Intradermal electroporation of HIV-DNA was well tolerated. Strong cell- and antibody-mediated immune responses were elicited by the HIV-DNA prime and HIV-MVA boosting regimen, with or without intradermal electroporation use. International Standard Randomised Controlled Trial Number (ISRCTN) 60284968.

  7. Combinational deletion of three membrane protein-encoding genes highly attenuates yersinia pestis while retaining immunogenicity in a mouse model of pneumonic plague.

    Science.gov (United States)

    Tiner, Bethany L; Sha, Jian; Kirtley, Michelle L; Erova, Tatiana E; Popov, Vsevolod L; Baze, Wallace B; van Lier, Christina J; Ponnusamy, Duraisamy; Andersson, Jourdan A; Motin, Vladimir L; Chauhan, Sadhana; Chopra, Ashok K

    2015-04-01

    mouse model while retaining the required immunogenicity needed for subsequent protection against infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  8. In a randomized trial, the live attenuated tetravalent dengue vaccine TV003 is well-tolerated and highly immunogenic in subjects with flavivirus exposure prior to vaccination.

    Directory of Open Access Journals (Sweden)

    Stephen S Whitehead

    2017-05-01

    Full Text Available Infection caused by the four serotypes of dengue virus (DENV-1-4 is a leading cause of mosquito-borne disease. Clinically-severe dengue disease is more common when secondary dengue infection occurs following prior infection with a heterologous dengue serotype. Other flaviviruses such as yellow fever virus, Japanese encephalitis virus, and Zika virus, can also elicit antibodies which are cross-reactive to DENV. As candidate dengue vaccines become available in endemic settings and for individuals who have received other flavivirus vaccines, it is important to examine vaccine safety and immunogenicity in these flavivirus-experienced populations. We performed a randomized, controlled trial of the National Institutes of Health live attenuated tetravalent dengue vaccine candidate (TV003 in fifty-eight individuals with prior exposure to flavivirus infection or vaccine. As in prior studies of this vaccine in flavivirus-naive volunteers, flavivirus-experienced subjects received two doses of vaccine six months apart and were followed closely for clinical events, laboratory changes, viremia, and neutralizing antibody titers. TV003 was well tolerated with few adverse events other than rash, which was predominately mild. Following one dose, 87% of vaccinees had an antibody response to all four serotypes (tetravalent response, suggesting a robust immune response. In addition, 76% of vaccinees were viremic; mean peak titers ranged from 0.68–1.1 log10 PFU/mL and did not differ by serotype. The second dose of TV003 was not associated with viremia, rash, or a sustained boost in antibody titers indicating that a single dose of the vaccine is likely sufficient to prevent viral replication and thus protect against disease. In comparison to the viremia and neutralizing antibody response elicited by TV003 in flavivirus-naïve subjects from prior studies, we found that subjects who were flavivirus-exposed prior to vaccination exhibited slightly higher DENV-3 viremia

  9. Combination Immunotherapy of B16 Melanoma Using Anti–Cytotoxic T Lymphocyte–Associated Antigen 4 (Ctla-4) and Granulocyte/Macrophage Colony-Stimulating Factor (Gm-Csf)-Producing Vaccines Induces Rejection of Subcutaneous and Metastatic Tumors Accompanied by Autoimmune Depigmentation

    Science.gov (United States)

    van Elsas, Andrea; Hurwitz, Arthur A.; Allison, James P.

    1999-01-01

    We examined the effectiveness of cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) blockade, alone or in combination with a granulocyte/macrophage colony-stimulating factor (GM-CSF)–expressing tumor cell vaccine, on rejection of the highly tumorigenic, poorly immunogenic murine melanoma B16-BL6. Recently established tumors could be eradicated in 80% (68/85) of the cases using combination treatment, whereas each treatment by itself showed little or no effect. Tumor rejection was dependent on CD8+ and NK1.1+ cells but occurred irrespective of the presence of CD4+ T cells. Mice surviving a primary challenge rejected a secondary challenge with B16-BL6 or the parental B16-F0 line. The same treatment regimen was found to be therapeutically effective against outgrowth of preestablished B16-F10 lung metastases, inducing long-term survival. Of all mice surviving B16-BL6 or B16-F10 tumors after combination treatment, 56% (38/68) developed depigmentation, starting at the site of vaccination or challenge and in most cases progressing to distant locations. Depigmentation was found to occur in CD4-depleted mice, strongly suggesting that the effect was mediated by CTLs. This study shows that CTLA-4 blockade provides a powerful tool to enhance T cell activation and memory against a poorly immunogenic spontaneous murine tumor and that this may involve recruitment of autoreactive T cells. PMID:10430624

  10. Gamma-irradiated scrub typhus immunogens: broad-spectrum immunity with combinations of rickettsial strains

    International Nuclear Information System (INIS)

    Eisenberg, G.H. Jr.; Osterman, J.V.

    1979-01-01

    Scrub typhus immunogens were prepared from Rickettsia tsutsugamushi strains Karp, Kato, Gilliam, Kostival, and Buie by exposing frozen infected yolk sac suspensions to 300 krad of gamma radiation. Mouse protection tests showed that each of the irradiated immunogens protected C3H/HeDub mice against high challenge levels of Karp and Gilliam, but that none of these single-strain immunogens were capable of protecting against all five of the challenge strains. Broad-spectrum protection was achieved by using combinations of three strains of irradiated rickettsiae in a vaccination regimen of three injections at 5-day intervals

  11. Eosinophil count, allergies, and rejection in pediatric heart transplant recipients.

    Science.gov (United States)

    Arbon, Kate S; Albers, Erin; Kemna, Mariska; Law, Sabrina; Law, Yuk

    2015-08-01

    Allograft rejection and long-term immunosuppression remain significant challenges in pediatric heart transplantation. Pediatric recipients are known to have fewer rejection episodes and to develop more allergic conditions than adults. A T-helper 2 cell dominant phenotype, manifested clinically by allergies and an elevated eosinophil count, may be associated with immunologic quiescence in transplant recipients. This study assessed whether the longitudinal eosinophil count and an allergic phenotype were associated with freedom from rejection. This single-center, longitudinal, observational study included 86 heart transplant patients monitored from 1994 to 2011. Post-transplant biannual complete blood counts, allergic conditions, and clinical characteristics related to rejection risk were examined. At least 1 episode of acute cellular rejection (ACR) occurred in 38 patients (44%), antibody-mediated rejection (AMR) occurred in 11 (13%), and 49 patients (57%) were diagnosed with an allergic condition. Patients with ACR or AMR had a lower eosinophil count compared with non-rejectors (p = 0.011 and p = 0.022, respectively). In the multivariable regression analysis, the presence of panel reactive antibodies to human leukocyte antigen I (p = 0.014) and the median eosinophil count (p = 0.011) were the only independent covariates associated with AMR. Eosinophil count (p = 0.010) and female sex (p = 0.009) were independent risk factors for ACR. Allergic conditions or young age at transplant were not protective from rejection. This study demonstrates a novel association between a high eosinophil count and freedom from rejection. Identifying a biomarker for low rejection risk may allow a reduction in immunosuppression. Further investigation into the role of the T-helper 2 cell phenotype and eosinophils in rejection quiescence is warranted. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  12. Rejection of micropollutants by clean and fouled forward osmosis membrane

    KAUST Repository

    Valladares Linares, Rodrigo

    2011-12-01

    As forward osmosis (FO) gains attention as an efficient technology to improve wastewater reclamation processes, it is fundamental to determine the influence of fouling in the rejection of emerging contaminants (micropollutants). This study focuses on the rejection of 13 selected micropollutants, spiked in a secondary wastewater effluent, by a FO membrane, using Red Sea water as draw solution (DS), differentiating the effects on the rejection caused by a clean and fouled membrane. The resulting effluent was then desalinated at low pressure with a reverse osmosis (RO) membrane, to produce a high quality permeate and determine the rejection with a coupled forward osmosis - low pressure reverse osmosis (FO-LPRO) system. When considering only FO with a clean membrane, the rejection of the hydrophilic neutral compounds was between 48.6% and 84.7%, for the hydrophobic neutrals the rejection ranged from 40.0% to 87.5%, and for the ionic compounds the rejections were between 92.9% and 96.5%. With a fouled membrane, the rejections were between 44.6% and 95.2%, 48.7%-91.5% and 96.9%-98.6%, respectively. These results suggest that, except for the hydrophilic neutral compounds, the rejection of the micropollutants is increased by the presence of a fouling layer, possibly due to the higher hydrophilicity of the FO fouled membrane compared to the clean one, the increased adsorption capacity of hydrophilic compounds and reduced mass transport capacity, membrane swelling, and the higher negative charge of the membrane surface, related to the foulants composition, mainly NOM acids (carboxylic radicals) and polysaccharides or polysaccharide-like substances. However, when coupled with RO, the rejections in both cases increased above 96%. The coupled FO-LPRO system was an effective double barrier against the selected micropollutants. © 2011 Elsevier Ltd.

  13. Rejection of micropollutants by clean and fouled forward osmosis membrane

    KAUST Repository

    Valladares Linares, Rodrigo; Yangali-Quintanilla, Victor; Li, Zhenyu; Amy, Gary L.

    2011-01-01

    As forward osmosis (FO) gains attention as an efficient technology to improve wastewater reclamation processes, it is fundamental to determine the influence of fouling in the rejection of emerging contaminants (micropollutants). This study focuses on the rejection of 13 selected micropollutants, spiked in a secondary wastewater effluent, by a FO membrane, using Red Sea water as draw solution (DS), differentiating the effects on the rejection caused by a clean and fouled membrane. The resulting effluent was then desalinated at low pressure with a reverse osmosis (RO) membrane, to produce a high quality permeate and determine the rejection with a coupled forward osmosis - low pressure reverse osmosis (FO-LPRO) system. When considering only FO with a clean membrane, the rejection of the hydrophilic neutral compounds was between 48.6% and 84.7%, for the hydrophobic neutrals the rejection ranged from 40.0% to 87.5%, and for the ionic compounds the rejections were between 92.9% and 96.5%. With a fouled membrane, the rejections were between 44.6% and 95.2%, 48.7%-91.5% and 96.9%-98.6%, respectively. These results suggest that, except for the hydrophilic neutral compounds, the rejection of the micropollutants is increased by the presence of a fouling layer, possibly due to the higher hydrophilicity of the FO fouled membrane compared to the clean one, the increased adsorption capacity of hydrophilic compounds and reduced mass transport capacity, membrane swelling, and the higher negative charge of the membrane surface, related to the foulants composition, mainly NOM acids (carboxylic radicals) and polysaccharides or polysaccharide-like substances. However, when coupled with RO, the rejections in both cases increased above 96%. The coupled FO-LPRO system was an effective double barrier against the selected micropollutants. © 2011 Elsevier Ltd.

  14. A technetium rejection flowsheet

    International Nuclear Information System (INIS)

    Baker, R.; Miles, J.H.; Roberts, P.T.

    1990-01-01

    A single contactor unit has been designed which enables Tc to be removed from a TBP/diluent stream bearing U and Pu, by means of a 5M HNO 3 wash. A Tc waste stream is produced which is virtually free from U and Pu. The flowsheet has been tested firstly with U and Tc, then with U, Pu and Tc, and finally in a highly active facility with real PWR fuel solution. About 97% of the Tc was removed from the organic phase and U and Pu levels in the Tc waste have usually been below 0.04% of those in the product stream. (author)

  15. Active disturbance rejection controller for chemical reactor

    International Nuclear Information System (INIS)

    Both, Roxana; Dulf, Eva H.; Muresan, Cristina I.

    2015-01-01

    In the petrochemical industry, the synthesis of 2 ethyl-hexanol-oxo-alcohols (plasticizers alcohol) is of high importance, being achieved through hydrogenation of 2 ethyl-hexenal inside catalytic trickle bed three-phase reactors. For this type of processes the use of advanced control strategies is suitable due to their nonlinear behavior and extreme sensitivity to load changes and other disturbances. Due to the complexity of the mathematical model an approach was to use a simple linear model of the process in combination with an advanced control algorithm which takes into account the model uncertainties, the disturbances and command signal limitations like robust control. However the resulting controller is complex, involving cost effective hardware. This paper proposes a simple integer-order control scheme using a linear model of the process, based on active disturbance rejection method. By treating the model dynamics as a common disturbance and actively rejecting it, active disturbance rejection control (ADRC) can achieve the desired response. Simulation results are provided to demonstrate the effectiveness of the proposed method

  16. Active disturbance rejection controller for chemical reactor

    Energy Technology Data Exchange (ETDEWEB)

    Both, Roxana; Dulf, Eva H.; Muresan, Cristina I., E-mail: roxana.both@aut.utcluj.ro [Technical University of Cluj-Napoca, 400114 Cluj-Napoca (Romania)

    2015-03-10

    In the petrochemical industry, the synthesis of 2 ethyl-hexanol-oxo-alcohols (plasticizers alcohol) is of high importance, being achieved through hydrogenation of 2 ethyl-hexenal inside catalytic trickle bed three-phase reactors. For this type of processes the use of advanced control strategies is suitable due to their nonlinear behavior and extreme sensitivity to load changes and other disturbances. Due to the complexity of the mathematical model an approach was to use a simple linear model of the process in combination with an advanced control algorithm which takes into account the model uncertainties, the disturbances and command signal limitations like robust control. However the resulting controller is complex, involving cost effective hardware. This paper proposes a simple integer-order control scheme using a linear model of the process, based on active disturbance rejection method. By treating the model dynamics as a common disturbance and actively rejecting it, active disturbance rejection control (ADRC) can achieve the desired response. Simulation results are provided to demonstrate the effectiveness of the proposed method.

  17. Immunogenicity of Anti-TNF-α Biotherapies

    DEFF Research Database (Denmark)

    Bendtzen, Klaus

    2015-01-01

    Immunogenicity of biopharmaceuticals is complex and influenced by both structural and pharmacological factors, and by patient-related conditions such as disease being treated, previous and concomitant therapies, and individual immune responsiveness. Essential for tailored therapeutic strategies b...

  18. Line-up member similarity influences the effectiveness of a salient rejection option for eyewitnesses

    OpenAIRE

    Bruer, Kaila C.; Fitzgerald, Ryan J.; Therrien, Natalie M.; Price, Heather L.

    2015-01-01

    Visually salient line-up rejection options have not been systematically studied with adult eyewitnesses. We explored the impact of using a non-verbal, salient rejection option on adults' identification accuracy for line-ups containing low- or high-similarity fillers. The non-verbal, salient rejection option had minimal impact on accuracy in low-similarity line-ups, but in high-similarity line-ups its inclusion increased correct rejections for target-absent line-ups as well as incorrect reject...

  19. Gene transfer preferentially selects MHC class I positive tumour cells and enhances tumour immunogenicity.

    Science.gov (United States)

    Hacker, Ulrich T; Schildhauer, Ines; Barroso, Margarita Céspedes; Kofler, David M; Gerner, Franz M; Mysliwietz, Josef; Buening, Hildegard; Hallek, Michael; King, Susan B S

    2006-05-01

    The modulated expression of MHC class I on tumour tissue is well documented. Although the effect of MHC class I expression on the tumorigenicity and immunogenicity of MHC class I negative tumour cell lines has been rigorously studied, less is known about the validity of gene transfer and selection in cell lines with a mixed MHC class I phenotype. To address this issue we identified a C26 cell subline that consists of distinct populations of MHC class I (H-2D/K) positive and negative cells. Transient transfection experiments using liposome-based transfer showed a lower transgene expression in MHC class I negative cells. In addition, MHC class I negative cells were more sensitive to antibiotic selection. This led to the generation of fully MHC class I positive cell lines. In contrast to C26 cells, all transfectants were rejected in vivo and induced protection against the parental tumour cells in rechallenge experiments. Tumour cell specificity of the immune response was demonstrated in in vitro cytokine secretion and cytotoxicity assays. Transfectants expressing CD40 ligand and hygromycin phosphotransferase were not more immunogenic than cells expressing hygromycin resistance alone. We suggest that the MHC class I positive phenotype of the C26 transfectants had a bearing on their immunogenicity, because selected MHC class I positive cells were more immunogenic than parental C26 cells and could induce specific anti-tumour immune responses. These data demonstrate that the generation of tumour cell transfectants can lead to the selection of subpopulations that show an altered phenotype compared to the parental cell line and display altered immunogenicity independent of selection marker genes or other immune modulatory genes. Our results show the importance of monitoring gene transfer in the whole tumour cell population, especially for the evaluation of in vivo therapies targeted to heterogeneous tumour cell populations.

  20. Allotransplanted neurons used to repair peripheral nerve injury do not elicit overt immunogenicity.

    Directory of Open Access Journals (Sweden)

    Weimin Liu

    Full Text Available A major problem hindering the development of autograft alternatives for repairing peripheral nerve injuries is immunogenicity. We have previously shown successful regeneration in transected rat sciatic nerves using conduits filled with allogeneic dorsal root ganglion (DRG cells without any immunosuppression. In this study, we re-examined the immunogenicity of our DRG neuron implanted conduits as a potential strategy to overcome transplant rejection. A biodegradable NeuraGen® tube was infused with pure DRG neurons or Schwann cells cultured from a rat strain differing from the host rats and used to repair 8 mm gaps in the sciatic nerve. We observed enhanced regeneration with allogeneic cells compared to empty conduits 16 weeks post-surgery, but morphological analyses suggest recovery comparable to the healthy nerves was not achieved. The degree of regeneration was indistinguishable between DRG and Schwann cell allografts although immunogenicity assessments revealed substantially increased presence of Interferon gamma (IFN-γ in Schwann cell allografts compared to the DRG allografts by two weeks post-surgery. Macrophage infiltration of the regenerated nerve graft in the DRG group 16 weeks post-surgery was below the level of the empty conduit (0.56 fold change from NG; p<0.05 while the Schwann cell group revealed significantly higher counts (1.29 fold change from NG; p<0.001. Major histocompatibility complex I (MHC I molecules were present in significantly increased levels in the DRG and Schwann cell allograft groups compared to the hollow NG conduit and the Sham healthy nerve. Our results confirmed previous studies that have reported Schwann cells as being immunogenic, likely due to MHC I expression. Nerve gap injuries are difficult to repair; our data suggest that DRG neurons are superior medium to implant inside conduit tubes due to reduced immunogenicity and represent a potential treatment strategy that could be preferable to the current gold

  1. Toxicity attenuation optimization of crotalic venom by gamma radiation and studies of its immunogenic properties

    International Nuclear Information System (INIS)

    Clissa, Patricia Bianca

    1997-01-01

    Literature data show that 2.0 kGy dose of gamma radiation, generated by 60 source, reduces the toxic activity of Crotalus durissus terrificus venom, without altering its immunogenic capacity. When crotoxin, main toxin from crotalic venom, was irradiated with the same dose, toxicity was also reduced and the immunogenicity was maintained. This fact was attributed to aggregates (compounds with high molecular weight generated during irradiation), that showed no toxicity but were able to induce the antibodies formation against native venom. Crotalus durissus terrificus venom was irradiated with 2.0, 3.0, 5.0 and 10.0 kGy doses and submitted to molecular exclusion chromatography, in order to find an efficient dose that produces large amounts of non toxic but still immunogenic aggregates. After being isolated, the products of irradiation were evaluated for the amount produced, molecular alteration, and toxic and immunogenic activities. These parameters were also analyzed for the whole venom irradiated. The results from different doses irradiated venom were compared with native one, and 2.0 kGy dose was confirmed to be the most efficient in the association of toxicity attenuation with maintenance of immunogenicity of the crotalic venom, while other doses, in spite of being efficient in the toxicity attenuation, they were not able to keep the immunogenicity property. So, the dose of 2.0 kGy could be used to immunize animals in order to improve anticrotalic sera production. (author)

  2. Results of radioiodine therapy using different radiation doses in patients suffering from immunogenic and non-immunogenic hyperthyroidism

    International Nuclear Information System (INIS)

    Moser, E.

    1992-01-01

    During the past few years high rates of recidivation have increasingly been reported following drug treatment for hyperthyroidism. In view of these unsatisfactory results it is only natural that the use of surgery and ratioiodine treatment is now more often considered in order to achieve complete elimination of the metabolic disorders caused by hyperactivity of the thyroid gland. The aim of this study was to investigate into the effectiveness of radioiodine therapy in a large cohort of patients (n = 925). Particular attention was given to the influence of the dose applied to the thyroid tissue on the rates of success achieved in immunogenic hyperthyroidism (IH) and autonomous disorders (non-immunogenic hyperthyroidism = NIH). (orig./GDG) [de

  3. Complement and hyper acute rejection

    Directory of Open Access Journals (Sweden)

    Al-Rabia Mohammed

    2009-01-01

    Full Text Available Organ transplantation has been a major development in clinical medicine but its success has been marred by the immune system′s capacity to respond to "non-self" cells and tissues. A full molecular understanding of this mechanism and the myriad triggers for immune rejection is yet to be elucidated. Consequently, immunosuppressive drugs remain the mainstay of post-transplant ma-nagement; however, these interventions have side effects such as increased incidence of cancer, post-transplant lymphoproliferative disorders, susceptibility to infection if not managed appro-priately and the inconvenience to the patient of lifelong treatment. Novel therapeutic approaches based on molecular understanding of immunological processes are thus needed in this field. The notion that factors influencing successful transplants might be of use as therapeutic approaches is both scientifically and medically appealing. Recent developments in the understanding of successful transplants are expected to provide new opportunities for safer transplantation. This article reviews the present understanding of the molecular basis of rejection and the role of complement in this process as well as the possibility of generating "intelligent" therapy that better target crucial components of hyper-acute rejections.

  4. Prediction of acute cardiac rejection using radionuclide techniques

    International Nuclear Information System (INIS)

    Novitzky, D.; Bonioszczuk, J.; Cooper, D.K.C.; Isaacs, S.; Rose, A.G.; Smith, J.A.; Uys, C.J.; Barnard, C.N.; Fraser, R.

    1984-01-01

    Radionuclide scanning of the donor left ventricle using technetium-99m-labelled red cells was used to monitor acute rejection after heterotopic heart transplantation and compared with histopathological evidence of rejection obtained at examination of an endomyocardial biopsy specimen. The ejection fraction and end-diastolic, end-systolic and stroke volumes were calculated at each examination; an equation was derived from these data to predict the degree of acute rejection, using histopathological examination of endomyocardial biopsy specimens as criteria of the presence and severity of rejection. A highly significant multiple correlation between radionuclide scanning parameters and endomyocardial biopsy was found. The advantages of non-invasive radionuclide scanning over the invasive procedure of endomyocardial biopsy are discussed

  5. Enhanced analogue front-end for the measurement of the high state of wide-band voltage pulses with 87 dB common-mode rejection ratio and ±0.65 ppm 1-day offset stability

    CERN Document Server

    AUTHOR|(SzGeCERN)712364; Arpaia, Pasquale; Martino, Michele

    2015-01-01

    An improved analogue front-end for measuring the high state of trapezoidal voltage pulses with transition duration of 3 μs is presented. A new measurement system, composed by a front-end and the state-of-the-art acquisition board NI PXI-5922, has been realized with improved Common Mode Rejection Ratio (CMRR) of more than 87 dB at DC and 3-sigma stability of }0.65 ppm over 1 day. After highlighting the main design enhancements with respect to state-of-the-art solutions, the CMRR measurement is reported. The output drift due to temperature and humidity is assessed to be negligible. Finally, the worst-case repeatability is measured both with shorted-to-ground inputs and with an applied common-mode voltage of 10 V, which represents the nominal working condition.

  6. Immunogenic Apoptosis as a Novel Tool for Anticancer Vaccine Development

    Directory of Open Access Journals (Sweden)

    Barbara Montico

    2018-02-01

    Full Text Available Immunogenic apoptosis, or more appropriately called immunogenic cell death (ICD, is a recently described form of apoptosis induced by a specific set of chemotherapeutic drugs or by physical therapeutic modalities, such as ionizing irradiation and photodynamic therapy. The peculiar characteristic of ICD is the ability to favor recognition and elimination of dying tumor cells by phagocytes in association with the release of pro-inflammatory molecules (such as cytokines and high-mobility group box-1. While in vitro and animal models pointed to ICD as one of the molecular mechanisms mediating the clinical efficacy of some anticancer agents, it is hard to clearly demonstrate its contribution in cancer patients. Clinical evidence suggests that the induction of ICD alone is possibly not sufficient to fully subvert the immunosuppressive tumor microenvironment. However, interesting results from recent studies contemplate the exploitation of ICD for improving the immunogenicity of cancer cells to use them as an antigen cargo in the development of dendritic cell (DC vaccines. Herein, we discuss the effects of danger signals expressed or released by cancer cells undergoing ICD on the maturation and activation of immature and mature DC, highlighting the potential added value of ICD in adoptive immunotherapy protocols.

  7. Social Causes and Consequences of Rejection Sensitivity

    Science.gov (United States)

    London, Bonita; Downey, Geraldine; Bonica, Cheryl; Paltin, Iris

    2007-01-01

    Predictions from the Rejection Sensitivity (RS) model concerning the social causes and consequences of RS were examined in a longitudinal study of 150 middle school students. Peer nominations of rejection, self-report measures of anxious and angry rejection expectations, and social anxiety, social withdrawal, and loneliness were assessed at two…

  8. 7 CFR 58.136 - Rejected milk.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Rejected milk. 58.136 Section 58.136 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Milk § 58.136 Rejected milk. A plant shall reject specific milk from a producer if the milk fails to...

  9. Peer Group Rejection and Children's Outgroup Prejudice

    Science.gov (United States)

    Nesdale, Drew; Durkin, Kevin; Maass, Anne; Kiesner, Jeff; Griffiths, Judith; Daly, Josh; McKenzie, David

    2010-01-01

    Two simulation studies examined the effect of peer group rejection on 7 and 9 year old children's outgroup prejudice. In Study 1, children (n = 88) pretended that they were accepted or rejected by their assigned group, prior to competing with a lower status outgroup. Results indicated that rejected versus accepted children showed increased…

  10. Using Compton scattering for random coincidence rejection

    International Nuclear Information System (INIS)

    Kolstein, M.; Chmeissani, M.

    2016-01-01

    The Voxel Imaging PET (VIP) project presents a new approach for the design of nuclear medicine imaging devices by using highly segmented pixel CdTe sensors. CdTe detectors can achieve an energy resolution of ≈ 1% FWHM at 511 keV and can be easily segmented into submillimeter sized voxels for optimal spatial resolution. These features help in rejecting a large part of the scattered events from the PET coincidence sample in order to obtain high quality images. Another contribution to the background are random events, i.e., hits caused by two independent gammas without a common origin. Given that 60% of 511 keV photons undergo Compton scattering in CdTe (i.e. 84% of all coincidence events have at least one Compton scattering gamma), we present a simulation study on the possibility to use the Compton scattering information of at least one of the coincident gammas within the detector to reject random coincidences. The idea uses the fact that if a gamma undergoes Compton scattering in the detector, it will cause two hits in the pixel detectors. The first hit corresponds to the Compton scattering process. The second hit shall correspond to the photoelectric absorption of the remaining energy of the gamma. With the energy deposition of the first hit, one can calculate the Compton scattering angle. By measuring the hit location of the coincident gamma, we can construct the geometric angle, under the assumption that both gammas come from the same origin. Using the difference between the Compton scattering angle and the geometric angle, random events can be rejected.

  11. Rational design of a live attenuated dengue vaccine: 2'-o-methyltransferase mutants are highly attenuated and immunogenic in mice and macaques.

    Directory of Open Access Journals (Sweden)

    Roland Züst

    Full Text Available Dengue virus is transmitted by Aedes mosquitoes and infects at least 100 million people every year. Progressive urbanization in Asia and South-Central America and the geographic expansion of Aedes mosquito habitats have accelerated the global spread of dengue, resulting in a continuously increasing number of cases. A cost-effective, safe vaccine conferring protection with ideally a single injection could stop dengue transmission. Current vaccine candidates require several booster injections or do not provide protection against all four serotypes. Here we demonstrate that dengue virus mutants lacking 2'-O-methyltransferase activity are highly sensitive to type I IFN inhibition. The mutant viruses are attenuated in mice and rhesus monkeys and elicit a strong adaptive immune response. Monkeys immunized with a single dose of 2'-O-methyltransferase mutant virus showed 100% sero-conversion even when a dose as low as 1,000 plaque forming units was administrated. Animals were fully protected against a homologous challenge. Furthermore, mosquitoes feeding on blood containing the mutant virus were not infected, whereas those feeding on blood containing wild-type virus were infected and thus able to transmit it. These results show the potential of 2'-O-methyltransferase mutant virus as a safe, rationally designed dengue vaccine that restrains itself due to the increased susceptibility to the host's innate immune response.

  12. High loading of graphene oxide/multi-walled carbon nanotubes into PDLLA: A route towards the design of osteoconductive, bactericidal and non-immunogenic 3D porous scaffolds

    International Nuclear Information System (INIS)

    Zanin, Hudson; Rodrigues, Bruno Vinícius Manzolli; Ribeiro Neto, Wilson Alves; Bretas, Rosario Elida Suman; Da-Silva, Newton Soares; Marciano, Fernanda Roberta; Oliveira Lobo, Anderson

    2016-01-01

    We have prepared a novel 3D porous biomaterial combining poly (DL-lactic acid) (PDLLA) and graphene and multi-walled carbon nanotubes oxides (MWCNTO-GO) composite. PDLLA as control and a high loading of PDLLA/MWCNTO-GO (50/50 w/w) bioscaffolds were prepared and functionalized. MWCNTs were exfoliated to form MWCNTO-GO by oxygen plasma etching. The later was also applied to enhance the scaffolds wettability, attaching oxygen-containing groups on their surfaces. This approach produced a porous architecture observed by scanning electron microscopy and semi-quantified by electrochemical analysis. The later also indicated a notable increase on the conductivity of PDLLA/MWCNTO-GO scaffold compared to MWCNTO-GO free PDLLA (about 5 orders of magnitudes at low frequencies). Thermogravimetric analysis showed that the MWCNTO-GO acted protecting the PDLLA matrix, enhancing its thermal stability. The PDLLA/MWCNTO-GO scaffolds had significant cellular adhesion, did not present cytotoxicity effect, besides reduced bactericidal proliferation and produced mineralized tissues in SBF media. The metallic MWCNTO-GO powder held together by PDLLA polymer opens a whole new branch of applications, including bioelectroanalyses, drug delivery systems and tissue engineering. - Highlights: • We produced a novel 3D porous material from PDLLA, graphene oxide and MWCNT oxide. • MWCNTO-GO loading (50/50 w/w) increased notably the conductivity of PDLLA scaffold. • MWCNTO-GO acted protecting the PDLLA matrix, enhancing its thermal stability. • PDLLA/MWCNTO-GO scaffolds did not present cytotoxicity effect. • PDLLA/MWCNTO-GO scaffolds presented bioactivity properties.

  13. High loading of graphene oxide/multi-walled carbon nanotubes into PDLLA: A route towards the design of osteoconductive, bactericidal and non-immunogenic 3D porous scaffolds

    Energy Technology Data Exchange (ETDEWEB)

    Zanin, Hudson [Laboratory of Biomedical Nanotechnology (NANOBIO), Institute of Research and Development - IP& D, University of Vale do Paraiba, Av. Shishima Hifumi 2911, Sao Jose dos Campos, 12244-000, Sao Paulo (Brazil); Laboratory of Energy Storage & Supply - ES& S, Institute of Research and Development - IP& D, University of Vale do Paraiba, Av. Shishima Hifumi 2911, Sao Jose dos Campos, CEP: 12.244-000, Sao Paulo (Brazil); Rodrigues, Bruno Vinícius Manzolli [Laboratory of Biomedical Nanotechnology (NANOBIO), Institute of Research and Development - IP& D, University of Vale do Paraiba, Av. Shishima Hifumi 2911, Sao Jose dos Campos, 12244-000, Sao Paulo (Brazil); Ribeiro Neto, Wilson Alves; Bretas, Rosario Elida Suman [Department of Materials Engineering, Federal University of Sao Carlos, Rodovia Washington Luis, km 235 – SP-310, Sao Carlos, Sao Paulo (Brazil); Da-Silva, Newton Soares [Laboratory of Cell Biology and Tissue, Institute of Research and Development - IP& D, University of Vale do Paraiba, Av. Shishima Hifumi 2911, Sao Jose dos Campos, CEP: 12244-000, Sao Paulo (Brazil); Marciano, Fernanda Roberta [Laboratory of Biomedical Nanotechnology (NANOBIO), Institute of Research and Development - IP& D, University of Vale do Paraiba, Av. Shishima Hifumi 2911, Sao Jose dos Campos, 12244-000, Sao Paulo (Brazil); Oliveira Lobo, Anderson, E-mail: aolobo@pq.cnpq.br [Laboratory of Biomedical Nanotechnology (NANOBIO), Institute of Research and Development - IP& D, University of Vale do Paraiba, Av. Shishima Hifumi 2911, Sao Jose dos Campos, 12244-000, Sao Paulo (Brazil)

    2016-07-01

    We have prepared a novel 3D porous biomaterial combining poly (DL-lactic acid) (PDLLA) and graphene and multi-walled carbon nanotubes oxides (MWCNTO-GO) composite. PDLLA as control and a high loading of PDLLA/MWCNTO-GO (50/50 w/w) bioscaffolds were prepared and functionalized. MWCNTs were exfoliated to form MWCNTO-GO by oxygen plasma etching. The later was also applied to enhance the scaffolds wettability, attaching oxygen-containing groups on their surfaces. This approach produced a porous architecture observed by scanning electron microscopy and semi-quantified by electrochemical analysis. The later also indicated a notable increase on the conductivity of PDLLA/MWCNTO-GO scaffold compared to MWCNTO-GO free PDLLA (about 5 orders of magnitudes at low frequencies). Thermogravimetric analysis showed that the MWCNTO-GO acted protecting the PDLLA matrix, enhancing its thermal stability. The PDLLA/MWCNTO-GO scaffolds had significant cellular adhesion, did not present cytotoxicity effect, besides reduced bactericidal proliferation and produced mineralized tissues in SBF media. The metallic MWCNTO-GO powder held together by PDLLA polymer opens a whole new branch of applications, including bioelectroanalyses, drug delivery systems and tissue engineering. - Highlights: • We produced a novel 3D porous material from PDLLA, graphene oxide and MWCNT oxide. • MWCNTO-GO loading (50/50 w/w) increased notably the conductivity of PDLLA scaffold. • MWCNTO-GO acted protecting the PDLLA matrix, enhancing its thermal stability. • PDLLA/MWCNTO-GO scaffolds did not present cytotoxicity effect. • PDLLA/MWCNTO-GO scaffolds presented bioactivity properties.

  14. Determinants of immunogenic response to protein therapeutics.

    Science.gov (United States)

    Singh, Satish K; Cousens, Leslie P; Alvarez, David; Mahajan, Pramod B

    2012-09-01

    Protein therapeutics occupy a very significant position in the biopharmaceutical market. In addition to the preclinical, clinical and post marketing challenges common to other drugs, unwanted immunogenicity is known to affect efficacy and/or safety of most biotherapeutics. A standard set of immunogenicity risk factors are routinely used to inform monitoring strategies in clinical studies. A number of in-silico, in vivo and in vitro approaches have also been employed to predict immunogenicity of biotherapeutics, but with limited success. Emerging data also indicates the role of immune tolerance mechanisms and impact of several product-related factors on modulating host immune responses. Thus, a comprehensive discussion of the impact of innate and adaptive mechanisms and molecules involved in induction of host immune responses on immunogenicity of protein therapeutics is needed. A detailed understanding of these issues is essential in order to fully exploit the therapeutic potential of this class of drugs. This Roundtable Session was designed to provide a common platform for discussing basic immunobiological and pharmacological issues related to the role of biotherapeutic-associated risk factors, as well as host immune system in immunogenicity against protein therapeutics. The session included overview presentations from three speakers, followed by a panel discussion with audience participation. Copyright © 2012. Published by Elsevier Ltd.. All rights reserved.

  15. Higher boron rejection with a new TFC forward osmosis membrane

    KAUST Repository

    Valladares Linares, Rodrigo; Li, Zhenyu; Sarp, Sarper; Park, Y. G.; Amy, Gary L.; Vrouwenvelder, Johannes S.

    2014-01-01

    Due to the stringent limits for boron in drinking and irrigation water, water treatment facilities have to incur additional treatment to remove boron down to a safe concentration. Forward osmosis (FO) is a membrane technology that may reduce the energy required to remove boron present in seawater. In direct FO desalination hybrid systems, fresh water is recovered from seawater using a recoverable draw solution, FO membranes are expected to show high boron rejection. This study focuses on determining the boron rejection capabilities of a new generation thin-film composite (TFC) FO membrane compared to a first generation cellulose triacetate (CTA) FO membrane. The effects of water permeate flux, membrane structure, draw solute charge, and reverse solute flux on boron rejection were determined. For TFC and CTA FO membranes, experiments showed that when similar operating conditions are applied (e.g. membrane type and draw solute type) boron rejection decreases with increase in permeate flux. Reverse draw solute flux and membrane fouling have no significant impact on boron rejection. Compared to the first generation CTA FO membrane operated at the same conditions, the TFC FO membrane showed a 40% higher boron rejection capability and a 20% higher water flux. This demonstrates the potential for boron removal for new generation TFC FO membranes. © 2014 © 2014 Balaban Desalination Publications. All rights reserved.

  16. Higher boron rejection with a new TFC forward osmosis membrane

    KAUST Repository

    Valladares Linares, Rodrigo

    2014-07-17

    Due to the stringent limits for boron in drinking and irrigation water, water treatment facilities have to incur additional treatment to remove boron down to a safe concentration. Forward osmosis (FO) is a membrane technology that may reduce the energy required to remove boron present in seawater. In direct FO desalination hybrid systems, fresh water is recovered from seawater using a recoverable draw solution, FO membranes are expected to show high boron rejection. This study focuses on determining the boron rejection capabilities of a new generation thin-film composite (TFC) FO membrane compared to a first generation cellulose triacetate (CTA) FO membrane. The effects of water permeate flux, membrane structure, draw solute charge, and reverse solute flux on boron rejection were determined. For TFC and CTA FO membranes, experiments showed that when similar operating conditions are applied (e.g. membrane type and draw solute type) boron rejection decreases with increase in permeate flux. Reverse draw solute flux and membrane fouling have no significant impact on boron rejection. Compared to the first generation CTA FO membrane operated at the same conditions, the TFC FO membrane showed a 40% higher boron rejection capability and a 20% higher water flux. This demonstrates the potential for boron removal for new generation TFC FO membranes. © 2014 © 2014 Balaban Desalination Publications. All rights reserved.

  17. Rejection index for pressure tubes

    International Nuclear Information System (INIS)

    Mitchell, A.B.; Meneley, D.

    1989-10-01

    The objective of the present study was to establish a set of criteria (or Rejection Index) which could be used to decide whether a zirconium-2 1/2 w/o niobium pressure tube in a CANDU reactor should be removed from service due to in-service degradation. A critique of key issues associated with establishing a realistic rejection index was prepared. Areas of uncertainty in available information were identified and recommendations for further analysis and laboratory testing made. A Rejection Index based on the following limits has been recommended: 1) Limits related to design intent and normal operation: any garter spring must remain within the tolerance band specified for its design location; the annulus gas system must normally be operated in a circulating mode with a procedure in place for purging to prevent accumulation of deuterium. It must remain sensitive to leaks into any part of the systems; and pressure tube dimensions and distortions must be limited to maintain the fuel channels within the original design intent; 2) Limits related to defect tolerance: adequate time margins between occurrence of a leaking crack and unstable failure must be demonstrated for all fuel channels; long lap-type flaws are unacceptable; crack-like defects of any size are unacceptable; and score marks, frat marks and other defects with contoured profiles must fall below certain depth, length and stress intensity limits; and 3) Limits related to property degradation: at operating temperature each pressure tube must be demonstrated to have a critical length in excess of a stipulated value; the maximum equivalent hydrogen level in any pressure tube should not exceed a limit which should be defined taking into account the known history of that tube; the maximum equivalent hydrogen level in any rolled joint should not exceed a limit which is presently recommended as 200 ppm equivalent hydrogen; and the maximum diametral creep strain should be limited to less than 5%

  18. Structure-Based Design of Head-Only Fusion Glycoprotein Immunogens for Respiratory Syncytial Virus.

    Directory of Open Access Journals (Sweden)

    Jeffrey C Boyington

    Full Text Available Respiratory syncytial virus (RSV is a significant cause of severe respiratory illness worldwide, particularly in infants, young children, and the elderly. Although no licensed vaccine is currently available, an engineered version of the metastable RSV fusion (F surface glycoprotein-stabilized in the pre-fusion (pre-F conformation by "DS-Cav1" mutations-elicits high titer RSV-neutralizing responses. Moreover, pre-F-specific antibodies, often against the neutralization-sensitive antigenic site Ø in the membrane-distal head region of trimeric F glycoprotein, comprise a substantial portion of the human response to natural RSV infection. To focus the vaccine-elicited response to antigenic site Ø, we designed a series of RSV F immunogens that comprised the membrane-distal head of the F glycoprotein in its pre-F conformation. These "head-only" immunogens formed monomers, dimers, and trimers. Antigenic analysis revealed that a majority of the 70 engineered head-only immunogens displayed reactivity to site Ø-targeting antibodies, which was similar to that of the parent RSV F DS-Cav1 trimers, often with increased thermostability. We evaluated four of these head-only immunogens in detail, probing their recognition by antibodies, their physical stability, structure, and immunogenicity. When tested in naïve mice, a head-only trimer, half the size of the parent RSV F trimer, induced RSV titers, which were statistically comparable to those induced by DS-Cav1. When used to boost DS-Cav1-primed mice, two head-only RSV F immunogens, a dimer and a trimer, boosted RSV-neutralizing titers to levels that were comparable to those boosted by DS-Cav1, although with higher site Ø-directed responses. Our results provide proof-of-concept for the ability of the smaller head-only RSV F immunogens to focus the vaccine-elicited response to antigenic site Ø. Decent primary immunogenicity, enhanced physical stability, potential ease of manufacture, and potent

  19. 111-Indium-labelled platelets for diagnosis of acute kidney transplant rejection and monitoring of prostacyclin anti-rejection treatment

    International Nuclear Information System (INIS)

    Leithner, C.; Pohanka, E.; Schwarz, M.; Sinzinger, H.; Syre, G.

    1984-01-01

    33 patients were examined daily under a gamma camera after weekly injections of 111-In-labelled autologous platelets over a period of at least 4 weeks after transplantation. A group of 33 patients with long-term stable and well-functioning grafts served as controls. By means of a computerized recording technique, platelet trapping in the graft was measured and expressed as platelet-uptake index (PUI). The method worked well for the early diagnosis of acute rejection signified by an increase in PUI, accompanied by a shortening of platelet half life (t/2). 6 patients suffering from acute rejection received infusions of prostacyclin in addition to conventional high-dose methylprednisolone therapy. In 4 cases the PUI decreased again and an improvement in graft function was observed. Prostacyclin infusion treatment was applied also in 12 patients with histologically-proven chronic transplant rejection. Decreased platelet consumption by the graft and a temporary improvement in transplant function were achieved. We suggest that prostacyclin could enrich the possibilities of anti-rejection treatment by providing a tool for the suppression of platelet trapping in the graft. The platelet scan served as a useful method for the early detection of acute rejection, as well as the monitoring of prostacyclin anti-rejection treatment. (Autor)

  20. The Influences of Glycosylation on the Antigenicity, Immunogenicity, and Protective Efficacy of Ebola Virus GP DNA Vaccines

    National Research Council Canada - National Science Library

    Dowling, William; Thompson, Elizabeth; Badger, Catherine; Mellquist, Jenny L; Garrison, Aura R; Smith, Jeffrey M; Paragas, Jason; Hogan, Robert J; Schmaljohn, Connie

    2006-01-01

    ... or with deletions in the central hypervariable mucin region. We showed that mutation of one of the two N-linked GP2 glycosylation sites was highly detrimental to the antigenicity and immunogenicity of GP...

  1. Intrinsic immunogenicity of rapidly-degradable polymers evolves during degradation.

    Science.gov (United States)

    Andorko, James I; Hess, Krystina L; Pineault, Kevin G; Jewell, Christopher M

    2016-03-01

    Recent studies reveal many biomaterial vaccine carriers are able to activate immunostimulatory pathways, even in the absence of other immune signals. How the changing properties of polymers during biodegradation impact this intrinsic immunogenicity is not well studied, yet this information could contribute to rational design of degradable vaccine carriers that help direct immune response. We use degradable poly(beta-amino esters) (PBAEs) to explore intrinsic immunogenicity as a function of the degree of polymer degradation and polymer form (e.g., soluble, particles). PBAE particles condensed by electrostatic interaction to mimic a common vaccine approach strongly activate dendritic cells, drive antigen presentation, and enhance T cell proliferation in the presence of antigen. Polymer molecular weight strongly influences these effects, with maximum stimulation at short degradation times--corresponding to high molecular weight--and waning levels as degradation continues. In contrast, free polymer is immunologically inert. In mice, PBAE particles increase the numbers and activation state of cells in lymph nodes. Mechanistic studies reveal that this evolving immunogenicity occurs as the physicochemical properties and concentration of particles change during polymer degradation. This work confirms the immunological profile of degradable, synthetic polymers can evolve over time and creates an opportunity to leverage this feature in new vaccines. Degradable polymers are increasingly important in vaccination, but how the inherent immunogenicity of polymers changes during degradation is poorly understood. Using common rapidly-degradable vaccine carriers, we show that the activation of immune cells--even in the absence of other adjuvants--depends on polymer form (e.g., free, particulate) and the extent of degradation. These changing characteristics alter the physicochemical properties (e.g., charge, size, molecular weight) of polymer particles, driving changes in

  2. Inherent Immunogenicity or Lack Thereof of Pluripotent Stem Cells: Implications for Cell Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Arvind Chhabra

    2017-08-01

    Full Text Available Donor-specific induced pluripotent stem cells (iPSCs offer opportunities for personalized cell replacement therapeutic approaches due to their unlimited self-renewal potential and ability to differentiate into different somatic cells. A significant progress has been made toward generating iPSC lines that are free of integrating viral vectors, development of xeno-free culture conditions, and differentiation of pluripotent stem cells (PSCs into functional somatic cell lineages. Since donor-specific iPSC lines are genetically identical to the individual, they are expected to be immunologically matched and these iPSC lines and their cellular derivatives are not expected to be immunologically rejected. However, studies in mouse models, utilizing rejection of teratomas as a model, have claimed that syngenic iPSC lines, especially the iPSC lines derived with integrating viral vectors, could be inherently immunogenic. This manuscript reviews current understanding of inherent immunogenicity of PSC lines, especially that of the human iPSC lines and their cellular derivatives, and strategies to overcome it.

  3. Allergenicity, immunogenicity and dose-relationship of three intact allergen vaccines and four allergoid vaccines for subcutaneous grass pollen immunotherapy.

    Science.gov (United States)

    Henmar, H; Lund, G; Lund, L; Petersen, A; Würtzen, P A

    2008-09-01

    Different vaccines containing intact allergens or chemically modified allergoids as active ingredients are commercially available for specific immunotherapy. Allergoids are claimed to have decreased allergenicity without loss of immunogenicity and this is stated to allow administration of high allergoid doses. We compared the allergenicity and immunogenicity of four commercially available chemically modified grass pollen allergoid products with three commercially available intact grass pollen allergen vaccines. The allergenicity was investigated with immunoglobulin (Ig)E-inhibition and basophil activation assays. Human T cell proliferation and specific IgG-titres following mouse immunizations were used to address immunogenicity. Furthermore, intact allergen vaccines with different contents of active ingredients were selected to study the influence of the allergen dose. In general, a lower allergenicity for allergen vaccines was clearly linked to a reduced immunogenicity. Compared with the vaccine with the highest amount of intact allergen, the allergoids caused reduced basophil activation as well as diminished immunogenicity demonstrated by reduced T cell activation and/or reduced induction of murine grass-specific IgG antibodies. Interestingly, intact allergen vaccines with lower content of active ingredient exhibited similarly reduced allergenicity, while immunogenicity was still higher or equal to that of allergoids. The low allergenicity observed for some allergoids was inherently linked to a significantly lower immunogenic response questioning the rationale behind the chemical modification into allergoids. In addition, the linkage between allergenicity, immunogenicity and dose found for intact allergen vaccines and the immunogen as well as allergenic immune responses observed for allergoids suggest that the modified allergen vaccines do not contain high doses of immunologically active ingredients.

  4. Toward precision manufacturing of immunogene T-cell therapies.

    Science.gov (United States)

    Xu, Jun; Melenhorst, J Joseph; Fraietta, Joseph A

    2018-05-01

    Cancer can be effectively targeted using a patient's own T cells equipped with synthetic receptors, including chimeric antigen receptors (CARs) that redirect and reprogram these lymphocytes to mediate tumor rejection. Over the past two decades, several strategies to manufacture genetically engineered T cells have been proposed, with the goal of generating optimally functional cellular products for adoptive transfer. Based on this work, protocols for manufacturing clinical-grade CAR T cells have been established, but these complex methods have been used to treat only a few hundred individuals. As CAR T-cell therapy progresses into later-phase clinical trials and becomes an option for more patients, a major consideration for academic institutions and industry is developing robust manufacturing processes that will permit scaling-out production of immunogene T-cell therapies in a reproducible and efficient manner. In this review, we will discuss the steps involved in cell processing, the major obstacles surrounding T-cell manufacturing platforms and the approaches for improving cellular product potency. Finally, we will address the challenges of expanding CAR T-cell therapy to a global patient population. Copyright © 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  5. Mammographic image reject rate analysis and cause – A National Maltese Study

    International Nuclear Information System (INIS)

    Mercieca, N.; Portelli, J.L.; Jadva-Patel, H.

    2017-01-01

    Mammography is used as a first-line investigation in the detection of breast cancer and imaging is required to be of optimal quality and achieved without adverse effects on the health of individuals. Repeated images come at a cost in terms of radiation dose, discomfort to clients and unnecessary financial burdens. No studies investigating mammography quality in Malta had been previously undertaken. Hence, this research aimed to investigate whether mammography is being performed at an acceptable level, through the investigation of reject rates. Quantitative methodology was used to collect data from eight participating mammography units, which were utilising screen film (SFM), computed radiography (CR) and direct digital mammography (DDM). Data relating to the total number of images performed, rejects and causes was prospectively collected over two weeks, resulting in a sample of 2291 images. All units were also asked to answer a questionnaire which provided other data that could be used for analysis. The national mammography reject rate was found to be 2.62%; within the 3% acceptable range. Individual rates' analysis revealed unacceptably high or low reject rates in some units. Positioning was the main reject cause. No significant difference in rejection was found between different types of mammography units or radiographers' experience. Alternatively, radiographers' qualifications, employment conditions and use of rejection criteria were proven to affect reject rates. Whilst on a national level, images are being rejected at an acceptable rate, individual units revealed suboptimal rates; at the cost of extra radiation, added discomfort and financial burden. - Highlights: • The national reject rate complied with the European Guidelines. • Reject rates in different units were found to vary. • Positioning was the commonest cause for repeats. • The equipment used and radiographers' experience did not affect reject rates. • Qualifications

  6. The Application of Auto-Disturbance Rejection Control Optimized by Least Squares Support Vector Machines Method and Time-Frequency Representation in Voltage Source Converter-High Voltage Direct Current System.

    Science.gov (United States)

    Liu, Ying-Pei; Liang, Hai-Ping; Gao, Zhong-Ke

    2015-01-01

    In order to improve the performance of voltage source converter-high voltage direct current (VSC-HVDC) system, we propose an improved auto-disturbance rejection control (ADRC) method based on least squares support vector machines (LSSVM) in the rectifier side. Firstly, we deduce the high frequency transient mathematical model of VSC-HVDC system. Then we investigate the ADRC and LSSVM principles. We ignore the tracking differentiator in the ADRC controller aiming to improve the system dynamic response speed. On this basis, we derive the mathematical model of ADRC controller optimized by LSSVM for direct current voltage loop. Finally we carry out simulations to verify the feasibility and effectiveness of our proposed control method. In addition, we employ the time-frequency representation methods, i.e., Wigner-Ville distribution (WVD) and adaptive optimal kernel (AOK) time-frequency representation, to demonstrate our proposed method performs better than the traditional method from the perspective of energy distribution in time and frequency plane.

  7. The Application of Auto-Disturbance Rejection Control Optimized by Least Squares Support Vector Machines Method and Time-Frequency Representation in Voltage Source Converter-High Voltage Direct Current System.

    Directory of Open Access Journals (Sweden)

    Ying-Pei Liu

    Full Text Available In order to improve the performance of voltage source converter-high voltage direct current (VSC-HVDC system, we propose an improved auto-disturbance rejection control (ADRC method based on least squares support vector machines (LSSVM in the rectifier side. Firstly, we deduce the high frequency transient mathematical model of VSC-HVDC system. Then we investigate the ADRC and LSSVM principles. We ignore the tracking differentiator in the ADRC controller aiming to improve the system dynamic response speed. On this basis, we derive the mathematical model of ADRC controller optimized by LSSVM for direct current voltage loop. Finally we carry out simulations to verify the feasibility and effectiveness of our proposed control method. In addition, we employ the time-frequency representation methods, i.e., Wigner-Ville distribution (WVD and adaptive optimal kernel (AOK time-frequency representation, to demonstrate our proposed method performs better than the traditional method from the perspective of energy distribution in time and frequency plane.

  8. Applying biotin-streptavidin binding for iscom (immunostimulating complex) association of recombinant immunogens.

    Science.gov (United States)

    Wikman, Maria; Friedman, Mikaela; Pinitkiatisakul, Sunan; Hemphill, Andrew; Lövgren-Bengtsson, Karin; Lundén, Anna; Ståhl, Stefan

    2005-04-01

    We have previously reported strategies for Escherichia coli production of recombinant immunogens fused to hydrophobic peptide or lipid tags to improve their capacity to be incorporated into an adjuvant formulation. In the present study, we have explored the strong interaction between biotin and SA (streptavidin) (K(D) approximately 10(-15) M) to couple recombinant immunogens to iscoms (immunostimulating complexes). Two different concepts were evaluated. In the first concept, a His(6)-tagged SA fusion protein (His(6)-SA) was bound to Ni(2+)-loaded iscom matrix (iscom without associated protein), and biotinylated immunogens were thereafter associated with the SA-coated iscoms. The immunogens were either biotinylated in vivo on E. coli expression or double biotinylated in vivo and in vitro. In the second concept, the recombinant immunogens were expressed as SA fusion proteins, which were directly bound to a biotinylated iscom matrix. A 53-amino-acid malaria peptide (M5), derived from the central repeat region of the Plasmodium falciparum blood-stage antigen Pf155/RESA, and a 232-amino-acid segment (SRS2') from the central region (from Pro-97 to Lys-328) of the major surface antigen NcSRS2 of the protozoan parasite Neospora caninum, served as model immunogens in the present study. All fusion proteins generated were found to be efficiently expressed and could be recovered to high purity using affinity chromatography. The association between the different immunogen-containing fusion proteins and the corresponding iscom matrix was demonstrated by analytical ultracentrifugation in a sucrose density gradient. However, some fusion proteins were, to a certain extent, also found to associate unspecifically with a regular iscom matrix. Furthermore, selected iscom fractions were demonstrated to induce high-titre antigen-specific antibody responses on immunization of mice. For the particular target immunogen SRS2', the induced antibodies demonstrated reactivity to the native

  9. Review: The transcripts associated with organ allograft rejection.

    Science.gov (United States)

    Halloran, Philip F; Venner, Jeffery M; Madill-Thomsen, Katelynn S; Einecke, Gunilla; Parkes, Michael D; Hidalgo, Luis G; Famulski, Konrad S

    2018-04-01

    The molecular mechanisms operating in human organ transplant rejection are best inferred from the mRNAs expressed in biopsies because the corresponding proteins often have low expression and short half-lives, while small non-coding RNAs lack specificity. Associations should be characterized in a population that rigorously identifies T cell-mediated (TCMR) and antibody-mediated rejection (ABMR). This is best achieved in kidney transplant biopsies, but the results are generalizable to heart, lung, or liver transplants. Associations can be universal (all rejection), TCMR-selective, or ABMR-selective, with universal being strongest and ABMR-selective weakest. Top universal transcripts are IFNG-inducible (eg, CXCL11 IDO1, WARS) or shared by effector T cells (ETCs) and NK cells (eg, KLRD1, CCL4). TCMR-selective transcripts are expressed in activated ETCs (eg, CTLA4, IFNG), activated (eg, ADAMDEC1), or IFNG-induced macrophages (eg, ANKRD22). ABMR-selective transcripts are expressed in NK cells (eg, FGFBP2, GNLY) and endothelial cells (eg, ROBO4, DARC). Transcript associations are highly reproducible between biopsy sets when the same rejection definitions, case mix, algorithm, and technology are applied, but exact ranks will vary. Previously published rejection-associated transcripts resemble universal and TCMR-selective transcripts due to incomplete representation of ABMR. Rejection-associated transcripts are never completely rejection-specific because they are shared with the stereotyped response-to-injury and innate immunity. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  10. Identification of immunogenic and virulence-associated Campylobacter jejuni proteins

    DEFF Research Database (Denmark)

    Nielsen, Lene Nørby; Luijkx, Thomas A.; Vegge, Christina Skovgaard

    2012-01-01

    With the aim of identifying proteins important for host interaction and virulence, we have screened an expression library of NCTC 11168 Campylobacter jejuni genes for highly immunogenic proteins. A commercial C. jejuni open reading frame (ORF) library consisting of more than 1,600 genes was trans......With the aim of identifying proteins important for host interaction and virulence, we have screened an expression library of NCTC 11168 Campylobacter jejuni genes for highly immunogenic proteins. A commercial C. jejuni open reading frame (ORF) library consisting of more than 1,600 genes...

  11. Immunogenicity of novel sulfadimethoxide conjugates | Chen ...

    African Journals Online (AJOL)

    Immunogenicity of novel sulfadimethoxide conjugates. L Chen, J Su, X Zhang, L Li, X He. Abstract. Sulfadimethoxine (SDM) is an antibiotic commonly added to animal feeds. Anti-SDM antibodies are useful for the detection of residual SDM in foods, feeds and biological fluids by ELISA. In this study, we show that SDM is ...

  12. LATE RENAL GRAFT REJECTION: PATHOLOGY AND PROGNOSIS

    Directory of Open Access Journals (Sweden)

    E.S. Stolyarevich

    2014-01-01

    Full Text Available Rejection has always been one of the most important cause of late renal graft dysfunction. Aim of the study was to analyze the prevalence of different clinico-pathological variants of rejection that cause late graft dysfunction, and evaluate their impact on long-term outcome. Materials and methods. This is a retrospective study that analyzed 294 needle core biopsy specimens from 265 renal transplant recipients with late (48,8 ± 46,1 months after transplantation allograft dysfunction caused by late acute rejection (LAR, n = 193 or chronic rejection (CR, n = 78 or both (n = 23. C4d staining was performed by immunofl uorescence (IF on frozen sections using a standard protocol. Results. Peritubular capillary C4d deposition was identifi ed in 36% samples with acute rejection and in 62% cases of chronic rejection (including 67% cases of transplant glomerulopathy, and 50% – of isolated chronic vasculopathy. 5-year graft survival for LAR vs CR vs their combination was 47, 13 and 25%, respectively. The outcome of C4d– LAR was (p < 0,01 better than of C4d+ acute rejection: at 60 months graft survival for diffuse C4d+ vs C4d− was 33% vs 53%, respectively. In cases of chronic rejection C4d+ vs C4d– it was not statistically signifi cant (34% vs 36%. Conclusion. In long-term allograft biopsy C4d positivity is more haracteristic for chronic rejection than for acute rejection. Only diffuse C4d staining affects the outcome. C4d– positivity is associated with worse allograft survival in cases of late acute rejection, but not in cases of chronic rejection

  13. Immunogenicity of therapeutic proteins: the use of animal models.

    Science.gov (United States)

    Brinks, Vera; Jiskoot, Wim; Schellekens, Huub

    2011-10-01

    Immunogenicity of therapeutic proteins lowers patient well-being and drastically increases therapeutic costs. Preventing immunogenicity is an important issue to consider when developing novel therapeutic proteins and applying them in the clinic. Animal models are increasingly used to study immunogenicity of therapeutic proteins. They are employed as predictive tools to assess different aspects of immunogenicity during drug development and have become vital in studying the mechanisms underlying immunogenicity of therapeutic proteins. However, the use of animal models needs critical evaluation. Because of species differences, predictive value of such models is limited, and mechanistic studies can be restricted. This review addresses the suitability of animal models for immunogenicity prediction and summarizes the insights in immunogenicity that they have given so far.

  14. Pulse amplifier with high 'common mode rejection'

    International Nuclear Information System (INIS)

    Ijlst, P.

    1987-01-01

    The input signal of a pulse amplifier contains large 'common-mode' signals which have to be suppressed. A transformer, especially constructed for this purpose, is described. It has been tried to optimize the signal to noise ratio of the pulse amplifier by means of noise analysis. (Auth.)

  15. EEG asymmetry in borderline personality disorder and depression following rejection.

    Science.gov (United States)

    Beeney, Joseph E; Levy, Kenneth N; Gatzke-Kopp, Lisa M; Hallquist, Michael N

    2014-04-01

    Borderline personality disorder (BPD) and major depressive disorder (MDD) share numerous features, including dysphoric affect, irritability, suicidality, and a heightened sensitivity to perceived interpersonal rejection. However, these disorders are associated with divergent profiles of reactivity to rejection: Individuals with MDD are more likely to respond with withdrawal and isolation, and those with BPD appear to respond with increased approach behaviors and greater hostility. Potential mechanisms underlying these divergent patterns of response have not been elaborated. The goal of the present study was to assess whether prefrontal cortical asymmetry is associated with these behavioral profiles. EEG alpha activity was recorded at baseline and after individuals with BPD, MDD and healthy controls (HCs) participated in a rejection task. Although no differences were found at baseline, results demonstrated that following rejection, individuals with BPD showed greater left cortical activation, consistent with approach motivation, whereas those with MDD showed greater right cortical activation, consistent with withdrawal motivation. HCs evidenced a more balanced cortical profile, as hypothesized. Although BPD and MDD are highly comorbid, are easily confused, and are phenomenologically similar in a number of ways, individuals with these two disorders respond in very different ways to perceived rejection. PsycINFO Database Record (c) 2014 APA, all rights reserved

  16. Microbial Proteases in Baked Goods: Modification of Gluten and Effects on Immunogenicity and Product Quality

    Directory of Open Access Journals (Sweden)

    Nina G. Heredia-Sandoval

    2016-08-01

    Full Text Available Gluten-related diseases are a range of inflammatory disorders of the small intestine, characterized by an adverse response to gluten ingestion; therefore, the treatment is a gluten withdrawal. In spite of the increased market of gluten-free products, widely available breads with high acceptability are still missing due to the technological challenge of substituting the special gluten properties. Instead of using alternative ingredients for baking, some attempts have been done to decrease gluten immunogenicity by its enzymatic degradation with microbial proteases. Although the gluten immunogenicity reduction has been reached to an acceptable level, some quality parameters of the products are affected. This review focus on the use of microbial peptidases to prepare less immunogenic baked goods and their effect on product quality.

  17. EVALUATION OF REACTOGENICITY, SAFETY AND IMMUNOGENICITY OF INACTIVATED MONOVALENT VACCINE IN CHILDREN

    Directory of Open Access Journals (Sweden)

    A.N. Mironov

    2010-01-01

    Full Text Available NPO «Microgen» developed vaccine «PANDEFLU» — influenza inactivated subunit adsorbed monovalent vaccine, strain A/California/7/2009 (H1N1, for specific prophylaxis of pandemic influenza in different age groups of citizens. Reactogenicity, safety and immunogenicity were analyzed in a study of volunteers 18–60 years old. The article presents results of administration of vaccine «PANDEFLU» in children. The study performed in two clinical centers proves good tolerability, reactogenicity, safety and high immunogenicity of this vaccine.Key words: children, influenza, influenza virus А/H1N1, inactivated influenza vaccine, reactogenicity, safety, immunogenicity.(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(4:106-109

  18. The safety and immunogenicity of influenza vaccine in children with asthma in Mexico.

    Science.gov (United States)

    Pedroza, Alvaro; Huerta, José G; Garcia, Maria de la Luz; Rojas, Arsheli; López-Martínez, Irma; Penagos, Martín; Franco-Paredes, Carlos; Deroche, Christele; Mascareñas, Cesar

    2009-07-01

    The morbidity and mortality associated with influenza is substantial in children with asthma. There are no available data on the safety and immunogenicity of influenza vaccine in children with asthma in Latin America. Furthermore, it is unclear if influenza vaccination may cause asthma exacerbations. We conducted a placebo-controlled trial to investigate the safety and immunogenicity of an inactivated trivalent split virus influenza vaccine in children with asthma in Mexico. We also measured the impact of influenza vaccination on pulmonary function tests in this population. The inactivated influenza vaccine was immunogenic and safe in terms of local and systemic side effects compared to placebo. We observed no significant impact on pulmonary function tests among vaccine recipients. Given the significant morbidity associated with influenza in children, strategies to promote increased influenza vaccination coverage in this high-risk group in Latin America and elsewhere are urgently needed.

  19. Microbial Proteases in Baked Goods: Modification of Gluten and Effects on Immunogenicity and Product Quality.

    Science.gov (United States)

    Heredia-Sandoval, Nina G; Valencia-Tapia, Maribel Y; Calderón de la Barca, Ana M; Islas-Rubio, Alma R

    2016-08-30

    Gluten-related diseases are a range of inflammatory disorders of the small intestine, characterized by an adverse response to gluten ingestion; therefore, the treatment is a gluten withdrawal. In spite of the increased market of gluten-free products, widely available breads with high acceptability are still missing due to the technological challenge of substituting the special gluten properties. Instead of using alternative ingredients for baking, some attempts have been done to decrease gluten immunogenicity by its enzymatic degradation with microbial proteases. Although the gluten immunogenicity reduction has been reached to an acceptable level, some quality parameters of the products are affected. This review focus on the use of microbial peptidases to prepare less immunogenic baked goods and their effect on product quality.

  20. Results of radioiodine therapy of patients with immunogenic and non-immunogenic hyperthyroidism using different radiation doses

    International Nuclear Information System (INIS)

    Moser, E.; Pickardt, C.R.; Mann, K.; Engelhardt, D.; Kirsch, C.M.; Knesewitsch, P.; Tatsch, K.; Kreisig, T.; Kurz, C.; Saller, B.; Klinikum Grosshadern, Muenchen; Muenchen Univ.

    1988-01-01

    The aim of this study was to check the efficacy of radioiodine ( 131 I) therapy (RIT) in a large number of patients (n = 506) suffering from immunogenic or non-immunogenic hyperthyroidism (Graves' disease, Plummer's disease). Since there is no causal cure for immunogenic hyperthyroidism RIT provides, like all other modalities, only a moderate rate of success which is clearly dose-related. Applying 60 Gy, normal thyroid function can be achieved is only 54% of the cases. A dose of 150 Gy succeeds in 86% of the cases. The solitary decompensated autonomous adenoma (DAA) can be eliminated surgically as well as by RIT with a high degree of success (95%). Contrary to surgery, RIT does not have any noticeable early or late morbidity. The high rate of success of RIT in patients with DAA could be confirmed in two groups with different follow-up periods (16 and 65 months). As expected, the rate of hypothyroidism increased from 11% in the early group to 23% in the late group. Multinodular autonomous adenomas can be eliminated successfully using RIT as well. The concept to apply a dose of 400 Gy to the total functional autonomous tissue as determined by ultrasound yields better results (95%) than 150 Gy to the whole thyroid gland as measured by ultrasound (88%). The rate of hypothyroidism as shown by these results (up to a maximum of 62% after RIT of Graves' disease using 150 Gy) is the lesser evil compared to remaining or recurrent hyperthyroidism since these patients can be treated with thyroid hormones without problems. (orig.) [de

  1. Study of Background Rejection Systems for the IXO Mission.

    Science.gov (United States)

    Laurent, Philippe; Limousin, O.; Tatischeff, V.

    2009-01-01

    The scientific performances of the IXO mission will necessitate a very low detector background level. This will imply thorough background simulations, and efficient background rejection systems. It necessitates also a very good knowledge of the detectors to be shielded. In APC, Paris, and CEA, Saclay, we got experience on these activities by conceiving and optimising in parallel the high energy detector and the active and passive background rejection system of the Simbol-X mission. Considering that this work may be naturally extended to other X-ray missions, we have initiated with CNES a R&D project on the study of background rejection systems mainly in view the IXO project. We will detail this activity in the poster.

  2. Synthesis of unsymmetrical dimethylhydrazine oxalate from rejected liquid rocket propellant

    Science.gov (United States)

    Mu, Xiaogang; Yang, Jingjing; Zhang, Youzhi

    2018-02-01

    The rejected liquid propellant unsymmetrical dimethylhydrazine (UDMH) was converted to UDMH oxalate, which has commercial value. The UDMH oxalate structure and stability were investigated by the Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, differential scanning calorimetry, and ultraviolet-visible spectrophotometric analysis. The results indicate that UDMH oxalate has good thermal and aqueous solution stability, a melting point of 144 °C, an initial decomposition temperature of 180 °C, and a peak wavelength of UV in aqueous solution at λ = 204 nm. This disposal method of rejected UDMH is highly efficient and environmentally safe.

  3. Listeriolysin o is strongly immunogenic independently of its cytotoxic activity.

    Directory of Open Access Journals (Sweden)

    Javier A Carrero

    Full Text Available The presentation of microbial protein antigens by Major Histocompatibility Complex (MHC molecules is essential for the development of acquired immunity to infections. However, most biochemical studies of antigen processing and presentation deal with a few relatively inert non-microbial model antigens. The bacterial pore-forming toxin listeriolysin O (LLO is paradoxical in that it is cytotoxic at nanomolar concentrations as well as being the source of dominant CD4 and CD8 T cell epitopes following infection with Listeria monocytogenes. Here, we examined the relationship of LLO toxicity to its antigenicity and immunogenicity. LLO offered to antigen presenting cells (APC as a soluble protein, was presented to CD4 T cells at picomolar to femtomolar concentrations- doses 3000-7000-fold lower than free peptide. This presentation required a dose of LLO below the cytotoxic level. Mutations of two key tryptophan residues reduced LLO toxicity by 10-100-fold but had no effect on its presentation to CD4 T cells. Thus there was a clear dissociation between the cytotoxic properties of LLO and its very high antigenicity. Presentation of LLO to CD8 T cells was not as robust as that seen in CD4 T cells, but still occurred in the nanomolar range. APC rapidly bound and internalized LLO, then disrupted endosomal compartments within 4 hours of treatment, allowing endosomal contents to access the cytosol. LLO was also immunogenic after in vivo administration into mice. Our results demonstrate the strength of LLO as an immunogen to both CD4 and CD8 T cells.

  4. "I'm worth more than that": trait positivity predicts increased rejection of unfair financial offers.

    Directory of Open Access Journals (Sweden)

    Barnaby D Dunn

    2010-12-01

    Full Text Available Humans react strongly to unfairness, sometimes rejecting inequitable proposals even if this sacrifices personal financial gain. Here we explored whether emotional dispositions--trait tendencies to experience positive or negative feelings--shape the rejection of unfair financial offers. Participants played an Ultimatum Game, where the division of a sum of money is proposed and the player can accept or reject this offer. Individuals high in trait positivity and low in trait negativity rejected more unfair offers. These relationships could not be explained by existing accounts which argue that rejection behaviour results from a failure to regulate negative emotions, or serves to arbitrate social relationships and identity. Instead, the relationship between dispositional affect and rejection behaviour may be underpinned by perceived self worth, with those of a positive disposition believing that they are "worth more than that" and those of a negative disposition resigning themselves to "taking the crumbs from under the table".

  5. Band rejection filter for measurement of electron cyclotron emission during electron cyclotron heating

    International Nuclear Information System (INIS)

    Iwase, Makoto; Ohkubo, Kunizo; Kubo, Shin; Idei, Hiroshi.

    1996-05-01

    For the measurement of electron cyclotron emission from the high temperature plasma, a band rejection filter in the range of 40-60 GHz is designed to reject the 53.2 GHz signal with large amplitude from the gyrotron for the purpose of plasma electron heating. The filter developed with ten sets of three quarters-wavelength coupled by TE 111 mode of tunable resonant cavity has rejection of 50 dB and 3 dB bandwidth of 500 MHz. The modified model of Tschebysheff type for the prediction of rejection is proposed. It is confirmed that the measured rejection as a function of frequency agrees well with the experimental results for small coupling hole, and also clarified that the rejection ratio increases for the large coupling hole. (author)

  6. "I'm worth more than that": trait positivity predicts increased rejection of unfair financial offers.

    Science.gov (United States)

    Dunn, Barnaby D; Makarova, Dasha; Evans, David; Clark, Luke

    2010-12-08

    Humans react strongly to unfairness, sometimes rejecting inequitable proposals even if this sacrifices personal financial gain. Here we explored whether emotional dispositions--trait tendencies to experience positive or negative feelings--shape the rejection of unfair financial offers. Participants played an Ultimatum Game, where the division of a sum of money is proposed and the player can accept or reject this offer. Individuals high in trait positivity and low in trait negativity rejected more unfair offers. These relationships could not be explained by existing accounts which argue that rejection behaviour results from a failure to regulate negative emotions, or serves to arbitrate social relationships and identity. Instead, the relationship between dispositional affect and rejection behaviour may be underpinned by perceived self worth, with those of a positive disposition believing that they are "worth more than that" and those of a negative disposition resigning themselves to "taking the crumbs from under the table".

  7. 21 CFR 1230.47 - Rejected containers.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rejected containers. 1230.47 Section 1230.47 Food... FEDERAL CAUSTIC POISON ACT Imports § 1230.47 Rejected containers. (a) In all cases where the containers... notification to the importer that the containers must be exported under customs supervision within 3 months...

  8. MR imaging of renal transplant rejection

    International Nuclear Information System (INIS)

    Hanna, S.; Helenon, O.; Legendre, C.; Chichie, J.F.; Di Stefano, D.; Kreis, H.; Moreau, J.F.; Hopital Necker, 75 - Paris

    1991-01-01

    The results of 62 consecutive MR examinations were correlated with the subsequent clinical course and histologic results. Twenty-six cases of rejection showed a marked diminution of cortico-medullary differentiation (CMD). The renal parenchymal vascular pattern and visibility of renal sinus fat were not markedly altered in rejection and there was no difference between normal and rejected allograft shape. The ability of MR imaging to diagnose renal transplant rejection is only based on CMD, which, however, is non-specific. In 2 cases of severe rejection, T2 weighted images showed an abnormal signal intensity of the cortex due to renal infarction. Our preliminary results in 8 patients with Gd-DOTA injection showed 2 cases with necrosis seen as areas with absent contrast enhancement. This technique seems to be promising in the detection of perfusion defects. (orig.)

  9. Risk of renal allograft rejection following angiography

    International Nuclear Information System (INIS)

    Heideman, M.; Claes, G.; Nilson, A.E.

    1976-01-01

    In a retrospective study of 173 immediately functioning primary kidney transplants, correlation between angiography and renal allograft rejection was studied during the first 14 days. It was found that rejection was more frequent in kidneys undergoing angiography than in those not undergoing angiography. It was also found that in kidneys undergoing angiography an overwhelming number of the rejections started the day after angiography. These differences in rejection frequency could not be explained by differences in HLA matching or the origin of the kidneys. These findings suggest a possible connection indicating that the angiography might elicit an acute rejection episode. A possible mechanism for starting this reaction might be activation of the complement system which was found in 50 percent of the patients undergoing angiography in peripheral blood and in 100 percent when studied in vitro

  10. Modeling of RO/NF membrane rejections of PhACs and organic compounds: a statistical analysis

    Directory of Open Access Journals (Sweden)

    G. Amy

    2008-07-01

    Full Text Available Rejections of pharmaceutical compounds (Ibuprofen, Diclofenac, Clofibric acid, Naproxen, Primidone, Phenacetin and organic compounds (Dichloroacetic acid, Trichloroacetic acid, Chloroform, Bromoform, Trichloroethene, Perchloroethene, Carbontetrachloride, Carbontetrabromide by NF (Filmtec, Saehan and RO (Filmtec, Saehan, Toray, Koch membranes were studied. Chloroform presented the lowest rejection due to small molar volume, equivalent width and length. Diclofenac and Primidone showed high rejections related to high molar volume and length. Dichloroacetic acid and Trichloroacetic acid presented good rejections caused by charge exclusion instead of steric hindrance mechanism influencing rejection. Bromoform and Trichloroethene showed low rejections due to small length and equivalent width. Carbontetrabromide, Perchloroethene and Carbontetrachloride with higher equivalent width than BF and TCE presented better rejections. A qualitative analysis of variables using Principal Component Analysis was successfully implemented for reduction of physical-chemical compound properties that influence membrane rejection of PhACs and organic compounds. Properties such as dipole moment, molar volume, hydrophobicity/hydrophilicity, molecular length and equivalent width were found to be important descriptors for simulation of membrane rejection. For membranes used in the experiments, we may conclude that charge repulsion was an important mechanism of rejection for ionic compounds. After analysis with Multiple Linear Regression, we also may conclude that membrane rejection of neutral compounds was well predicted by molar volume, length, equivalent width, hydrophobicity/hydrophilicity and dipole moment. Molecular weight was a poor descriptor variable for rejection modelling. We were able to provide acceptable statistical significance for important results.

  11. Remembering rejection: specificity and linguistic styles of autobiographical memories in borderline personality disorder and depression.

    Science.gov (United States)

    Rosenbach, Charlotte; Renneberg, Babette

    2015-03-01

    High levels of rejection sensitivity are assumed to be the result of early and prolonged experiences of rejection. Aim of this study was to investigate autobiographical memories of rejection in clinical samples high in rejection sensitivity (Borderline Personality Disorder, BPD, and Major Depressive Disorder, MDD) and to identify group differences in the quality of the memories. Memories of rejection were retrieved using an adapted version of the Autobiographical Memory Test (AMT; five positive cue words, five cue words referring to rejection). Specificity of memories and linguistic word usage was analyzed in 30 patients with BPD, 27 patients with MDD and 30 healthy controls. Patients with BPD retrieved less specific memories compared to the healthy control group, whereas patients with MDD did not differ from controls in this regard. The group difference was no longer significant when controlling for rejection sensitivity. Linguistic analysis indicated that compared to both other groups, patients with BPD showed a higher self-focus, used more anger-related words, referred more frequently to social environments, and rated memories of rejection as more relevant for today's life. Clinical symptoms were not assessed in the control group. Moreover, the written form of the AMT might reduce the total number of specific memories. The level of rejection sensitivity influenced the specificity of the retrieved memories. Analysis of linguistic styles revealed specific linguistic patterns in BPD compared to non-clinical as well as depressed participants. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Image rejects/retakes--radiographic challenges.

    Science.gov (United States)

    Waaler, D; Hofmann, B

    2010-01-01

    A general held position among radiological personnel prior to digitalisation was that the problem of image rejects/retakes should more or less vanish. However, rejects/retakes still impose several challenges within radiographic imaging; they occupy unnecessary resources, expose patients to unnecessary ionizing radiation and may also indicate suboptimal quality management. The latter is the main objective of this paper, which is based on a survey of international papers published both for screen/film and digital technology. The digital revolution in imaging seems to have reduced the percentage of image rejects/retakes from 10-15 to 3-5 %. The major contribution to the decrease appears to be the dramatic reduction of incorrect exposures. At the same time, rejects/retakes due to lack of operator competence (positioning, etc.) are almost unchanged, or perhaps slightly increased (due to lack of proper technical competence, incorrect organ coding, etc.). However, the causes of rejects/retakes are in many cases defined and reported with reference to radiographers' subjective evaluations. Thus, unless radiographers share common views on image quality and acceptance criteria, objective measurements and assessments of reject/retake rates are challenging tasks. Interestingly, none of the investigated papers employs image quality parameters such as 'too much noise' as categories for rejects/retakes. Surprisingly, no reject/retake analysis seems yet to have been conducted for direct digital radiography departments. An increased percentage of rejects/retakes is related to 'digital skills' of radiographers and therefore points to areas for extended education and training. Furthermore, there is a need to investigate the inter-subjectivity of radiographers' perception of, and attitude towards, both technical and clinical image quality criteria. Finally, there may be a need to validate whether reject/retake rate analysis is such an effective quality indicator as has been asserted.

  13. Image rejects/retakes-radiographic challenges

    International Nuclear Information System (INIS)

    Waaler, D.; Hofmann, B.

    2010-01-01

    A general held position among radiological personnel prior to digitalisation was that the problem of image rejects/retakes should more or less vanish. However, rejects/retakes still impose several challenges within radiographic imaging; they occupy unnecessary resources, expose patients to unnecessary ionizing radiation and may also indicate suboptimal quality management. The latter is the main objective of this paper, which is based on a survey of international papers published both for screen/film and digital technology. The digital revolution in imaging seems to have reduced the percentage of image rejects/retakes from 10-15 to 3-5%. The major contribution to the decrease appears to be the dramatic reduction of incorrect exposures. At the same time, rejects/retakes due to lack of operator competence (positioning, etc.) are almost unchanged, or perhaps slightly increased (due to lack of proper technical competence, incorrect organ coding, etc.). However, the causes of rejects/retakes are in many cases defined and reported with reference to radiographers' subjective evaluations. Thus, unless radiographers share common views on image quality and acceptance criteria, objective measurements and assessments of reject/retake rates are challenging tasks. Interestingly, none of the investigated papers employs image quality parameters such as 'too much noise' as categories for rejects/retakes. Surprisingly, no reject/retake analysis seems yet to have been conducted for direct digital radiography departments. An increased percentage of rejects/retakes is related to 'digital skills' of radiographers and therefore points to areas for extended education and training. Furthermore, there is a need to investigate the inter subjectivity of radiographers' perception of, and attitude towards, both technical and clinical image quality criteria. Finally, there may be a need to validate whether reject/retake rate analysis is such an effective quality indicator as has been asserted

  14. T-regulatory cells in chronic rejection versus stable grafts.

    Science.gov (United States)

    Al-Wedaie, Fatima; Farid, Eman; Tabbara, Khaled; El-Agroudy, Amgad E; Al-Ghareeb, Sumaya M

    2015-04-01

    Studying regulatory T cells in kidney allograft acceptance versus chronic rejection may help in the understanding of more mechanisms of immune tolerance and, in the future, may enable clinicians to induce immune tolerance and decrease the use of immunosuppressive drugs. The aim of the current study was to evaluate regulatory T cells in kidney transplant patients with stable graft versus transplant with biopsy-proven chronic rejection. The 3 groups that were studied included: kidney transplanted patients with no rejection episodes (n = 43); transplanted patients with biopsy-proven renal rejection (n = 27); and healthy age-matched nontransplanted individuals as controls (n = 42).The percentage of regulatory T cells (CD4+CD25+Foxp3+) in blood was determined by flow cytometry. The regulatory T cell percentage was significantly lower in chronic rejection patients than control or stable graft groups. No significant difference was observed in regulatory T cell percentage between the stable graft and control groups. In the stable graft group, patients on rapamycin had a significantly higher regulatory T cell percentage than patients on cyclosporine. No effect of donor type, infection, or duration after transplant was observed on regulatory T cell percentage. The results of the current study are consistent with previous studies addressing the function of regulatory T cells in inducing immunotolerance after kidney transplant. Considering the established role of regulatory T cells in graft maintenance and our observation of high regulatory T cell percentage in patients receiving rapamycin than cyclosporine, we recommend including rapamycin when possible in immunosuppressive protocols. The findings from the current study on the chronic rejection group support ongoing research of having treatment with regulatory T cells, which may constitute a novel, efficient antirejection therapy in the future.

  15. Trajectories of Italian Children's Peer Rejection: Associations with Aggression, Prosocial Behavior, Physical Attractiveness, and Adolescent Adjustment.

    Science.gov (United States)

    Di Giunta, Laura; Pastorelli, Concetta; Thartori, Eriona; Bombi, Anna Silvia; Baumgartner, Emma; Fabes, Richard A; Martin, Carol Lynn; Enders, Craig K

    2017-12-08

    In the present study, the predictors and outcomes associated with the trajectories of peer rejection were examined in a longitudinal sample of Italian children (338 boys, 269 girls) ages 10 to 14 years. Follow-up assessments included 60% of the original sample at age 16-17. Low, medium, and high rejection trajectory groups were identified using growth mixture models. Consistent with previous studies, we found that (a) being less prosocial and more physically aggressive at age 10 was characteristic of those children with the high rejection trajectory; (b) being less attractive was related to higher peer rejection from age 10 to 14; and (c) boys with a high rejection trajectory showed high levels of delinquency and anxiety-depression and low levels of academic aspiration at age 16-17, whereas girls with a high rejection trajectory showed low levels of academic aspiration and social competence at age 16-17. Our findings indicate the detrimental consequences of peer rejection on children's development and adjustment and shed light on the mechanisms that contribute to maintaining or worsening (e.g., being attractive, prosocial, and aggressive) a child's negative status (e.g., being rejected) within his or her peer group over time.

  16. Novel autoantigens immunogenic in COPD patients

    Directory of Open Access Journals (Sweden)

    Stephan Bernhard

    2009-03-01

    Full Text Available Abstract Background Chronic obstructive pulmonary disease (COPD is a respiratory inflammatory condition with autoimmune features including IgG autoantibodies. In this study we analyze the complexity of the autoantibody response and reveal the nature of the antigens that are recognized by autoantibodies in COPD patients. Methods An array of 1827 gridded immunogenic peptide clones was established and screened with 17 sera of COPD patients and 60 healthy controls. Protein arrays were evaluated both by visual inspection and a recently developed computer aided image analysis technique. By this computer aided image analysis technique we computed the intensity values for each peptide clone and each serum and calculated the area under the receiver operator characteristics curve (AUC for each clone and the separation COPD sera versus control sera. Results By visual evaluation we detected 381 peptide clones that reacted with autoantibodies of COPD patients including 17 clones that reacted with more than 60% of the COPD sera and seven clones that reacted with more than 90% of the COPD sera. The comparison of COPD sera and controls by the automated image analysis system identified 212 peptide clones with informative AUC values. By in silico sequence analysis we found an enrichment of sequence motives previously associated with immunogenicity. Conclusion The identification of a rather complex humoral immune response in COPD patients supports the idea of COPD as a disease with strong autoimmune features. The identification of novel immunogenic antigens is a first step towards a better understanding of the autoimmune component of COPD.

  17. Prosthesis rejection in acquired major upper-limb amputees: a population-based survey.

    Science.gov (United States)

    Østlie, Kristin; Lesjø, Ingrid Marie; Franklin, Rosemary Joy; Garfelt, Beate; Skjeldal, Ola Hunsbeth; Magnus, Per

    2012-07-01

    To estimate the rates of primary and secondary prosthesis rejection in acquired major upper-limb amputees (ULAs), to describe the most frequently reported reasons for rejection and to estimate the influence of background factors on the risk of rejection. Cross-sectional study analysing population-based questionnaire data (n = 224). Effects were analysed by logistic regression analyses and Cox regression analyses. Primary prosthesis rejection was found in 4.5% whereas 13.4% had discontinued prosthesis use. The main reasons reported for primary non-wear were a perceived lack of need and discrepancies between perceived need and the prostheses available. The main reasons reported for secondary prosthesis rejection were dissatisfaction with prosthetic comfort, function and control. Primary prosthesis rejection was more likely in ULAs amputated at high age and in ULAs with proximal amputations. Secondary prosthesis rejection was more likely in proximal ULAs and in women. Clinicians should be aware of the increased risk of rejection in proximal ULAs, elderly ULAs and in women. Emphasising individual needs will probably facilitate successful prosthetic fitting. Improved prosthesis quality and individualised prosthetic training may increase long-term prosthesis use. Further studies of the effect of prosthetic training and of the reasons for rejection of different prosthetic types are suggested.

  18. The convergence of radiation and immunogenic cell death signaling pathways

    International Nuclear Information System (INIS)

    Golden, Encouse B.; Pellicciotta, Ilenia; Demaria, Sandra; Barcellos-Hoff, Mary H.; Formenti, Silvia C.

    2012-01-01

    Ionizing radiation (IR) triggers programmed cell death in tumor cells through a variety of highly regulated processes. Radiation-induced tumor cell death has been studied extensively in vitro and is widely attributed to multiple distinct mechanisms, including apoptosis, necrosis, mitotic catastrophe (MC), autophagy, and senescence, which may occur concurrently. When considering tumor cell death in the context of an organism, an emerging body of evidence suggests there is a reciprocal relationship in which radiation stimulates the immune system, which in turn contributes to tumor cell kill. As a result, traditional measurements of radiation-induced tumor cell death, in vitro, fail to represent the extent of clinically observed responses, including reductions in loco-regional failure rates and improvements in metastases free and overall survival. Hence, understanding the immunological responses to the type of radiation-induced cell death is critical. In this review, the mechanisms of radiation-induced tumor cell death are described, with particular focus on immunogenic cell death (ICD). Strategies combining radiotherapy with specific chemotherapies or immunotherapies capable of inducing a repertoire of cancer specific immunogens might potentiate tumor control not only by enhancing cell kill but also through the induction of a successful anti-tumor vaccination that improves patient survival.

  19. The clinical utility of indium-111 labelled platelet scintigraphy in the diagnoses of renal transplant rejection

    International Nuclear Information System (INIS)

    Desir, G.V.; Bia, M.; Lange, R.C.; Smith, E.O.; Flye, W.; Kashgarian, M.; Schiff, M.; Ezekowitz, M.D.

    1990-01-01

    It is demonstrated that indium-111 labelled platelet scintigraphy is a highly accurate test for detecting acute untreated renal allograft rejection and it is shown that changes in platelet uptake can precede signs and symptoms of rejection by at least 48 hours. (author). 34 refs.; 2 figs.; 1 tab

  20. PHOSPHATES REMOVAL FROM REJECT WATER FROM DIGESTION OF SLUDGE

    Directory of Open Access Journals (Sweden)

    Elżbieta Sperczyńska

    2016-06-01

    Full Text Available The aim of the research work was to evaluate if coagulants used on technical scale are useful in phosphates removal from reject water. Effectiveness of phosphorus compounds removal from reject water from digestion of sewage sludge was examined. Selected prehydrolysed alkaline aluminium polychlorides were used. The results were compared to the ones obtained with aluminium sulphate. Reject water from digestion of sewage sludge form WWTP of 100 000 PE were examined. Commercial agents – prehydrolysed PAX 18, PAX XL10, PAX-XL1905 as well as aluminium sulphate were used. Various doses of coagulants: 0.7; 1.0; 1.5 – time higher than stoichiometric dose were applied. Stoichiometric dose was calculated based on chemical reaction of insoluble aluminium phosphate formation. Concentrations of Kiejdahl nitrogen (891 mgNKj/dm3, phosphates (125 mgPO43-/dm3 and organic compounds - COD (592 mgO2/dm3 in reject water were very high. The effectiveness of coagulation process increased as the doses of chemical agents increased. The most effective doses were the highest ones used during the experiment. The most effective agent was PAX 18 (96% removal efficiency. As the phosphates concentration decreased COD content declined simultaneously. Maximum COD removal (47% was obtained when highly alkaline PAX XL 1905 was used. Use of the lowest dose of Al2(SO43 allowed for 50% phosphates removal, whereas the lowest dose of PAX 18 decreased phosphates concentration by 83%.

  1. Immunogenicity and tolerability of inactivated flu vaccine In high risk and healthy children Inmunogenicidad y tolerancia de la vacuna inactivada anti-influenza en niños en alto riesgo y en controles sanos

    Directory of Open Access Journals (Sweden)

    Maria Luisa Avila Aguero

    2007-08-01

    Full Text Available We conducted this open study to evaluate the immunogenicity and safety of the inactivated influenza vaccine, Imovax Gripe® in 154 children between 6 and 36 months of age at high risk of influenza- related complications, and in a reference group of 64 healthy children. The study was conducted over two flu seasons, in which the vaccine contained the same A strains but different B strains. The results for the A/H3N2 and A/H1N1 strains from the two flu seasons were pooled, but those for the B strains were not. Anti-hemagglutinin (HA antibody titers were determined before, and one month after each vaccination, and safety was evaluated based on diary card reporting any adverse event observed, either included or not in the list of "solicited events". Within each group of vaccines, the seroconversion rates, seroprotection rates, and ratio of post- to prevaccination geometric mean titers (GMTR for the A/H3N2 and the A/H1N1 strains fulfilled all requirements of the criteria of the European Union Committee for Proprietary Medicinal Products (CPMP. The immune responses in high-risk and in healthy children were similar, and consistent with those observed in previous studies conducted in healthy children. The vaccine was equally well tolerated by all study groups. Reactogenicity was low and similar in both high-risk and healthy children. Overall from 9.5% to 15.4% of at-risk children and 12% of healthy children reported a solicited local reaction; 23.0 to 28.8% of high-risk and 25.3% of healthy children reported a solicited systemic reaction. The study results provide support for vaccination of children at high-risk of influenza related complications.Se realizó un estudio clínico abierto para evaluar la inmunogenícidad y la seguridad de la vacuna inactivada anti-influenza, Imovax Gripe®, en 154 niños entre 6 y 36 meses de edad con alto riesgo de complicaciones ligadas a la influenza, y en un grupo de referencia de 64 niños sanos. El estudio fue

  2. ERROR VS REJECTION CURVE FOR THE PERCEPTRON

    OpenAIRE

    PARRONDO, JMR; VAN DEN BROECK, Christian

    1993-01-01

    We calculate the generalization error epsilon for a perceptron J, trained by a teacher perceptron T, on input patterns S that form a fixed angle arccos (J.S) with the student. We show that the error is reduced from a power law to an exponentially fast decay by rejecting input patterns that lie within a given neighbourhood of the decision boundary J.S = 0. On the other hand, the error vs. rejection curve epsilon(rho), where rho is the fraction of rejected patterns, is shown to be independent ...

  3. Immunogenic hyperthyroidism following radioiodine ablation of focal autonomy

    International Nuclear Information System (INIS)

    Boddenberg, B.; Voth, E.; Schicha, H.

    1993-01-01

    Immunogenic hyperthyroidism rarely develops after radioiodine elimination of focal autonomous thyroid tissue. We observed this phenomenon in 8 patients between 1989 and 1992. The occurrence of immunogenic hyperthyroidism shortly after elimination of autonomous nodules has not been studied nor is it properly understood. Most studies known today describe the development of autonomous nodules in the course of immunogenic hyperthyroidism or ignore the chronologic order of occurrence. The possibility that immunogenic hyperthyroidism may occur after radioiodine therapy of autonomous nodules, makes a consequent follow-up within the first year following radioiodine therapy mandatory. (orig.) [de

  4. Thallium kinetics in rat cardiac transplant rejection

    International Nuclear Information System (INIS)

    Barak, J.H.; LaRaia, P.J.; Boucher, C.A.; Fallon, J.T.; Buckley, M.J.

    1988-01-01

    Cardiac transplant rejection is a very complex process involving both cellular and vascular injury. Recently, thallium imaging has been used to assess acute transplant rejection. It has been suggested that changes in thallium kinetics might be a sensitive indicator of transplant rejection. Accordingly, thallium kinetics were assessed in vivo in acute untreated rat heterotopic (cervical) transplant rejection. Male Lewis rats weighing 225-250 g received heterotopic heart transplants from syngeneic Lewis rats (group A; n = 13), or allogeneic Brown Norway rats (group B; n = 11). Rats were imaged serially on the 2nd and the 7th postoperative days. Serial cardiac thallium content was determined utilizing data collected every 150 sec for 2 hr. The data were fit to a monoexponential curve and the decay rate constant (/sec) derived. By day 7 all group B hearts had histological evidence of severe acute rejection, and demonstrated decreased global contraction. Group A hearts showed normal histology and contractility. However, thallium uptakes and washout of the two groups were the same. Peak thallium uptake of group B was +/- 3758 1166 counts compared with 3553 +/- 950 counts in the control group A (P = 0.6395); The 2-hr percentage of washout was 12.1 +/- 1.04 compared with 12.1 +/- 9.3 (P = 1.0000); and the decay constant was -0.00002065 +/- 0.00001799 compared with -0.00002202 +/- 0.00001508 (P = 0.8409). These data indicate that in vivo global thallium kinetics are preserved during mild-to-severe acute transplant rejection. These findings suggest that the complex cellular and extracellular processes of acute rejection limit the usefulness of thallium kinetics in the detection of acute transplant rejection

  5. Structural Decoupling and Disturbance Rejection in a Distillation Column

    DEFF Research Database (Denmark)

    Bahar, Mehrdad; Jantzen, Jan; Commault, C.

    1996-01-01

    Introduction, distillation column model, input-output decoupling, disturbance rejection, concluding remarks, references.......Introduction, distillation column model, input-output decoupling, disturbance rejection, concluding remarks, references....

  6. Stomaching rejection: Self-compassion and self-esteem moderate the impact of daily social rejection on restrictive eating behaviours among college women.

    Science.gov (United States)

    Beekman, Janine B; Stock, Michelle L; Howe, George W

    2017-11-01

    The present study examined whether having high self-esteem or a self-compassionate perspective help mitigate the impact of daily social rejection on negative affect and restrictive eating behaviours. Following a baseline survey assessing self-esteem and self-compassion, 121 college women completed online daily diaries for one week. Negative affect and restrictive eating behaviours. On days when women reported more rejection, they also reported higher restrictive eating behaviours and greater negative affect. Effects were moderated by self-esteem and self-compassion, such that the lower participants were in self-esteem or self-compassion, the stronger the positive relation between rejection and negative affect and restrictive eating. However, only the common humanity/isolation dimension of self-compassion significantly moderated daily effects of rejection when controlling for self-esteem. Mediated moderation results reveal different mechanisms by which self-esteem and self-compassion buffer against rejections' effects on affect and restrictive eating. Self-compassion and self-esteem influence the complex impact that social rejection has on affect and restrictive eating. More than other dimensions of self-compassion or self-esteem, remembering one's common humanity can result in a healthier response to social rejection.

  7. Corneal Graft Rejection: Incidence and Risk Factors

    Directory of Open Access Journals (Sweden)

    Alireza Baradaran-Rafii

    2008-12-01

    Full Text Available

    PURPOSE: To determine the incidence and risk factors of late corneal graft rejection after penetrating keratoplasty (PKP. METHODS: Records of all patients who had undergone PKP from 2002 to 2004 without immunosuppressive therapy other than systemic steroids and with at least one year of follow up were reviewed. The role of possible risk factors such as demographic factors, other host factors, donor factors, indications for PKP as well as type of rejection were evaluated. RESULTS: During the study period, 295 PKPs were performed on 286 patients (176 male, 110 female. Mean age at the time of keratoplasty was 38±20 (range, 40 days to 90 years and mean follow up period was 20±10 (range 12-43 months. Graft rejection occurred in 94 eyes (31.8% at an average of 7.3±6 months (range, 20 days to 39 months after PKP. The most common type of rejection was endothelial (20.7%. Corneal vascularization, regrafting, anterior synechiae, irritating sutures, active inflammation, additional anterior segment procedures, history of trauma, uncontrolled glaucoma, prior graft rejection, recurrence of herpetic infection and eccentric grafting increased the rate of rejection. Patient age, donor size and bilateral transplantation had no significant influence on graft rejection. CONCLUSION: Significant risk factors for corneal graft rejection include

  8. Immunogenicity of Anti-TNF-α Biotherapies

    DEFF Research Database (Denmark)

    Bendtzen, Klaus

    2015-01-01

    % of patients do not respond and about 50% of those who do loose response with time. Furthermore, safety may be compromised by immunogenicity with the induction of anti-drug-antibodies (ADA). Assessment of drug pharmacokinetics and ADA is increasingly recognized as a requirement for safe and rational use...... article - and the accompanying article - is to discuss the reasons for recommending assessments of circulating drug and ADA levels in patients treated with anti-TNF biopharmaceuticals and to detail some of the methodological issues that obscure cost-effective and safer therapies....

  9. Preclinical models used for immunogenicity prediction of therapeutic proteins.

    Science.gov (United States)

    Brinks, Vera; Weinbuch, Daniel; Baker, Matthew; Dean, Yann; Stas, Philippe; Kostense, Stefan; Rup, Bonita; Jiskoot, Wim

    2013-07-01

    All therapeutic proteins are potentially immunogenic. Antibodies formed against these drugs can decrease efficacy, leading to drastically increased therapeutic costs and in rare cases to serious and sometimes life threatening side-effects. Many efforts are therefore undertaken to develop therapeutic proteins with minimal immunogenicity. For this, immunogenicity prediction of candidate drugs during early drug development is essential. Several in silico, in vitro and in vivo models are used to predict immunogenicity of drug leads, to modify potentially immunogenic properties and to continue development of drug candidates with expected low immunogenicity. Despite the extensive use of these predictive models, their actual predictive value varies. Important reasons for this uncertainty are the limited/insufficient knowledge on the immune mechanisms underlying immunogenicity of therapeutic proteins, the fact that different predictive models explore different components of the immune system and the lack of an integrated clinical validation. In this review, we discuss the predictive models in use, summarize aspects of immunogenicity that these models predict and explore the merits and the limitations of each of the models.

  10. The Comparative Immunogenicity Of Three Lentogenic Brands Of ...

    African Journals Online (AJOL)

    The comparative immunogenicity of a new lentogenic viscerotropic Newcastle disease vaccine, NDvac-1 (VG/GA strain) and two other existing proprietary pneumotropic lentogenic Newcastle disease vaccines in Nigeria, NDvac-2 (R2B) and NDvac-3 (LaSota) were studied. Immunogenicity was assessed on the basis of ...

  11. Immunogenicity of therapeutic proteins. Part 2: impact of container closures.

    Science.gov (United States)

    Sharma, Basant

    2007-01-01

    Immunogenicity as a potential consequence of therapeutic protein administration is increasingly being scrutinized in the biopharmaceuticals industry, particularly with the imminent introduction of biosimilar products. Immunogenicity is an important safety aspect requiring rigorous investigation to fully appreciate its impact. Factors involved in product handling, such as storage temperature, light exposure, and shaking, have been implicated in immunogenicity, while container closure systems are no less important. Intended to provide a stable environment for the dosage form, container closures may also interact with a product, affecting performance and potentially enhancing immunogenicity. Glass surfaces, air-liquid interfaces, and lubricants can mediate protein denaturation, while phthalates in plastics and latex rubber are sources of extractables and leachates that may contaminate a product, causing allergic reactions and increasing immunogenicity. The manufacture of therapeutic proteins therefore requires rigorous safety evaluations not just in the context of the product, but also product containment.

  12. Posttranslational Modifications and the Immunogenicity of Biotherapeutics

    Directory of Open Access Journals (Sweden)

    Roy Jefferis

    2016-01-01

    Full Text Available Whilst the amino acid sequence of a protein is determined by its gene sequence, the final structure and function are determined by posttranslational modifications (PTMs, including quality control (QC in the endoplasmic reticulum (ER and during passage through the Golgi apparatus. These processes are species and cell specific and challenge the biopharmaceutical industry when developing a production platform for the generation of recombinant biologic therapeutics. Proteins and glycoproteins are also subject to chemical modifications (CMs both in vivo and in vitro. The individual is naturally tolerant to molecular forms of self-molecules but nonself variants can provoke an immune response with the generation of anti-drug antibodies (ADA; aggregated forms can exhibit enhanced immunogenicity and QC procedures are developed to avoid or remove them. Monoclonal antibody therapeutics (mAbs are a special case because their purpose is to bind the target, with the formation of immune complexes (ICs, a particular form of aggregate. Such ICs may be removed by phagocytic cells that have antigen presenting capacity. These considerations may frustrate the possibility of ameliorating the immunogenicity of mAbs by rigorous exclusion of aggregates from drug product. Alternate strategies for inducing immunosuppression or tolerance are discussed.

  13. Allorecognition pathways in transplant rejection and tolerance.

    Science.gov (United States)

    Ali, Jason M; Bolton, Eleanor M; Bradley, J Andrew; Pettigrew, Gavin J

    2013-10-27

    With the advent of cellular therapies, it has become clear that the success of future therapies in prolonging allograft survival will require an intimate understanding of the allorecognition pathways and effector mechanisms that are responsible for chronic rejection and late graft loss.Here, we consider current understanding of T-cell allorecognition pathways and discuss the most likely mechanisms by which these pathways collaborate with other effector mechanisms to cause allograft rejection. We also consider how this knowledge may inform development of future strategies to prevent allograft rejection.Although both direct and indirect pathway CD4 T cells appear active immediately after transplantation, it has emerged that indirect pathway CD4 T cells are likely to be the dominant alloreactive T-cell population late after transplantation. Their ability to provide help for generating long-lived alloantibody is likely one of the main mechanisms responsible for the progression of allograft vasculopathy and chronic rejection.Recent work has suggested that regulatory T cells may be an effective cellular therapy in transplantation. Given the above, adoptive therapy with CD4 regulatory T cells with indirect allospecificity is a rational first choice in attempting to attenuate the development and progression of chronic rejection; those with additional properties that enable inhibition of germinal center alloantibody responses hold particular appeal.

  14. Evaluation of the immunogenicity and protective effects of a trivalent chimeric norovirus P particle immunogen displaying influenza HA2 from subtypes H1, H3 and B.

    Science.gov (United States)

    Gong, Xin; Yin, He; Shi, Yuhua; He, Xiaoqiu; Yu, Yongjiao; Guan, Shanshan; Kuai, Ziyu; Haji, Nasteha M; Haji, Nafisa M; Kong, Wei; Shan, Yaming

    2016-05-25

    The ectodomain of the influenza A virus (IAV) hemagglutinin (HA) stem is highly conserved across strains and has shown promise as a universal influenza vaccine in a mouse model. In this study, potential B-cell epitopes were found through sequence alignment and epitope prediction in a stem fragment, HA2:90-105, which is highly conserved among virus subtypes H1, H3 and B. A norovirus (NoV) P particle platform was used to express the HA2:90-105 sequences from subtypes H1, H3 and B in loops 1, 2 and 3 of the protrusion (P) domain, respectively. Through mouse immunization and microneutralization assays, the immunogenicity and protective efficacy of the chimeric NoV P particle (trivalent HA2-PP) were tested against infection with three subtypes (H1N1, H3N2 and B) of IAV in Madin-Darby canine kidney cells. The protective efficacy of the trivalent HA2-PP was also evaluated preliminarily in vivo by virus challenge in the mouse model. The trivalent HA2-PP immunogen induced significant IgG antibody responses, which could be enhanced by a virus booster vaccination. Moreover, the trivalent HA2-PP immunogen also demonstrated in vitro neutralization of the H3 and B viruses, and in vivo protection against the H3 virus. Our results support the notion that a broadly protective vaccine approach using an HA2-based NoV P particle platform can provide cross-protection against challenge viruses of different IAV subtypes. The efficacy of the immunogen should be further enhanced for practicality, and a better understanding of the protective immune mechanism will be critical for the development of HA2-based multivalent vaccines.

  15. Safety and immunogenicity of a CRM or TT conjugated meningococcal vaccine in healthy toddlers.

    Science.gov (United States)

    Bona, Gianni; Castiglia, Paolo; Zoppi, Giorgio; de Martino, Maurizio; Tasciotti, Annaelisa; D'Agostino, Diego; Han, Linda; Smolenov, Igor

    2016-06-17

    MenACWY-CRM (Menveo(®); GlaxoSmithKline) and MenACWY-TT (Nimenrix(®); Pfizer) are two meningococcal vaccines licensed in the European Union for use in both children and adults. While both vaccines target meningococcal serogroups A, C, W and Y, immunogenicity and reactogenicity of these quadrivalent meningococcal conjugate vaccines may differ due to differences in formulation processes and chemical structure. Yet data on the comparability of these two vaccines are limited. The reactogenicity and immunogenicity of one dose of either MenACWY-CRM or MenACWY-TT were evaluated in healthy toddlers aged 12-15 months. Immunogenicity was assessed using serum bactericidal antibody assays (SBA) with human (hSBA) and rabbit (rSBA) complement. A total of 202 children aged 12-15 months were enrolled to receive one dose of MenACWY-CRM or MenACWY-TT. Similar numbers of subjects reported solicited reactions within 7 days following either vaccination. Tenderness at the injection site was the most common local reaction. Systemic reactions reported were similar for both vaccines and mostly mild to moderate in severity: irritability, sleepiness and change in eating habits were most commonly reported. Immunogenicity at 1 month post-vaccination was generally comparable for both vaccines across serogroups. At 6 months post-vaccination antibody persistence against serogroups C, W, and Y was substantial for both vaccines, as measured by both assay methodologies. For serogroup A, hSBA titers declined in both groups, while rSBA titers remained high. Despite differences in composition, the MenACWY-CRM and MenACWY-TT vaccines have comparable reactogenicity and immunogenicity profiles. Immediate immune responses and short-term antibody persistence were largely similar between groups. Both vaccines were well-tolerated and no safety concerns were identified. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. The significance of parenchymal changes of acute cellular rejection in predicting chronic liver graft rejection

    NARCIS (Netherlands)

    Gouw, ASH; van den Heuvel, MC; van den Berg, AP; Slooff, NJH; de Jong, KP; Poppema, S

    2002-01-01

    Background. Chronic rejection (CR) in liver allografts shows a rapid onset and progressive course, leading to graft failure within the first year after transplantation. Most cases are preceded by episodes of acute cellular rejection (AR), but histological features predictive for the transition

  17. [Immunogenicity of attenuated Salmonella choleraesuis vaccine strain expressing immunogenic genes of Mycoplasma hyopneumoniae in mice].

    Science.gov (United States)

    Ma, Fengying; Zou, Haoyong; He, Qigai

    2011-09-01

    The study was carried out to construct and characterize Salmonella choleraesuis vaccine strain expressing immunogenic genes of Mycoplasma hyopneumoniae and to test its immunogenicity in mice. We made p36, p46, p65 and p97R1-Nrdf, the main immunogenic genes of Mycoplasma hyopneumoniae, to insert into the prokaryotic expression plasmid pYA3493. Then these recombinant plasmids and pYA3493 were electroporated into C500 asd-mutant, resulting in the recombinant Salmonella choleraesuis vaccine strains C36 (pYA-36), C46 (pYA-46), C65 (pYA-65), C97R1-Nrdf(pYA-97R1-Nrdf) and CpYA(pYA3493). We characterized these recombinant Salmonella choleraesuis vaccine strains and tested the immunogenicity in mice by intramuscular injection or orally immunized. The results of the immunogenicity in mice indicated that the group orally immunized with C36, C46, C65, C97R1-Nrdf showed significantly higher Mycoplasma pneumoniae antibody than both the group orally immunized with C36, C46, C65 and the group intramuscular injected with the Mycoplasma hyopneumoniae bacterin (M + PAC) (P Mycoplasma hyopneumoniae bacterin (M + PAC) (P 0.05). The highest level of IL-4 was found in the group orally immunized with C36, C46, C65; higher levels of IL-4 was observed in the group orally immunized with C36, C46, C65, C97R1-Nrdf than the group injected with the Mycoplasma hyopneumoniae bacterin (M + PAC); and the lowest IL-4 level was found in the group injected with C36, C46, C65. There were no significant differences among them (P > 0.05). The Mycoplasma pneumoniae antibody, IFN-gamma or IL-4 production of the each group was obviously higher than the control group (P Mycoplasma hyopneumoniae which has immunogenicity in mice especially by intramuscular injection could probably serve as a vaccine against mycoplasmal pneumonia of swine.

  18. Preventing Allograft Rejection by Targeting Immune Metabolism

    Directory of Open Access Journals (Sweden)

    Chen-Fang Lee

    2015-10-01

    Full Text Available Upon antigen recognition and co-stimulation, T lymphocytes upregulate the metabolic machinery necessary to proliferate and sustain effector function. This metabolic reprogramming in T cells regulates T cell activation and differentiation but is not just a consequence of antigen recognition. Although such metabolic reprogramming promotes the differentiation and function of T effector cells, the differentiation of regulatory T cells employs different metabolic reprogramming. Therefore, we hypothesized that inhibition of glycolysis and glutamine metabolism might prevent graft rejection by inhibiting effector generation and function and promoting regulatory T cell generation. We devised an anti-rejection regimen involving the glycolytic inhibitor 2-deoxyglucose (2-DG, the anti-type II diabetes drug metformin, and the inhibitor of glutamine metabolism 6-diazo-5-oxo-L-norleucine (DON. Using this triple-drug regimen, we were able to prevent or delay graft rejection in fully mismatched skin and heart allograft transplantation models.

  19. Soluble CD30 and HLA antibodies as potential risk factors for kidney transplant rejection.

    Science.gov (United States)

    Slavcev, Antonij; Lácha, Jiri; Honsová, Eva; Sajdlová, Helena; Lodererová, Alena; Vitko, Stefan; Skibová, Jelena; Striz, Ilja

    2005-06-01

    Recent literary data suggest that high pre- and post-transplant serum levels of the soluble CD30 (sCD30) molecule may be a risk factor for acute rejection and worse prognosis of the transplanted kidney. The aim of our study was to correlate the concentrations of sCD30 and the presence of HLA antibodies as defined by flow cytometry and ELISA with the clinical course and graft prognosis after transplantation. One hundred and seventeen kidney transplant patients were included into the study. The incidence of rejection episodes, graft function and graft survival for up to 1 year post-transplant were evaluated. Soluble CD30 levels before transplantation were virtually the same in patients who experienced rejection and in non-rejecting patients. In both patient groups, a significant decrease of sCD30 was detected 2 weeks after transplantation (104.4 U/ml before vs. 37.0 U/ml post-transplant, P sCD30 between rejecting and non-rejecting patients. Patients without rejection had lower sCD30 values (31.2 U/ml post-transplant) compared to patients who experienced rejection episodes (62.9 U/ml), P antigens and elevated concentrations of sCD30 shortly after transplantation were associated with increased risk for acute rejection in the first post-transplant year. Measurement of soluble CD30 after transplantation, taken into consideration with the presence of HLA class II antibodies, might be helpful for evaluating the potential risk for acute rejection.

  20. Identification of an Immunogenic Subset of Metastatic Uveal Melanoma.

    Science.gov (United States)

    Rothermel, Luke D; Sabesan, Arvind C; Stephens, Daniel J; Chandran, Smita S; Paria, Biman C; Srivastava, Abhishek K; Somerville, Robert; Wunderlich, John R; Lee, Chyi-Chia R; Xi, Liqiang; Pham, Trinh H; Raffeld, Mark; Jailwala, Parthav; Kasoji, Manjula; Kammula, Udai S

    2016-05-01

    Uveal melanoma is a rare melanoma variant with no effective therapies once metastases develop. Although durable cancer regression can be achieved in metastatic cutaneous melanoma with immunotherapies that augment naturally existing antitumor T-cell responses, the role of these treatments for metastatic uveal melanoma remains unclear. We sought to define the relative immunogenicity of these two melanoma variants and determine whether endogenous antitumor immune responses exist against uveal melanoma. We surgically procured liver metastases from uveal melanoma (n = 16) and cutaneous melanoma (n = 35) patients and compared the attributes of their respective tumor cell populations and their infiltrating T cells (TIL) using clinical radiology, histopathology, immune assays, and whole-exomic sequencing. Despite having common melanocytic lineage, uveal melanoma and cutaneous melanoma metastases differed in their melanin content, tumor differentiation antigen expression, and somatic mutational profile. Immunologic analysis of TIL cultures expanded from these divergent forms of melanoma revealed cutaneous melanoma TIL were predominantly composed of CD8(+) T cells, whereas uveal melanoma TIL were CD4(+) dominant. Reactivity against autologous tumor was significantly greater in cutaneous melanoma TIL compared with uveal melanoma TIL. However, we identified TIL from a subset of uveal melanoma patients which had robust antitumor reactivity comparable in magnitude with cutaneous melanoma TIL. Interestingly, the absence of melanin pigmentation in the parental tumor strongly correlated with the generation of highly reactive uveal melanoma TIL. The discovery of this immunogenic group of uveal melanoma metastases should prompt clinical efforts to determine whether patients who harbor these unique tumors can benefit from immunotherapies that exploit endogenous antitumor T-cell populations. Clin Cancer Res; 22(9); 2237-49. ©2015 AACR. ©2015 American Association for Cancer Research.

  1. Entropy-Based Clutter Rejection for Intrawall Diagnostics

    Directory of Open Access Journals (Sweden)

    Raffaele Solimene

    2012-01-01

    Full Text Available The intrawall diagnostic problem of detecting localized inhomogeneities possibly present within the wall is addressed. As well known, clutter arising from masonry structure can impair detection of embedded scatterers due to high amplitude reflections that wall front face introduces. Moreover, internal multiple reflections also can make it difficult ground penetrating radar images (radargramms interpretation. To counteract these drawbacks, a clutter rejection method, properly tailored on the wall features, is mandatory. To this end, here we employ a windowing strategy based on entropy measures of temporal traces “similarity.” Accordingly, instants of time for which radargramms exhibit entropy values greater than a prescribed threshold are “silenced.” Numerical results are presented in order to show the effectiveness of the entropy-based clutter rejection algorithm. Moreover, a comparison with the standard average trace subtraction is also included.

  2. Background rejection in NEXT using deep neural networks

    CERN Document Server

    Renner, J.

    2017-01-01

    We investigate the potential of using deep learning techniques to reject background events in searches for neutrinoless double beta decay with high pressure xenon time projection chambers capable of detailed track reconstruction. The differences in the topological signatures of background and signal events can be learned by deep neural networks via training over many thousands of events. These networks can then be used to classify further events as signal or background, providing an additional background rejection factor at an acceptable loss of efficiency. The networks trained in this study performed better than previous methods developed based on the use of the same topological signatures by a factor of 1.2 to 1.6, and there is potential for further improvement.

  3. Background rejection in NEXT using deep neural networks

    International Nuclear Information System (INIS)

    Renner, J.; Farbin, A.; Vidal, J. Muñoz; Benlloch-Rodríguez, J. M.; Botas, A.

    2017-01-01

    Here, we investigate the potential of using deep learning techniques to reject background events in searches for neutrinoless double beta decay with high pressure xenon time projection chambers capable of detailed track reconstruction. The differences in the topological signatures of background and signal events can be learned by deep neural networks via training over many thousands of events. These networks can then be used to classify further events as signal or background, providing an additional background rejection factor at an acceptable loss of efficiency. The networks trained in this study performed better than previous methods developed based on the use of the same topological signatures by a factor of 1.2 to 1.6, and there is potential for further improvement.

  4. Chicken IgY Fc expressed by Eimeria mitis enhances the immunogenicity of E. mitis.

    Science.gov (United States)

    Qin, Mei; Tang, Xinming; Yin, Guangwen; Liu, Xianyong; Suo, Jingxia; Tao, Geru; Ei-Ashram, Saeed; Li, Yuan; Suo, Xun

    2016-03-21

    Eimeria species are obligate intracellular apicomplexan parasites, causing great economic losses in the poultry industry. Currently wild-and attenuated- type anticoccidial vaccines are used to control coccidiosis. However, their use in fast growing broilers is limited by vaccination side effects caused by medium and/or low immunogenic Eimeria spp. There is, therefore, a need for a vaccine with high immunogenicity for broilers. The avian yolk sac IgY Fc is the avian counterpart of the mammalian IgG Fc, which enhances immunogenicity of Fc-fusion proteins. Here, we developed a stable transgenic Eimeria mitis expressing IgY Fc (Emi.chFc) and investigated whether the avian IgY Fc fragment enhances the immunogenicity of E. mitis. Two-week-old broilers were immunized with either Emi.chFc or wild type Eimeria and challenged with wild type E. mitis to analyze the protective properties of transgenic Emi.chFc. Chickens immunized with Emi.chFc had significantly lower oocyst output, in comparison with PBS, mock control (transgenic E. mitis expressing HA1 from H9N2 avian influenza virus) and wildtype E. mitis immunized groups after challenge, indicating that IgY Fc enhanced the immunogenicity of E. mitis. Our findings suggest that IgY Fc-expressing Eimeria may be a better coccidiosis vaccine, and transgenic Eimeria expressing Fc-fused exogenous antigens may be used as a novel vaccine-delivery vehicle against a wide variety of pathogens.

  5. Recombinant Brucella abortus gene expressing immunogenic protein

    Energy Technology Data Exchange (ETDEWEB)

    Mayfield, J.E.; Tabatabai, L.B.

    1991-06-11

    This patent describes a synthetic recombinant DNA molecule containing a DNA sequence. It comprises a gene of Brucella abortus encoding an immunogenic protein having a molecular weight of approximately 31,000 daltons as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis under denaturing conditions, the protein having an isoelectric point around 4.9, and containing a twenty-five amino acid sequence from its amino terminal end consisting of Gln-Ala-Pro-Thr-Phe-Phe-Arg-Ile-Gly-Thr-Gly-Gly-Thr-Ala-Gly-Thr-Tyr-Tyr-Pro-Ile-Gly-Gly-Leu-Ile-Ala, wherein Gln, Ala, Pro, Thr, Phe, Arg, Ile, Gly, Tyr, and Leu, respectively, represent glutamine, alanine, proline, threonine, phenylalanine, arginine, isolecuine, glycine, tyrosine, and leucine.

  6. Immunogenicity of UV-inactivated measles virus

    International Nuclear Information System (INIS)

    Zahorska, R.; Mazur, N.; Korbecki, M.

    1978-01-01

    By means of the antigen extinction limit test it was shown that a triple dose vaccination of guinea pigs with UV-inactivated measles virus gave better results, than a single dose vaccination which was proved by the very low immunogenicity index. For both vaccination schemes (single and triple) the immune response was only sligthly influenced by a change of dose from 10 5 to 10 6 HadU 50 /ml or by the addition of aluminum adjuvant. In the antigen extinction limit test the antibody levels were determined by two methods (HIT and NT) the results of which were statistically equivalent. The UV-inactivated measles virus was also found to induce hemolysis-inhibiting antibodies. (orig.) [de

  7. Music genre recognition with risk and rejection

    DEFF Research Database (Denmark)

    Sturm, Bob L.

    2013-01-01

    We explore risk and rejection for music genre recognition (MGR) within the minimum risk framework of Bayesian classification. In this way, we attempt to give an MGR system knowledge that some misclassifications are worse than others, and that deferring classification to an expert may be a better...

  8. Antimyosin imaging in cardiac transplant rejection

    International Nuclear Information System (INIS)

    Johnson, L.L.; Cannon, P.J.

    1991-01-01

    Fab fragments of antibodies specific for cardiac myosin have been labeled with indium-111 and injected intravenously into animals and into patients with heart transplants. The antibodies, developed by Khaw, Haber, and co-workers, localize in cardiac myocytes that have been damaged irreversibly by ischemia, myocarditis, or the rejection process. After clearance of the labeled antibody from the cardiac blood pool, planar imaging or single photon emission computed tomography is performed. Scintigrams reveal the uptake of the labeled antimyosin in areas of myocardium undergoing transplant rejection. In animal studies, the degree of antimyosin uptake appears to correlate significantly with the degree of rejection assessed at necropsy. In patients, the correlation between scans and pathologic findings from endomyocardial biopsy is not as good, possibly because of sampling error in the endomyocardial biopsy technique. The scan results at 1 year correlate with either late complications (positive) or benign course (negative). Current limitations of the method include slow blood clearance, long half-life of indium-111, and hepatic uptake. Overcoming these limitations represents a direction for current research. It is possible that from these efforts a noninvasive approach to the diagnosis and evaluation of cardiac transplantation may evolve that will decrease the number of endomyocardial biopsies required to evaluate rejection. This would be particularly useful in infants and children. 31 references

  9. Development of enhanced sulfur rejection processes

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, R.H.; Luttrell, G.H.; Adel, G.T.; Richardson, P.E.

    1996-03-01

    Research at Virginia Tech led to the development of two complementary concepts for improving the removal of inorganic sulfur from many eastern U.S. coals. These concepts are referred to as Electrochemically Enhanced Sulfur Rejection (EESR) and Polymer Enhanced Sulfur Rejection (PESR) processes. The EESR process uses electrochemical techniques to suppress the formation of hydrophobic oxidation products believed to be responsible for the floatability of coal pyrite. The PESR process uses polymeric reagents that react with pyrite and convert floatable middlings, i.e., composite particles composed of pyrite with coal inclusions, into hydrophilic particles. These new pyritic-sulfur rejection processes do not require significant modifications to existing coal preparation facilities, thereby enhancing their adoptability by the coal industry. It is believed that these processes can be used simultaneously to maximize the rejection of both well-liberated pyrite and composite coal-pyrite particles. The project was initiated on October 1, 1992 and all technical work has been completed. This report is based on the research carried out under Tasks 2-7 described in the project proposal. These tasks include Characterization, Electrochemical Studies, In Situ Monitoring of Reagent Adsorption on Pyrite, Bench Scale Testing of the EESR Process, Bench Scale Testing of the PESR Process, and Modeling and Simulation.

  10. Real-Life Efficacy, Immunogenicity and Safety of Biosimilar Infliximab.

    Science.gov (United States)

    Vegh, Zsuzsanna; Kurti, Zsuzsanna; Lakatos, Peter L

    2017-01-01

    Recently, the use of biosimilar infliximab (IFX) in the treatment of inflammatory bowel diseases has become widespread in some European and non-European countries. Data on the efficacy, safety and immunogenicity from real-life cohorts are accumulating. The first reports showed similar outcomes in the induction and maintenance of remission, mucosal healing, safety and immunogenicity profile to the originator IFX. In the present review, we aimed to summarize the existing knowledge on the efficacy, safety and immunogenicity profile of biosimilar IFX reported from real-life cohorts. © 2017 S. Karger AG, Basel.

  11. Hybrid pulse pile-up rejection system as applied to Rutherford backscattering

    International Nuclear Information System (INIS)

    Boie, R.A.; Wildnauer, K.R.

    1977-01-01

    The problems of pulse on pulse pile-up and noise limited pile-up rejectors are considered in detail for Rutherford backscattering spectra. The forms of these spectra allow the distortions from pile-up and the residual pile-up after rejection to be understood via a simple model. Extended calculations allow us to predict the effects quite accurately. A new pile-up rejection system is described. The ''linear'' rejection method is implemented with peak stretchers and advantageously combined with an event counting rejector to provide a versatile high performance system

  12. Exceptional ion rejection ability of directional solvent for non-membrane desalination

    Energy Technology Data Exchange (ETDEWEB)

    Rish, Daniel [Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, Indiana 46556 (United States); Department of Civil Engineering, University of Notre Dame, Notre Dame, Indiana 46556 (United States); Luo, Shirui; Kurtz, Brien [Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, Indiana 46556 (United States); Luo, Tengfei, E-mail: tluo@nd.edu [Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, Indiana 46556 (United States); Center for Sustainable Energy at Notre Dame, University of Notre Dame, Notre Dame, Indiana 46556 (United States)

    2014-01-13

    The recently demonstrated directional solvent extraction (DSE) is promising for very low temperature, membrane-free water desalination. In this paper, we combine atomistic simulations and experimental validation to demonstrate that the currently used directional solvent, decanoic acid, can reject all major salt ions in seawater, with very high rejection rates. The salinities of the DSE recovered water show that ion rejection rates are ∼98%–99%—similar to those of the best reverse osmosis membranes. Our test also shows that the DSE process can desalt seawater to produce fresh water that meets drinking water standards.

  13. Exceptional ion rejection ability of directional solvent for non-membrane desalination

    International Nuclear Information System (INIS)

    Rish, Daniel; Luo, Shirui; Kurtz, Brien; Luo, Tengfei

    2014-01-01

    The recently demonstrated directional solvent extraction (DSE) is promising for very low temperature, membrane-free water desalination. In this paper, we combine atomistic simulations and experimental validation to demonstrate that the currently used directional solvent, decanoic acid, can reject all major salt ions in seawater, with very high rejection rates. The salinities of the DSE recovered water show that ion rejection rates are ∼98%–99%—similar to those of the best reverse osmosis membranes. Our test also shows that the DSE process can desalt seawater to produce fresh water that meets drinking water standards

  14. Peripheral blood transcriptome sequencing reveals rejection-relevant genes in long-term heart transplantation.

    Science.gov (United States)

    Chen, Yan; Zhang, Haibo; Xiao, Xue; Jia, Yixin; Wu, Weili; Liu, Licheng; Jiang, Jun; Zhu, Baoli; Meng, Xu; Chen, Weijun

    2013-10-03

    Peripheral blood-based gene expression patterns have been investigated as biomarkers to monitor the immune system and rule out rejection after heart transplantation. Recent advances in the high-throughput deep sequencing (HTS) technologies provide new leads in transcriptome analysis. By performing Solexa/Illumina's digital gene expression (DGE) profiling, we analyzed gene expression profiles of PBMCs from 6 quiescent (grade 0) and 6 rejection (grade 2R&3R) heart transplant recipients at more than 6 months after transplantation. Subsequently, quantitative real-time polymerase chain reaction (qRT-PCR) was carried out in an independent validation cohort of 47 individuals from three rejection groups (ISHLT, grade 0,1R, 2R&3R). Through DGE sequencing and qPCR validation, 10 genes were identified as informative genes for detection of cardiac transplant rejection. A further clustering analysis showed that the 10 genes were not only effective for distinguishing patients with acute cardiac allograft rejection, but also informative for discriminating patients with renal allograft rejection based on both blood and biopsy samples. Moreover, PPI network analysis revealed that the 10 genes were connected to each other within a short interaction distance. We proposed a 10-gene signature for heart transplant patients at high-risk of developing severe rejection, which was found to be effective as well in other organ transplant. Moreover, we supposed that these genes function systematically as biomarkers in long-time allograft rejection. Further validation in broad transplant population would be required before the non-invasive biomarkers can be generally utilized to predict the risk of transplant rejection. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. A comparative study of boron and arsenic (III) rejection from brackish water by reverse osmosis membranes

    KAUST Repository

    Teychene, Benoî t; Collet, Gaelle; Gallard, Hervé ; Croue, Jean Philippe

    2013-01-01

    This study aims to compare at lab-scale the rejection efficiency of several reverse osmosis membranes (RO) toward arsenic (III) and boron during the filtration of a synthetic brackish water. The effect of pH and operating conditions on the rejection of each RO membrane was studied. Two types of membrane were investigated: "brackish water" and "sea water" membranes. Our results showed that the metalloid rejection depends on the membrane type, pH and transmembrane pressure applied. Increasing pH above the dissociation constant (pKa) of each specie improves significantly the metalloid rejection by RO membranes, whatever the membrane type. Moreover, at identical operating conditions (pH, transmembrane pressure), results showed that the brackish water membranes have a higher water flux and exhibit lower metalloid rejection. The highest As(III) rejection value for the tested brackish water membranes was 99% obtained at pH = 9.6 and 40 bars, whereas it was found that the sea water RO membranes could highly reject As(III), more than 99%, even at low pH and low pressure (pH = 7.6 and 24 bars).Regarding Boron rejection, similar conclusions could be drawn. The sea water RO membranes exert higher removal, with a high rejection value above 96% over the tested conditions. More generally, this study showed that, whatever the operating conditions or the tested membranes, the boron and As(III) permeate concentrations are below the WHO guidelines. In addition, new data about the boron and arsenic permeability of each tested RO membrane was brought thanks to a theoretical calculation. © 2012 Elsevier B.V.

  16. A comparative study of boron and arsenic (III) rejection from brackish water by reverse osmosis membranes

    KAUST Repository

    Teychene, Benoît

    2013-02-01

    This study aims to compare at lab-scale the rejection efficiency of several reverse osmosis membranes (RO) toward arsenic (III) and boron during the filtration of a synthetic brackish water. The effect of pH and operating conditions on the rejection of each RO membrane was studied. Two types of membrane were investigated: "brackish water" and "sea water" membranes. Our results showed that the metalloid rejection depends on the membrane type, pH and transmembrane pressure applied. Increasing pH above the dissociation constant (pKa) of each specie improves significantly the metalloid rejection by RO membranes, whatever the membrane type. Moreover, at identical operating conditions (pH, transmembrane pressure), results showed that the brackish water membranes have a higher water flux and exhibit lower metalloid rejection. The highest As(III) rejection value for the tested brackish water membranes was 99% obtained at pH = 9.6 and 40 bars, whereas it was found that the sea water RO membranes could highly reject As(III), more than 99%, even at low pH and low pressure (pH = 7.6 and 24 bars).Regarding Boron rejection, similar conclusions could be drawn. The sea water RO membranes exert higher removal, with a high rejection value above 96% over the tested conditions. More generally, this study showed that, whatever the operating conditions or the tested membranes, the boron and As(III) permeate concentrations are below the WHO guidelines. In addition, new data about the boron and arsenic permeability of each tested RO membrane was brought thanks to a theoretical calculation. © 2012 Elsevier B.V.

  17. Exploitation of herpesvirus immune evasion strategies to modify the immunogenicity of human mesenchymal stem cell transplants.

    Directory of Open Access Journals (Sweden)

    Anabel S de la Garza-Rodea

    Full Text Available BACKGROUND: Mesenchymal stem cells (MSCs are multipotent cells residing in the connective tissue of many organs and holding great potential for tissue repair. In culture, human MSCs (hMSCs are capable of extensive proliferation without showing chromosomal aberrations. Large numbers of hMSCs can thus be acquired from small samples of easily obtainable tissues like fat and bone marrow. MSCs can contribute to regeneration indirectly by secretion of cytokines or directly by differentiation into specialized cell types. The latter mechanism requires their long-term acceptance by the recipient. Although MSCs do not elicit immune responses in vitro, animal studies have revealed that allogeneic and xenogeneic MSCs are rejected. METHODOLOGY/PRINCIPAL FINDINGS: We aim to overcome MSC immune rejection through permanent down-regulation of major histocompatibility complex (MHC class I proteins on the surface of these MHC class II-negative cells through the use of viral immune evasion proteins. Transduction of hMSCs with a retroviral vector encoding the human cytomegalovirus US11 protein resulted in strong inhibition of MHC class I surface expression. When transplanted into immunocompetent mice, persistence of the US11-expressing and HLA-ABC-negative hMSCs at levels resembling those found in immunodeficient (i.e., NOD/SCID mice could be attained provided that recipients' natural killer (NK cells were depleted prior to cell transplantation. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate the potential utility of herpesviral immunoevasins to prevent rejection of xenogeneic MSCs. The observation that down-regulation of MHC class I surface expression renders hMSCs vulnerable to NK cell recognition and cytolysis implies that multiple viral immune evasion proteins are likely required to make hMSCs non-immunogenic and thereby universally transplantable.

  18. Antimyosin monoclonal antibodies for early detection of cardiac allograft rejection

    International Nuclear Information System (INIS)

    Schuetz, A.; Fritsch, S.; Kemkes, B.M.; Kugler, C.; Angermann, C.; Spes, C.; Anthuber, M.; Weiler, A.; Wenke, K.; Gokel, J.M.

    1990-01-01

    Sixty-eight indium 111-labeled antimyosin Fab-DTPA imaging studies (0.5 mg intravenously with a radioactivity of 65 to 75 MBq) were executed on 37 of 116 patients undergoing heart transplantation to assess diagnostic accuracy and clinical utility. As controls, 21 patients with cardiomyopathy (n = 8), unstable angina (n = 9), and myocardial infarction (n = 4) were selected. After 48 hours, single photon emission computed tomographic images were evaluated visually, and heart/lung ratios were measured, using the region of interest technique. They were compared with echocardiographic and endomyocardial biopsy results. In 40 studies a heart/lung ratio less than or equal to 1.6 corresponded to a negative biopsy result in 98% (40/41). Echocardiography enabled correct identification of 95% of the patients with normal biopsy findings. In 91% (22/24) a positive biopsy finding correlated with a heart/lung ratio greater than 1.6 including 20 mild rejections, but in only 64%, with an increase in wall thickness and/or decrease of fractional diameter shortening seen on echocardiogram. In addition, the various stages of rejection episodes determined the amount of the heart-lung ratio. There was a significant relationship between the histologic findings and the antimyosin uptake. In 13 patients a second investigation was performed after rejection therapy. All patients had a negative biopsy result, and the heart/lung ratio decreased to normal ranges (less than or equal to 1.6). Five antimyosin antibody studies were excluded, as in these cases, negative uptake results were found during rejection therapy with high-dose steroids. The overall sensitivity was calculated at 93% and the specificity at 98%

  19. Redistribution of wastewater alkalinity with a microbial fuel cell to support nitrification of reject water.

    Science.gov (United States)

    Modin, Oskar; Fukushi, Kensuke; Rabaey, Korneel; Rozendal, René A; Yamamoto, Kazuo

    2011-04-01

    In wastewater treatment plants, the reject water from the sludge treatment processes typically contains high ammonium concentrations, which constitute a significant internal nitrogen load in the plant. Often, a separate nitrification reactor is used to treat the reject water before it is fed back into the plant. The nitrification reaction consumes alkalinity, which has to be replenished by dosing e.g. NaOH or Ca(OH)(2). In this study, we investigated the use of a two-compartment microbial fuel cell (MFC) to redistribute alkalinity from influent wastewater to support nitrification of reject water. In an MFC, alkalinity is consumed in the anode compartment and produced in the cathode compartment. We use this phenomenon and the fact that the influent wastewater flow is many times larger than the reject water flow to transfer alkalinity from the influent wastewater to the reject water. In a laboratory-scale system, ammonium oxidation of synthetic reject water passed through the cathode chamber of an MFC, increased from 73.8 ± 8.9 mgN/L under open-circuit conditions to 160.1 ± 4.8 mgN/L when a current of 1.96 ± 0.37 mA (15.1 mA/L total MFC liquid volume) was flowing through the MFC. These results demonstrated the positive effect of an MFC on ammonium oxidation of alkalinity-limited reject water. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Golimumab in the treatment of inflammatory diseases: A role of immunogenicity

    Directory of Open Access Journals (Sweden)

    D. E. Karateev

    2015-01-01

    Full Text Available The review considers the specific features of golimumab (GLM, a representative of a group of tumor necrosis factor-α inhibitors primarily by comparing its immunogenicity parameters with other drugs in this group (infliximab, adalimumab, certolizumab pegol, etanercept. Despite its fundamental similarity with other biologicals from a category of monoclonal antibodies, GLM is shown to be characterized by a significantly lower detection rate for antibodies to the drug and by its high serum concentration stabilities and a sustained clinical response.

  1. Optimal heat rejection pressure in transcritical carbon dioxide air conditioning and heat pump systems

    DEFF Research Database (Denmark)

    Liao, Shengming; Jakobsen, Arne

    1998-01-01

    Due to the urgent need for environmentally benign refrigerants, the use of the natural substance carbon dioxide in refrigeration systems has gained more and more attention. In systems such as automobile air-conditioners and heat pumps, owing to the relatively high heat rejection temperatures, the...... dioxide air conditioning or heat pump systems and for intelligent controlling such systems.......Due to the urgent need for environmentally benign refrigerants, the use of the natural substance carbon dioxide in refrigeration systems has gained more and more attention. In systems such as automobile air-conditioners and heat pumps, owing to the relatively high heat rejection temperatures......, the cycles using carbon dioxide as refrigerant will have to operate in the transcritical area. In a transcritical carbon dioxide system, there is an optimal heat rejection pressure that gives a maximum COP. In this paper, it is shown that the value of this optimal heat rejection pressure mainly depends...

  2. Glycan bioengineering in immunogen design for tumor T antigen immunotargeting

    DEFF Research Database (Denmark)

    Sendra, Victor G; Zlocowski, Natacha; Ditamo, Yanina

    2009-01-01

    MM2 energy function showed that pentalysine (Lys5) linker and benzyl (Bzl) residue enhance TFD rigidity of the glycosidic bond. Antibodies raised against BzlalphaTFD-Lys5 immunogen recognize tumor T antigen. Competitive assays confirm that TFD-related structures are the main glycan epitope...... to the bioengineered glycoconjugate inhibited CT26 tumor cell proliferation and reduced tumor growth in an in vivo mouse model. These results show that TFD bioengineering is a useful immunogenic strategy with potential application in cancer therapy. The same approach can be extended to other glycan immunogens......Bioengineering of Galbeta3GalNAcalpha, known as Thomsen-Friedenreich disaccharide (TFD), is studied to promote glycan immunogenicity and immunotargeting to tumor T antigen (Galbeta3GalNAcalpha-O-Ser/Thr). Theoretical studies on disaccharide conformations by energy minimization of structures using...

  3. Immunogenicity of virus-like particles containing modified goose parvovirus VP2 protein.

    Science.gov (United States)

    Chen, Zongyan; Li, Chuanfeng; Zhu, Yingqi; Wang, Binbin; Meng, Chunchun; Liu, Guangqing

    2012-10-01

    The major capsid protein VP2 of goose parvovirus (GPV) expressed using a baculovirus expression system (BES) assembles into virus-like particles (VLPs). To optimize VP2 gene expression in Sf9 cells, we converted wild-type VP2 (VP2) codons into codons that are more common in insect genes. This change greatly increased VP2 protein production in Sf9 cells. The protein generated from the codon-optimized VP2 (optVP2) was detected by immunoblotting and an indirect immunofluorescence assay (IFA). Transmission electron microscopy analysis revealed the formation of VLPs. These findings indicate that optVP2 yielded stable and high-quality VLPs. Immunogenicity assays revealed that the VLPs are highly immunogenic, elicit a high level of neutralizing antibodies and provide protection against lethal challenge. The antibody levels appeared to be directly related to the number of GP-Ag-positive hepatocytes. The variation trends for GP-Ag-positive hepatocytes were similar in the vaccine groups. In comparison with the control group, the optVP2 VLPs groups exhibited obviously better responses. These data indicate that the VLPs retained immunoreactivity and had strong immunogenicity in susceptible geese. Thus, GPV optVP2 appears to be a good candidate for the vaccination of goslings. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Active Disturbance Rejection Control of a Heat Integrated Distillation Column

    DEFF Research Database (Denmark)

    Al-Kalbani, Fahad; Zhang, Jie; Bisgaard, Thomas

    2016-01-01

    pressure. However, the control of some HiDC processesis generally difficult due to the strong control loop interaction, high purity of the components and undesired disturbances. Active disturbance rejection control (ADRC) is used in this paperto control a simulated HiDC for separating benzene-toluene......Heat integrated distillation column (HiDC) is the most energy efficient distillation approach making efficient utilization of internal heat integration through heat pump. The rectifying section acts as a heat source with high pressure, while the stripping section operates as a heat sink with low...

  5. Battlefield-Acquired Immunogenicity to Metals Affects Orthopaedic Implant Outcome

    Science.gov (United States)

    2015-10-01

    Award Number: W81XWH-10-2-0138 TITLE: Battlefield-Acquired Immunogenicity to Metals Affects Orthopaedic Implant Outcome PRINCIPAL INVESTIGATOR...Immunogenicity to Metals Affects Orthopaedic pla t Outcome 5b. GRANT NUMBER W91ZSQ0135N646 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Nadim James...DISTRIBUTION / AVAILABILITY STATEMENT Approved for public release; distribution unlimited 13. SUPPLEM ENTARY NOTES 14. ABSTRACT The effects of battlefield

  6. Impact of product-related factors on immunogenicity of biotherapeutics.

    Science.gov (United States)

    Singh, Satish Kumar

    2011-02-01

    All protein therapeutics have the potential to be immunogenic. Several factors, including patient characteristics, disease state, and the therapy itself, influence the generation of an immune response. Product-related factors such as the molecule design, the expression system, post-translational modifications, impurities, contaminants, formulation and excipients, container, closure, as well as degradation products are all implicated. However, a critical examination of the available data shows that clear unequivocal evidence for the impact of these latter factors on clinical immunogenicity is lacking. No report could be found that clearly deconvolutes the clinical impact of the product attributes on patient susceptibility. Aggregation carries the greatest concern as a risk factor for immunogenicity, but the impact of aggregates is likely to depend on their structure as well as on the functionality (e.g., immunostimulatory or immunomodulatory) of the therapeutic. Preclinical studies are not yet capable of assessing the clinically relevant immunogenicity potential of these product-related factors. Simply addressing these risk factors as part of product development will not eliminate immunogenicity. Minimization of immunogenicity has to begin at the molecule design stage by reducing or eliminating antigenic epitopes and building in favorable physical and chemical properties. Copyright © 2010 Wiley-Liss, Inc.

  7. Modulating immunogenic properties of HIV-1 gp41 membrane-proximal external region by destabilizing six-helix bundle structure

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, Saikat; Shi, Heliang; Habte, Habtom H.; Qin, Yali; Cho, Michael W., E-mail: mcho@iastate.edu

    2016-03-15

    The C-terminal alpha-helix of gp41 membrane-proximal external region (MPER; {sup 671}NWFDITNWLWYIK{sup 683}) encompassing 4E10/10E8 epitopes is an attractive target for HIV-1 vaccine development. We previously reported that gp41-HR1-54Q, a trimeric protein comprised of the MPER in the context of a stable six-helix bundle (6HB), induced strong immune responses against the helix, but antibodies were directed primarily against the non-neutralizing face of the helix. To better target 4E10/10E8 epitopes, we generated four putative fusion intermediates by introducing double point mutations or deletions in the heptad repeat region 1 (HR1) that destabilize 6HB in varying degrees. One variant, HR1-∆10-54K, elicited antibodies in rabbits that targeted W672, I675 and L679, which are critical for 4E10/10E8 recognition. Overall, the results demonstrated that altering structural parameters of 6HB can influence immunogenic properties of the MPER and antibody targeting. Further exploration of this strategy could allow development of immunogens that could lead to induction of 4E10/10E8-like antibodies. - Highlights: • Four gp41 MPER-based immunogens that resemble fusion intermediates were generated. • C-terminal region of MPER that contains 4E10/10E8 epitopes was highly immunogenic. • Altering 6HB structure can influence immunogenic properties of the MPER. • Induced antibodies targeted multiple residues critical for 4E10/10E8 binding. • Development of immunogens based on fusion intermediates is a promising strategy.

  8. Involvement of dendritic cells in allograft rejection new implications of dendritic cell-endothelial cell interactions.

    Science.gov (United States)

    Schlichting, C L; Schareck, W D; Kofler, S; Weis, M

    2007-04-01

    For almost half a century immunologists have tried to tear down the MHC barrier, which separates two unrelated individuals during transplantation. Latest experimental data suggest that a breakthrough in vitro is imminent. Dendritic cells (DCs), which activate naïve allo-reactive T-cells (TCs), play a central role in the establishment of allo-antigen-specific immunity. Allograft solid organ rejection is initiated at the foreign endothelial cell (EC) layer, which forms an immunogenic barrier for migrating DCs. Thus, DC/EC interactions might play a crucial role in antigen-specific allograft rejection. Organ rejection is mediated by host allo-reactive TCs, which are activated by donor DCs (direct activation) or host DCs (indirect activation). Direct allo-antigen presentation by regulatory dendritic cells (DCreg) can play an instructive role towards tolerance induction. Several groups established that, DCregs, if transplanted beforehand, enter host thymus, spleen, or bone marrow where they might eventually establish allo-antigen-specific tolerance. A fundamental aspect of DC function is migration throughout the entire organism. After solid organ transplantation, host DCs bind to ECs, invade allograft tissues, and finally transmigrate into lymphoid vessels and secondary lymphoid organs, where they present allo-antigens to naïve host TCs. Recent data suggest that in vitro manipulated DCregs may mediate allo-transplantation tolerance induction. However, the fundamental mechanisms on how such DCregs cause host TCs in the periphery towards tolerance remain unclear. One very promising experimental concept is the simultaneous manipulation of DC direct and indirect TC activation/suppression, towards donor antigen-specific allo-transplantation tolerance. The allo-antigen-specific long-term tolerance induction mediated by DCreg pre-transplantation (with simultaneous short-term immunosuppression) has become reproducible in the laboratory animal setting. Despite the shortcomings

  9. Mechanisms of allograft rejection of corneal endothelium

    International Nuclear Information System (INIS)

    Tagawa, Y.; Silverstein, A.M.; Prendergast, R.A.

    1982-01-01

    The local intraocular graft-vs.-host (GVH) reaction, involving the destruction of the corneal endothelial cells of the rabbit host by sensitized donor lymphoid cells, has been used to study the mechanism of corneal allograft rejection. Pretreatment of donor cells with a specific mouse monoclonal hybridoma anti-T cell antibody and complement suppresses the destructive reaction, suggesting that a cellular-immune mechanism is primarily involved. Pretreatment of donor cells with mitomycin-C completely abolishes the local GVH reaction, indicating that the effector lymphocytes must undergo mitosis within the eye before they can engage in target cell destruction. Finally, studies of the local GVH reaction in irradiated leukopenic recipients or in preinflamed rabbit eyes suggest that host leukocytes may contribute nonspecifically to enhance the destructive process. These studies show that the local ocular GVH reaction may provide a useful model for the study of the mechanisms involved in the rejection of corneal allografts

  10. A new rejection of moral expertise.

    Science.gov (United States)

    Cowley, Christopher

    2005-01-01

    There seem to be two clearly-defined camps in the debate over the problem of moral expertise. On the one hand are the "Professionals", who reject the possibility entirely, usually because of the intractable diversity of ethical beliefs. On the other hand are the "Ethicists", who criticise the Professionals for merely stipulating science as the most appropriate paradigm for discussions of expertise. While the subject matter and methodology of good ethical thinking is certainly different from that of good clinical thinking, they argue, this is no reason for rejecting the possibility of a distinctive kind of expertise in ethics, usually based on the idea of good justification. I want to argue that both are incorrect, partly because of the reasons given by one group against the other, but more importantly because both neglect what is most distinctive about ethics: that it is personal in a very specific way, without collapsing into relativism.

  11. Stable transfection of Eimeria intestinalis and investigation of its life cycle, reproduction and immunogenicity

    Directory of Open Access Journals (Sweden)

    Tuanyuan eShi

    2016-05-01

    Full Text Available Rabbit coccidiosis, caused by infection of Eimeria spp. is one of the most severe parasitic diseases in rabbits. E. intestinalis is one of the most immunogenic species in rabbit coccidia. Due to the lack of genomic information and unsuccessful in vitro cultivation, genetic manipulation of rabbit coccidia lagged behind other apicomplexan parasites. Using regulatory sequences from E. tenella, we obtained a transgenic line of E. intestinalis expressing yellow fluorescent protein (YFP. YFP was continuously expressed throughout the whole life cycle. Morphological features of E. intestinalis in the different developmental stages were dynamically observed with the transgenic line. Some important features in the endogenous development stages were observed. Trophozoites were found as early as 4 h post inoculation. Two-types of schizonts and merozoites were observed in first three of the four schizogonies. Beside jejunum and ileum, gametogony stage and oocysts were also found in the duodenum and vermiform appendix. In addition, the transgenic strain was highly immunogenic but less pathogenic than the wild type. Considering the high immunogenicity of E. intestinalis and amenability to transfection with foreign genes, transgenic E. intestinalis could be a promising oral eukaryotic vaccine vector.

  12. [Eukaryotic Expression and Immunogenic Research of Recombination Ebola Virus Membrane Protein Gp-Fc].

    Science.gov (United States)

    Zhang, Xiaoguang; Yang, Ren; Wang, Jiao; Wang, Xuan; Hou, Mieling; An, Lina; Zhu, Ying; Cao, Yuxi; Zeng, Yi

    2016-01-01

    We used 293 cells to express the recombinant membrane protein of the Ebola virus. Then, the immunogenicity of the recombinant protein was studied by immunized BALB/c mice. According to the codon use frequency of humans, the gene encoding the extracellular domain of the Ebola virus membrane protein was optimized, synthesized, and inserted into the eukaryotic expression plasmid pXG-Fc to construct the human IgG Fc and Ebola GP fusion protein expression plasmid pXG-modGP-Fc. To achieve expression, the fusion protein expression vector was transfected into high-density 293 cells using transient transfection technology. The recombinant protein was purified by protein A affinity chromatography. BALB/c mice were immunized with the purified fusion protein, and serum antibody titers evaluated by an indirect enzyme-linked immunosorbent assay (ELISA). Purification and analyses of the protein revealed that the eukaryotic expression vector could express the recombinant protein GP-Fc effectively, and that the recombinant protein in the supernatant of the cell culture was present as a dimer. After immunization with the purified recombinant protein, a high titer of antigen-specific IgG could be detected in the serum of immunized mice by indirect ELISA, showing that the recombinant protein had good immunogenicity. These data suggest that we obtained a recombinant protein with good immunogenicity. Our study is the basis for development of a vaccine against the Ebola virus and for screening of monoclonal antibodies.

  13. Optimization of a photon rejecter to separate electronic noise in a photon-counting detector

    International Nuclear Information System (INIS)

    Cho, Hyo-Min; Choi, Yu-Na; Lee, Seung-Wan; Lee, Young-Jin; Ryu, Hyun-Ju; Kim, Hee-Joung

    2012-01-01

    Photon-counting-based X-ray imaging technology provides the capability to count individual photons and to characterize photon energies. The cadmium telluride (CdTe)-based photon-counting detector is limited in capability, however, under a high X-ray flux. A photon rejecter composed of aluminum, for example, can reduce this limitation by modulating the incident number of photons. In addition to this function, the optimal photon rejecter can separate electronic noise, which degrades image quality. The aim of this work was to optimize a photon rejecter for high-quality image acquisition by removing electronic noise from the actual pulse signal. The images and spectra were acquired using a micro-focus X-ray source with a CdTe-based photon-counting detector. We acquired data with various types of photon-rejecter materials composed of aluminum (Al) and iodine at three different tube voltages (50, 70, and 90 kVp). A phantom composed of high-atomic-number materials was imaged to evaluate the efficiency of the photon rejecter. Photon rejecters composed of 1-mm Al, 10-mm Al, and a combination of 10-mm Al and iodine provided optimum capability at 50, 70, and 90 kVp, respectively. Each optimal combination of photon-rejecter material and voltage effectively separated electronic noise from the actual pulse signal and gave the highest contrast-to-noise ratio for materials on the image. These optimized types of photon rejecters can effectively discriminate electronic noise and improve image quality at different tube voltages.

  14. Prediction of acute cardiac rejection by changes in left ventricular volumes

    International Nuclear Information System (INIS)

    Novitzky, D.; Cooper, D.K.; Boniaszczuk, J.

    1988-01-01

    Sixteen patients underwent heart transplantation (11 orthotopic, five heterotopic). Monitoring for acute rejection was by both endomyocardial biopsy (EMB) and multigated equilibrium blood pool scanning with technetium 99m-labelled red blood cells. From the scans information was obtained on left ventricular volumes (stroke, end-diastolic, and end-systolic), ejection fraction, and heart rate. Studies (208) were made in the 16 patients. There was a highly significant correlation between the reduction in stroke volume and end-diastolic volume (and a less significant correlation in end-systolic volume) and increasing acute rejection seen on EMB. Heart rate and ejection fraction did not correlate with the development of acute rejection. Correlation of a combination of changes in stroke volume and end-diastolic volume with EMB showed a sensitivity of 85% and a specificity of 96%. Radionuclide scanning is therefore a useful noninvasive tool for monitoring acute rejection

  15. Crosslinked cellulose thin film composite nanofiltration membranes with zero salt rejection

    KAUST Repository

    Puspasari, Tiara

    2015-05-14

    We report a new synthetic route of fabricating regenerated cellulose nanofiltration membranes. The membranes are composite membranes with a thin selective layer of cellulose, which was prepared by regeneration of trimethylsilyl cellulose (a hydrophobic cellulose derivative) film followed by crosslinking. Filtration experiments using mixtures of sugar and sodium chloride showed that solutes above 300 Da were highly rejected whereas practically no rejection was observed for NaCl. This is a big advantage for a complete desalination as the existing commercial nanofiltration membranes typically exhibit NaCl rejection in the range of 30–60%. Membranes with zero NaCl rejection are required for recovery and purification applications in food, chemical and pharmaceutical industry.

  16. A Multisurface Interpersonal Circumplex Assessment of Rejection Sensitivity.

    Science.gov (United States)

    Cain, Nicole M; De Panfilis, Chiara; Meehan, Kevin B; Clarkin, John F

    2017-01-01

    Individuals high in rejection sensitivity (RS) are at risk for experiencing high levels of interpersonal distress, yet little is known about the interpersonal profiles associated with RS. This investigation examined the interpersonal problems, sensitivities, and values associated with RS in 2 samples: 763 multicultural undergraduate students (Study 1) and 365 community adults (Study 2). In Study 1, high anxious RS was associated with socially avoidant interpersonal problems, whereas low anxious RS was associated with vindictive interpersonal problems. In Study 2, we assessed both anxious and angry expectations of rejection. Circumplex profile analyses showed that the high anxious RS group reported socially avoidant interpersonal problems, sensitivities to remoteness in others, and valuing connections with others, whereas the high angry RS group reported vindictive interpersonal problems, sensitivities to submissiveness in others, and valuing detached interpersonal behavior. Low anxious RS was related to domineering interpersonal problems, sensitivity to attention-seeking behavior, and valuing detached interpersonal behavior, whereas low angry RS was related to submissive interpersonal problems, sensitivity to attention-seeking behavior, and valuing receiving approval from others. Overall, results suggest that there are distinct interpersonal profiles associated with varying levels and types of RS.

  17. Effects of composite mango ( Mangifera indica ) fruit reject meal on ...

    African Journals Online (AJOL)

    Effects of composite mango ( Mangifera indica ) fruit reject meal on growth performance, digestibility and economics of production of rabbits. ... The experiment was conducted to determine the effect of mango fruit reject ... HOW TO USE AJOL.

  18. Immunogenicity and immunomodulatory properties of umbilical cord lining mesenchymal stem cells.

    Science.gov (United States)

    Deuse, Tobias; Stubbendorff, Mandy; Tang-Quan, Karis; Phillips, Neil; Kay, Mark A; Eiermann, Thomas; Phan, Thang T; Volk, Hans-Dieter; Reichenspurner, Hermann; Robbins, Robert C; Schrepfer, Sonja

    2011-01-01

    We here present an immunologic head-to-head comparison between human umbilical cord lining mesenchymal stem cells (clMSCs) and adult bone marrow MSCs (bmMSCs) from patients >65 years of age. clMSCs had significantly lower HLA class I expression, higher production of tolerogenic TGF-β and IL-10, and showed significantly faster proliferation. In vitro activation of allogeneic lymphocytes and xenogeneic in vivo immune activation was significantly stronger with bmMSCs, whereas immune recognition of clMSCs was significantly weaker. Thus, bmMSCs were more quickly rejected in immunocompetent mice. IFN-γ at 25 ng/ml increased both immunogenicity by upregulation of HLA class I/ HLA-DR expression and tolerogenicity by increasing intracellular HLA-G and surface HLA-E expression, augmenting TGF-β and IL-10 release, and inducing indoleamine 2,3-dioxygenase (IDO) expression. Higher concentrations of IFN-γ (>50 ng/ml) further enhanced the immunosuppressive phenotype of clMSCs, more strongly downregulating HLA-DR expression and further increasing IDO production (at 500 ng/ml). The net functional immunosuppressive efficacy of MSCs was tested in mixed lymphocyte cultures. Although both clMSCs and bmMSCs significantly reduced in vitro immune activation, clMSCs were significantly more effective than bmMSCs. The veto function of both MSC lines was enhanced in escalating IFN-γ environments. In conclusion, clMSCs show a more beneficial immunogeneic profile and stronger overall immunosuppressive potential than aged bmMSCs.

  19. Immunogenicity of Anti-HLA Antibodies in Pancreas and Islet Transplantation.

    Science.gov (United States)

    Chaigne, Benjamin; Geneugelijk, Kirsten; Bédat, Benoît; Ahmed, Mohamed Alibashe; Hönger, Gideon; De Seigneux, Sophie; Demuylder-Mischler, Sandrine; Berney, Thierry; Spierings, Eric; Ferrari-Lacraz, Sylvie; Villard, Jean

    2016-11-01

    The aim of the current study was to characterize the anti-HLA antibodies before and after pancreatic islet or pancreas transplantation. We assessed the risk of anti-donor-specific antibody (DSA) sensitization in a single-center, retrospective clinical study at Geneva University Hospital. Data regarding clinical characteristics, graft outcome, HLA mismatch, donor HLA immunogenicity, and anti-HLA antibody characteristics were collected. Between January 2008 and July 2014, 18 patients received islet transplants, and 26 patients received a pancreas transplant. Eleven out of 18 patients (61.1%) in the islet group and 12 out of 26 patients (46.2%) in the pancreas group had anti-HLA antibodies. Six patients (33.3%) developed DSAs against HLA of the islets, and 10 patients (38.4%) developed DSAs against HLA of the pancreas. Most of the DSAs were at a low level. Several parameters such as gender, number of times cells were transplanted, HLA mismatch, eplet mismatch and PIRCHE-II numbers, rejection, and infection were analyzed. Only the number of PIRCHE-II was associated with the development of anti-HLA class II de novo DSAs. Overall, the development of de novo DSAs did not influence graft survival as estimated by insulin independence. Our results indicated that pretransplant DSAs at low levels do not restrict islet or pancreas transplantation [especially islet transplantation (27.8% vs. 15.4.%)]. De novo DSAs do occur at a similar rate in both pancreas and islet transplant recipients (mainly of class II), and the immunogenicity of donor HLA is a parameter that should be taken into consideration. When combined with an immunosuppressive regimen and close follow-up, development of low levels of DSAs was not found to result in reduced graft survival or graft function in the current study.

  20. THE DIAGNOSIS OF LIVER ALLOGRAFT ACUTE REJECTION IN LIVER BIOPSIES

    Directory of Open Access Journals (Sweden)

    L. V. Shkalova

    2011-01-01

    Full Text Available We performed histological examination of 80 liver allograft biopsies, the diagnosis of acute rejection was proved in 34 cases. Histological changes in liver biopsies in different grades of acute rejection were estimated according to Banff classification 1995, 1997 and were compared with current literature data. The article deals with the question of morphological value of grading acute rejection on early and late, also we analyze changes in treat- ment tactics after morphological verification of liver allograft acute rejection

  1. Adaptive Disturbance Rejection Control for Automatic Carrier Landing System

    Directory of Open Access Journals (Sweden)

    Xin Wang

    2016-01-01

    Full Text Available An adaptive disturbance rejection algorithm is proposed for carrier landing system in the final-approach. The carrier-based aircraft dynamics and the linearized longitudinal model under turbulence conditions in the final-approach are analyzed. A stable adaptive control scheme is developed based on LDU decomposition of the high-frequency gain matrix, which ensures closed-loop stability and asymptotic output tracking. Finally, simulation studies of a linearized longitudinal-directional dynamics model are conducted to demonstrate the performance of the adaptive scheme.

  2. Ineffective Degradation of Immunogenic Gluten Epitopes by Currently Available Digestive Enzyme Supplements

    Science.gov (United States)

    Janssen, George; Christis, Chantal; Kooy-Winkelaar, Yvonne; Edens, Luppo; Smith, Drew

    2015-01-01

    Background Due to the high proline content of gluten molecules, gastrointestinal proteases are unable to fully degrade them leaving large proline-rich gluten fragments intact, including an immunogenic 33-mer from α-gliadin and a 26-mer from γ-gliadin. These latter peptides can trigger pro-inflammatory T cell responses resulting in tissue remodeling, malnutrition and a variety of other complications. A strict lifelong gluten-free diet is currently the only available treatment to cope with gluten intolerance. Post-proline cutting enzymes have been shown to effectively degrade the immunogenic gluten peptides and have been proposed as oral supplements. Several existing digestive enzyme supplements also claim to aid in gluten degradation. Here we investigate the effectiveness of such existing enzyme supplements in comparison with a well characterized post-proline cutting enzyme, Prolyl EndoPeptidase from Aspergillus niger (AN-PEP). Methods Five commercially available digestive enzyme supplements along with purified digestive enzymes were subjected to 1) enzyme assays and 2) mass spectrometric identification. Gluten epitope degradation was monitored by 1) R5 ELISA, 2) mass spectrometric analysis of the degradation products and 3) T cell proliferation assays. Findings The digestive enzyme supplements showed comparable proteolytic activities with near neutral pH optima and modest gluten detoxification properties as determined by ELISA. Mass spectrometric analysis revealed the presence of many different enzymes including amylases and a variety of different proteases with aminopeptidase and carboxypeptidase activity. The enzyme supplements leave the nine immunogenic epitopes of the 26-mer and 33-mer gliadin fragments largely intact. In contrast, the pure enzyme AN-PEP effectively degraded all nine epitopes in the pH range of the stomach at much lower dose. T cell proliferation assays confirmed the mass spectrometric data. Conclusion Currently available digestive enzyme

  3. Ineffective degradation of immunogenic gluten epitopes by currently available digestive enzyme supplements.

    Directory of Open Access Journals (Sweden)

    George Janssen

    Full Text Available Due to the high proline content of gluten molecules, gastrointestinal proteases are unable to fully degrade them leaving large proline-rich gluten fragments intact, including an immunogenic 33-mer from α-gliadin and a 26-mer from γ-gliadin. These latter peptides can trigger pro-inflammatory T cell responses resulting in tissue remodeling, malnutrition and a variety of other complications. A strict lifelong gluten-free diet is currently the only available treatment to cope with gluten intolerance. Post-proline cutting enzymes have been shown to effectively degrade the immunogenic gluten peptides and have been proposed as oral supplements. Several existing digestive enzyme supplements also claim to aid in gluten degradation. Here we investigate the effectiveness of such existing enzyme supplements in comparison with a well characterized post-proline cutting enzyme, Prolyl EndoPeptidase from Aspergillus niger (AN-PEP.Five commercially available digestive enzyme supplements along with purified digestive enzymes were subjected to 1 enzyme assays and 2 mass spectrometric identification. Gluten epitope degradation was monitored by 1 R5 ELISA, 2 mass spectrometric analysis of the degradation products and 3 T cell proliferation assays.The digestive enzyme supplements showed comparable proteolytic activities with near neutral pH optima and modest gluten detoxification properties as determined by ELISA. Mass spectrometric analysis revealed the presence of many different enzymes including amylases and a variety of different proteases with aminopeptidase and carboxypeptidase activity. The enzyme supplements leave the nine immunogenic epitopes of the 26-mer and 33-mer gliadin fragments largely intact. In contrast, the pure enzyme AN-PEP effectively degraded all nine epitopes in the pH range of the stomach at much lower dose. T cell proliferation assays confirmed the mass spectrometric data.Currently available digestive enzyme supplements are ineffective in

  4. Provocation of skin graft rejection across murine class II differences by non--bone-marrow-derived cells

    International Nuclear Information System (INIS)

    Stuart, P.M.; Beck-Maier, B.; Melvold, R.W.

    1984-01-01

    We have evaluated the relative contribution of bone-marrow-derived cells to skin allograft immunogenicity in mice differing only at class II major histocompatibility genes by using bone marrow radiation chimeras as donors. The mouse strains used were C57BL/6Kh (B6) and B6.C-H-2bm12 (bm12), which differ only at at A beta gene of the I region of the mouse H-2 complex. Our results demonstrated that skin from (B6----bm12) chimeras was accepted by bm12 recipients and rejected by B6 mice in a manner indistinguishable from that of normal bm12 skin. Likewise, naive bm12 mice rejected (bm12----B6) chimeric skin and normal B6 skin equally well, and B6 animals accepted both types of skin grafts. Our data argues that the donor cell-type leading to graft rejection across limited I region differences is not of bone marrow origin, and that these cells must--at least under certain circumstances--express class II antigens

  5. Graft rejection after hematopoietic cell transplantation with nonmyeloablative conditioning

    DEFF Research Database (Denmark)

    Masmas, T.N.; Petersen, S.L.; Madsen, H.O.

    2008-01-01

    over time. The storage temperature of the apheresis products was identified as a risk factor for rejection. Storage of the apheresis products at 5 degrees C diminished the risk of rejection. Low donor T cell chimerism at Day +14 significantly increased the risk of rejection. Seven patients were...

  6. Predicting outcome of acute kidney transplant rejection using

    NARCIS (Netherlands)

    Rekers, Niels Vincent

    2014-01-01

    Acute kidney transplant rejection is an important risk factors for adverse graft outcome. Once diagnosed, it remains difficult to predict the risk of graft loss and the response to anti-rejection treatment. The aim of this thesis was to identify biomarkers during acute rejection, which predict the

  7. Immunogenicity of Phleum pratense depigmented allergoid vaccines: experimental study in rabbits.

    Science.gov (United States)

    Iraola, V; Gallego, M T; López-Matas, M A; Morales, M; Bel, I; García, N; Carnés, J

    2012-01-01

    Immunogenicity studies are based on accurate preclinical and clinical assessment of pharmaceutical products. The immunogenicity of modified allergen vaccines has not been fully elucidated, and the mechanisms involved are not well understood. Animal and human models have recently shown that depigmented allergoids induce specific immunoglobulin (Ig) G against individual allergens, thus supporting the clinical efficacy of these vaccines. The aim of this study was to investigate the production of specific IgG against individual antigens and their isoforms in rabbits injected with depigmented allergoid extracts of Phleum pratense pollen. Two New Zealand rabbits were immunized with depigmented-polymerized extracts adsorbed onto aluminum hydroxide (Depigoid) of P pratense. Rabbits were injected 3 times (35 microg Phl p 5). Specific IgG titers against native, depigmented, and depigmented-polymerized extracts and individual allergens (rPhl p 1 and rPhl p 5a) were analyzed by direct enzyme-linked immunosorbent assay. The capacity of these synthesized antibodies to recognize individual native and depigmented allergens and different isoforms was evaluated by immunoblot and 2-D analysis. All rabbits produced high titers of specific IgG against the 3 extracts. Rabbits injected with depigmented allergoids produced similar specific antibody titers against native, depigmented, and depigmented-polymerized extracts. Serum samples recognized individual allergens and their isoforms in the nonmodified extracts. Vaccines containing depigmented allergoid extracts of P pratense induce immunogenicity in vivo. The antibodies produced after injection of these extracts clearly recognized allergens and different isoforms in their native configuration.

  8. Drug Target Interference in Immunogenicity Assays: Recommendations and Mitigation Strategies.

    Science.gov (United States)

    Zhong, Zhandong Don; Clements-Egan, Adrienne; Gorovits, Boris; Maia, Mauricio; Sumner, Giane; Theobald, Valerie; Wu, Yuling; Rajadhyaksha, Manoj

    2017-11-01

    Sensitive and specific methodology is required for the detection and characterization of anti-drug antibodies (ADAs). High-quality ADA data enables the evaluation of potential impact of ADAs on the drug pharmacokinetic profile, patient safety, and efficacious response to the drug. Immunogenicity assessments are typically initiated at early stages in preclinical studies and continue throughout the drug development program. One of the potential bioanalytical challenges encountered with ADA testing is the need to identify and mitigate the interference mediated by the presence of soluble drug target. A drug target, when present at sufficiently high circulating concentrations, can potentially interfere with the performance of ADA and neutralizing antibody (NAb) assays, leading to either false-positive or, in some cases, false-negative ADA and NAb assay results. This publication describes various mechanisms of assay interference by soluble drug target, as well as strategies to recognize and mitigate such target interference. Pertinent examples are presented to illustrate the impact of target interference on ADA and NAb assays as well as several mitigation strategies, including the use of anti-target antibodies, soluble versions of the receptors, target-binding proteins, lectins, and solid-phase removal of targets. Furthermore, recommendations for detection and mitigation of such interference in different formats of ADA and NAb assays are provided.

  9. A semi-learning algorithm for noise rejection: an fNIRS study on ADHD children

    Science.gov (United States)

    Sutoko, Stephanie; Funane, Tsukasa; Katura, Takusige; Sato, Hiroki; Kiguchi, Masashi; Maki, Atsushi; Monden, Yukifumi; Nagashima, Masako; Yamagata, Takanori; Dan, Ippeita

    2017-02-01

    In pediatrics studies, the quality of functional near infrared spectroscopy (fNIRS) signals is often reduced by motion artifacts. These artifacts likely mislead brain functionality analysis, causing false discoveries. While noise correction methods and their performance have been investigated, these methods require several parameter assumptions that apparently result in noise overfitting. In contrast, the rejection of noisy signals serves as a preferable method because it maintains the originality of the signal waveform. Here, we describe a semi-learning algorithm to detect and eliminate noisy signals. The algorithm dynamically adjusts noise detection according to the predetermined noise criteria, which are spikes, unusual activation values (averaged amplitude signals within the brain activation period), and high activation variances (among trials). Criteria were sequentially organized in the algorithm and orderly assessed signals based on each criterion. By initially setting an acceptable rejection rate, particular criteria causing excessive data rejections are neglected, whereas others with tolerable rejections practically eliminate noises. fNIRS data measured during the attention response paradigm (oddball task) in children with attention deficit/hyperactivity disorder (ADHD) were utilized to evaluate and optimize the algorithm's performance. This algorithm successfully substituted the visual noise identification done in the previous studies and consistently found significantly lower activation of the right prefrontal and parietal cortices in ADHD patients than in typical developing children. Thus, we conclude that the semi-learning algorithm confers more objective and standardized judgment for noise rejection and presents a promising alternative to visual noise rejection

  10. Soluble CD30 in renal transplant recipients: is it a good biomarker to predict rejection?

    Science.gov (United States)

    Azarpira, Negar; Aghdaie, Mahdokht Hosein; Malekpour, Zahra

    2010-01-01

    It has been suggested that the serum soluble CD30 (sCD30) level may be a poten-tial marker for the prediction of acute allograft rejection in kidney transplant recipients. Therefore, its serum concentrations might offer a promising non-invasive tool to recognize patients with an increased risk for developing an acute graft rejection. We retrospectively correlate pre and post transplant level on post transplant graft survival, incidence of acute rejection and graft function using stored serum samples. Ninety-nine patients were divided in two separate groups: Group A in whom sample collection was done one day before transplantation and Group B where sample collection was done five days after transplantation. Younger recipients (aged less than 20 years) had higher sCD30 levels (P= 0.02). There was neither significant difference in the incidence of acute rejection nor incomplete response rate after anti rejection therapy in relation to pre transplant or post transplant sCD30. We could not find a significantly inferior graft survival rate in the high sCD30 group. In conclusion, younger patients had higher sCD30 concentrations however no correlation existed between the serum concentrations and occurrence of rejection episodes or graft survival.

  11. USA: California rejects mandatory GMO labelling

    OpenAIRE

    Paull, John

    2012-01-01

    Buying organic remains the best strategy for US consumers to avoid eating GM food. The voters of California have rejected the proposal to label GMO food. The proposition was narrowly lost, 47% to 53% (4,326,770 ‘Yes’ votes vs. 4,884,961 ‘No’ votes). Proposition 47 was supported by the organic sector but opposed by a coalition of GMO companies and US multinational food companies. Californians were invited to vote into law ‘The California Right to Know Genetically Engineered Food Act’. Section ...

  12. Cancer vaccine development: Designing tumor cells for greater immunogenicity

    Science.gov (United States)

    Bozeman, Erica N.; Shashidharamurthy, Rangaiah; Paulos, Simon A.; Palaniappan, Ravi; D’Souza, Martin; Selvaraj, Periasamy

    2014-01-01

    Cancer vaccine development is one of the most hopeful and exhilarating areas in cancer research. For this reason, there has been a growing interest in the development and application of novel immunotherapies for the treatment of cancer with the focus being on stimulating the immune system to target tumor cells specifically while leaving normal cells unharmed. From such research has emerged a host of promising immunotherapies such as dendritic cell-based vaccines, cytokine therapies and gene transfer technology. These therapies seek to counteract the poor immunogenicity of tumors by augmenting the host’s immune system with a variety of immunostimulatory proteins such as cytokines and costimulatory molecules. While such therapies have proven effective in the induction of anti-tumor immunity in animal models, they are less than optimal and pose a high risk of clinical infeasibility. Herein, we further discuss these immunotherapies as well as a feasible and efficient alternative that, in pre-clinical animal models, allows for the expression of specific immunostimulatory molecules on the surface of tumor cells by a novel protein transfer technology. PMID:20036822

  13. Immune response and histology of humoral rejection in kidney transplantation.

    Science.gov (United States)

    González-Molina, Miguel; Ruiz-Esteban, Pedro; Caballero, Abelardo; Burgos, Dolores; Cabello, Mercedes; Leon, Miriam; Fuentes, Laura; Hernandez, Domingo

    2016-01-01

    The adaptive immune response forms the basis of allograft rejection. Its weapons are direct cellular cytotoxicity, identified from the beginning of organ transplantation, and/or antibodies, limited to hyperacute rejection by preformed antibodies and not as an allogenic response. This resulted in allogenic response being thought for decades to have just a cellular origin. But the experimental studies by Gorer demonstrating tissue damage in allografts due to antibodies secreted by B lymphocytes activated against polymorphic molecules were disregarded. The special coexistence of binding and unbinding between antibodies and antigens of the endothelial cell membranes has been the cause of the delay in demonstrating the humoral allogenic response. The endothelium, the target tissue of antibodies, has a high turnover, and antigen-antibody binding is non-covalent. If endothelial cells are attacked by the humoral response, immunoglobulins are rapidly removed from their surface by shedding and/or internalization, as well as degrading the components of the complement system by the action of MCP, DAF and CD59. Thus, the presence of complement proteins in the membrane of endothelial cells is transient. In fact, the acute form of antibody-mediated rejection was not demonstrated until C4d complement fragment deposition was identified, which is the only component that binds covalently to endothelial cells. This review examines the relationship between humoral immune response and the types of acute and chronic histological lesion shown on biopsy of the transplanted organ. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  14. Rejection of Bromide and Bromate Ions by a Ceramic Membrane.

    Science.gov (United States)

    Moslemi, Mohammadreza; Davies, Simon H; Masten, Susan J

    2012-12-01

    Effects of pH and the addition of calcium chloride (CaCl(2)) on bromate (BrO(3) (-)) and bromide (Br(-)) rejection by a ceramic membrane were investigated. Rejection of both ions increased with pH. At pH 8, the rejection of BrO(3) (-) and Br(-) was 68% and 63%, respectively. Donnan exclusion appears to play an important role in determining rejection of BrO(3) (-) and Br(-). In the presence of CaCl(2), rejection of BrO(3) (-) and Br(-) ions was greatly reduced, confirming the importance of electrostatic interactions in determining rejection of BrO(3) (-) and Br(-). The effect of Ca(2+) is so pronounced that in most natural waters, rejection of both BrO(3) (-) and Br(-) by the membrane would be extremely small.

  15. Understanding maladaptive responses to rejection: Aggression with an audience.

    Science.gov (United States)

    DeBono, Amber; Layton, Rebekah L; Freeman, Nicholas; Muraven, Mark

    2017-01-01

    Logically, responding aggressively to rejection is maladaptive because one is unlikely to seek a relationship with an aggressor. We predict that when concealed, the illogical aggressive response to rejection is more likely, whereas when the rejected individuals' aggressive responses are perceived as public, the aggressive acts may be reduced. Participants were rejected by others (Experiment 1) or were either accepted or rejected during an online ball-tossing game (Experiment 2) and were then given an opportunity to aggress publicly or privately. Across experiments, when the opportunity to aggress was made public, rejected participants exhibited less aggressive behavior. When concerned about the perception of their public aggressive responses by others, rejected individuals' aggressive responses diminished compared with those whose actions were private. Crucially, this extended to aggression visible only to neutral others, suggesting that effects cannot solely be due to fear of retribution.

  16. A pseudotype baculovirus expressing the capsid protein of foot-and-mouth disease virus and a T-Cell immunogen shows enhanced immunogenicity in mice

    Directory of Open Access Journals (Sweden)

    Liu Xiangtao

    2011-02-01

    Full Text Available Abstract Background Foot-and-mouth disease (FMD is a highly contagious disease of livestock which causes severe economic loss in cloven-hoofed animals. Vaccination is still a major strategy in developing countries to control FMD. Currently, inactivated vaccine of FMDV has been used in many countries with limited success and safety concerns. Development of a novel effective vaccine is must. Methods In the present study, two recombinant pseudotype baculoviruses, one expressing the capsid of foot-and-mouth disease virus (FMDV under the control of a cytomegalovirus immediate early enhancer/promoter (CMV-IE, and the other the caspid plus a T-cell immunogen coding region under a CAG promoter were constructed, and their expression was characterized in mammalian cells. In addition, their immunogenicity in a mouse model was investigated. The humoral and cell-mediated immune responses induced by pseudotype baculovirus were compared with those of inactivated vaccine. Results Indirect immunofluorescence assay (IFA and indirect sandwich-ELISA (IS-ELISA showed both recombinant baculoviruses (with or without T-cell epitopes were transduced efficiently and expressed target proteins in BHK-21 cells. In mice, intramuscular inoculation of recombinants with 1 × 109 or 1 × 1010 PFU/mouse induced the production of FMDV-specific neutralizing antibodies and gamma interferon (IFN-γ. Furthermore, recombinant baculovirus with T-cell epitopes had better immunogenicity than the recombinant without T-cell epitopes as demonstrated by significantly enhanced IFN-γ production (P P Conclusions These results indicate that pseudotype baculovirus-mediated gene delivery could be a alternative strategy to develop a new generation of vaccines against FMDV infection.

  17. Oxygen-boosted immunogenic photodynamic therapy with gold nanocages@manganese dioxide to inhibit tumor growth and metastases.

    Science.gov (United States)

    Liang, Ruijing; Liu, Lanlan; He, Huamei; Chen, Zhikuan; Han, Zhiqun; Luo, Zhenyu; Wu, Zhihao; Zheng, Mingbin; Ma, Yifan; Cai, Lintao

    2018-09-01

    Metastatic triple-negative breast cancer (mTNBC) is an aggressive disease among women worldwide, characterized by high mortality and poor prognosis despite systemic therapy with radiation and chemotherapies. Photodynamic therapy (PDT) is an important strategy to eliminate the primary tumor, however its therapeutic efficacy against metastases and recurrence is still limited. Here, we employed a template method to develop the core-shell gold nanocage@manganese dioxide (AuNC@MnO 2 , AM) nanoparticles as tumor microenvironment responsive oxygen producers and near-infrared (NIR)-triggered reactive oxygen species (ROS) generators for oxygen-boosted immunogenic PDT against mTNBC. In this platform, MnO 2 shell degrades in acidic tumor microenvironment pH/H 2 O 2 conditions and generates massive oxygen to boost PDT effect of AM nanoparticles under laser irradiation. Fluorescence (FL)/photoacoustic (PA)/magnetic resonance (MR) multimodal imaging confirms the effective accumulation of AM nanoparticles with sufficient oxygenation in tumor site to ameliorate local hypoxia. Moreover, the oxygen-boosted PDT effect of AM not only destroys primary tumor effectively but also elicits immunogenic cell death (ICD) with damage-associated molecular patterns (DAMPs) release, which subsequently induces DC maturation and effector cells activation, thereby robustly evoking systematic antitumor immune responses against mTNBC. Hence, this oxygen-boosted immunogenic PDT nanosystem offers a promising approach to ablate primary tumor and simultaneously prevent tumor metastases via immunogenic abscopal effects. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. The TLR7 agonist Imiquimod promote the immunogenicity of msenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Li Zhang

    2015-01-01

    Full Text Available BACKGROUND: Mesenchymal stem cells (MSCs are considered the best candidate in stem cells therapy due to their multipotent differentiation ability, low expression of co-stimulatory molecules (CD80, CD86, CD34 and HLA-II and immunosuppression effects on in vivo immune responses. MSCs were now widely used in clinical trials but received no encourage results. The major problem was the fate of engrafted MSCs in vivo could not be defined. Some studies indicated that MSCs could induce immune response and result in the damage and rejection of MSCs. As toll like receptors (TLRs are important in inducing of immune responses, in this study we study the role of TLR7 in mediating the immune status of MSCs isolated from umbilical cord. RESULTS: Our results indicated that TLR7 agonist Imiquimod could increase the proliferation of PBMC isolated from healthy human volunteers and release of lactate dehydrogenase (LDH in supernatant from PBMC-UCMSCs co-culture system. Flow cytometry and quantitative PCR also confirmed the regulated expression of surface co-stimulatory molecules and pro-inflammatory genes (IL-6, IL-8, IL-12, TGF-β and TNF-α. And the down-regulation expression of stem cell markers also confirmed the loss of stemness of UCMSCs. We also found that the osteo-differentiation ability of UCMSCs was enhanced in the presence of Imiquimod. CONCLUSION: To our knowledge, this is the first report that activation of TLR7 pathway increases the immunogenicity of UCMSCs. Extensive researches have now been conducted to study whether the change of immune status will be help in tumor rejection based on the tumor-tropism of MSCs.

  19. Effective immunotherapy of weakly immunogenic solid tumours using a combined immunogene therapy and regulatory T-cell inactivation.

    LENUS (Irish Health Repository)

    Whelan, M C

    2012-01-31

    Obstacles to effective immunotherapeutic anti-cancer approaches include poor immunogenicity of the tumour cells and the presence of tolerogenic mechanisms in the tumour microenvironment. We report an effective immune-based treatment of weakly immunogenic, growing solid tumours using a locally delivered immunogene therapy to promote development of immune effector responses in the tumour microenvironment and a systemic based T regulatory cell (Treg) inactivation strategy to potentiate these responses by elimination of tolerogenic or immune suppressor influences. As the JBS fibrosarcoma is weakly immunogenic and accumulates Treg in its microenvironment with progressive growth, we used this tumour model to test our combined immunotherapies. Plasmids encoding GM-CSF and B7-1 were electrically delivered into 100 mm(3) tumours; Treg inactivation was accomplished by systemic administration of anti-CD25 antibody (Ab). Using this approach, we found that complete elimination of tumours was achieved at a level of 60% by immunogene therapy, 25% for Treg inactivation and 90% for combined therapies. Moreover, we found that these responses were immune transferable, systemic, tumour specific and durable. Combined gene-based immune effector therapy and Treg inactivation represents an effective treatment for weakly antigenic solid growing tumours and that could be considered for clinical development.

  20. Factors contributing to the immunogenicity of meningococcal conjugate vaccines

    Science.gov (United States)

    Bröker, Michael; Berti, Francesco; Costantino, Paolo

    2016-01-01

    ABSTRACT Various glycoprotein conjugate vaccines have been developed for the prevention of invasive meningococcal disease, having significant advantages over pure polysaccharide vaccines. One of the most important features of the conjugate vaccines is the induction of a T-cell dependent immune response, which enables both the induction of immune memory and a booster response after repeated immunization. The nature of the carrier protein to which the polysaccharides are chemically linked, is often regarded as the main component of the vaccine in determining its immunogenicity. However, other factors can have a significant impact on the vaccine's profile. In this review, we explore the physico-chemical properties of meningococcal conjugate vaccines, which can significantly contribute to the vaccine's immunogenicity. We demonstrate that the carrier is not the sole determining factor of the vaccine's profile, but, moreover, that the conjugate vaccine's immunogenicity is the result of multiple physico-chemical structures and characteristics. PMID:26934310

  1. Genome-Derived Cytosolic DNA Mediates Type I Interferon-Dependent Rejection of B Cell Lymphoma Cells

    Directory of Open Access Journals (Sweden)

    Yu J. Shen

    2015-04-01

    Full Text Available The DNA damage response (DDR induces the expression of type I interferons (IFNs, but the underlying mechanisms are poorly understood. Here, we show the presence of cytosolic DNA in different mouse and human tumor cells. Treatment of cells with genotoxic agents increased the levels of cytosolic DNA in a DDR-dependent manner. Cloning of cytosolic DNA molecules from mouse lymphoma cells suggests that cytosolic DNA is derived from unique genomic loci and has the potential to form non-B DNA structures, including R-loops. Overexpression of Rnaseh1, which resolves R-loops, reduced the levels of cytosolic DNA, type I Ifn transcripts, and type I IFN-dependent rejection of lymphoma cells. Live-cell imaging showed a dynamic contact of cytosolic DNA with mitochondria, an important organelle for innate immune recognition of cytosolic nucleotides. In summary, we found that cytosolic DNA is present in many tumor cells and contributes to the immunogenicity of tumor cells.

  2. Acute humoral rejection and C4d immunostaining in ABO blood type-incompatible liver transplantation.

    Science.gov (United States)

    Haga, Hironori; Egawa, Hiroto; Fujimoto, Yasuhiro; Ueda, Mikiko; Miyagawa-Hayashino, Aya; Sakurai, Takaki; Okuno, Tomoko; Koyanagi, Itsuko; Takada, Yasutsugu; Manabe, Toshiaki

    2006-03-01

    Complement C4d deposition in graft capillaries has been reported to be associated with antibody-mediated rejection in kidney and other solid organ transplantation. The correlation of C4d deposits and humoral rejection in liver transplants, however, is not well understood. We investigated the C4d immunostaining pattern in 34 patients whose liver biopsy was taken within the first 3 postoperative weeks for suspected acute rejection after ABO blood type-incompatible liver transplantation. The staining pattern was classified as positive (portal stromal staining), indeterminate (endothelial staining only), and negative (no staining). Positive C4d immunostaining was seen in 17 (50%) patients and was significantly associated with high (x64 or more) postoperative antidonor A/B antibody (immunoglobulin M (IgM)) titers (88 vs. 35%, P = 0.002) and poorer overall survival rate (41 vs. 88%, P = 0.007). Ten of 11 (91%) cases with histological acute humoral rejection (periportal edema and necrosis (PEN) or portal hemorrhagic edema) were positive for C4d, all of which showed high postoperative antibody titers. The other histologies associated with C4d positivity was purulent cholangitis (n = 4), coagulative hepatocyte necrosis (n = 1), acute cellular rejection (n = 1), and hepatocanalicular cholestasis (n = 1). Full clinical recovery was observed in only 6 of 17 (35%) C4d-positive patients, and tended to be associated with a lower rejection activity index (RAI). In conclusion, our study indicates that C4d deposits in the portal stroma can be a hallmark of acute humoral rejection in ABO-incompatible liver transplantation, and allograft damage can be reversible in a minority of cases. Copyright 2006 AASLD

  3. Delay discounting, risk-taking, and rejection sensitivity among individuals with Internet and Video Gaming Disorders.

    Science.gov (United States)

    Weinstein, Aviv; Abu, Hodaya Ben; Timor, Ayelet; Mama, Yaniv

    2016-12-01

    Background and aims There is a previous evidence for impulsivity in individuals with Internet and Video Gaming Disorders. The aim of this study was to examine whether Internet and video game addictions are associated with experiential delay discounting, risk-taking, and sensitivity to social rejection using computerized tasks and questionnaires. Methods Twenty participants (mean age 24, SD = 1.55) with high score on the Problematic Online Gaming Questionnaire (POGQ) were compared with 20 participants (mean age 24.8, SD = 1.34) with low score on the POGQ. They performed on computerized Balloon Analog Risk Task and Experiential Delay discounting Task (EDT), and filled in the sensitivity to social rejection questionnaire. Results Participants with high POGQ scores had lower measures of delay discounting, higher measures of risk-taking, and higher measures of sensitivity to social rejection compared with participants with low POGQ scores. Discussion The results of this study support the previous evidence of risk-taking and provide new evidence for difficulties in delay discounting and sensitivity to social rejection among those who score high on Internet and video games. Conclusions The results suggest that Internet- and video game-addicted individuals seek immediate gratification and cannot wait for later reward. Furthermore, these individuals spend time in the virtual world, where they feel safe, and avoid social interactions presumably due to fears of social rejection.

  4. The role of CD8+ T cells during allograft rejection

    Directory of Open Access Journals (Sweden)

    V. Bueno

    2002-11-01

    Full Text Available Organ transplantation can be considered as replacement therapy for patients with end-stage organ failure. The percent of one-year allograft survival has increased due, among other factors, to a better understanding of the rejection process and new immunosuppressive drugs. Immunosuppressive therapy used in transplantation prevents activation and proliferation of alloreactive T lymphocytes, although not fully preventing chronic rejection. Recognition by recipient T cells of alloantigens expressed by donor tissues initiates immune destruction of allogeneic transplants. However, there is controversy concerning the relative contribution of CD4+ and CD8+ T cells to allograft rejection. Some animal models indicate that there is an absolute requirement for CD4+ T cells in allogeneic rejection, whereas in others CD4-depleted mice reject certain types of allografts. Moreover, there is evidence that CD8+ T cells are more resistant to immunotherapy and tolerance induction protocols. An intense focal infiltration of mainly CD8+CTLA4+ T lymphocytes during kidney rejection has been described in patients. This suggests that CD8+ T cells could escape from immunosuppression and participate in the rejection process. Our group is primarily interested in the immune mechanisms involved in allograft rejection. Thus, we believe that a better understanding of the role of CD8+ T cells in allograft rejection could indicate new targets for immunotherapy in transplantation. Therefore, the objective of the present review was to focus on the role of the CD8+ T cell population in the rejection of allogeneic tissue.

  5. Rejection of Tetracycline and Oxytetracycline in Water by a Nanofiltration Membrane

    Science.gov (United States)

    Li, Weiying; Sun, Xiuli; Wang, Qing; Xu, Jingjing; Lu, Junyu

    2010-11-01

    The removal of tetracycline (TC) and oxytetracycline (OTC) by a nanofiltration (NF) membrane was studied using synthetic solutions. The effects of operation parameters (recovery and flux), feed concentration and salinity on the rejection of tetracyclines and their adsorption on membranes were investigated. TC was observed to show a high adsorptive affinity for the membrane. Almost 80% of TC and 70% of OTC were adsorbed on the membrane surface after stirring for 2000 min and over 50% of them had been adsorbed just 120 min after stir. High removal efficiencies (>90%) were observed for TC and OTC with NF membrane. Rejection ratio of OTC by NF was slightly higher than that of TC.

  6. Esophageal motor disorders are frequent during pre and post lung transplantation. Can they influence lung rejection?

    Science.gov (United States)

    Ciriza de Los Ríos, Constanza; Canga Rodríguez-Valcárcel, Fernando; de Pablo Gafas, Alicia; Castel de Lucas, Isabel; Lora Pablos, David; Castellano Tortajada, Gregorio

    2018-06-01

    lung transplantation (LTx) is a viable option for most patients with end-stage lung diseases. Esophageal motor disorders (EMD) are frequent in candidates for LTx, but there is very little data about changes in esophageal motility post-LTx. the aim of our study was to assess esophageal motor disorders by high resolution manometry (HRM) both pre-LTx and six months post-LTx in patients with and without organ rejection. HRM (Manoscan®) was performed in 57 patients both pre-LTx and six months post-LTx. HRM plots were analyzed according to the Chicago classification 3.0. EMD were found in 33.3% and in 49.1% of patients pre-LTx and post-LTx, respectively, and abnormal peristalsis was more frequently found post-LTx (p = 0.018). Hypercontractile esophagus was frequently found post-LTx (1.8% and 19.3% pre-LTx and post-LTx, respectively). Esophagogastric junction (EGJ) morphology changed significantly pre-LTx and post-LTx; type I (normal) was more frequent post-LTx (63-2% and 82.5% respectively, p = 0.007). EMD were more frequent post-LTx in both the non-rejection and rejection group, although particularly in the rejection group (43.2% and 69.2% respectively, p = 0.09). EMD such as distal spasm, hypercontractile esophagus and EGJ outflow obstruction were also observed more frequently post-LTx in the rejection group. significant changes in esophageal motility were observed pre-LTx and particularly post-LTx; hypercontractile esophagus was a frequent EMD found post-LTx. EMD were more frequent in the group of patients that experienced organ rejection compared to the non-rejection group. EMD leading to an impaired esophageal clearance should be considered as an additional factor that contributes to LTx failure.

  7. Posttransplant soluble CD30 as a predictor of acute renal allograft rejection.

    Science.gov (United States)

    Kamali, Koosha; Abbasi, Mohammad Amin; Farokhi, Babak; Abbasi, Ata; Fallah, Parvane; Seifee, Mohammad Hasan; Ghadimi, Naime; Rezaie, Alireza R

    2009-12-01

    Recent results have indicated that high prerenal and postrenal transplant soluble CD30 levels may be associated with an increased acute rejection and graft loss. The aim of this study was to evaluate the feasibility of using serum sCD30 as a marker for predicting acute graft rejection. In this prospective study,we analyzed clinical data of 80 patients, whose pretransplant and posttransplant serum levels of sCD30 were detected by enzyme-linked immunoassay. Eight patients developed acute rejection, 7 patients showed delayed graft function, and 65 recipients experienced an uncomplicated course group. The patients were followed for 12 months, and there were no deaths. Preoperative sCD30 levels of 3 groups were 96.2 -/+ 32.5, 80.2 -/+ 28.3, and 76.8 -/+ 29.8 U/mL (P = .28). After transplant, a significant decrease in the sCD30 level was detected in 3 groups on day 14 posttransplant (P sCD30 levels of acute rejection group remained significantly higher than delayed graft function and nonrejecting patients (28.3 -/+ 5.2, 22.1 -/+ 3.2, and 19.8 -/+ 4.7 U/mL) (P = .02). Positive panel reactive antibody was not statistically different among groups (P = .05). Also, hemodialysis did not affect sCD30 levels (P = .05). Receiver operating characteristic curve demonstrated that the sCD30 level on day 14 posttransplant could discriminate patients who subsequently suffered acute allograft rejection (area under receiver operating characteristic curve, 0.95). According to receiver operating characteristic curve, 20 U/mL may be the optimal operational cutoff level to predict impending graft rejection (specificity 93.8%, sensitivity 83.3%). Measurement of the soluble CD30 level on day 14 after transplant might offer a noninvasive means for recognizing patients at risk of acute graft rejection during the early posttransplant period.

  8. PREVENTION AND TREATMENT OF REJECTION AFTER SIMULTANEOUS PANCREAS-KIDNEY TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    Lei Yang; Yong-feng Liu; Shu-rong Liu; Gang Wu; Jia-lin Zhang; Yi-man Meng; Shao-wei Shong; Gui-chen Li

    2005-01-01

    Objective To explore methods of preventing and reversing rejection after simultaneous pancreas-kidney (SPK) tran splantation. Methods Seventeen patients underwent SPK transplantation from September 1999 to September 2003 were reviewed retrospectively. Immunosuppression was achieved by a triple drug regimen consisting of cyclosporine, mycophenolate mofteil (MMF), and steroids. Three patients were treated with anti-CD3 monoclone antibody (OKT3, 5 mg· d-1) for induction therapy for a mean period of 5-7 days. One patients received IL-2 receptor antibodies (daclizumab) in a dose of 1 mg· kg-1 on the day of transplant and the 5th day posttransplant. One patient was treated with both OKT3 and daclizumab for induction. Results No primary non-functionality of either kidney or pancreas occurred in this series of transplantations. Function of all the kidney grafts recovered within 2 to 4 days after transplantation. The level of serum creatinine was 94 ± 11 μmol/L on the 7th day posttransplant. One patient experienced the accelerated rejection, resulting in the resection of the pancreas and kidney grafts because of the failure of conservative therapy. The incidence of the first rejection episodes at 3 months was 47.1% (8/17). Only the kidney was involved in 35.3% (6/17); and both the pancreas and kidney were involved in 11.8% (2/17). All these patients received a high-dose pulse of methylprednisone (0.5 g·d-1) for 3 days. OKT3 (0.5 mg·d-1) was administered for 7-10 days in two patients with both renal and pancreas rejection. All the grafts were successfully rescued. Conclusion Rejection, particularly acute rejection, is the major cause influencing graft function in SPK transplantation. Monitoring renal function and pancreas exocrine secretion, and reasonable application of immunosuppressants play important roles in the diagnosis and treatment of rejection.

  9. Total lymphoid irradiation for treatment of intractable cardiac allograft rejection

    International Nuclear Information System (INIS)

    Hunt, S.A.; Strober, S.; Hoppe, R.T.; Stinson, E.B.

    1991-01-01

    The ability of postoperative total lymphoid irradiation to reverse otherwise intractable cardiac allograft rejection was examined in a group of 10 patients in whom conventional rejection therapy (including pulsed steroids and monoclonal or polyclonal anti-T-cell antibody therapy) had failed to provide sustained freedom from rejection. Follow-up periods range from 73 to 1119 days since the start of total lymphoid irradiation. No patient died or sustained serious morbidity because of the irradiation. Three patients have had no further rejection (follow-up periods, 105 to 365 days). Two patients died--one in cardiogenic shock during the course of total lymphoid irradiation, the other with recurrent rejection caused by noncompliance with his medical regimen. Total lymphoid irradiation appears to be a safe and a moderately effective immunosuppressive modality for 'salvage' therapy of cardiac allograft rejection unresponsive to conventional therapy

  10. A common rejection module (CRM) for acute rejection across multiple organs identifies novel therapeutics for organ transplantation.

    Science.gov (United States)

    Khatri, Purvesh; Roedder, Silke; Kimura, Naoyuki; De Vusser, Katrien; Morgan, Alexander A; Gong, Yongquan; Fischbein, Michael P; Robbins, Robert C; Naesens, Maarten; Butte, Atul J; Sarwal, Minnie M

    2013-10-21

    Using meta-analysis of eight independent transplant datasets (236 graft biopsy samples) from four organs, we identified a common rejection module (CRM) consisting of 11 genes that were significantly overexpressed in acute rejection (AR) across all transplanted organs. The CRM genes could diagnose AR with high specificity and sensitivity in three additional independent cohorts (794 samples). In another two independent cohorts (151 renal transplant biopsies), the CRM genes correlated with the extent of graft injury and predicted future injury to a graft using protocol biopsies. Inferred drug mechanisms from the literature suggested that two FDA-approved drugs (atorvastatin and dasatinib), approved for nontransplant indications, could regulate specific CRM genes and reduce the number of graft-infiltrating cells during AR. We treated mice with HLA-mismatched mouse cardiac transplant with atorvastatin and dasatinib and showed reduction of the CRM genes, significant reduction of graft-infiltrating cells, and extended graft survival. We further validated the beneficial effect of atorvastatin on graft survival by retrospective analysis of electronic medical records of a single-center cohort of 2,515 renal transplant patients followed for up to 22 yr. In conclusion, we identified a CRM in transplantation that provides new opportunities for diagnosis, drug repositioning, and rational drug design.

  11. Fish Rejections in the Marine Aquarium Trade: An Initial Case Study Raises Concern for Village-Based Fisheries.

    Directory of Open Access Journals (Sweden)

    Thane A Militz

    Full Text Available A major difficulty in managing wildlife trade is the reliance on trade data (rather than capture data to monitor exploitation of wild populations. Collected organisms that die or are rejected before a point of sale often go unreported. For the global marine aquarium trade, identifying the loss of collected fish from rejection, prior to export, is a first step in assessing true collection levels. This study takes a detailed look at fish rejections by buyers before export using the Papua New Guinea marine aquarium fishery as a case study. Utilizing collection invoices detailing the species and quantity of fish (Actinopteri and Elasmobranchii accepted or rejected by the exporting company it was determined that, over a six month period, 24.2% of the total fish catch reported (n = 13,886 was rejected. Of the ten most collected fish families, rejection frequency was highest for the Apogonidae (54.2%, Chaetodontidae (26.3%, and Acanthuridae (18.2% and lowest for Labridae (6.6% and Hemiscylliidae (0.7%. The most frequently cited reasons for rejection were fin damage (45.6% of cases, undersized fish (21.8%, and fish deemed too thin (11.1%. Despite fishers receiving feedback on invoices explaining rejections, there was no improvement in rejection frequencies over time (r = -0.33, P = 0.15 with weekly rejection frequencies being highly inconsistent (range: 2.8% to 79.4%; s = 16.3%. These findings suggest that export/import statistics can greatly underestimate collection for the marine aquarium trade as additional factors such as fisher discards, escapees, post-collection mortalities, and unregulated domestic trade would further contribute to this disparity.

  12. Cell-Free DNA and Active Rejection in Kidney Allografts.

    Science.gov (United States)

    Bloom, Roy D; Bromberg, Jonathan S; Poggio, Emilio D; Bunnapradist, Suphamai; Langone, Anthony J; Sood, Puneet; Matas, Arthur J; Mehta, Shikha; Mannon, Roslyn B; Sharfuddin, Asif; Fischbach, Bernard; Narayanan, Mohanram; Jordan, Stanley C; Cohen, David; Weir, Matthew R; Hiller, David; Prasad, Preethi; Woodward, Robert N; Grskovic, Marica; Sninsky, John J; Yee, James P; Brennan, Daniel C

    2017-07-01

    Histologic analysis of the allograft biopsy specimen is the standard method used to differentiate rejection from other injury in kidney transplants. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive test of allograft injury that may enable more frequent, quantitative, and safer assessment of allograft rejection and injury status. To investigate this possibility, we prospectively collected blood specimens at scheduled intervals and at the time of clinically indicated biopsies. In 102 kidney recipients, we measured plasma levels of dd-cfDNA and correlated the levels with allograft rejection status ascertained by histology in 107 biopsy specimens. The dd-cfDNA level discriminated between biopsy specimens showing any rejection (T cell-mediated rejection or antibody-mediated rejection [ABMR]) and controls (no rejection histologically), P rejection at a cutoff of 1.0% dd-cfDNA were 61% and 84%, respectively. The AUC for discriminating ABMR from samples without ABMR was 0.87 (95% CI, 0.75 to 0.97). Positive and negative predictive values for ABMR at a cutoff of 1.0% dd-cfDNA were 44% and 96%, respectively. Median dd-cfDNA was 2.9% (ABMR), 1.2% (T cell-mediated types ≥IB), 0.2% (T cell-mediated type IA), and 0.3% in controls ( P =0.05 for T cell-mediated rejection types ≥IB versus controls). Thus, dd-cfDNA may be used to assess allograft rejection and injury; dd-cfDNA levels rejection (T cell-mediated type ≥IB or ABMR) and levels >1% indicate a probability of active rejection. Copyright © 2017 by the American Society of Nephrology.

  13. Field Evaluation of Immunogenicity of Five Commercial Vaccines ...

    African Journals Online (AJOL)

    Field Evaluation of Immunogenicity of Five Commercial Vaccines Against Newcastle Disease in Poultry Farms in Ibadan, Nigeria. ... The PDF file you selected should load here if your Web browser has a PDF reader plug-in installed (for example, a recent version of Adobe Acrobat Reader). If you would like more information ...

  14. Immunogenicity moderation effect of interleukin-24 on myelogenous leukemia cells.

    Science.gov (United States)

    Yu, Xin; Miao, Jingcheng; Xia, Wei; Gu, Zong-Jiang

    2018-04-01

    Previous studies have shown that interleukin-24 (IL-24) has tumor-suppressing activity by multiple pathways. However, the immunogenicity moderation effect of IL-24 on malignant cells has not been explored extensively. In this study, we investigated the role of IL-24 in immunogenicity modulation of the myelogenous leukemia cells. Data show that myelogenous leukemia cells express low levels of immunogenicity molecules. Treatment with IL-24 could enhance leukemia cell immunogenicity, predominantly regulate leukemia cells to produce immune-associated cytokines, and improve the cytotoxic sensitivity of these cells to immune effector cells. IL-24 expression could retard transplanted leukemia cell tumor growth in vivo in athymic nude mice. Moreover, IL-24 had marked effects on downregulating the expression of angiogenesis-related proteins vascular endothelial growth factor, cluster of differentiation (CD) 31, CD34, collagen IV and metastasis-related factors CD147, membrane type-1 matrix metalloproteinase (MMP), and MMP-2 and MMP-9 in transplanted tumors. These findings indicated novel functions of this antitumor gene and characterized IL-24 as a promising agent for further clinical trial for hematologic malignancy immunotherapy.

  15. Immunogenicity and safety of an acellular pertussis, diphtheria ...

    African Journals Online (AJOL)

    Objective. To assess the immunogenicity and safety data for a pentavalent combination vaccine containing acellular pertussis, inactivated poliovirus, and Haemophilus influenzae (Hib) polysaccharide-conjugate antigens. Methods. A DTaP-IPV//PRP~T vaccine (Pentaxim™) was given at 6, 10 and 14 weeks of age to 212 ...

  16. Dealing with immunogenicity of biologicals: assessment and clinical relevance

    NARCIS (Netherlands)

    Wolbink, Gerrit J.; Aarden, Lucien A.; Dijkmans, B. A. C.

    2009-01-01

    PURPOSE OF REVIEW: In the last decade, biologicals revolutionized rheumatology. An increasing number of patients benefit from biotherapeuticals. However, some patients do not respond to treatment and others lose their response after a certain time. Immunogenicity is one of the factors linked to

  17. Safety and immunogenicity of two Haemophilus influenzae type b ...

    African Journals Online (AJOL)

    Objectives. Haemophilus influenzae type b (Hib) infection remains a major public health problem inthe developing world. We evaluated the safety and immunogenicity of a new PRP-CRM197 conjugate Hib vaccine (Vaxem Hib, Chiron Vacdnes), compared with theHibTITER vaccine (WyethLederle Vaccines), following the ...

  18. Comparative immunogenicity of local and imported infectious bursal ...

    African Journals Online (AJOL)

    A comparative immunogenicity and efficacy study of local and imported infectious bursal disease (IBD) vaccines administered to chicks (cockerels) at varying regimes (10 and 18, 10 and 28, 14 and 35 days of age) was carried out. The test birds were challenged seven days after the booster dose of the IBD vaccine by ...

  19. Novel Techniques for Background / Foreground Rejection in Particle Instruments

    Data.gov (United States)

    National Aeronautics and Space Administration — The Novel Techniques for Background / Foreground Rejection in Particle Instruments project addresses the need for signal contamination and background signal...

  20. Community rejection following sexual assault as ‘forced migration’

    OpenAIRE

    AJ Morgen

    2013-01-01

    When women are banished from their communities following sexual assault, this rejection should be considered an act of forced migration by the administrators of truth commission reparations programmes.

  1. Online monitoring of N-nitrosodimethylamine rejection as a performance indicator of trace organic chemical removal by reverse osmosis.

    Science.gov (United States)

    Fujioka, Takahiro; Takeuchi, Haruka; Tanaka, Hiroaki; Kodamatani, Hitoshi

    2018-06-01

    The security of recycled water quality in potable reuse can be enhanced by improving the credibility of reverse osmosis (RO) treatment for the removal of trace organic chemicals (TOrCs). This study evaluated the potential of online monitoring of N-nitrosodimethylamine (NDMA) before and after RO treatment as a surrogate indicator for TOrC removal by RO. This pilot-scale study monitored NDMA concentrations in RO feedwater (ultrafiltration-treated wastewater) and RO permeate every 22 min using novel online NDMA analyzers-high-performance liquid chromatography followed by photochemical reaction and chemiluminescence detection. NDMA rejection by RO varied considerably in response to changes in operating conditions (permeate flux and feedwater temperature). A high linear correlation between NDMA rejection and the rejection of six other TOrCs was observed. The linear correlation was also identified for an RO membrane damaged with chlorine. The correlation between another potential surrogate indicator (conductivity rejection) and TOrC rejection was relatively low. NDMA, which is the smallest compound among regulated TOrCs, revealed rejections lower than the other TOrCs, indicating that NDMA rejection can be a conservative surrogate indicator capable of predicting changes in TOrC removal. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Safety and immunogenicity of GMZ2 - a MSP3-GLURP fusion protein malaria vaccine candidate

    DEFF Research Database (Denmark)

    Esen, Meral; Kremsner, Peter G; Schleucher, Regina

    2009-01-01

    Malaria is a major public health problem in Sub-Saharan Africa. In highly endemic regions infants, children and pregnant women are mostly affected. An effective malaria vaccine would complement existing malaria control strategies because it can be integrated in existing immunization programs easily....... Here we present the results of the first phase Ia clinical trial of GMZ2 adjuvanted in aluminium hydroxide. GMZ2 is a malaria vaccine candidate, designed upon the rationale to induce immune responses against asexual blood stages of Plasmodium falciparum similar to those encountered in semi...... is a safe and immunogenic malaria vaccine candidate suitable for further clinical development....

  3. Soluble HIV-1 envelope immunogens derived from an elite neutralizer elicit cross-reactive V1V2 antibodies and low potency neutralizing antibodies.

    Directory of Open Access Journals (Sweden)

    Sara Carbonetti

    Full Text Available We evaluated four gp140 Envelope protein vaccine immunogens that were derived from an elite neutralizer, subject VC10042, whose plasma was able to potently neutralize a wide array of genetically distinct HIV-1 isolates. We sought to determine whether soluble Envelope proteins derived from the viruses circulating in VC10042 could be used as immunogens to elicit similar neutralizing antibody responses by vaccination. Each gp140 was tested in its trimeric and monomeric forms, and we evaluated two gp140 trimer vaccine regimens in which adjuvant was supplied at all four immunizations or at only the first two immunizations. Interestingly, all four Envelope immunogens elicited high titers of cross-reactive antibodies that recognize the variable regions V1V2 and are potentially similar to antibodies linked with a reduced risk of HIV-1 acquisition in the RV144 vaccine trial. Two of the four immunogens elicited neutralizing antibody responses that neutralized a wide array of HIV-1 isolates from across genetic clades, but those responses were of very low potency. There were no significant differences in the responses elicited by trimers or monomers, nor was there a significant difference between the two adjuvant regimens. Our study identified two promising Envelope immunogens that elicited anti-V1V2 antibodies and broad, but low potency, neutralizing antibody responses.

  4. Lymphocele: a possible relationship with acute cellular rejection in kidney transplantation

    Directory of Open Access Journals (Sweden)

    Marco Aurélio Silva Lipay

    1999-11-01

    Full Text Available CONTEXT: The incidence of lymphocele after renal transplantation varies between 0.6 and 18% of cases, and many factors have been associated to its etiology. Cellular rejection of the kidney allograft has been described as a possible causal factor of lymphocele. OBJECTIVE: To analyze the possible relationship between lymphocele and acute cellular rejection. DESIGN: A retrospective study. SETTING: A referral hospital center. SAMPLE: 170 patients submitted to kidney transplantation from March 1992 to January 1997. A standard technique for renal transplantation was used. RESULTS: Of the 19 patients that developed lymphocele, 16 presented at least one episode of acute cell rejection (84%, and were treated with methylprednisolone. The relation between lymphocele and rejection was statistically significant (p = 0.04. Treatment of lymphocele consisted of peritoneal marsupialization in 3 patients (15.3%, percutaneous drainage in 7 (36.8%, laparascopic marsupialization in 2 (10.5%, and conservative treatment in 7 patients (36.8%. Evolution was favorable in 15 patients (78.9%, 1 patient (5.3% died due to a cause unrelated to lymphocele, and 3 (15.8% lost the graft due to immunological factors. The average follow-up period was 24.5 months. CONCLUSION: The high incidence of acute cell rejection in patients with lymphocele suggests a possible causal relationship between both conditions.

  5. Immunogenicity of novel mumps vaccine candidates generated by genetic modification.

    Science.gov (United States)

    Xu, Pei; Chen, Zhenhai; Phan, Shannon; Pickar, Adrian; He, Biao

    2014-03-01

    Mumps is a highly contagious human disease, characterized by lateral or bilateral nonsuppurative swelling of the parotid glands and neurological complications that can result in aseptic meningitis or encephalitis. A mumps vaccination program implemented since the 1960s reduced mumps incidence by more than 99% and kept the mumps case numbers as low as hundreds of cases per year in the United States before 2006. However, a large mumps outbreak occurred in vaccinated populations in 2006 and again in 2009 in the United States, raising concerns about the efficacy of the vaccination program. Previously, we have shown that clinical isolate-based recombinant mumps viruses lacking expression of either the V protein (rMuVΔV) or the SH protein (rMuVΔSH) are attenuated in a neurovirulence test using newborn rat brains (P. Xu et al., Virology 417:126-136, 2011, http://dx.doi.org/10.1016/j.virol.2011.05.003; P. Xu et al., J. Virol. 86:1768-1776, 2012, http://dx.doi.org/10.1128/JVI.06019-11) and may be good candidates for vaccine development. In this study, we examined immunity induced by rMuVΔSH and rMuVΔV in mice. Furthermore, we generated recombinant mumps viruses lacking expression of both the V protein and the SH protein (rMuVΔSHΔV). Analysis of rMuVΔSHΔV indicated that it was stable in tissue culture cell lines. Importantly, rMuVΔSHΔV was immunogenic in mice, indicating that it is a promising candidate for mumps vaccine development.

  6. [Expression, purification and immunogenicity of human papillomavirus type 11 virus-like particles from Escherichia coli].

    Science.gov (United States)

    Yan, Chunyan; Li, Shaowei; Wang, Jin; Wei, Minxi; Huang, Bo; Zhuang, Yudi; Li, Zhongyi; Pan, Huirong; Zhang, Jun; Xia, Ningshao

    2009-11-01

    To produce human papillomavirus type 11 virus-like particles (HPV11 VLPs) from Escherichia coli and to investigate its immunogenicity and type cross neutralization nature. We expressed the major capsid protein of HPV11 (HPV11-L1) in Escherichia coli ER2566 in non fusion fashion and purified by amino sulfate precipitation, ion-exchange chromatography and hydrophobic interaction chromatography, sequentially. Then we removed the reductant DTT to have the purified HPV11-L1 self-assemble into VLPs in vitro. We investigated the morphology of these VLPs with dynamic light scattering and transmission electron microscopy. We assayed the immunogenicity of the resultant HPV11 VLPs by vaccinations on mice and evaluated by HPV6/11/16/18 pseudovirion neutralization cell models. We expressed HPV11 L1 in Escherichia coli with two forms, soluble and inclusion body. The soluble HPV11 L1 with over 95% purity can self assemble to VLPs in high efficiency. Morphologically, these VLPs were globular, homogeneous and with a diameter of - 50 nm, which is quite similar with native HPV11 virions. The half effective dosage (ED50) of HPV11 VLPs is 0.031 microg, and the maximum titer of neutralizing antibody elicited is averaged to 10(6). The cross neutralization activity (against HPV6/16/18) of the anti-HPV11 serum was found to have exact correlation to the inter-type homology in amino acid alignment. We can provide HPV11 VLPs with highly immunogenicity from prokaryote expression system, which may pave a new way for research and development of prophylactic vaccine for HPV11.

  7. Impact of adipose tissue or umbilical cord derived mesenchymal stem cells on the immunogenicity of human cord blood derived endothelial progenitor cells.

    Directory of Open Access Journals (Sweden)

    Kefang Tan

    Full Text Available The application of autologous endothelial progenitor cell (EPC transplantation is a promising approach in therapeutic cardiovascular diseases and ischemic diseases. In this study, we compared the immunogenicity of EPCs, adipose tissue (AD-derived mesenchymal stem cells (MSCs and umbilical cord (UC-derived MSCs by flow cytometry and the mixed lymphocyte reaction. The impact of AD-MSCs and UC-MSCs on the immunogenicity of EPCs was analyzed by the mixed lymphocyte reaction and cytokine secretion in vitro and was further tested by allogenic peripheral blood mononuclear cell (PBMC induced immuno-rejection on a cell/matrigel graft in an SCID mouse model. EPCs and AD-MSCs express higher levels of MHC class I than UC-MSCs. All three kinds of cells are negative for MHC class II. UC-MSCs also express lower levels of IFN-γ receptor mRNA when compared with EPCs and AD-MSCs. EPCs can stimulate higher rates of proliferation of lymphocytes than AD-MSCs and UC-MSCs. Furthermore, AD-MSCs and UC-MSCs can modulate immune response and inhibit lymphocyte proliferation induced by EPCs, mainly through inhibition of the proliferation of CD8+ T cells. Compared with UC-MSCs, AD-MSCs can significantly improve vessel formation and maintain the integrity of neovascular structure in an EPC+MSC/matrigel graft in SCID mice, especially under allo-PBMC induced immuno-rejection. In conclusion, our study shows that AD-MSC is a powerful candidate to minimize immunological rejection and improve vessel formation in EPC transplantation treatment.

  8. CARDIAC TRANSPLANT REJECTION AND NON-INVASIVE COMON CAROTID ARTERY WALL FUNCTIONAL INDICES

    Directory of Open Access Journals (Sweden)

    A. O. Shevchenko

    2015-01-01

    Full Text Available Allograft rejection would entail an increase in certain blood biomarkers and active substances derived from activated inflammatory cells which could influence entire vascular endothelial function and deteriorate arterial wall stiffness. We propose that carotid wall functional indices measured with non-invasive ultrasound could we valuable markers of the subclinical cardiac allograft rejection. Aim. Our goal was to analyze the clinical utility of functional common carotid wall (CCW variables measured with high-resolution Doppler ultrasound as a non-invasive screening tool for allograft rejection in cardiac transplant patients (pts. Methods. One hundred and seventy one pts included 93 cardiac recipients, 30 dilated cardiomyopathy waiting list pts, and 48 stable coronary artery disease (SCAD pts without decompensated heart failure were included. Along with resistive index (Ri, pulsative index (Pi, and CCW intima-media thickness (IMT, CCW rigidity index (iRIG was estimated using empirical equation. Non-invasive evaluation was performed in cardiac transplant recipients prior the endomyo- cardial biopsy. Results. Neither of Ri, Pi, or CCW IMT were different in studied subgroups. iRIG was signifi- cantly lower in SCAD pts when compared to the dilated cardiomyopathy subgroup. The later had similar values with cardiac transplant recipients without rejection. Antibody-mediated and cellular rejection were found in 22 (23.7% and 17 (18.3% cardiac recipients, respectively. Mean iRIG in pts without rejection was significantly lower in comparison to antibody-mediated rejection and cell-mediated (5514.7 ± 2404.0 vs 11856.1 ± 6643.5 and 16071.9 ± 10029.1 cm/sec2, respectively, p = 0.001. Area under ROC for iRIG was 0.90 ± 0.03 units2. Analysis showed that iRIG values above estimated treshold 7172 cm/sec2 suggested relative risk of any type of rejection 17.7 (95%CI = 6.3–49.9 sensitivity 80.5%, specificity – 81.1%, negative predictive value – 84

  9. Long-term results of total lymphoid irradiation in the treatment of cardiac allograft rejection

    International Nuclear Information System (INIS)

    Wolden, Suzanne L.; Tate, David J.; Hunt, Sharon A.; Strober, Samuel; Hoppe, Richard T.

    1997-01-01

    Purpose: To evaluate the short and long-term effects of total lymphoid irradiation (TLI) in the treatment of cardiac transplant rejection. Methods and Materials: Between 1986 and 1995, 48 courses of TLI were delivered to 47 cardiac transplant patients. In 37 patients, TLI was administered for intractable allograft rejection despite conventional therapy while 10 patients received TLI prophylactically. The prescribed radiation dose was 8 Gy in 0.8 Gy fractions twice weekly to mantle and inverted-Y plus spleen fields. Postirradiation follow-up ranged from 6 months to 9.1 years, with a mean of 3.1 years. Results: The actual mean dose was 7.3 Gy delivered over a mean of 39 days. Fifty-six percent of patients required treatment delay or abbreviation because of thrombocytopenia, leukopenia, infection, or unrelated problems. In patients treated for intractable rejection, rejection rates dropped from 0.46 to 0.14 and to 0.06 episodes/patient/month before, during, and after TLI (p < 0.0001). Rejection rates continued to drop throughout follow-up. Prednisone requirements decreased from 0.41 mg/kg before treatment to 0.21 mg/kg afterward (p < 0.0001). The ratio of helper to cytotoxic-suppressor T-cells decreased during TLI from 1.33 to 0.89, and remained low at 0.44, 2-4 months after treatment. Infection rates were not increased and two patients developed malignancy. Rejection rates were high during prophylactic treatment and this protocol was abandoned. Three-year actuarial survival after irradiation was 60% for patients with intractable rejection and 70% for the prophylactic cohort. Conclusion: TLI is an effective treatment for control of intractable cardiac rejection. Episodes of rejection and steroid dosage requirements are decreased for up to 9.1 years. A possible mechanism of action is long term alteration in T-lymphocyte subsets. Patients experience transient bone marrow suppression but no increase in infection or bleeding. Long-term complications of TLI are not

  10. Neutral Pion Rejection at L2 using the CMS Endcap Preshower

    CERN Document Server

    Kyriakis, Aristotelis; Loukas, Demetrios; Mousa, Jehad; Seez, Christopher

    1999-01-01

    Applying a general Artificial Neural Network approach, we have examined the possibility of neutral pion rejection at the Level 2 Trigger stage ( L2) principally using information from the CMS Endcap Preshower. We have studied both pion/photon and pion/electron discrimination. For L2 the hope was to achieve some useful pion/electron discrimination for a high electron efficiency. For a single electron/photon efficiency of 95% the results show that no useful rejection of neutral pions against electrons/photons can be obtained using this algorithm alone, due to the presence of tracker material. If the efficiency is lowered or information from the tracker is available, the rejection can increase dramatically. This will be the case for off-line analyses.

  11. An audit of rejected repeated x-ray films as a quality assurance element in a radiology department.

    Science.gov (United States)

    Eze, K C; Omodia, N; Okegbunam, B; Adewonyi, T; Nzotta, C C

    2008-12-01

    To find out the causes, number, percentage and sizes of rejected radiographic films with a view of adopting measures that will reduce the rate and number of rejected films. Radiology Department of a University Teaching Hospital. Over a two-year period (1st April 2002 to 31st March 2004), the total number of x-ray films utilized for radiographic examinations, rejected films and sizes of rejected films were collected retrospectively from the medical record of radiology department. All the rejected films were viewed by a radiologist and three radiographers for the causes of the rejects which was arrived at by consensus. The data was analysed. A total of 15,095 films were used in the study period and 1,338 films (8.86%) were rejected or wasted. The rate of rejected films varied from 7.69% to 13.82% with average of 8.86%. The greatest cause of film rejects was radiographers' faults 547 (40.88%), followed by equipments faults 255 (19.06%), and patients' faults 250 (18.90%). The highest reject rate (13.82%) was for films used for examination of the spine (15 x 30) cm size. This is followed by 9.92% for skull (18 x 24) cm films and 8.83% for small sized films (24 x 30) cm used for paediatric patients. Of a total of 1,338 rejected films, 1276 (95.37%) additional exposure were done to obtain the basic desired diagnostic information involving 1151 patients; 885 (76.89%) of these patients needed at least one additional hospital visit to take the repeat exposure. Rejected films are not billable; patients receive additional radiation and may even come to hospital in another day for the repeat. Radiographer's work is increased as well as that of the support staff. The waiting room may be congested and waiting time increased. The cost of processing chemical and films are increased, thus if work is quantified in monetary terms, the cost of repeats is high. Rejected-repeated film analysis is cheap, simple, practicable, easy to interpret and an effective indictor of quality assurance

  12. Disabled infectious single cycle-herpes simplex virus (DISC-HSV) as a vector for immunogene therapy of cancer.

    Science.gov (United States)

    Rees, Robert C; McArdle, Stephanie; Mian, Shahid; Li, Geng; Ahmad, Murrium; Parkinson, Richard; Ali, Selman A

    2002-02-01

    Disabled infectious single cycle-herpes simplex viruses (DISC-HSV) have been shown to be safe for use in humans and may be considered efficacious as vectors for immunogene therapy in cancer. Preclinical studies show that DISC-HSV is an efficient delivery system for cytokine genes and antigens. DISC-HSV infects a high proportion of cells, resulting in rapid gene expression for at least 72 h. The DISC-HSV-mGM-CSF vector, when inoculated into tumors, induces tumor regression in a high percentage of animals, concomitant with establishing a cytotoxic T-cell response, which is MHC class I restricted and directed against peptides of known tumor antigens. The inherent properties of DISC-HSV makes it a suitable vector for consideration in human immunogene therapy trials.

  13. Quantum Communication Using Coherent Rejection Sampling

    Science.gov (United States)

    Anshu, Anurag; Devabathini, Vamsi Krishna; Jain, Rahul

    2017-09-01

    Compression of a message up to the information it carries is key to many tasks involved in classical and quantum information theory. Schumacher [B. Schumacher, Phys. Rev. A 51, 2738 (1995), 10.1103/PhysRevA.51.2738] provided one of the first quantum compression schemes and several more general schemes have been developed ever since [M. Horodecki, J. Oppenheim, and A. Winter, Commun. Math. Phys. 269, 107 (2007); , 10.1007/s00220-006-0118-xI. Devetak and J. Yard, Phys. Rev. Lett. 100, 230501 (2008); , 10.1103/PhysRevLett.100.230501A. Abeyesinghe, I. Devetak, P. Hayden, and A. Winter, Proc. R. Soc. A 465, 2537 (2009), 10.1098/rspa.2009.0202]. However, the one-shot characterization of these quantum tasks is still under development, and often lacks a direct connection with analogous classical tasks. Here we show a new technique for the compression of quantum messages with the aid of entanglement. We devise a new tool that we call the convex split lemma, which is a coherent quantum analogue of the widely used rejection sampling procedure in classical communication protocols. As a consequence, we exhibit new explicit protocols with tight communication cost for quantum state merging, quantum state splitting, and quantum state redistribution (up to a certain optimization in the latter case). We also present a port-based teleportation scheme which uses a fewer number of ports in the presence of information about input.

  14. Radiographic rejection index using statistical process control

    International Nuclear Information System (INIS)

    Savi, M.B.M.B.; Camozzato, T.S.C.; Soares, F.A.P.; Nandi, D.M.

    2015-01-01

    The Repeat Analysis Index (IRR) is one of the items contained in the Quality Control Program dictated by brazilian law of radiological protection and should be performed frequently, at least every six months. In order to extract more and better information of IRR, this study presents the Statistical Quality Control applied to reject rate through Statistical Process Control (Control Chart for Attributes ρ - GC) and the Pareto Chart (GP). Data collection was performed for 9 months and the last four months of collection was given on a daily basis. The Limits of Control (LC) were established and Minitab 16 software used to create the charts. IRR obtained for the period was corresponding to 8.8% ± 2,3% and the generated charts analyzed. Relevant information such as orders for X-ray equipment and processors were crossed to identify the relationship between the points that exceeded the control limits and the state of equipment at the time. The GC demonstrated ability to predict equipment failures, as well as the GP showed clearly what causes are recurrent in IRR. (authors) [pt

  15. Adolescent externalizing behaviour, psychological control, and peer rejection: Transactional links and dopaminergic moderation.

    Science.gov (United States)

    Janssens, Annelies; Van Den Noortgate, Wim; Goossens, Luc; Verschueren, Karine; Colpin, Hilde; Claes, Stephan; Van Heel, Martijn; Van Leeuwen, Karla

    2017-09-01

    This study investigated (1) reciprocal links among parental psychological control, peer rejection, and adolescent externalizing (aggressive and rule-breaking behaviour), and (2) the moderating effect of an adolescent genetic factor (biologically informed polygenic score for dopamine signalling). Three-year longitudinal data from 1,116 adolescents (51% boys; M age = 13.79) and their parents included psychological measures (adolescent-reported psychological control, peer-reported rejection, and parent-reported aggressive and rule-breaking behaviour). Cross-lagged analyses showed bidirectional effects between psychological control and both aggressive and rule-breaking behaviour and a unidirectional effect of peer rejection on both forms of problem behaviour over time. Multigroup structural equation modelling revealed genetic moderation only for rule-breaking behaviour: for adolescents with intermediate levels of dopamine signalling significant environmental effects were present, whereas adolescent effects of rule-breaking behaviour on psychological control were significant for adolescents with both intermediate and high profiles and effects on peer rejection only for adolescents with high dopamine profiles. Statement of contribution What is already known on this subject? Parental psychological control is related to adolescent externalizing problems. Experiencing peer rejection reinforces aggressive and rule-breaking behaviour. Single-gene studies show that dopaminergic genes influence externalizing problems directly or in interaction with the environment. What does this study add? Parental psychological control and adolescent aggressive and rule-breaking behaviour exacerbate one another longitudinally. Longitudinal associations between peer rejection and both subtypes of externalizing behaviour are unidirectional. With a polygenic approach, dopaminergic moderation is present for rule-breaking behaviour only. © 2017 The British Psychological Society.

  16. [Immunogenicity of L5178Y cells modified by different reagents].

    Science.gov (United States)

    Gómez-Estrada, H; López-de la Rosa, L M; Becerril-Meza, G; Arellano-Blanco, J; Fernández-Quintero, P

    1977-01-01

    Lymphoma L5178Y cells were treated with neuraminidase of Vibrio cholerae, potassium iodine, dithiotreitol (DTT), mercaptoethanol, glutaraldehyde, iodoacetamide, merthiolate, sodium periodate, urea, papaine, trypsine and EDTA, to increase immunoreaction in tumor cells. Mice were immunized with modified tumor cells every week for one month. Thereafter non modified tumor cells were transplanted to previously immunized mice. Only the immunization with neuraminidase-treated cells rejected the tumor. Although the immunization with cells treated with potassium iodine, DTT and mercaptoethanol did not reject tumor, prolonged significantly span of life. The other reactives had neither effect on tumor rejection nor on span of life.

  17. Refusals and Rejections: Designing Messages to Serve Multiple Goals.

    Science.gov (United States)

    Saeki, Mimako; O'Keefe, Barbara J.

    1994-01-01

    Tests a rational model of the elaboration of themes found in rejection messages, using Japanese and American participants. Finds partial support for the initial rational model but notes two key revisions: identifies two new themes in rejection messages and suggests substantial differences in the way Americans and Japanese elaborate themes to serve…

  18. Perception of Parental Acceptance and Rejection among Swedish University Students.

    Science.gov (United States)

    Kitahara, Michio

    1987-01-01

    Results of administering the Parental Acceptance-Rejection and Personality Assessment Questionnaires to 71 Swedish university students showed significant relationships between various forms of parental rejection in childhood and negative personality assessment of the self as an adult. Females showed more dependence and emotional instability than…

  19. Heterosexual Rejection and Mate Choice: A Sociometer Perspective

    Directory of Open Access Journals (Sweden)

    Lin eZHANG

    2015-12-01

    Full Text Available Previous studies about the effects of social rejection on individuals’ social behaviors have produced mixed results and tend to study mating behaviors from a static point of view. However, mate selection in essence is a dynamic process, and therefore sociometer theory opens up a new perspective for studying mating and its underlying practices. Based on this theory and using self-perceived mate value in the relationship between heterosexual rejection and mate choice as a mediating role, this current study examined the effects of heterosexual rejection on mate choice in two experiments. Results showed that heterosexual rejection significantly reduced self-perceived mate value, expectation, and behavioral tendencies, while heterosexual acceptance indistinctively increased these measures. Self-perceived mate value did not serve as a mediator in the relationship between heterosexual rejection and mate expectation, but it mediated the relationship between heterosexual rejection and mating behavior tendencies towards potential objects. Moreover, individuals evaded both rejection and irrelevant people when suffering from rejection.

  20. Indium-labeled platelet uptake in rejecting renal transplants

    International Nuclear Information System (INIS)

    Chandler, S.T.; Buckels, J.; Hawker, R.J.; Smith, N.; Barnes, A.D.; McCollum, C.N.

    1983-01-01

    The uptake of 111 In autologous platelets in transplanted kidneys was measured in 16 patients shortly after operation. Each patient was then observed for two years. When transplant radioactivity had increased, despite treatment for acute rejection, the kidney was ultimately lost because of rejection

  1. Peer victimization and peer rejection during early childhood

    Science.gov (United States)

    Godleski, Stephanie A.; Kamper, Kimberly E.; Ostrov, Jamie M.; Hart, Emily J.; Blakely-McClure, Sarah J.

    2014-01-01

    Objective The development and course of the subtypes of peer victimization is a relatively understudied topic despite the association of victimization with important developmental and clinical outcomes. Moreover, understanding potential predictors, such as peer rejection and emotion regulation, in early childhood may be especially important to elucidate possible bi-directional pathways between relational and physical victimization and rejection. The current study (N = 97) was designed to explore several gaps and limitations in the peer victimization and peer rejection literature. In particular, the prospective associations between relational and physical victimization and peer rejection over the course of 3.5 months during early childhood (i.e., 3- to 5- years-old) were investigated in an integrated model. Method The study consisted of 97 (42 girls) preschool children recruited from four early childhood schools in the northeast of the US. Using observations, research assistant report and teacher report, relational and physical aggression, relational and physical victimization, peer rejection, and emotion regulation were measured in a short-term longitudinal study. Path analyses were conducted to test the overall hypothesized model. Results Peer rejection was found to predict increases in relational victimization. In addition, emotion regulation was found to predict decreases in peer rejection and physical victimization. Conclusions Implications for research and practice are discussed, including teaching coping strategies for peer rejection and emotional distress. PMID:25133659

  2. 48 CFR 14.404-2 - Rejection of individual bids.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Rejection of individual... of individual bids. (a) Any bid that fails to conform to the essential requirements of the invitation... total price of the bid, but the prices for individual line items as well. (g) Any bid may be rejected if...

  3. 48 CFR 814.404-2 - Rejection of individual bids.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Rejection of individual... Rejection of individual bids. (a) When a contracting officer finds a bid that is being considered for an... nonresponsive an individual bid that is not in compliance with the Government's bid acceptance time, since...

  4. A protocol for arguing about rejections in negotiation

    NARCIS (Netherlands)

    Prakken, Henry; van Veenen, J.; Parsons, S; Maudet, N; Moraitis, P; Rahwan,

    2006-01-01

    One form of argument-based negotiation is when agents argue about why an offer was rejected. If an agent can state a reason for a rejection of an offer, the negotiation process may become more efficient since the other agent can take this reason into account when making new offers. Also, if a reason

  5. Prevalence and characteristics of foal rejection in Arabian mares.

    Science.gov (United States)

    Juarbe-Díaz, S V; Houpt, K A; Kusunose, R

    1998-09-01

    Separate surveys of Thoroughbred, Paint, and Arabian mare owners revealed a higher than expected rate of foal rejection in Arabian mares. A behavioural history form was submitted by owners of foal rejecting and nonrejecting Arabian mares, and maternal behaviour and management practices compared. Four generation pedigrees of rejecting and nonrejecting Arabian mares were also examined. Foal rejecting mares were more likely to avoid, threaten, squeal at, chase, bite, and kick their foals post partum than nonrejecting mares. Nonrejecting mares were more likely to lick, nicker and defend their foals post partum than rejecting mares. No statistically significant relationship was found between foal rejection and the type of breeding method (natural vs. artificial insemination), the presence of people at birth, the presence of nearby horses at birth, or assistance of the first nursing bout. The presence at least once of 1 of 2 related sires was statistically higher in the pedigrees of rejecting vs. nonrejecting mares. Inherited and learned or environmental factors are likely to affect the expression of foal rejection behaviour.

  6. Acute antibody-mediated rejection in pancreas and kidney transplantation

    NARCIS (Netherlands)

    Kort, Hanneke de

    2013-01-01

    In this thesis, acute rejection after kidney, simultaneous pancreas and kidney (SPKT), and islets of Langerhans transplantation was addressed. The focus is on acute antibody-mediated rejection (AMR) after transplantation and on a potential strategy using cellular immune modulation to prevent acute

  7. Apoptosis of acinar cells in pancreas allograft rejection

    NARCIS (Netherlands)

    Boonstra, J. G.; Wever, P. C.; Laterveer, J. C.; Bruijn, J. A.; van der Woude, F. J.; ten Berge, I. J.; Daha, M. R.

    1997-01-01

    BACKGROUND: Recently it has been recognized that apoptosis of target cells may occur during liver and kidney allograft rejection and is probably induced by infiltrating cells. Pancreas rejection is also characterized by a cellular infiltrate, however, the occurrence of apoptosis has not been

  8. Efficacy, Immunogenicity and Safety of a Human Rotavirus Vaccine RIX4414 in Singaporean Infants.

    Science.gov (United States)

    Phua, Kong Boo; Lim, Fong Seng; Quak, Seng Hock; Lee, Bee Wah; Teoh, Yee Leong; Suryakiran, Pemmaraju V; Han, Htay Htay; Bock, Hans L

    2016-02-01

    This was the first study conducted to evaluate the efficacy of 2 oral doses of the human rotavirus vaccine, RIX4414 in Singaporean infants during the first 3 years of life. Healthy infants, 11 to 17 weeks of age were enrolled in this randomised (1:1), double-blinded, placebo-controlled study to receive 2 oral doses of RIX4414 vaccine/placebo following a 0-, 1-month schedule. Vaccine efficacy against severe rotavirus (RV) gastroenteritis (Vesikari score ≥11) caused by wild-type RV strains from a period starting from 2 weeks post-Dose 2 until 2 and 3 years of age was calculated with 95% confidence interval (CI). Immunogenicity and safety of the vaccine were also assessed. Of 6542 infants enrolled, 6466 were included in the efficacy analysis and a subset of 100 infants was included in the immunogenicity analysis. Fewer severe RV gastroenteritis episodes were reported in the RIX4414 group when compared to placebo at both 2 and 3 year follow-up periods. Vaccine efficacy against severe RV gastroenteritis at the respective time points were 93.8% (95% CI, 59.9 to 99.9) and 95.2% (95% CI, 70.5 to 99.9). One to 2 months post-Dose 2 of RIX4414, 97.5% (95% CI, 86.8 to 99.9) of infants seroconverted for anti-RV IgA antibodies. The number of serious adverse events recorded from Dose 1 until 3 years of age was similar in both groups. Two oral doses of RIX4414 vaccine was immunogenic and provided high level of protection against severe RV gastroenteritis in Singaporean children, during the first 3 years of life when the disease burden is highest.

  9. Uptake of myocardial imaging agents by rejected hearts

    International Nuclear Information System (INIS)

    Bergsland, J.; Carr, E.A.; Carroll, M.; Wright, J.W.; Feldman, M.J.; Massucci, J.; Bhayana, J.N.; Gona, J.M.

    1985-01-01

    Technetium 99 m pyrophosphate, Gallium 67 and Thallium 201 uptakes were measured in heterotopically transplanted rat hearts. Five days after transplantation, Technetium 99 m pyrophosphate, and Gallium 67 uptakes were significantly higher in allogeneic grafts than in syngeneic grafts. At an early stage of rejection (three days after transplantation), only Technetium 99 m pyrophosphate uptake in the left ventricle of allogeneic grafts showed a significant difference (p less than 0.04). At five days, Thallium 201 uptake was significantly lower in allo- than syngeneic grafts. There was a positive correlation between radionuclide uptake and histologic degree of rejection for Technetium 99 m pyrophosphate and Gallium 67 while Thallium 201 uptake correlated negatively. Analysis of variance revealed that hearts with no or minimal rejection had statistically different uptakes than hearts with mild to moderate rejection. These results suggest that uptake of imaging agents might be useful in the diagnosis of rejection of the transplanted heart

  10. Diagnosis of cardiac allograft rejection with MR imaging

    International Nuclear Information System (INIS)

    Soulen, R.L.; Fraser, C.D.; Hutchins, G.M.; Baumgartner, W.A.; Reitz, B.A.

    1987-01-01

    Serial MR images and endomyocardial biopsy specimens of heterotopic cervical cardiac allotransplants were obtained in six dogs during 2 weeks of immunosuppression followed by 1 week without such therapy. A surface coil and gated spin-echo technique were used. Myocardial intensity (MI) measurements and histopathologic interpretations were performed independently. All six dogs showed a decrease in MI between their first and second MR studies, while showing no rejection. One dog had no rejection and died; in five dogs studies gated to every other beat showed progressive increase in MI that correlated significantly with increasing rejection, though absolute MI values did not correlated with a specific biopsy score. Severe rejection also caused overt increase in myocardial mass. The MI in the early postoperative period may reflect reperfusion injury. Absolute intensity values cannot predict rejection. Serial studies in transplant patients may prove clinically useful

  11. Non-clairvoyant weighted flow time scheduling with rejection penalty

    DEFF Research Database (Denmark)

    Chan, Ho-Leung; Chan, Sze-Hang; Lam, Tak-Wah

    2012-01-01

    is defined as the weighted flow time of the job plus the penalty if it is rejected before completion. Previous work on minimizing the total user cost focused on the clairvoyant single-processor setting [BBC+03,CLL11] and has produced O(1)-competitive online algorithm for jobs with arbitrary weights...... algorithm has to decide job rejection and determine the order and speed of job execution. It is interesting to study the tradeoff between the above-mentioned user cost and energy. This paper gives two O(1)-competitive non-clairvoyant algorithms for minimizing the user cost plus energy on a single processor......This paper initiates the study of online scheduling with rejection penalty in the non-clairvoyant setting, i.e., the size (processing time) of a job is not assumed to be known at its release time. In the rejection penalty model, jobs can be rejected with a penalty, and the user cost of a job...

  12. Zbtb7a induction in alveolar macrophages is implicated in anti-HLA-mediated lung allograft rejection.

    Science.gov (United States)

    Nayak, Deepak K; Zhou, Fangyu; Xu, Min; Huang, Jing; Tsuji, Moriya; Yu, Jinsheng; Hachem, Ramsey; Gelman, Andrew E; Bremner, Ross M; Smith, Michael A; Mohanakumar, Thalachallour

    2017-07-12

    Chronic rejection significantly limits long-term success of solid organ transplantation. De novo donor-specific antibodies (DSAs) to mismatched donor human leukocyte antigen after human lung transplantation predispose lung grafts to chronic rejection. We sought to delineate mediators and mechanisms of DSA pathogenesis and to define early inflammatory events that trigger chronic rejection in lung transplant recipients and obliterative airway disease, a correlate of human chronic rejection, in mouse. Induction of transcription factor zinc finger and BTB domain containing protein 7a (Zbtb7a) was an early response critical in the DSA-induced chronic rejection. A cohort of human lung transplant recipients who developed DSA and chronic rejection demonstrated greater Zbtb7a expression long before clinical diagnosis of chronic rejection compared to nonrejecting lung transplant recipients with stable pulmonary function. Expression of DSA-induced Zbtb7a was restricted to alveolar macrophages (AMs), and selective disruption of Zbtb7a in AMs resulted in less bronchiolar occlusion, low immune responses to lung-restricted self-antigens, and high protection from chronic rejection in mice. Additionally, in an allogeneic cell transfer protocol, antigen presentation by AMs was Zbtb7a-dependent where AMs deficient in Zbtb7a failed to induce antibody and T cell responses. Collectively, we demonstrate that AMs play an essential role in antibody-induced pathogenesis of chronic rejection by regulating early inflammation and lung-restricted humoral and cellular autoimmunity. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  13. Specimen rejection in laboratory medicine: Necessary for patient safety?

    Science.gov (United States)

    Dikmen, Zeliha Gunnur; Pinar, Asli; Akbiyik, Filiz

    2015-01-01

    The emergency laboratory in Hacettepe University Hospitals receives specimens from emergency departments (EDs), inpatient services and intensive care units (ICUs). The samples are accepted according to the rejection criteria of the laboratory. In this study, we aimed to evaluate the sample rejection ratios according to the types of pre-preanalytical errors and collection areas. The samples sent to the emergency laboratory were recorded during 12 months between January to December, 2013 in which 453,171 samples were received and 27,067 specimens were rejected. Rejection ratios was 2.5% for biochemistry tests, 3.2% for complete blood count (CBC), 9.8% for blood gases, 9.2% for urine analysis, 13.3% for coagulation tests, 12.8% for therapeutic drug monitoring, 3.5% for cardiac markers and 12% for hormone tests. The most frequent rejection reasons were fibrin clots (28%) and inadequate volume (9%) for biochemical tests. Clotted samples (35%) and inadequate volume (13%) were the major causes for coagulation tests, blood gas analyses and CBC. The ratio of rejected specimens was higher in the EDs (40%) compared to ICUs (30%) and inpatient services (28%). The highest rejection ratio was observed in neurology ICU (14%) among the ICUs and internal medicine inpatient service (10%) within inpatient clinics. We detected an overall specimen rejection rate of 6% in emergency laboratory. By documentation of rejected samples and periodic training of healthcare personnel, we expect to decrease sample rejection ratios below 2%, improve total quality management of the emergency laboratory and promote patient safety.

  14. Early and late humoral rejection: a clinicopathologic entity in two times.

    Science.gov (United States)

    Péfaur, J; Díaz, P; Panace, R; Salinas, P; Fiabane, A; Quinteros, N; Chea, R; Naranjo, E; Wurgaft, A; Beltran, E; Elgueta, S; Wegmann, M E; Gajardo, J G; Contreras, L

    2008-11-01

    Humoral rejection is an important cause of early and late graft loss. The late variant is difficult to diagnose and treat. There is a close correlation between sclerosing nephropathy and anti-HLA antibodies. We analyzed 113 renal allograft recipients between August 2004 and April 2007. Acute humoral rejection was defined as acute graft dysfunction in presence of donor-specific antibodies (DSA) detected by flow panel reactive antibodies (PRA) and/or C4d positive pericapilary tubules (PTC) detected histopathologically by immunofluorescent or immunoperoxidase at less than 3 months postransplantation. Late humoral rejection was defined as dysfunction occurring after 3 months postransplantation with histopathologic glomerulopathy or vasculopathy and positive C4d PTC. We included all patients who were diagnosed with early or late graft dysfunction and underwent biopsy, all of which were examined for C4d. Four patients had acute humoral rejection treated with IVIG or plasmapheresis. The patient and graft survivals were 100% and serum creatinine averaged 1.7 mg/dL. Three recipients experienced late humoral rejection at 3 to 10 years posttransplantation All received high-dose IVIG; one also was treated with thymoglobulin. Immunosuppression was switched to tacrolimus, mycophenolate mofetil, and steroids. Only one patient recovered renal function; the others returned to dialysis. Among seven patients only one had an actual PRA (>20%) and three showed 10% to 20%. However, six had a positive historical PRA of 10% to 50%. In conclusion, Recognition of acute humoral rejection has contributed to graft rescue by controlling alloantibody production through new specific immunosuppressive therapies in contrast with the clinical response to acute therapy, treatment of a chronic entity has shown poor outcomes, probably because antibody mediated chronic graft damage is already present when the late diagnosis is established by biopsy.

  15. Radiation therapy for renal transplant rejection refractory to pulse steroids and OKT3

    International Nuclear Information System (INIS)

    Noyes, William R.; Rodriguez, Rey; Knechtle, Stuart J.; Pirsch, John D.; Sollinger, Hans W.; D'Alessandro, Anthony M.; Chappell, Rick; Belzer, Folkert O.; Kinsella, Timothy J.

    1996-01-01

    Purpose: To determine the response rate and kidney graft survival following local irradiation to the transplanted renal graft undergoing persistent rejection after medical management including pulse steroids and OKT3. The role of radiation for renal transplant rejection after failure of OKT3 has not been previously reported. Methods and Materials: From July 1, 1988 to July 1, 1994, 72 consecutive patients with kidney graft rejection were treated with local irradiation to the transplanted renal graft following failure of medical management. All patients received pulse steroids and OKT3, an anti-CD3 immunosuppressant. Patients who failed to respond to methylprednisolone and OKT3 therapy were referred for radiation therapy. The median time from the diagnosis of rejection to irradiation was 8 days. All kidney grafts received local graft irradiation to a total of 8 Gy delivered in four daily fractions. Results: Sixty (83%) patients initially responded to radiotherapy at 7 days after completion of radiotherapy, as defined by a decrease in serum creatinine. Thirty-five responding patients have not experienced a second episode of graft rejection. Overall, 43 (60%) patients have renal graft survival, with a median follow-up of 16 months (range of 6-73 months). Conclusion: It is concluded that there is a subgroup of kidney graft patients undergoing graft rejection who are refractory to pulse steroids and OKT3 therapy where irradiation may be an effective modality with high rates of response and a moderate rate of graft survival. However, a prospective, randomized trial in these medically refractory patients is needed to ascertain whether these results are clinically significant

  16. Mutual best friendship involvement, best friends' rejection sensitivity, and psychological maladaptation.

    Science.gov (United States)

    Bowker, Julie C; Thomas, Katelyn K; Norman, Kelly E; Spencer, Sarah V

    2011-05-01

    Rejection sensitivity (RS) refers to the tendency to anxiously expect, readily perceive, and overreact to experiences of possible rejection. RS is a clear risk factor for psychological maladaptation during early adolescence. However, there is growing evidence of significant heterogeneity in the psychological correlates of RS. To investigate when RS poses the greatest psychological risk during early adolescence, this study examines mutual best friendship involvement (or lack thereof) and the best friends' RS as potential moderators of the associations between RS and psychological difficulties. Participants were 150 7th grade students (58 boys; M age = 13.05 years) who nominated their best friends, and reported on their RS, social anxiety, and self-esteem. Results from a series of hierarchical multiple regression analyses indicated that mutual best friendship involvement and best friends' RS were both significant moderators when fear of negative evaluation (a type of social anxiety) served as the dependent variable. The association between RS and fear of negative evaluation was stronger for adolescents without mutual best friends than adolescents with mutual best friends. In addition, the association between RS and fear of negative evaluation was the strongest for adolescents whose best friends were highly rejection sensitive (relative to adolescents whose best friends were moderately or low in RS). Findings highlight the importance of considering best friendships in studies of RS and strongly suggest that, although having mutual best friendships may be protective for rejection sensitive adolescents, having a rejection sensitive best friend may exacerbate difficulties. The significance of friends in the lives of rejection sensitive adolescents is discussed as well as possible applied implications of the findings and study limitations.

  17. Acute rejection episodes after kidney transplantation

    Directory of Open Access Journals (Sweden)

    Hamida Fethi

    2009-01-01

    Full Text Available Acute rejection episodes (AREs are a major determinant of renal allograft survival. The incorporation of new immunosuppressive agents explains, at least partially, the improvement seen in the results of transplantation in recent years. The objectives of this study are to analyze the incidence and severity of AREs, their risk factors and their influence on graft and patient survival. We retrospectively studied 280 kidney transplants performed in adults at the Charles Nicolle Hospital, Tunis, between 1986 and 2004. The diagnosis of ARE was based on clinical data and response to treatment. Allograft biopsies were performed in ten cases. The treatment of AREs consisted of pulse methylprednisolone and anti-thymocyte globulin. There were 186 males (66.4% and 94 females (33.6%, and their mean age was 31 ± 8.9 years. Overall, the 280 study patients experienced a total of 113 AREs. Of them, 85 had only one ARE, 28 had two to three and none had more than three AREs. A total of 68 AREs were completely re-versible, 42 were partially reversible while three could not be reversed with treatment. The mean inci-dence of AREs was 40.4%. The incidence was > 45% between 1986 and 1997, decreased to 20.5% between 1998 and 2000 and to 9% between 2001 and 2004. Graft survival rates in patients with and without AREs were respectively 91% and 93% at three years, 82% and 90% at five years and 73% and 83% at 10 years. We found a decrease in the incidence of AREs in recent years in our study patients, and this was related to the introduction of sensitized cross-match and the newer immunosuppressive agents, particularly MMF. Additionally, AREs had a deleterious impact on late graft survival in our study population.

  18. Quantum Communication Using Coherent Rejection Sampling.

    Science.gov (United States)

    Anshu, Anurag; Devabathini, Vamsi Krishna; Jain, Rahul

    2017-09-22

    Compression of a message up to the information it carries is key to many tasks involved in classical and quantum information theory. Schumacher [B. Schumacher, Phys. Rev. A 51, 2738 (1995)PLRAAN1050-294710.1103/PhysRevA.51.2738] provided one of the first quantum compression schemes and several more general schemes have been developed ever since [M. Horodecki, J. Oppenheim, and A. Winter, Commun. Math. Phys. 269, 107 (2007); CMPHAY0010-361610.1007/s00220-006-0118-xI. Devetak and J. Yard, Phys. Rev. Lett. 100, 230501 (2008); PRLTAO0031-900710.1103/PhysRevLett.100.230501A. Abeyesinghe, I. Devetak, P. Hayden, and A. Winter, Proc. R. Soc. A 465, 2537 (2009)PRLAAZ1364-502110.1098/rspa.2009.0202]. However, the one-shot characterization of these quantum tasks is still under development, and often lacks a direct connection with analogous classical tasks. Here we show a new technique for the compression of quantum messages with the aid of entanglement. We devise a new tool that we call the convex split lemma, which is a coherent quantum analogue of the widely used rejection sampling procedure in classical communication protocols. As a consequence, we exhibit new explicit protocols with tight communication cost for quantum state merging, quantum state splitting, and quantum state redistribution (up to a certain optimization in the latter case). We also present a port-based teleportation scheme which uses a fewer number of ports in the presence of information about input.

  19. Dying to Be Noticed: Epigenetic Regulation of Immunogenic Cell Death for Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Brianne Cruickshank

    2018-04-01

    Full Text Available Immunogenic cell death (ICD activates both innate and adaptive arms of the immune system during apoptotic cancer cell death. With respect to cancer immunotherapy, the process of ICD elicits enhanced adjuvanticity and antigenicity from dying cancer cells and consequently, promotes the development of clinically desired antitumor immunity. Cancer ICD requires the presentation of various “hallmarks” of immunomodulation, which include the cell-surface translocation of calreticulin, production of type I interferons, and release of high-mobility group box-1 and ATP, which through their compatible actions induce an immune response against cancer cells. Interestingly, recent reports investigating the use of epigenetic modifying drugs as anticancer therapeutics have identified several connections to ICD hallmarks. Epigenetic modifiers have a direct effect on cell viability and appear to fundamentally change the immunogenic properties of cancer cells, by actively subverting tumor microenvironment-associated immunoevasion and aiding in the development of an antitumor immune response. In this review, we critically discuss the current evidence that identifies direct links between epigenetic modifications and ICD hallmarks, and put forward an otherwise poorly understood role for epigenetic drugs as ICD inducers. We further discuss potential therapeutic innovations that aim to induce ICD during epigenetic drug therapy, generating highly efficacious cancer immunotherapies.

  20. Stratification of antibody-positive subjects by antibody level reveals an impact of immunogenicity on pharmacokinetics.

    Science.gov (United States)

    Zhou, Lei; Hoofring, Sarah A; Wu, Yu; Vu, Thuy; Ma, Peiming; Swanson, Steven J; Chirmule, Narendra; Starcevic, Marta

    2013-01-01

    The availability of highly sensitive immunoassays enables the detection of antidrug antibody (ADA) responses of various concentrations and affinities. The analysis of the impact of antibody status on drug pharmacokinetics (PK) is confounded by the presence of low-affinity or low-concentration antibody responses within the dataset. In a phase 2 clinical trial, a large proportion of subjects (45%) developed ADA following weekly dosing with AMG 317, a fully human monoclonal antibody therapeutic. The antibody responses displayed a wide range of relative concentrations (30 ng/mL to >13 μg/mL) and peaked at various times during the study. To evaluate the impact of immunogenicity on PK, AMG 317 concentration data were analyzed following stratification by dose group, time point, antibody status (positive or negative), and antibody level (relative concentration). With dose group as a stratifying variable, a moderate reduction in AMG 317 levels (AMG 317 levels was revealed when antibody data was stratified by both time point and antibody level. In general, high ADA concentrations (>500 ng/mL) and later time points (week 12) were associated with significantly (up to 97%) lower trough AMG 317 concentrations. The use of quasi-quantitative antibody data and appropriate statistical methods was critical for the most comprehensive evaluation of the impact of immunogenicity on PK.

  1. A microneedle patch containing measles vaccine is immunogenic in non-human primates.

    Science.gov (United States)

    Edens, Chris; Collins, Marcus L; Goodson, James L; Rota, Paul A; Prausnitz, Mark R

    2015-09-08

    Very high vaccination coverage is required to eliminate measles, but achieving high coverage can be constrained by the logistical challenges associated with subcutaneous injection. To simplify the logistics of vaccine delivery, a patch containing micron-scale polymeric needles was formulated to encapsulate the standard dose of measles vaccine (1000 TCID₅₀) and the immunogenicity of the microneedle patch was compared with subcutaneous injection in rhesus macaques. The microneedle patch was administered without reconstitution with diluent, dissolved in skin within 10 min, and caused only mild, transient skin erythema. Both groups of rhesus macaques generated neutralizing antibody responses to measles that were consistent with protection and the neutralizing antibody titers were equivalent. In addition, the microneedle patches maintained an acceptable level of potency after storage at elevated temperature suggesting improved thermostability compared to standard lyophilized vaccine. In conclusion, a measles microneedle patch vaccine was immunogenic in non-human primates, and this approach offers a promising delivery method that could help increase vaccination coverage. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Working memory predicts the rejection of false memories.

    Science.gov (United States)

    Leding, Juliana K

    2012-01-01

    The relationship between working memory capacity (WMC) and false memories in the memory conjunction paradigm was explored. Previous research using other paradigms has shown that individuals high in WMC are not as likely to experience false memories as low-WMC individuals, the explanation being that high-WMC individuals are better able to engage in source monitoring. In the memory conjunction paradigm participants are presented at study with parent words (e.g., eyeglasses, whiplash). At test, in addition to being presented with targets and foils, participants are presented with lures that are composed of previously studied features (e.g., eyelash). It was found that high-WMC individuals had lower levels of false recognition than low-WMC individuals. Furthermore, recall-to-reject responses were analysed (e.g., "I know I didn't see eyelash because I remember seeing eyeglasses") and it was found that high-WMC individuals were more likely to utilise this memory editing strategy, providing direct evidence that one reason that high-WMC individuals are not as prone to false memories is because they are better able to engage in source monitoring.

  3. Appearance-based rejection sensitivity: implications for mental and physical health, affect, and motivation.

    Science.gov (United States)

    Park, Lora E

    2007-04-01

    Appearance-Based Rejection Sensitivity (Appearance-RS) is a personality-processing system characterized by anxious concerns and expectations about being rejected based on one's physical attractiveness. People differ in their sensitivity to rejection based on appearance, with consequences for mental and physical health, self-esteem, affect, and feelings of belonging. Study 1 describes the development and validation of the Appearance-RS scale, its relation to personality variables and to health-related outcomes. Study 2 provides experimental evidence that high Appearance-RS people feel more alone and rejected when asked to think about negative aspects of their appearance. Finally, Study 3 tests ways to reduce the negative effects of receiving an appearance threat among high Appearance-RS participants. Specifically, high Appearance-RS participants who engaged in self-affirmation (thought of their personal strengths) or received a secure attachment prime (thought of a close, caring relationship) were buffered from the negative effects of an appearance threat on subsequent state self-esteem and mood.

  4. Exceptionally fast water desalination at complete salt rejection by pristine graphyne monolayers

    International Nuclear Information System (INIS)

    Xue, Minmin; Qiu, Hu; Guo, Wanlin

    2013-01-01

    Desalination that produces clean freshwater from seawater holds the promise of solving the global water shortage for drinking, agriculture and industry. However, conventional desalination technologies such as reverse osmosis and thermal distillation involve large amounts of energy consumption, and the semipermeable membranes widely used in reverse osmosis face the challenge to provide a high throughput at high salt rejection. Here we find by comprehensive molecular dynamics simulations and first principles modeling that pristine graphyne, one of the graphene-like one-atom-thick carbon allotropes, can achieve 100% rejection of nearly all ions in seawater including Na + , Cl − , Mg 2+ , K + and Ca 2+ , at an exceptionally high water permeability about two orders of magnitude higher than those for commercial state-of-the-art reverse osmosis membranes at a salt rejection of ∼98.5%. This complete ion rejection by graphyne, independent of the salt concentration and the operating pressure, is revealed to be originated from the significantly higher energy barriers for ions than for water. This intrinsic specialty of graphyne should provide a new possibility for the efforts to alleviate the global shortage of freshwater and other environmental problems. (paper)

  5. Exceptionally fast water desalination at complete salt rejection by pristine graphyne monolayers.

    Science.gov (United States)

    Xue, Minmin; Qiu, Hu; Guo, Wanlin

    2013-12-20

    Desalination that produces clean freshwater from seawater holds the promise of solving the global water shortage for drinking, agriculture and industry. However, conventional desalination technologies such as reverse osmosis and thermal distillation involve large amounts of energy consumption, and the semipermeable membranes widely used in reverse osmosis face the challenge to provide a high throughput at high salt rejection. Here we find by comprehensive molecular dynamics simulations and first principles modeling that pristine graphyne, one of the graphene-like one-atom-thick carbon allotropes, can achieve 100% rejection of nearly all ions in seawater including Na(+), Cl(-), Mg(2+), K(+) and Ca(2+), at an exceptionally high water permeability about two orders of magnitude higher than those for commercial state-of-the-art reverse osmosis membranes at a salt rejection of ~98.5%. This complete ion rejection by graphyne, independent of the salt concentration and the operating pressure, is revealed to be originated from the significantly higher energy barriers for ions than for water. This intrinsic specialty of graphyne should provide a new possibility for the efforts to alleviate the global shortage of freshwater and other environmental problems.

  6. Trial Watch: Immunogenic cell death inducers for anticancer chemotherapy.

    Science.gov (United States)

    Pol, Jonathan; Vacchelli, Erika; Aranda, Fernando; Castoldi, Francesca; Eggermont, Alexander; Cremer, Isabelle; Sautès-Fridman, Catherine; Fucikova, Jitka; Galon, Jérôme; Spisek, Radek; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2015-04-01

    The term "immunogenic cell death" (ICD) is now employed to indicate a functionally peculiar form of apoptosis that is sufficient for immunocompetent hosts to mount an adaptive immune response against dead cell-associated antigens. Several drugs have been ascribed with the ability to provoke ICD when employed as standalone therapeutic interventions. These include various chemotherapeutics routinely employed in the clinic (e.g., doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin) as well as some anticancer agents that are still under preclinical or clinical development (e.g., some microtubular inhibitors of the epothilone family). In addition, a few drugs are able to convert otherwise non-immunogenic instances of cell death into bona fide ICD, and may therefore be employed as chemotherapeutic adjuvants within combinatorial regimens. This is the case of cardiac glycosides, like digoxin and digitoxin, and zoledronic acid. Here, we discuss recent developments on anticancer chemotherapy based on ICD inducers.

  7. Human monoclonal antibodies: the residual challenge of antibody immunogenicity.

    Science.gov (United States)

    Waldmann, Herman

    2014-01-01

    One of the major reasons for seeking human monoclonal antibodies has been to eliminate immunogenicity seen with rodent antibodies. Thus far, there has yet been no approach which absolutely abolishes that risk for cell-binding antibodies. In this short article, I draw attention to classical work which shows that monomeric immunoglobulins are intrinsically tolerogenic if they can be prevented from creating aggregates or immune complexes. Based on these classical studies two approaches for active tolerization to therapeutic antibodies are described.

  8. Tahyna virus genetics, infectivity, and immunogenicity in mice and monkeys

    Directory of Open Access Journals (Sweden)

    Whitehead Stephen S

    2011-03-01

    Full Text Available Abstract Background Tahyna virus (TAHV is a human pathogen of the California encephalitis virus (CEV serogroup (Bunyaviridae endemic to Europe, Asia, and Africa. TAHV maintains an enzootic life cycle with several species of mosquito vectors and hares, rabbits, hedgehogs, and rodents serving as small mammal amplifying hosts. Human TAHV infection occurs in summer and early fall with symptoms of fever, headache, malaise, conjunctivitis, pharyngitis, and nausea. TAHV disease can progress to CNS involvement, although unlike related La Crosse virus (LACV, fatalities have not been reported. Human infections are frequent with neutralizing antibodies present in 60-80% of the elderly population in endemic areas. Results In order to determine the genomic sequence of wild-type TAHV, we chose three TAHV isolates collected over a 26-year period from mosquitoes. Here we present the first complete sequence of the TAHV S, M, and L segments. The three TAHV isolates maintained a highly conserved genome with both nucleotide and amino acid sequence identity greater than 99%. In order to determine the extent of genetic relatedness to other members of the CEV serogroup, we compared protein sequences of TAHV with LACV, Snowshoe Hare virus (SSHV, Jamestown Canyon virus (JCV, and Inkoo virus (INKV. By amino acid comparison, TAHV was most similar to SSHV followed by LACV, JCV, and INKV. The sequence of the GN protein is most conserved followed by L, N, GC, NSS, and NSM. In a weanling Swiss Webster mouse model, all three TAHV isolates were uniformly neurovirulent, but only one virus was neuroinvasive. In rhesus monkeys, the virus was highly immunogenic even in the absence of viremia. Cross neutralization studies utilizing monkey immune serum demonstrated that TAHV is antigenically distinct from North American viruses LACV and JCV. Conclusions Here we report the first complete sequence of TAHV and present genetic analysis of new-world viruses, LACV, SSHV, and JCV with old

  9. Immunogenic properties of the human gut-associated archaeon Methanomassiliicoccus luminyensis and its susceptibility to antimicrobial peptides.

    Directory of Open Access Journals (Sweden)

    Corinna Bang

    Full Text Available The methanogenic archaeon Methanomassiliicoccus luminyensis strain B10T was isolated from human feces just a few years ago. Due to its remarkable metabolic properties, particularly the degradation of trimethylamines, this strain was supposed to be used as "Archaebiotic" during metabolic disorders of the human intestine. However, there is still no data published regarding adaptations to the natural habitat of M. luminyensis as it has been shown for the other two reported mucosa-associated methanoarchaea. This study aimed at unraveling susceptibility of M. luminyensis to antimicrobial peptides as well as its immunogenicity. By using the established microtiter plate assay adapted to the anaerobic growth requirements of methanogenic archaea, we demonstrated that M. luminyensis is highly sensitive against LL32, a derivative of human cathelicidin (MIC = 2 μM. However, the strain was highly resistant against the porcine lysin NK-2 (MIC = 10 μM and the synthetic antilipopolysaccharide peptide (Lpep (MIC>10 μM and overall differed from the two other methanoarchaea, Methanobrevibacter smithii and Methanosphaera stadtmanae in respect to AMP sensitivity. Moreover, only weak immunogenic potential of M. luminyensis was demonstrated using peripheral blood mononuclear cells (PBMCs and monocyte-derived dendritic cells (moDCs by determining release of pro-inflammatory cytokines. Overall, our findings clearly demonstrate that the archaeal gut inhabitant M. luminyensis is susceptible to the release of human-derived antimicrobial peptides and exhibits low immunogenicity towards human immune cells in vitro-revealing characteristics of a typical commensal gut microbe.

  10. Detection of cardiac transplant rejection with radiolabeled lymphocytes

    International Nuclear Information System (INIS)

    Bergmann, S.R.; Lerch, R.A.; Carlson, E.M.; Saffitz, J.E.; Sobel, B.E.

    1982-01-01

    To determine whether rejections of cardiac transplants could be detected specifically and non-invasively by lymphocytes labeled with indium-111 (111In), we studied 36 allogeneic and 14 isogeneic heterotopic cardiac transplants in rats. Allogeneic grafts accumulated autologous 111In-lymphocytes, detectable scintigraphically 24 hours after i.v. injection of the labeled cells. At the time of peak histologic rejection, the allogeneic grafts accumulated 92. +/- 4.8 times more activity than the native hearts (determined by well counting). The tissue-to-blood ratio in the rejecting transplants was 3.7 +/- 2.2; total uptake by the graft was 2.9 +/- 2.1% of the injected dose. Autoradiography confirmed that graft radioactivity was associated with labeled lymphocytes. In contrast, isogeneic grafts showed no signs of rejection and did not accumulate radioactivity. Because conventionally isolated and labeled lymphocytes are often contaminated with platelets, we prepared both 111In-platelets and purified 111In-lymphocytes for use in additional experiments. Allogeneic grafts accumulated platelets and purified lymphocytes independently. Thus, deposition of immunologically active cells in the rejecting graft representing specific pathophysiologic events can be detected. The results suggest that rejection of cardiac transplants can be detected noninvasively, potentially facilitating objective early clinical detection of rejection and titration of antirejection therapy

  11. Rejection of Organic Micropollutants by Clean and Fouled Nanofiltration Membranes

    Directory of Open Access Journals (Sweden)

    Lifang Zhu

    2015-01-01

    Full Text Available The rejection of organic micropollutants, including three polycyclic aromatic hydrocarbons (PAHs and three phthalic acid esters (PAEs, by clean and fouled nanofiltration membranes was investigated in the present study. The rejection of organic micropollutants by clean NF90 membranes varied from 87.9 to more than 99.9%, while that of NF270 membranes ranged from 32.1 to 92.3%. Clear time-dependence was observed for the rejection of hydrophobic micropollutants, which was attributed to the adsorption of micropollutants on the membrane. Fouling with humic acid had a negligible influence on the rejection of organic micropollutants by NF90 membranes, while considerable effects were observed with NF270 membranes, which are significantly looser than NF90 membranes. The observed enhancement in the rejection of organic micropollutants by fouled NF270 membranes was attributed to pore blocking, which was a dominating fouling mechanism for loose NF membranes. Changes in the ionic strength (from 10 to 20 mM reduced micropollutant rejection by both fouled NF membranes, especially for the rejection of dimethyl phthalate and diethyl phthalate by NF270 membranes (from 65.8 to 25.0% for dimethyl phthalate and 75.6 to 33.3% for diethyl phthalate.

  12. Immunogenicity of ascites tumor cells following in vitro hyperthermia

    International Nuclear Information System (INIS)

    Dickson, J.A.; Jasiewicz, M.L.; Simpson, A.C.

    1982-01-01

    The concept that host immunization may be achieved by heat-induced antigenic modifications of cancer cells and/or the release of immunogenic products by dead or dying tumor cells following in vitro heating was examined. Ehrlich ascites cells were used, inasmuch as it was claimed that in vitro hyperthermia increased the immunogenicity of these cells. Tumor cell populations of different viability were obtained by heating Ehrlich cells at 42.5 degrees, 45 degrees, or 60 degrees C. Viable and nonviable cells were separated by Ficoll-Hypaque density centrifugation; viable nonreplicating cells were obtained by treatment with mitomycin C. Cell populations of different viability after heating were left to die slowly over 3 days at 37 degrees C. Swiss TO mice were then given injections of the treated cells and/or medium. No survival benefit occurred in mice inoculated with any of these different components and then challenged with viable tumor cells. Injection of irradiated cells, however, did produce host immunity. Similarly, D23 rat hepatoma ascites cells produced host immunity after 15,000 rad but not after heating. The claim that in vitro hyperthermia increases the immunogenicity of tumor cells was not confirmed

  13. Meningococcal B vaccine. An immunogenic vaccine possibly useful during outbreaks.

    Science.gov (United States)

    2014-09-01

    Invasive meningococcal infections can be life-threatening and cause severe sequelae. Antibiotic therapy is only partially effective. Bexsero is the first meningococcal B vaccine to be approved in the European Union. It contains four capsular antigens from various strains of group B meningococci. Clinical trials of this meningococcal B vaccine did not assess clinical protection. Two immunogenicity studies in adults, one in adolescents and six in infants, are available. They established the immunogenicity of the meningococcal B vaccine, determined age-appropriate vaccination schedules, and verified that concomitant administration of other vaccines did not undermine its immunogenicity. In the absence of relevant clinical trials, an in vitro study showed that sera from vaccinated individuals were likely to have bactericidal activity against 85% of 200 invasive meningococcal B strains isolated in France in 2007-2008. The meningococcal B vaccine provoked local adverse effects in most vaccinees, including local erythema, induration and pain. Fever occurred in about half of vaccinated children. Six cases of Kawasaki syndrome have been reported in children who received the vaccine, compared to only one case in control groups. In practice, the harm-benefit balance of this meningococcal B vaccine justify using it during outbreaks, provided the outbreak strain is covered by the vaccine antigens. Vaccinees should be enrolled in studies designed to evaluate clinical efficacy and to better determine the risk of Kawasaki syndrome.

  14. An Albumin-Free Formulation for Escherichia coli-Derived Interferon Beta-1b with Decreased Immunogenicity in Immune Tolerant Mice

    NARCIS (Netherlands)

    Haji Abdolvahab, Mohadeseh; Fazeli, Ahmad; Radmalekshahi, Mazda; Nejadnik, M Reza; Fazeli, Mohammad Reza; Schellekens, Huub

    2016-01-01

    Human serum albumin (HSA)-free formulation of Escherichia coli-derived human interferon beta (IFNβ-1b) with a high percentage of monomeric protein and low immunogenicity is developed and characterized in the current study. UV spectroscopy, fluorescence spectroscopy, dynamic light scattering, sodium

  15. Elevated mRNA levels of CTLA-4, FoxP3, and granzyme B in BAL, but not in blood, during acute rejection of lung allografts

    DEFF Research Database (Denmark)

    Madsen, Caroline B; Nørgaard, Astrid; Iversen, Martin

    2010-01-01

    Regulatory T cells (Tregs) have been related to acute rejection as have the cytotoxic T cells, their immunological counterpart. High expression of cytotoxic markers has been related to acute rejection incidents following both kidney and intestine transplantation, while the correlation between Fox...

  16. CMV driven CD8(+) T-cell activation is associated with acute rejection in lung transplantation.

    Science.gov (United States)

    Roux, Antoine; Mourin, Gisèle; Fastenackels, Solène; Almeida, Jorge R; Iglesias, Maria Candela; Boyd, Anders; Gostick, Emma; Larsen, Martin; Price, David A; Sacre, Karim; Douek, Daniel C; Autran, Brigitte; Picard, Clément; Miranda, Sandra de; Sauce, Delphine; Stern, Marc; Appay, Victor

    2013-07-01

    Lung transplantation is the definitive treatment for terminal respiratory disease, but the associated mortality rate is high. Acute rejection of the transplanted lung is a key determinant of adverse prognosis. Furthermore, an epidemiological relationship has been established between the occurrence of acute lung rejection and cytomegalovirus infection. However, the reasons for this association remain unclear. Here, we performed a longitudinal characterization of CMV-specific T-cell responses and immune activation status in the peripheral blood and bronchoalveolar lavage fluid of forty-four lung transplant patients. Acute rejection was associated with high levels of cellular activation in the periphery, reflecting strong CMV-specific CD8(+) T-cell activity post-transplant. Peripheral and lung CMV-specific CD8(+) T-cell responses were very similar, and related to the presence of CMV in the transplanted organ. These findings support that activated CMV-specific CD8(+) T-cells in the lung may play a role in promoting acute rejection. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Donor-specific rejection: Clinical and scan correlation

    International Nuclear Information System (INIS)

    Wilson, M.A.; Mehta, R.C.; Perlman, S.B.; Servilla, K.; Sollinger, H.W.; Deierhoi, M.H.; Belzer, F.O.

    1986-01-01

    All 470 scans on 132 consecutive renal transplantation patients were reviewed. Scan patterns identified included acute tubular necrosis and conventional rejection. A new pattern, donor specific rejection (DSR), was identified in 24 of 42 patients on the living related donor specific transfusion (DST) protocol. This was characterized by good perfusion and extraction but significant renal stasis of tracer. This pattern was unique to the DST recipients and improved with antirejection therapy. The clinical features (incidence, temporal onset) and severity (duration, serum creatinines) are compared in these patient populations. DSR occurs more frequently than conventional rejection but is a milder process

  18. Identification of Novel Immunogenic Proteins of Neisseria gonorrhoeae by Phage Display.

    Directory of Open Access Journals (Sweden)

    Daniel O Connor

    Full Text Available Neisseria gonorrhoeae is one of the most prevalent sexually transmitted diseases worldwide with more than 100 million new infections per year. A lack of intense research over the last decades and increasing resistances to the recommended antibiotics call for a better understanding of gonococcal infection, fast diagnostics and therapeutic measures against N. gonorrhoeae. Therefore, the aim of this work was to identify novel immunogenic proteins as a first step to advance those unresolved problems. For the identification of immunogenic proteins, pHORF oligopeptide phage display libraries of the entire N. gonorrhoeae genome were constructed. Several immunogenic oligopeptides were identified using polyclonal rabbit antibodies against N. gonorrhoeae. Corresponding full-length proteins of the identified oligopeptides were expressed and their immunogenic character was verified by ELISA. The immunogenic character of six proteins was identified for the first time. Additional 13 proteins were verified as immunogenic proteins in N. gonorrhoeae.

  19. Immunotherapeutic Potential of Oncolytic H-1 Parvovirus: Hints of Glioblastoma Microenvironment Conversion towards Immunogenicity.

    Science.gov (United States)

    Angelova, Assia L; Barf, Milena; Geletneky, Karsten; Unterberg, Andreas; Rommelaere, Jean

    2017-12-15

    Glioblastoma, one of the most aggressive primary brain tumors, is characterized by highly immunosuppressive microenvironment. This contributes to glioblastoma resistance to standard treatment modalities and allows tumor growth and recurrence. Several immune-targeted approaches have been recently developed and are currently under preclinical and clinical investigation. Oncolytic viruses, including the autonomous protoparvovirus H-1 (H-1PV), show great promise as novel immunotherapeutic tools. In a first phase I/IIa clinical trial (ParvOryx01), H-1PV was safe and well tolerated when locally or systemically administered to recurrent glioblastoma patients. The virus was able to cross the blood-brain (tumor) barrier after intravenous infusion. Importantly, H-1PV treatment of glioblastoma patients was associated with immunogenic changes in the tumor microenvironment. Tumor infiltration with activated cytotoxic T cells, induction of cathepsin B and inducible nitric oxide (NO) synthase (iNOS) expression in tumor-associated microglia/macrophages (TAM), and accumulation of activated TAM in cluster of differentiation (CD) 40 ligand (CD40L)-positive glioblastoma regions was detected. These are the first-in-human observations of H-1PV capacity to switch the immunosuppressed tumor microenvironment towards immunogenicity. Based on this pilot study, we present a tentative model of H-1PV-mediated modulation of glioblastoma microenvironment and propose a combinatorial therapeutic approach taking advantage of H-1PV-induced microglia/macrophage activation for further (pre)clinical testing.

  20. The Role of Aggregates of Therapeutic Protein Products in Immunogenicity: An Evaluation by Mathematical Modeling

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    Liusong Yin

    2015-01-01

    Full Text Available Therapeutic protein products (TPP have been widely used to treat a variety of human diseases, including cancer, hemophilia, and autoimmune diseases. However, TPP can induce unwanted immune responses that can impact both drug efficacy and patient safety. The presence of aggregates is of particular concern as they have been implicated in inducing both T cell-independent and T cell-dependent immune responses. We used mathematical modeling to evaluate several mechanisms through which aggregates of TPP could contribute to the development of immunogenicity. Modeling interactions between aggregates and B cell receptors demonstrated that aggregates are unlikely to induce T cell-independent immune responses by cross-linking B cell receptors because the amount of signal transducing complex that can form under physiologically relevant conditions is limited. We systematically evaluate the role of aggregates in inducing T cell-dependent immune responses using a recently developed multiscale mechanistic mathematical model. Our analysis indicates that aggregates could contribute to T cell-dependent immune response by inducing high affinity epitopes which may not be present in the nonaggregated TPP and/or by enhancing danger signals to break tolerance. In summary, our computational analysis is suggestive of novel insights into the mechanisms underlying aggregate-induced immunogenicity, which could be used to develop mitigation strategies.

  1. Egr2 induced during DC development acts as an intrinsic negative regulator of DC immunogenicity.

    Science.gov (United States)

    Miah, Mohammad Alam; Byeon, Se Eun; Ahmed, Md Selim; Yoon, Cheol-Hee; Ha, Sang-Jun; Bae, Yong-Soo

    2013-09-01

    Early growth response gene 2 (Egr2), which encodes a zinc finger transcription factor, is rapidly and transiently induced in various cell types independently of de novo protein synthesis. Although a role for Egr2 is well established in T-cell development, Egr2 expression and its biological function in dendritic cells (DCs) have not yet been described. Here, we demonstrate Egr2 expression during DC development, and its role in DC-mediated immune responses. Egr2 is expressed in the later stage of DC development from BM precursor cells. Even at steady state, Egr2 is highly expressed in mouse splenic DCs. Egr2-knockdown (Egr2-KD) DCs showed increased levels of major histocompatability complex (MHC) class I and II and co-stimulatory molecules, and enhanced antigen uptake and migratory capacities. Furthermore, Egr2-KD abolished SOCS1 expression and signal transducer and activator of transcription 5 (STAT5) activation during DC development, probably resulting in the enhancement of IL-12 expression and Th1 immunogenicity of a DC vaccine. DC-mediated cytotoxic T lymphocyte (CTL) activation and antitumor immunity were significantly enhanced by Egr2-KD, and impaired by Egr2 overexpression in antigen-pulsed DC vaccines. These data suggest that Egr2 acts as an intrinsic negative regulator of DC immunogenicity and can be an attractive molecular target for DC vaccine development. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. A Directed Molecular Evolution Approach to Improved Immunogenicity of the HIV-1 Envelope Glycoprotein

    Science.gov (United States)

    Du, Sean X.; Xu, Li; Zhang, Wenge; Tang, Susan; Boenig, Rebecca I.; Chen, Helen; Mariano, Ellaine B.; Zwick, Michael B.; Parren, Paul W. H. I.; Burton, Dennis R.; Wrin, Terri; Petropoulos, Christos J.; Ballantyne, John A.; Chambers, Michael; Whalen, Robert G.

    2011-01-01

    A prophylactic vaccine is needed to slow the spread of HIV-1 infection. Optimization of the wild-type envelope glycoproteins to create immunogens that can elicit effective neutralizing antibodies is a high priority. Starting with ten genes encoding subtype B HIV-1 gp120 envelope glycoproteins and using in vitro homologous DNA recombination, we created chimeric gp120 variants that were screened for their ability to bind neutralizing monoclonal antibodies. Hundreds of variants were identified with novel antigenic phenotypes that exhibit considerable sequence diversity. Immunization of rabbits with these gp120 variants demonstrated that the majority can induce neutralizing antibodies to HIV-1. One novel variant, called ST-008, induced significantly improved neutralizing antibody responses when assayed against a large panel of primary HIV-1 isolates. Further study of various deletion constructs of ST-008 showed that the enhanced immunogenicity results from a combination of effective DNA priming, an enhanced V3-based response, and an improved response to the constant backbone sequences. PMID:21738594

  3. Effects of gamma rays on the immunogenicity (IgG types) of ovalbumin

    Energy Technology Data Exchange (ETDEWEB)

    Baptista, J.A. E-mail: jbalves@ipen.br; Spencer, P.J.; Aroeira, L.G.S.; Casare, M.S.; Nascimento, N

    2004-10-01

    Ionizing radiation has been successfully employed to modify the immunological properties of biomolecules. Very promising results were obtained when crude animal venoms, as well as isolated toxins, were treated with gamma rays, yielding toxoids with good immunogenicity. However, little is known about the modifications that irradiated molecules undergo and even less about the immunological response that such antigens elicit. In the present work, we used ovalbumin as a model to investigate possible immunogenic differences between native and irradiated proteins. Native ovalbumin (2 mg/ml in 150 mM NaCl) was irradiated with 2 kGy of {sup 60}Co gamma rays with a 570 Gy/h dose rate. B10.PL mice (n=5) were then immunized with either the native or the irradiated protein. After three immunizations, serum samples were collected and the antibody titers and isotypes were determined by enzyme-linked immunoadsorbant assay. Our data indicate that no difference could be noticed when the antibody titers of the two groups were compared. However, the isotyping assays indicates that the native protein induced high levels of IgG1, while its irradiated counterpart displayed mostly IgG2b antibodies. These data suggest that after irradiation, an antigen known to induce a Th2 response, is able to switch the immune system towards a Th1 pattern.

  4. Immunogenicity Studies of Bivalent Inactivated Virions of EV71/CVA16 Formulated with Submicron Emulsion Systems

    Directory of Open Access Journals (Sweden)

    Chih-Wei Lin

    2014-01-01

    Full Text Available We assessed two strategies for preparing candidate vaccines against hand, foot, and mouth disease (HFMD caused mainly by infections of enterovirus (EV 71 and coxsackievirus (CV A16. We firstly design and optimize the potency of adjuvant combinations of emulsion-based delivery systems, using EV71 candidate vaccine as a model. We then perform immunogenicity studies in mice of EV71/CVA16 antigen combinations formulated with PELC/CpG. A single dose of inactivated EV71 virion (0.2 μg emulsified in submicron particles was found (i to induce potent antigen-specific neutralizing antibody responses and (ii consistently to elicit broad antibody responses against EV71 neutralization epitopes. A single dose immunogenicity study of bivalent activated EV71/CVA16 virion formulated with either Alum or PELC/CpG adjuvant showed that CVA16 antigen failed to elicit CVA16 neutralizing antibody responses and did not affect EV71-specific neutralizing antibody responses. A boosting dose of emulsified EV71/CVA16 bivalent vaccine candidate was found to be necessary to achieve high seroconversion of CVA16-specific neutralizing antibody responses. The current results are important for the design and development of prophylactic vaccines against HFMD and other emerging infectious diseases.

  5. Full scale application of the autotrophic denitrification in trickling filters for treatment of rejection water with high ammonia concentrations from sludge dewatering. Final report; Untersuchungen zur autotrophen Stickstoffentfernung aus ammoniumreichem Filtratwasser der Schlammentwaesserung mit grosstechnischer Realisierung in Tropfkoerpern. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Neumueller, B.; Metzger, J.W.; Pinnekamp, J.

    2003-07-01

    At many municipal wastewater treatment plants a considerable fraction of nitrogen is recirculated from the anaerobic sludge dewatering. This amounts up to 20% of the total influent nitrogen load of the wastewater treatment plant. The separate treatment of this sludge liquor creates new capacities for the treatment plant and improves effluent quality. A new process for treatment of this sludge liquor with ammonium-nitrogen concentrations above 600 mg/l is the autotrophic denitrification after partial nitritation. At the University of Stuttgart the first semi-technical trickling filter plant was built by which autotrophic denitrification was achieved. At the wastewater treatment plant of Sindelfingen the first full-scale implementation of the autotrophic denitrification in trickling filters has been designed and built. In a first trickling filter 60% of ammonia is transformed to nitrite. The investigations showed, that a few mg/l of free ammonia in this trickling filter were sufficient to inhibit the nitratation but not the nitritation. To achieve this, operating conditions as pH and temperature are of great importance. The concentration of free ammonia should be kept constant because there is an adaption of the microorganisms to free ammonia. After a decrease of the free ammonia concentration the inhibition of the nitratation declines. By thermally killing the biomass and restarting the process, can guarantee a total inhibition of the nitratation, while the concentration of free ammonia is low. In the second, closed trickling filter (anoxic conditions) ammonium is converted autotrophically to nitrogen with nitrite as electron acceptor. It was possible to set up the anoxic ammonium oxidation in full scale without inoculating the process. The very slow growth of the anammox-bacteria leads to a long adaptation phase of the process. All operating conditions such as anoxic conditions, high temperature and a concentration of nitrite below 70 mg/l have to be observed

  6. Diverse manifestations of tumorigenicity and immunogenicity displayed by the poorly immunogenic B16-BL6 melanoma transduced with cytokine genes.

    Science.gov (United States)

    Arca, M J; Krauss, J C; Strome, S E; Cameron, M J; Chang, A E

    1996-05-01

    We evaluated the in vivo response to the poorly immunogenic B16-BL6 (BL6) murine melanoma genetically altered to secrete interleukin-2 (IL-2), IL-4, interferon gamma (IFN gamma) and granulocyte/macrophage-colony-stimulating factor (GM-CSF). Three parameters were evaluated: (1) tumorigenicity, (2) vaccination of naive animals, and (3) assessment of antitumor reactivity of T cells derived from tumor-draining lymph nodes (TDLN). Secretion of IL-2 abrogated the tumorigenicity of BL6, while IFN gamma and IL-4 partially reduced tumorigenicity, and GM-CSF had no effect. Protective immunity to wild-type tumor challenge could not be achieved by vaccination with irradiated cytokine-secreting tumors, although IL-2 and IL-4 secretion appeared to retard the growth of the challenge inoculum significantly. An alternative method to evaluate the immunogenicity of the cytokine-secreting tumors was to measure the ability of T cells obtained from TDLN to mediate regression of wild-type tumor in adoptive immunotherapy. Neither IL-2 nor IFN gamma secretion resulted in the induction of immune T cells. By contrast, GM-CSF and IL-4 secretion were found to induce immune T cells in the TDLN with GM-CSF being superior to IL-4. The combined secretion of GM-CSF and IL-4 did not lead to enhanced induction of immune T cells. GM-CSF secretion was found to upregulate B7-1 expression in TDLN, consistent with an increase in the population of antigen-presenting cells. These studies demonstrated that reduced tumorigenicity by cytokine secretion did not correlate with increased immunogenicity. With the cytokines examined, there was limited capability of developing protective immunity against the BL6 tumor. Nevertheless, GM-CSF and IL-4 secretion significantly enhanced T cell immune reactivity to the poorly immunogenic BL6 tumor.

  7. Exploring virulence and immunogenicity in the emerging pathogen Sporothrix brasiliensis.

    Science.gov (United States)

    Della Terra, Paula Portella; Rodrigues, Anderson Messias; Fernandes, Geisa Ferreira; Nishikaku, Angela Satie; Burger, Eva; de Camargo, Zoilo Pires

    2017-08-01

    Sporotrichosis is a polymorphic chronic infection of humans and animals classically acquired after traumatic inoculation with soil and plant material contaminated with Sporothrix spp. propagules. An alternative and successful route of transmission is bites and scratches from diseased cats, through which Sporothrix yeasts are inoculated into mammalian tissue. The development of a murine model of subcutaneous sporotrichosis mimicking the alternative route of transmission is essential to understanding disease pathogenesis and the development of novel therapeutic strategies. To explore the impact of horizontal transmission in animals (e.g., cat-cat) and zoonotic transmission on Sporothrix fitness, the left hind footpads of BALB/c mice were inoculated with 5×106 yeasts (n = 11 S. brasiliensis, n = 2 S. schenckii, or n = 1 S. globosa). Twenty days post-infection, our model reproduced both the pathophysiology and symptomology of sporotrichosis with suppurating subcutaneous nodules that progressed proximally along lymphatic channels. Across the main pathogenic members of the S. schenckii clade, S. brasiliensis was usually more virulent than S. schenckii and S. globosa. However, the virulence in S. brasiliensis was strain-dependent, and we demonstrated that highly virulent isolates disseminate from the left hind footpad to the liver, spleen, kidneys, lungs, heart, and brain of infected animals, inducing significant and chronic weight loss (losing up to 15% of their body weight). The weight loss correlated with host death between 2 and 16 weeks post-infection. Histopathological features included necrosis, suppurative inflammation, and polymorphonuclear and mononuclear inflammatory infiltrates. Immunoblot using specific antisera and homologous exoantigen investigated the humoral response. Antigenic profiles were isolate-specific, supporting the hypothesis that different Sporothrix species can elicit a heterogeneous humoral response over time, but cross reaction was observed

  8. Laughter as a social rejection cue: Influence of prior explicit experience of social rejection on cardiac signs of "freezing".

    Science.gov (United States)

    Lackner, Helmut K; Reiter-Scheidl, Katharina; Aydin, Nilüfer; Perchtold, Corinna M; Weiss, Elisabeth M; Papousek, Ilona

    2018-06-01

    The study aimed at investigating the immediate cardiac effect of the sudden perception of other people's laughter after experimentally manipulating healthy participants' proneness to experience laughter as a cue of social threat. We expected that participants would show cardiac signs of freezing (i.e., sustained heart rate deceleration immediately after perception of the laughter) after prior social rejection but not or less so after prior acceptance, due to an increased bias to perceive the ambiguous social signal as a cue of social threat and rejection after rejection had been primed. Contrary to expectations, the perception of other people's laughter elicited a decelerative (freezing) response regardless of whether it was preceded by the experience of social rejection or acceptance. The response was prolonged in participants who had been accepted beforehand compared to those who had been rejected. The findings indicate that, given a relevant social context, other people's laughter can be a powerful cue of social threat and rejection also in healthy individuals. Prolonged heart rate deceleration after an ambiguous social signal may facilitate the processing of significant social information in the socially threatening situation. The study adds to the literature rendering the course of the immediate transient heart rate response a useful tool in social rejection research. Additionally, the findings suggested that in some cases the further progress of transient heart rate changes in more extended time-windows (about 30 s) may provide additional relevant information about the processing of social cues. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Low Immunogenic Endothelial Cells Maintain Morphological and Functional Properties Required for Vascular Tissue Engineering.

    Science.gov (United States)

    Lau, Skadi; Eicke, Dorothee; Carvalho Oliveira, Marco; Wiegmann, Bettina; Schrimpf, Claudia; Haverich, Axel; Blasczyk, Rainer; Wilhelmi, Mathias; Figueiredo, Constança; Böer, Ulrike

    2018-03-01

    The limited availability of native vessels suitable for the application as hemodialysis shunts or bypass material demands new strategies in cardiovascular surgery. Tissue-engineered vascular grafts containing autologous cells are considered ideal vessel replacements due to the low risk of rejection. However, endothelial cells (EC), which are central components of natural blood vessels, are difficult to obtain from elderly patients of poor health. Umbilical cord blood represents a promising alternative source for EC, but their allogeneic origin corresponds with the risk of rejection after allotransplantation. To reduce this risk, the human leukocyte antigen class I (HLA I) complex was stably silenced by lentiviral vector-mediated RNA interference (RNAi) in EC from peripheral blood and umbilical cord blood and vein. EC from all three sources were transduced by 93.1% ± 4.8% and effectively, HLA I-silenced by up to 67% compared to nontransduced (NT) cells or transduced with a nonspecific short hairpin RNA, respectively. Silenced EC remained capable to express characteristic endothelial surface markers such as CD31 and vascular endothelial cadherin important for constructing a tight barrier, as well as von Willebrand factor and endothelial nitric oxide synthase important for blood coagulation and vessel tone regulation. Moreover, HLA I-silenced EC were still able to align under unidirectional flow, to take up acetylated low-density lipoprotein, and to form capillary-like tube structures in three-dimensional fibrin gels similar to NT cells. In particular, addition of adipose tissue-derived mesenchymal stem cells significantly improved tube formation capability of HLA I-silenced EC toward long and widely branched vascular networks necessary for prevascularizing vascular grafts. Thus, silencing HLA I by RNAi represents a promising technique to reduce the immunogenic potential of EC from three different sources without interfering with EC-specific morphological and

  10. Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals

    DEFF Research Database (Denmark)

    Rup, B; Pallardy, M; Sikkema, D

    2015-01-01

    scientists are involved in: interpretation and management of clinical and biological outcomes of BP immunogenicity, improvement of methods for describing, predicting and mitigating immunogenicity risk and elucidation of underlying causes. Collaboration and alignment of efforts across these communities...... the Risk; www.abirisk.eu] was formed by leading clinicians, academic scientists and EFPIA (European Federation of Pharmaceutical Industries and Associations) members to elucidate underlying causes, improve methods for immunogenicity prediction and mitigation and establish common definitions around terms...

  11. Efficacy, immunogenicity, and safety of a 9-valent human papillomavirus vaccine in Latin American girls, boys, and young women

    Directory of Open Access Journals (Sweden)

    Ángela María Ruiz-Sternberg

    2018-06-01

    Full Text Available Background: A 9-valent human papillomavirus (HPV6/11/16/18/31/33/45/52/58; 9vHPV vaccine was developed to expand coverage of the previously developed quadrivalent (HPV6/11/16/18; qHPV vaccine. Methods: Efficacy, immunogenicity, and safety outcomes were assessed in Latin American participants enrolled in 2 international studies of the 9vHPV vaccine, including a randomized, double-blinded, controlled with qHPV vaccine, efficacy, immunogenicity, and safety study in young women aged 16–26 years, and an immunogenicity and safety study in girls and boys aged 9–15 years. Participants (N=5312 received vaccination at Day 1, Month 2, and Month 6. Gynecological swabs were collected regularly in young women for cytological and HPV DNA testing. Serum was analyzed for HPV antibodies in all participants. Adverse events (AEs were also monitored in all participants. Results: The 9vHPV vaccine prevented HPV 31-, 33-, 45-, 52-, and 58-related high-grade cervical, vulvar, and vaginal dysplasia with 92.3% efficacy (95% confidence interval 54.4, 99.6. Anti-HPV6, 11, 16, and 18 geometric mean titers at Month 7 were similar in the 9vHPV and qHPV vaccination groups. Anti-HPV antibody responses following vaccination were higher among girls and boys than in young women. Most (>99% 9vHPV vaccine recipients seroconverted for all 9 HPV types at Month 7. Antibody responses to the 9 HPV types persisted over 5 years. The most common AEs were injection-site related, mostly of mild to moderate intensity. Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Latin American young women, girls, and boys. These data support 9vHPV vaccination programs in Latin America, a region with substantial cervical cancer burden. Keywords: Human papillomavirus, Vaccine, Cervical cancer, Persistent infection, 9vHPV

  12. Efficacy, immunogenicity, and safety of a 9-valent human papillomavirus vaccine in Latin American girls, boys, and young women.

    Science.gov (United States)

    Ruiz-Sternberg, Ángela María; Moreira, Edson D; Restrepo, Jaime A; Lazcano-Ponce, Eduardo; Cabello, Robinson; Silva, Arnaldo; Andrade, Rosires; Revollo, Francisco; Uscanga, Santos; Victoria, Alejandro; Guevara, Ana María; Luna, Joaquín; Plata, Manuel; Dominguez, Claudia Nossa; Fedrizzi, Edison; Suarez, Eugenio; Reina, Julio C; Ellison, Misoo C; Moeller, Erin; Ritter, Michael; Shields, Christine; Cashat, Miguel; Perez, Gonzalo; Luxembourg, Alain

    2018-06-01

    A 9-valent human papillomavirus (HPV6/11/16/18/31/33/45/52/58; 9vHPV) vaccine was developed to expand coverage of the previously developed quadrivalent (HPV6/11/16/18; qHPV) vaccine. Efficacy, immunogenicity, and safety outcomes were assessed in Latin American participants enrolled in 2 international studies of the 9vHPV vaccine, including a randomized, double-blinded, controlled with qHPV vaccine, efficacy, immunogenicity, and safety study in young women aged 16-26 years, and an immunogenicity and safety study in girls and boys aged 9-15 years. Participants (N=5312) received vaccination at Day 1, Month 2, and Month 6. Gynecological swabs were collected regularly in young women for cytological and HPV DNA testing. Serum was analyzed for HPV antibodies in all participants. Adverse events (AEs) were also monitored in all participants. The 9vHPV vaccine prevented HPV 31-, 33-, 45-, 52-, and 58-related high-grade cervical, vulvar, and vaginal dysplasia with 92.3% efficacy (95% confidence interval 54.4, 99.6). Anti-HPV6, 11, 16, and 18 geometric mean titers at Month 7 were similar in the 9vHPV and qHPV vaccination groups. Anti-HPV antibody responses following vaccination were higher among girls and boys than in young women. Most (>99%) 9vHPV vaccine recipients seroconverted for all 9 HPV types at Month 7. Antibody responses to the 9 HPV types persisted over 5 years. The most common AEs were injection-site related, mostly of mild to moderate intensity. The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Latin American young women, girls, and boys. These data support 9vHPV vaccination programs in Latin America, a region with substantial cervical cancer burden. Copyright © 2018 Merck Sharp & Dohme Corp., and The Authors. Published by Elsevier B.V. All rights reserved.

  13. Stromal Cells Act as Guardians for Endothelial Progenitors by Reducing Their Immunogenicity After Co-Transplantation.

    Science.gov (United States)

    Souidi, Naima; Stolk, Meaghan; Rudeck, Juliane; Strunk, Dirk; Schallmoser, Katharina; Volk, Hans-Dieter; Seifert, Martina

    2017-05-01

    Regeneration of injured tissues requires effective therapeutic strategies supporting vasculogenesis. The lack of instantly available autologous cell sources and immunogenicity of allogeneic endothelial (progenitor) cells limits clinical progress. Based on the immunosuppressive potency of mesenchymal stem/progenitor cells (MSCs), we investigated whether crosstalk between endothelial colony-forming progenitor cells (ECFCs) and MSCs during vasculogenesis could lower allogeneic T cell responses against ECFCs allowing long-term engraftment in vivo. Immunodeficient mice received subcutaneous grafts containing human ECFCs alone, or pairs of human ECFCs/MSCs from the same umbilical cord (UC) to study vasculogenesis in the presence of human leukocyte antigen (HLA)-mismatched human peripheral blood mononuclear cells (PBMCs). In vitro, cell surface marker changes due to interferon gamma (IFNγ) stimulation during ECFC/MSC coculture were determined and further effects on allostimulated T cell proliferation and cytotoxic lysis were measured. IFNγ-induced HLA-DR expression on ECFCs and MSCs, but both cell types had significantly less HLA-DR in cocultures. ECFC-induced T cell proliferation was abolished after MSC coculture as a result of HLA-DR downregulation and indolamin-2,3-dioxygenase activation. Additionally, allospecific CD8 + T cell-mediated lysis of ECFCs was reduced in cocultures. ECFC/MSC coapplication in immunodeficient mice not only promoted the generation of improved blood vessel architecture after 6 weeks, but also reduced intragraft immune cell infiltration and endothelial HLA-DR expression following PBMC reconstitution. Crosstalk between UC-derived ECFCs and MSCs after combined transplantation can lower the risk of ECFC rejection, thus enabling their coapplication for therapeutic vasculogenesis. Stem Cells 2017;35:1233-1245. © 2017 AlphaMed Press.

  14. Homology analysis and cross-immunogenicity of OmpA from pathogenic Yersinia enterocolitica, Yersinia pseudotuberculosis and Yersinia pestis.

    Science.gov (United States)

    Chen, Yuhuang; Duan, Ran; Li, Xu; Li, Kewei; Liang, Junrong; Liu, Chang; Qiu, Haiyan; Xiao, Yuchun; Jing, Huaiqi; Wang, Xin

    2015-12-01

    The outer membrane protein A (OmpA) is one of the intra-species conserved proteins with immunogenicity widely found in the family of Enterobacteriaceae. Here we first confirmed OmpA is conserved in the three pathogenic Yersinia: Yersinia pestis, Yersinia pseudotuberculosis and pathogenic Yersinia enterocolitica, with high homology at the nucleotide level and at the amino acid sequence level. The identity of ompA sequences for 262 Y. pestis strains, 134 Y. pseudotuberculosis strains and 219 pathogenic Y. enterocolitica strains are 100%, 98.8% and 97.7% similar. The main pattern of OmpA of pathogenic Yersinia are 86.2% and 88.8% identical at the nucleotide and amino acid sequence levels, respectively. Immunological analysis showed the immunogenicity of each OmpA and cross-immunogenicity of OmpA for pathogenic Yersinia where OmpA may be a vaccine candidate for Y. pestis and other pathogenic Yersinia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Enhanced structural stability of Concholepas hemocyanin increases its immunogenicity and maintains its non-specific immunostimulatory effects.

    Science.gov (United States)

    Arancibia, Sergio; Del Campo, Miguel; Nova, Esteban; Salazar, Fabián; Becker, María Inés

    2012-03-01

    Hemocyanins, which boost the immune system of mammals, have been used as carrier-adjuvants to promote Ab production against haptens and peptides, as immunostimulants during therapy for bladder carcinoma and as a component in therapeutic vaccines for cancer. These biomedical applications have led to growing interest in obtaining hemocyanins with high immunogenicity. Here, we study the immunological properties of a modified oxidized Concholepas concholepas hemocyanin (Ox-CCH) obtained by the oxidation of its carbohydrates using sodium periodate. We assessed the internalization of Ox-CCH into DCs and its immunogenicity and antitumor effects. Transmission electron microscopy showed no changes in Ox-CCH quaternary structure with respect to native CCH, although proteolytic treatment followed by SDS-PAGE analysis demonstrated that Schiff bases were formed. Interestingly, DCs internalized Ox-CCH faster than CCH, mainly through macropinocytosis. During this process, Ox-CCH remained inside endosome-like structures for a longer period. Mouse immunization experiments demonstrated that Ox-CCH is more immunogenic and a better carrier than CCH. Moreover, Ox-CCH showed a significant antitumor effect in the B16F10 melanoma model similar to that produced by CCH, inducing IFN-γ secretion. Together, these data demonstrate that the aldehydes formed by the periodate oxidation of sugar moieties stabilizes the CCH structure, increasing its adjuvant/immunostimulatory carrier effects. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. [Safety and immunogenicity of a 7-valent pneumococcal conjugate vaccine (Prevenar) booster dose in healthy Chinese toddlers].

    Science.gov (United States)

    Li, Rong-cheng; Li, Feng-xiang; Li, Yan-ping

    2009-06-01

    To evaluate the safety and immunogenicity of the booster dose of 7 valent pneumococcal conjugate vaccine (PCV7) to the healthy Chinese toddlers who had received 3 primary doses. Four hundred and eighty-eight Chinese toddlers received a booster dose of PCV7 at age of 12-15 months following a primary series of the vaccine given at ages 3, 4, 5 months separately with Diphtheria Tetanus Acellular Pertussis Combined Vaccine (DTaP) in Group 1 or concurrently with DTaP in Group 2. Following the booster dose immunization, each subject was followed up for 30 days to observe the safety of the vaccine. Blood samples were taken from a subset of subjects prior and post 30 days the booster dose immunization to evaluate immunogenicity. A high proportion of subjects in Group 1 (89%) and Group 2 (91%) remained afebrile after the booster dose. Local reactions to the PCV7 booster dose were generally mild. For each serotype, the rise in GMC (post-/pre-vaccination) showed a statistically significant difference (P<0.0001) between both groups. PCV7 administered as a booster dose is generally safe, well tolerate, and immunogenic in healthy Chinese toddlers.

  17. New scoring system identifies kidney outcome with radiation therapy in acute renal allograft rejection

    International Nuclear Information System (INIS)

    Chen, Luci M.; Godinez, Juan; Thisted, Ronald A.; Woodle, E. Steve; Thistlewaite, J. Richard; Powers, Claire; Haraf, Daniel

    2000-01-01

    concomitant immunosuppressive therapy. Independent factors examined by Cox regression modeling were: gender (p 0.005), creatinine levels (p = 0.000), HLA-DR (p = 0.05), PRA-Maximum >70% (p = 0.014). Each factor was scored using integral coefficients to generate four different groups. The Kaplan-Meier survival analyzed by group produces an interpretable separation of the risk factors for graft loss. Conclusions: The outcome in patients treated with radiation therapy for acute renal graft rejection can be predicted by a novel scoring system. Patients with scores of three or less are able to achieve 100% renal graft salvage, while patients who have scores of 12 or higher are not able to be salvaged with the current radiation therapy regimen. Future studies should be directed toward identifying more effective treatment for patients who have a high score based on our criteria. The scoring system should be utilized to identify patients at risk who could benefit from radiation therapy. Further study with a randomized trial utilizing this scoring system is needed to confirm the validity of the scoring system in predicting graft survival and the efficacy of radiation in patients who receive radiation therapy for acute graft rejection

  18. Family Planning: Between Rejection And Acceptance In Islam ...

    African Journals Online (AJOL)

    Family Planning: Between Rejection And Acceptance In Islam. ... factor for health workers and policy makers to impact positively on their communities. ... who are likely to work in such communities for effective negotiation and application of ...

  19. Perceived parental rejection mediates the effects of previous ...

    African Journals Online (AJOL)

    Behavioural problems, parental rejection scores and child abuse ... evaluated by the Child Behavior Checklist (parental version), the Memories of Parental Rearing ... However, mental illness had no moderating effect on these relationships.

  20. Reliability and construct validity for scale of rejection of Christianity.

    Science.gov (United States)

    Robbins, Mandy; Francis, Leslie J; Bradford, Amanda

    2003-02-01

    A sample of 16 male and 30 female undergraduates completed the Greer and Francis Scale of Rejection of Christianity. The data support the internal consistency reliability and construct validity of the scale for this sample.

  1. Outside advantage: can social rejection fuel creative thought?

    Science.gov (United States)

    Kim, Sharon H; Vincent, Lynne C; Goncalo, Jack A

    2013-08-01

    Eminently creative people working in fields as disparate as physics and literature refer to the experience of social rejection as fuel for creativity. Yet, the evidence of this relationship is anecdotal, and the psychological process that might explain it is as yet unknown. We theorize that the experience of social rejection may indeed stimulate creativity but only for individuals with an independent self-concept. In 3 studies, we show that individuals who hold an independent self-concept performed more creatively after social rejection relative to inclusion. We also show that this boost in creativity is mediated by a differentiation mind-set, or salient feelings of being different from others. Future research might investigate how the self-concept--for example, various cultural orientations-may shape responses to social rejection by mitigating some of the negative consequences of exclusion and potentially even motivating creative exploration. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  2. Behavioral and Personality Predictors of Acceptance and Rejection in University

    Directory of Open Access Journals (Sweden)

    Daniel Bartholomeu

    Full Text Available Abstract: Acceptance and rejection in the group are related to both personality characteristics and social skills and most studies focus on children instead of college students. The objective of this study was to investigate whether acceptance and rejection would be more associated with personality tendencies, specifically socialization or social skills. We collected data from 187 college students attending the Physical Education (67% and Psychology (32% courses. The instruments were the sociometric test, the Factorial Scale of Socialization and the Social Skills Inventory. A moderating effect of gender in the relationship between assertiveness and acceptance and rejection to go out on college was observed. Social skills were better predictors of acceptance and social rejection in the university group.

  3. Associations between rejection sensitivity and mental health outcomes : A meta-analytic review

    NARCIS (Netherlands)

    Gao, S.; Assink, M.; Cipriani, A.; Lin, K.

    2017-01-01

    Rejection sensitivity is a personality disposition characterized by oversensitivity to social rejection. Using a three-level meta-analytic model, 75 studies were reviewed that examined associations between rejection sensitivity and five mental health outcomes: depression, anxiety, loneliness,

  4. Immune response to UV-induced tumors: mediation of progressor tumor rejection by natural killer cells

    International Nuclear Information System (INIS)

    Streeter, P.R.; Fortner, G.W.

    1986-01-01

    Skin tumors induced in mice by chronic ultraviolet (UV) irradiation are highly antigenic and can induce a state of transplantation immunity in syngeneic animals. In the present study, the authors compared the in vitro cytolytic activity of splenic lymphocytes from mice immunized with either regressor or progressor UV-tumors. The results of this comparison implicated tumor-specific cytolytic T (Tc) lymphocytes in rejection of regressor UV-tumors, and revealed that immunization with the progressor UV-tumor 2237 failed to elicit detectable levels of progressor tumor-specific Tc cells even as the tumors rejected. Following in vitro resensitization of spleen cells from either regressor or progressor tumor immune animals, the authors found NK-like lymphocytes with anti-tumor activity. As the authors had not detected cells with this activity in splenic lymphocyte preparations prior to in vitro resensitization, the authors examined lymphocytes from the local tumor environment during the course of progressor tumor rejection for this activity. This analysis revealed NK lymphocytes exhibiting significant levels of cytolytic activity against UV-tumors. These results implicate NK cells as potential effector cells in the rejection of progressor UV-tumors by immune animals, and suggests that these cells may be regulated by T lymphocytes

  5. ADAPTIVE METHODS FOR STOCHASTIC DIFFERENTIAL EQUATIONS VIA NATURAL EMBEDDINGS AND REJECTION SAMPLING WITH MEMORY.

    Science.gov (United States)

    Rackauckas, Christopher; Nie, Qing

    2017-01-01

    Adaptive time-stepping with high-order embedded Runge-Kutta pairs and rejection sampling provides efficient approaches for solving differential equations. While many such methods exist for solving deterministic systems, little progress has been made for stochastic variants. One challenge in developing adaptive methods for stochastic differential equations (SDEs) is the construction of embedded schemes with direct error estimates. We present a new class of embedded stochastic Runge-Kutta (SRK) methods with strong order 1.5 which have a natural embedding of strong order 1.0 methods. This allows for the derivation of an error estimate which requires no additional function evaluations. Next we derive a general method to reject the time steps without losing information about the future Brownian path termed Rejection Sampling with Memory (RSwM). This method utilizes a stack data structure to do rejection sampling, costing only a few floating point calculations. We show numerically that the methods generate statistically-correct and tolerance-controlled solutions. Lastly, we show that this form of adaptivity can be applied to systems of equations, and demonstrate that it solves a stiff biological model 12.28x faster than common fixed timestep algorithms. Our approach only requires the solution to a bridging problem and thus lends itself to natural generalizations beyond SDEs.

  6. Use of radionuclide imaging in the early diagnosis and treatment of renal allograft rejection

    International Nuclear Information System (INIS)

    Mandel, S.R.; Mattern, W.D.; Staab, E.; Johnson, G. Jr.

    1975-01-01

    Data are presented on the clinical application of radionuclide imaging to evaluate changes in cadaver transplant function in the immediate postoperative period. The method uses orthoiodohippuric acid (hippuran) administered IV, with scintillation imaging, and curve analysis by a digital computer. An initial study is always obtained 24 hours after transplantation. Serial studies are then obtained, as needed, to interpret the clinical course. Selected cases are presented which illustrate the use of this protocol in various clinical settings. In the oliguric patient serial studies have been of particular value. They have identified ATN so that overenthusiastic treatment for rejection could be avoided. They have also identified acute rejection complicating ATN so that high dose steroid therapy could be administered appropriately. In the nonoliguric patient they have frequently contributed to the early diagnosis of acute rejection, and they have been useful in monitoring the effect and duration of treatment for severe rejection crisis. It is concluded that radionuclide imaging studies, when carefully applied and interpreted, are a valuable adjunct to the management of patients in this complex clinical setting

  7. The outcast-lash-out effect in youth: alienation increases aggression following peer rejection.

    Science.gov (United States)

    Reijntjes, Albert; Thomaes, Sander; Bushman, Brad J; Boelen, Paul A; de Castro, Bram Orobio; Telch, Michael J

    2010-10-01

    Although there are good theoretical reasons to believe that youth who are high in alienation (i.e., estranged from society, significant others, and themselves) are prone to behave aggressively, empirical evidence is lacking. The present experiment tested whether alienation moderates the effects of acute peer rejection on aggression in youth. Participants (N = 121; mean age = 11.5 years) completed a personal profile (e.g., "How do you describe yourself?") that was allegedly evaluated online by a panel of peer judges. After randomly receiving negative or positive feedback from peer judges, participants were given the opportunity to aggress against them (i.e., by reducing their monetary reward and by posting negative comments about them online). As predicted, alienation increased participants' aggression against peers who had rejected them, but not against peers who had praised them, even after controlling for peer-nominated chronic rejection and peer-nominated aggression. Thus, alienated youth are more aggressive than others when they experience acute peer rejection.

  8. An Objective Measure of Splitting in Parental Alienation: The Parental Acceptance-Rejection Questionnaire.

    Science.gov (United States)

    Bernet, William; Gregory, Nilgun; Reay, Kathleen M; Rohner, Ronald P

    2018-05-01

    Both clinicians and forensic practitioners should distinguish parental alienation (rejection of a parent without legitimate justification) from other reasons for contact refusal. Alienated children-who were not abused-often engage in splitting and lack ambivalence with respect to the rejected parent; children who were maltreated usually perceive the abusive parent in an ambivalent manner. The purpose of this study was to assess the usefulness of the Parental Acceptance-Rejection Questionnaire (PARQ) in identifying and quantifying the degree of splitting, which may assist in diagnosing parental alienation. Results showed that severely alienated children engaged in a high level of splitting, by perceiving the preferred parent in extremely positive terms and the rejected parent in extremely negative terms. Splitting was not manifested by the children in other family groups. The PARQ may be useful for both clinicians and forensic practitioners in evaluating children of divorced parents when there is a concern about the possible diagnosis of parental alienation. © 2017 American Academy of Forensic Sciences.

  9. Self-esteem moderates neuroendocrine and psychological responses to interpersonal rejection.

    Science.gov (United States)

    Ford, Máire B; Collins, Nancy L

    2010-03-01

    In this study, the authors investigated self-esteem as a moderator of psychological and physiological responses to interpersonal rejection and tested an integrative model detailing the mechanisms by which self-esteem may influence cognitive, affective, and physiological responses. Seventy-eight participants experienced an ambiguous interpersonal rejection (or no rejection) from an opposite sex partner in the context of an online dating interaction. Salivary cortisol was assessed at 5 times, and self-reported cognitive and affective responses were assessed. Compared with those with high self-esteem, individuals with low self-esteem responded to rejection by appraising themselves more negatively, making more self-blaming attributions, exhibiting greater cortisol reactivity, and derogating the rejector. Path analysis indicated that the link between low self-esteem and increased cortisol reactivity was mediated by self-blame attributions; cortisol reactivity, in turn, mediated the link between low self-esteem and increased partner derogation. Discussion centers on the role of self-esteem as part of a broader psychobiological system for regulating and responding to social threat and on implications for health outcomes.

  10. Patterns of Early Rejection in Renal Retransplantation: A Single-Center Experience

    Directory of Open Access Journals (Sweden)

    Lan Zhu

    2016-01-01

    Full Text Available It has been reported that kidney retransplant patients had high rates of early acute rejection due to previous sensitization. In addition to the acute antibody-mediated rejection (ABMR that has received widespread attention, the early acute T-cell-mediated rejection (TCMR may be another important issue in renal retransplantation. In the current single-center retrospective study, we included 33 retransplant patients and 90 first transplant patients with similar protocols of induction and maintenance therapy. Analysis focused particularly on the incidence and patterns of early acute rejection episodes, as well as one-year graft and patient survival. Excellent short-term clinical outcomes were obtained in both groups, with one-year graft and patient survival rates of 93.9%/100% in the retransplant group and 92.2%/95.6% in the first transplant group. Impressively, with our strict immunological selection and desensitization criteria, the retransplant patients had a very low incidence of early acute ABMR (6.1%, which was similar to that in the first transplant patients (4.4%. However, a much higher rate of early acute TCMR was observed in the retransplant group than in the first transplant group (30.3% versus 5.6%, P<0.001. Acute TCMR that develops early after retransplantation should be monitored in order to obtain better transplant outcomes.

  11. A conservative and a hybrid early rejection schemes for accelerating Monte Carlo molecular simulation

    KAUST Repository

    Kadoura, Ahmad Salim

    2014-03-17

    Molecular simulation could provide detailed description of fluid systems when compared to experimental techniques. They can also replace equations of state; however, molecular simulation usually costs considerable computational efforts. Several techniques have been developed to overcome such high computational costs. In this paper, two early rejection schemes, a conservative and a hybrid one, are introduced. In these two methods, undesired configurations generated by the Monte Carlo trials are rejected earlier than it would when using conventional algorithms. The methods are tested for structureless single-component Lennard-Jones particles in both canonical and NVT-Gibbs ensembles. The computational time reduction for both ensembles is observed at a wide range of thermodynamic conditions. Results show that computational time savings are directly proportional to the rejection rate of Monte Carlo trials. The proposed conservative scheme has shown to be successful in saving up to 40% of the computational time in the canonical ensemble and up to 30% in the NVT-Gibbs ensemble when compared to standard algorithms. In addition, it preserves the exact Markov chains produced by the Metropolis scheme. Further enhancement for NVT-Gibbs ensemble is achieved by combining this technique with the bond formation early rejection one. The hybrid method achieves more than 50% saving of the central processing unit (CPU) time.

  12. Acute Hepatic Allograft Rejection in Pediatric Recipients: Independent Factors

    OpenAIRE

    Dehghani, S. M.; Shahramian, I.; Afshari, M.; Bahmanyar, M.; Ataollahi, M.; Sargazi, A.

    2017-01-01

    Background: Acute cellular rejection (ACR) has a reversible effect on graft and its survival. Objective: To evaluate the relation between ACR and clinical factors in recipients of liver transplant allografts. Methods: 47 consecutive liver recipients were retrospectively studied. Their data were extracted from records and analyzed. Results: 38 (81%) of the 47 recipients experienced ACR during a 24-month follow-up. The rate of rejection was associated with none of the studied factors—recipient’...

  13. EEG Asymmetry in Borderline Personality Disorder and Depression Following Rejection

    OpenAIRE

    Beeney, Joseph E.; Levy, Kenneth N.; Gatzke-Kopp, Lisa M.; Hallquist, Michael N.

    2013-01-01

    Borderline personality disorder (BPD) and major depressive disorder (MDD) share numerous features including dysphoric affect, irritability, suicidality, and a heightened sensitivity to perceived interpersonal rejection. However, these disorders are associated with divergent profiles of reactivity to rejection; individuals with MDD are more likely to respond with withdrawal and isolation, and those with BPD appear to respond with increased approach behaviors and greater hostility. Potential me...

  14. Maternal Predictors of Rejecting Parenting and Early Adolescent Antisocial Behavior

    OpenAIRE

    Trentacosta, Christopher J.; Shaw, Daniel S.

    2007-01-01

    The present study examined relations among maternal psychological resources, rejecting parenting, and early adolescent antisocial behavior in a sample of 231 low-income mothers and their sons with longitudinal assessments from age 18 months to 12 years. The maternal resources examined were age at first birth, aggressive personality, and empathy. Each of the maternal resources predicted rejecting parenting during early childhood in structural equation models that controlled for toddler difficu...

  15. COTRANSA simulation of Chinshan unit one generator load rejection test

    International Nuclear Information System (INIS)

    Wu, C.H.

    1984-01-01

    A simulation of the plant behavior during a BWR generator load rejection transient using Exxon Nuclear Company's COTRANSA code is presented in this paper. The results are compared to measurements obtained by Taiwan Power Company during a generator load rejection transient, initiated at full power condition, which was one of the Chinshan Unit 1 initial cycle startup tests. Good agreement between the COTRANSA predicted and the measured values, indicates that the COTRANSA code can simulate this transient satisfactorily

  16. Community structure analysis of rejection sensitive personality profiles: A common neural response to social evaluative threat?

    Science.gov (United States)

    Kortink, Elise D; Weeda, Wouter D; Crowley, Michael J; Gunther Moor, Bregtje; van der Molen, Melle J W

    2018-06-01

    Monitoring social threat is essential for maintaining healthy social relationships, and recent studies suggest a neural alarm system that governs our response to social rejection. Frontal-midline theta (4-8 Hz) oscillatory power might act as a neural correlate of this system by being sensitive to unexpected social rejection. Here, we examined whether frontal-midline theta is modulated by individual differences in personality constructs sensitive to social disconnection. In addition, we examined the sensitivity of feedback-related brain potentials (i.e., the feedback-related negativity and P3) to social feedback. Sixty-five undergraduate female participants (mean age = 19.69 years) participated in the Social Judgment Paradigm, a fictitious peer-evaluation task in which participants provided expectancies about being liked/disliked by peer strangers. Thereafter, they received feedback signaling social acceptance/rejection. A community structure analysis was employed to delineate personality profiles in our data. Results provided evidence of two subgroups: one group scored high on attachment-related anxiety and fear of negative evaluation, whereas the other group scored high on attachment-related avoidance and low on fear of negative evaluation. In both groups, unexpected rejection feedback yielded a significant increase in theta power. The feedback-related negativity was sensitive to unexpected feedback, regardless of valence, and was largest for unexpected rejection feedback. The feedback-related P3 was significantly enhanced in response to expected social acceptance feedback. Together, these findings confirm the sensitivity of frontal midline theta oscillations to the processing of social threat, and suggest that this alleged neural alarm system behaves similarly in individuals that differ in personality constructs relevant to social evaluation.

  17. Rejection with hemodynamic compromise in the current era of pediatric heart transplantation: a multi-institutional study.

    Science.gov (United States)

    Everitt, Melanie D; Pahl, Elfriede; Schechtman, Kenneth B; Zheng, Jie; Ringewald, Jeremy M; L'ecuyer, Thomas; Naftel, David C; Kirklin, James K; Blume, Elizabeth D; Bullock, Emily A; Canter, Charles E

    2011-03-01

    Survival after pediatric heart transplant has improved over time, as has the incidence of overall rejection. We studied the effect of era on the occurrence and outcome of rejection with hemodynamic compromise (HC). Data from 2227 patients who received allografts between 1993 and 2006 at 36 centers in the Pediatric Heart Transplant Study were analyzed to determine incidence, outcome, and risk factors for rejection with HC in early (1993-1999) and recent (2000-2006) eras. Rejection with HC was classified as severe (RSHC) when inotropes were used for circulatory support and mild (RMHC) when inotropes were not used. Of 1217 patients with any episode of rejection, 541 had rejection with HC. Freedom from RMHC improved at 1 year (81% vs 90%, p RMHC (87% at 1 year and 72% at 5 years, p RMHC was earlier era of transplant (HR, 1.94; 95% CI, 1.56-2.41; p RMHC has declined over time but the same era effect has not occurred with RSHC. Close follow-up after RSHC is crucial because mortality is so high. Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  18. Pre-transplant immune state defined by serum markers and alloreactivity predicts acute rejection after living donor kidney transplantation.

    Science.gov (United States)

    Vondran, Florian W R; Timrott, Kai; Kollrich, Sonja; Steinhoff, Ann-Kristin; Kaltenborn, Alexander; Schrem, Harald; Klempnauer, Juergen; Lehner, Frank; Schwinzer, Reinhard

    2014-09-01

    Acute rejection (AR) remains a major cause for long-term kidney allograft failure. Reliable immunological parameters suitable to define the pre-transplant immune state and hence the individual risk of graft rejection are highly desired to preferably adapt the immunosuppressive regimen in advance. Donor and third party alloreactivities were determined by mixed lymphocyte cultures. Soluble forms of CD25, CD30, and CD44 were detected in patients' serum by ELISA. Various lymphocyte subpopulations were measured using flow cytometry. All patients received triple immunosuppression (tacrolimus/mycophenolate mofetil/steroids) and were grouped according to biopsy results within the first year: rejection-free (RF, n = 13), borderline (BL, n = 5), or acute rejection (AR, n = 7). Patients with AR showed the highest pre-transplant alloreactivities and serum levels (sCD25/sCD30/sCD44) according to the pattern RF transplant frequencies of CD4(+) /CD8(+) T cells lacking CD28, but lower numbers of CD8(+) CD161(bright) T cells and NK cells than RF individuals. Pre-transplant immune state defined by alloreactivity, serum markers, and particular lymphocyte subsets seems to correlate with occurrence of graft rejection after kidney transplantation. A prognostic score based on pre-transplant serum levels has shown great potential for prediction of rejection episodes and should be further evaluated. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. New clutter-rejection algorithm for Doppler ultrasound

    Science.gov (United States)

    Cloutier, Guy; Chen, Danmin; Durand, Louis-Gilles

    2002-04-01

    Several strategies, known as clutter or wall Doppler filtering, were proposed to remove the strong echoes produced by stationary or slow moving tissue structures from the Doppler blood flow signal. In this study, the matching pursuit (MP) method is proposed to remove clutter components. The MP method decomposes the Doppler signal into wavelet atoms that are selected in a decreasing energy order. Thus, the high-energy clutter components are extracted first. In the present study, the pulsatile Doppler signal s(n) was simulated by a sum of random-phase sinusoids. Two types of high-amplitude clutter signals were then superimposed on s(n): a time-varying low frequency component (type 1), covering systole and early diastole, and short transient clutter signals (type 2), distributed within the whole cardiac cycle. The Doppler signals were modeled with the MP method and the most dominant atoms were subtracted until the signal-to-clutter (S/C) ratio reached a maximum. For the type 1 clutter signal, the improvement in the S/C ratio was 19.0 +/- 0.6 dB, and 72.0 +/- 4.5 atoms were required to reach this performance. For the transient type 2 clutter signal, exactly 10 atoms were required and the maximum improvement in S/C ratio was 5.5 +/- 0.5 dB. These results suggest the possibility of using this signal processing approach to implement clutter rejection filters on ultrasound commercial instruments.

  20. Brain Region-Dependent Rejection of Neural Precursor Cell Transplants

    Directory of Open Access Journals (Sweden)

    Nina Fainstein

    2018-04-01

    Full Text Available The concept of CNS as an immune-privileged site has been challenged by the occurrence of immune surveillance and allogeneic graft rejection in the brain. Here we examined whether the immune response to allogeneic neural grafts is determined by the site of implantation in the CNS. Dramatic regional differences were observed between immune responses to allogeneic neural precursor/stem cell (NPC grafts in the striatum vs. the hippocampus. Striatal grafts were heavily infiltrated with IBA-1+ microglia/macrophages and CD3+ T cells and completely rejected. In contrast, hippocampal grafts exhibited milder IBA-1+ cell infiltration, were not penetrated efficiently by CD3+ cells, and survived efficiently for at least 2 months. To evaluate whether the hippocampal protective effect is universal, astrocytes were then transplanted. Allogeneic astrocyte grafts elicited a vigorous rejection process from the hippocampus. CD200, a major immune-inhibitory signal, plays an important role in protecting grafts from rejection. Indeed, CD200 knock out NPC grafts were rejected more efficiently than wild type NPCs from the striatum. However, lack of CD200 expression did not elicit NPC graft rejection from the hippocampus. In conclusion, the hippocampus has partial immune-privilege properties that are restricted to NPCs and are CD200-independent. The unique hippocampal milieu may be protective for allogeneic NPC grafts, through host-graft interactions enabling sustained immune-regulatory properties of transplanted NPCs. These findings have implications for providing adequate immunosuppression in clinical translation of cell therapy.

  1. Rejection or selection: influence of framing in investment decisions.

    Science.gov (United States)

    Cheng, Pi-Yueh; Chiou, Wen-Bin

    2010-02-01

    According to prospect theory, reflection effects result in preferences for risk-averse choices in gain situations and risk-seeking choices in loss situations. However, relevant literature in regard to decision making has suggested that positive information receives more weight in a selection task, whereas negative information receives more weight in a rejection task. The present study examined whether the nature of a decision task (selection vs rejection) would moderate the reflection effects. Undergraduates (47 men, 49 women; M age = 20.5 yr., SD = 1.1), selected according to specific screening criteria, participated in an experimental study. Typical reflection effects were observed in both selection and rejection task conditions. More importantly, negative information (i.e., the information about probable loss in risky choice of gain situations and the information about certain loss in cautious choice of loss situations) provided in the context of a rejection task received more weight and resulted in more frequent endorsements of the cautious choice in gain situations and of the risky choice in loss situations. Hence, the findings suggest that a decision context characterized by rejection may expand the reflection effects and thereby provide important information about situations in which investment decisions occur in a context characterized by rejection.

  2. Structure-guided Design and Immunological Characterization of Immunogens Presenting the HIV-1 gp120 V3 Loop on a CTB Scaffold

    Energy Technology Data Exchange (ETDEWEB)

    M Totrov; X Jiang; X Kong; S Cohen; C Krachmarov; A Salomon; C Williams; M Seaman; R Abagyan; et al.

    2011-12-31

    V3 loop is a major neutralizing determinant of the HIV-1 gp120. Using 3D structures of cholera toxin B subunit (CTB), complete V3 in the gp120 context, and V3 bound to a monoclonal antibody (mAb), we designed two V3-scaffold immunogen constructs (V3-CTB). The full-length V3-CTB presenting the complete V3 in a structural context mimicking gp120 was recognized by the large majority of our panel of 24 mAbs. The short V3-CTB presenting a V3 fragment in the conformation observed in the complex with the 447-52D Fab, exhibited high-affinity binding to this mAb. The immunogens were evaluated in rabbits using DNA-prime/protein-boost protocol. Boosting with the full-length V3-CTB induced high anti-V3 titers in sera that potently neutralize multiple HIV virus strains. The short V3-CTB was ineffective. The results suggest that very narrow antigenic profile of an immunogen is associated with poor Ab response. An immunogen with broader antigenic activity elicits robust Ab response.

  3. When rejection stings: how self-esteem constrains relationship-enhancement processes.

    Science.gov (United States)

    Murray, Sandra L; Rose, Paul; Bellavia, Gina M; Holmes, John G; Kusche, Anna Garrett

    2002-09-01

    Three experiments examined how needs for acceptance might constrain low versus high self-esteem people's capacity to protect their relationships in the face of difficulties. The authors led participants to believe that their partner perceived a problem in their relationship. They then measured perceptions of the partner's acceptance, partner enhancement, and closeness. Low but not high self-esteem participants read too much into problems, seeing them as a sign that their partner's affections and commitment might be waning. They then derogated their partner and reduced closeness. Being less sensitive to rejection, however, high self-esteem participants affirmed their partner in the face of threat. Ironically, chronic needs for acceptance may result in low self-esteem people seeing signs of rejection where none exist, needlessly weakening attachments.

  4. Anti-enrofloxacin antibody production by using enrofloxacin-screened HSA as an immunogen

    Science.gov (United States)

    Liu, Chune; Lin, Hong; Cao, Limin; Jiang, Jie

    2005-07-01

    A two-step zero-length cross-linking procedure using active esters was successfully adopted for conjugating enrofloxacin (EF) to human serum albumin (HSA). The derived conjugate was characterized by UV spectrum and then used for immunization of BALB/C mice. In enzyme-linked immunosorbent assay (ELISA) and competitive inhibition ELISA experiments, the derived antiserum exhibited high antibody titer (greater than 1:250 000) as well as varied cross-reactivity (from 97.8% to 161.7%) to three analogs of EF belonging to fluoroquinolones family. But over the concentration range studied, no significant cross-reactivity was observed to other group of antibiotics (chloramphenicol, oxytetracycline, sulphamethoxazole and nysfungin). It was confirmed that the synthesized immunogen was highly antigenic and elicited specific antibody responses in BALB/C mice against EF.

  5. [Immunogenicity and safety of the influenza vaccine, in a population older than 55-years in Mexico].

    Science.gov (United States)

    Ayala-Montiel, Octavio; Mascareñas, César; García-Hernández, Delfino; Rendón-Muñiz, Jorge; López, Irma; Felipe Montaño, Luis; Zenteno, I; Franco-Paredes, C

    2005-01-01

    To confirm the immunogenicity and tolerance of the inactivated, fractionated, and purified influenza vaccine, in a Mexican adult population aged 55 and older, medically served at a Petróleos Mexicanos Hospital (Pemex, Mexican Oil Company). The study was conducted between November and December, 2000, among ninety adult subjects aged 55 years and older who were seen at the Hospital Central Sur Pemex. The primary endpoints regarding immunogenicity were the percentage of individuals with protective antibodies targeting hemagglutinins higher than or equal to 1:40, and the percentage of subjects who seroconverted as measured by a four-fold increase in protective antibody production. Secondary endpoints included the frequency of local and systemic reactions to the vaccine. An additional criterion that was evaluated included antigen-antibody affinity assays to measure the polyclonal antibody response to the vaccine and the specific generation of high-affinity antibodies to viral proteins, before and after vaccination. The antibody protection rate was 95.6% against the HINI strain, 98.9% against the H3N2 strain, and a 100% against the B/Yamanashi strain. Seroconversion to the HINI strain was elicited in 74.4% of subjects, to the H3N2 strain in 88.9%, and to the B/Yamanashi strain in 82.2%. Eighteen (20%) subjects developed local reactions; 17 (18.8%) developed a systemic reaction post vaccination at day 5 and nine subjects (10%) at day 28. Local reactions consisted of pain in 10 (11.1%) subjects, redness in 8 (8.8%), and induration in 6 (6.6%). General malaise, headache, and fever were identified in 10, 8.8, and 0% of subjects, respectively, at day 5, and in 4.4, 6.6, and 0%, respectively, at day 28. Influenza vaccine was highly immunogenic in a healthy Mexican adult population aged 55 years and older. The generation of high-affinity antibodies to the virus after vaccination was also demonstrated. Local and systemic adverse reactions to the vaccine identified in our study

  6. A computational assessment of the permeability and salt rejection of carbon nanotube membranes and their application to water desalination

    Science.gov (United States)

    Thomas, Michael; Corry, Ben

    2016-01-01

    Membranes made from nanomaterials such as nanotubes and graphene have been suggested to have a range of applications in water filtration and desalination, but determining their suitability for these purposes requires an accurate assessment of the properties of these novel materials. In this study, we use molecular dynamics simulations to determine the permeability and salt rejection capabilities for membranes incorporating carbon nanotubes (CNTs) at a range of pore sizes, pressures and concentrations. We include the influence of osmotic gradients and concentration build up and simulate at realistic pressures to improve the reliability of estimated membrane transport properties. We find that salt rejection is highly dependent on the applied hydrostatic pressure, meaning high rejection can be achieved with wider tubes than previously thought; while membrane permeability depends on salt concentration. The ideal size of the CNTs for desalination applications yielding high permeability and high salt rejection is found to be around 1.1 nm diameter. While there are limited energy gains to be achieved in using ultra-permeable CNT membranes in desalination by reverse osmosis, such membranes may allow for smaller plants to be built as is required when size or weight must be minimized. There are diminishing returns in further increasing membrane permeability, so efforts should focus on the fabrication of membranes containing narrow or functionalized CNTs that yield the desired rejection or selection properties rather than trying to optimize pore densities. PMID:26712639

  7. Safety and immunogenicity of a live attenuated mumps vaccine

    Science.gov (United States)

    Liang, Yan; Ma, Jingchen; Li, Changgui; Chen, Yuguo; Liu, Longding; Liao, Yun; Zhang, Ying; Jiang, Li; Wang, Xuan-Yi; Che, Yanchun; Deng, Wei; Li, Hong; Cui, Xiaoyu; Ma, Na; Ding, Dong; Xie, Zhongping; Cui, Pingfang; Ji, Qiuyan; Wang, Jingjing; Zhao, Yuliang; Wang, Junzhi; Li, Qihan

    2014-01-01

    Background: Mumps, a communicable, acute and previously well-controlled disease, has had recent and occasional resurgences in some areas. Methods: A randomized, double-blind, controlled and multistep phase I study of an F-genotype attenuated mumps vaccine produced in human diploid cells was conducted. A total of 300 subjects were enrolled and divided into 4 age groups: 16–60 years, 5–16 years, 2–5 years and 8–24 months. The groups were immunized with one injection per subject. Three different doses of the F-genotype attenuated mumps vaccine, A (3.5 ± 0.25 logCCID50), B (4.25 ± 0.25 logCCID50) and C (5.0 ± 0.25 logCCID50), as well as a placebo control and a positive control of a licensed A-genotype vaccine (S79 strain) were used. The safety and immunogenicity of this vaccine were compared with those of the controls. Results: The safety evaluation suggested that mild adverse reactions were observed in all groups. No serious adverse event (SAE) was reported throughout the trial. The immunogenicity test showed a similar seroconversion rate of the neutralizing and ELISA antibody in the 2- to 5-year-old and 8- to 24-month-old groups compared with the seroconversion rate in the positive control. The GMT of the neutralizing anti-F-genotype virus antibodies in the vaccine groups was slightly higher than that in the positive control group. Conclusions: The F-genotype attenuated mumps vaccine evaluated in this clinical trial was demonstrated to be safe and have effective immunogenicity vs. control. PMID:24614759

  8. Relation between pretransplant serum levels of soluble CD30 and acute rejection during the first 6 months after a kidney transplant.

    Science.gov (United States)

    Shooshtarizadeh, Tina; Mohammadali, Ali; Ossareh, Shahrzad; Ataipour, Yousef

    2013-06-01

    The immunologic status of kidney allograft recipients affects transplant outcome. High levels of pretransplant serum soluble CD30 correlate with an increased risk of acute rejection. Studies show conflicting results. We evaluated the relation between pretransplant serum sCD30 levels with the risk of posttransplant acute kidney rejection in renal transplant recipients. This prospective cohort study was performed between March 2010 and March 2011 on 77 kidney transplant recipients (53 men [68.8%], 24 women [31.2%]; mean age, 41 ± 14 y). Serum samples were collected 24 hours before transplant and analyzed for soluble CD30 levels by enzyme-linked immunosorbent assay. Patients were followed for 6 months after transplant. Acute biopsy-proven rejection episodes were recorded, serum creatinine levels were measured, and glomerular filtration rates were calculated at the first and sixth months after transplant. Preoperative serum soluble CD30 levels were compared in patients with and without rejection. The mean pretransplant serum soluble CD30 level was 92.1 ± 47.3 ng/mL. At 6 months' follow-up, 10 patients experienced acute rejection. Mean pretransplant soluble CD30 levels were 128.5 ± 84 ng/mL versus 86.7 ± 37 ng/mL in patients with and without acute rejection episodes (P = .008). At 100 ng/mL, the sensitivity, specificity, and positive and negative predictive values of pretransplant serum soluble CD30 level to predict acute rejection were 70%, 73.6%, 29.1%, and 94.3%. We showed a significant relation between pretransplant serum soluble CD30 levels and acute allograft rejection. High pretransplant levels of serum soluble CD30 can be a risk factor for kidney transplant rejection, and its high negative predictive value at various cutoffs make it useful to find candidates with a low risk of acute rejection after transplant.

  9. A paramyxovirus-vectored intranasal vaccine against Ebola virus is immunogenic in vector-immune animals.

    Science.gov (United States)

    Yang, Lijuan; Sanchez, Anthony; Ward, Jerrold M; Murphy, Brian R; Collins, Peter L; Bukreyev, Alexander

    2008-08-01

    Ebola virus (EBOV) causes outbreaks of a highly lethal hemorrhagic fever in humans. The virus can be transmitted by direct contact as well as by aerosol and is considered a potential bioweapon. Because direct immunization of the respiratory tract should be particularly effective against infection of mucosal surfaces, we previously developed an intranasal vaccine based on replication-competent human parainfluenza virus type 3 (HPIV3) expressing EBOV glycoprotein GP (HPIV3/EboGP) and showed that it is immunogenic and protective against a high dose parenteral EBOV challenge. However, because the adult human population has considerable immunity to HPIV3, which is a common human pathogen, replication and immunogenicity of the vaccine in this population might be greatly restricted. Indeed, in the present study, replication of the vaccine in the respiratory tract of HPIV3-immune guinea pigs was found to be restricted to undetectable levels. This restriction appeared to be based on both neutralizing antibodies and cellular or other components of the immunity to HPIV3. Surprisingly, even though replication of HPIV3/EboGP was highly restricted in HPIV3-immune animals, it induced a high level of EBOV-specific antibodies that nearly equaled that obtained in HPIV3-naive animals. We also show that the previously demonstrated presence of functional GP in the vector particle was not associated with increased replication in the respiratory tract nor with spread beyond the respiratory tract of HPIV3-naive guinea pigs, indicating that expression and functional incorporation of the attachment/penetration glycoprotein of this systemic virus did not mediate a change in tissue tropism.

  10. Adaptive sidelobe control for clutter rejection of atmospheric radars

    Directory of Open Access Journals (Sweden)

    K. Kamio

    2004-11-01

    Full Text Available Clutter rejection is among the most important issues in radar signal processing, for which the adaptive antenna technique can be a powerful means. Compared to other applications of the adaptive antenna, however, atmospheric radars require strict conditions, which have prevented application of this technique; the main antenna beam pattern should not be altered since the target region is defined by its shape. In particular, the loss of the antenna gain should be kept to no more than about 0.5dB, in order to maintain the high sensitivity of the system. Also, clutter from surrounding mountains is often stronger than the desired weak scattering from atmospheric turbulence. We introduce a new algorithm which satisfies the above conditions, and confirms its capability by applying it to actual data taken by the MU radar. This paper presents the first report that demonstrates the effectiveness of the adaptive antenna technique in atmospheric radar applications. Despite the fact that no information is given on the spectral features of the desired and undesired signals, only the clutter echoes from surrounding mountains were effectively cancelled without affecting the desired echoes from atmospheric turbulence.

  11. Sexual orientation, handedness, sex ratio and fetomaternal tolerance-rejection

    Directory of Open Access Journals (Sweden)

    Carlos Y Valenzuela

    2010-01-01

    Full Text Available Fraternal birth order (FBO appears as a prenatal cause of 15% of homosexual males (gays through mnemonic maternal anti-male factors. Non-right-handed men seem to be protected from homosexuality. Four hypotheses are proposed: (1 androgenic factors of non-right-handedness neutralize anti-male factors; (2 non-right-handedness and homosexuality are lethal or produce mental impairment; (3 non-right-handed male embryos are insensitive to anti-male factors; (4 mothers of non-right-handed fetuses do not produce anti-male factors. Studies of the sex ratio (SR of older and younger siblings show: (1 a significant heterogeneity in the SR of siblings of right or non-right handed heterosexual men and women; (2 lesbians are born among siblings with high SR; (3 siblings of right-handed gays show a higher SR than non-right-handed gays that present a low SR. Based on our discovery of maternal tolerance-rejection processes, associated with genetic systems (ABO, Rh, where zygotes or embryos different from their mother induce better pregnancy and maternal tolerance than do those that share antigens with their mothers, I propose a new explanation for sexual relationships, sexual orientation, handedness and sibling SR. Lesbian embryos could induce tolerance from mothers with anti-female factors. Non-right-handedness could induce maternal tolerance, or change the maternal compatibility of "gay" embryos. Alternatively, gay embryos could be poor inducers of maternal tolerance towards male traits.

  12. Sexual orientation, handedness, sex ratio and fetomaternal tolerance-rejection.

    Science.gov (United States)

    Valenzuela, Carlos Y

    2010-01-01

    Fraternal birth order (FBO) appears as a prenatal cause of 15% of homosexual males (gays) through mnemonic maternal anti-male factors. Non-right-handed men seem to be protected from homosexuality. Four hypotheses are proposed: (1) androgenic factors of non-right-handedness neutralize anti-male factors; (2) non-right-handedness and homosexuality are lethal or produce mental impairment; (3) non-right-handed male embryos are insensitive to anti-male factors; (4) mothers of non-right-handed fetuses do not produce anti-male factors. Studies of the sex ratio (SR) of older and younger siblings show: (1) a significant heterogeneity in the SR of siblings of right or non-right handed heterosexual men and women; (2) lesbians are born among siblings with high SR; (3) siblings of right-handed gays show a higher SR than non-right-handed gays that present a low SR. Based on our discovery of maternal tolerance-rejection processes, associated with genetic systems (ABO, Rh), where zygotes or embryos different from their mother induce better pregnancy and maternal tolerance than do those that share antigens with their mothers, I propose a new explanation for sexual relationships, sexual orientation, handedness and sibling SR. Lesbian embryos could induce tolerance from mothers with anti-female factors. Non-right-handedness could induce maternal tolerance, or change the maternal compatibility of "gay" embryos. Alternatively, gay embryos could be poor inducers of maternal tolerance towards male traits.

  13. Delayed allogeneic skin graft rejection in CD26-deficient mice.

    Science.gov (United States)

    Zhao, Xiangli; Zhang, Kai; Daniel, Peter; Wisbrun, Natali; Fuchs, Hendrik; Fan, Hua

    2018-03-23

    Organ transplantation is an effective therapeutic tool for treating many terminal diseases. However, one of the biggest challenges of transplantation is determining how to achieve the long-term survival of the allogeneic or xenogeneic transplant by, for example, preventing transplant rejection. In the current study, CD26 gene-knockout mice were used to investigate the potential role of CD26/dipeptidyl peptidase-4 (DPPIV) in allogeneic skin graft rejection by tail-skin transplantation. Compared with wild-type (CD26 +/+ ) counterparts, CD26 -/- mice showed reduced necrosis of grafts and delayed graft rejection after skin transplantation. Concentrations of serum IgG, including its subclasses IgG1 and IgG2a, were significantly reduced in CD26 -/- mice during graft rejection. Moreover, after allogeneic skin transplantation, the secretion levels of the cytokines IFN-γ, IL-2, IL-6, IL-4, and IL-13 were significantly reduced, whereas the level of the cytokine IL-10 was increased in the serum of CD26 -/- mice compared with that in the serum of CD26 +/+ mice. Additionally, the concentration of IL-17 in serum and the percentage of cells secreting IL-17 in mouse peripheral blood lymphocytes (MPBLs) were both significantly lower, while the percentage of regulatory T cells (Tregs) was significantly higher in MPBLs of CD26 -/- mice than in those of CD26 +/+ mice. Furthermore, a lower percentage of CD8 + T cells in MPBLs and fewer infiltrated macrophages and T cells in graft tissues of CD26 -/- mice were detected during graft rejection. These results indicate that CD26 is involved in allogeneic skin graft rejection and provides another hint that CD26 deficiency leads to less rejection due to lower activation and proliferation of host immune cells.

  14. Virulence, immunogenicity and vaccine properties of a novel chimeric pestivirus

    DEFF Research Database (Denmark)

    Rasmussen, Thomas Bruun; Uttenthal, Åse; Reimann, Ilona

    2007-01-01

    A chimeric pestivirus of border disease virus Gifhorn and bovine viral diarrhea virus CP7 (Meyers et al., 1996) was constructed. Virulence, immunogenicity and vaccine properties of the chimeric virus were studied in a vaccination–challenge experiment in pigs. The chimeric virus proved...... to be avirulent and neither chimeric virus nor viral RNA was detected in serum after vaccination. The safety of the vaccine was tested by horizontal transmission to sentinel pigs, which remained uninfected. The vaccine efficacy was examined by challenge infection with classical swine fever virus (CSFV) Eystrup...

  15. Immunogenic Targets for Specific Immunotherapy in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Lu Zhang

    2012-01-01

    Full Text Available Multiple myeloma remains an incurable disease although the prognosis has been improved by novel therapeutics and agents recently. Relapse occurs in the majority of patients and becomes fatal finally. Immunotherapy might be a powerful intervention to maintain a long-lasting control of minimal residual disease or to even eradicate disseminated tumor cells. Several tumor-associated antigens have been identified in patients with multiple myeloma. These antigens are expressed in a tumor-specific or tumor-restricted pattern, are able to elicit immune response, and thus could serve as targets for immunotherapy. This review discusses immunogenic antigens with therapeutic potential for multiple myeloma.

  16. Safety and Immunogenicity of a Candidate Parvovirus B19 Vaccine

    OpenAIRE

    Bernstein, David I; El Sahly, Hana M; Keitel, Wendy A; Wolff, Mark; Simone, Gina; Segawa, Claire; Wong, Susan; Shelly, Daniel; Young, Neal S; Dempsey, Walla

    2011-01-01

    Parvovirus B19 is an important human pathogen causing erythema infectiosum, transient aplastic crisis in individuals with underlying hemolytic disorders and hydrops fetalis. We therefore evaluated a parvovirus B19 virus like particle (VLP) vaccine. The safety and immunogenicity of a 25 μg dose of parvovirus B19 recombinant capsid; 2.5 and 25 μg doses of the recombinant capsid given with MF59; and saline placebo were assessed in healthy adults. Because of 3 unexplained cutaneous events the stu...

  17. Identification and characterization of immunogenic proteins of Mycoplasma genitalium

    DEFF Research Database (Denmark)

    Svenstrup, Helle Friis; Jensen, J.S.; Gevaert, K.

    2006-01-01

    serum against M. genitalium G37, determine their identity by mass spectrometry, and develop an M. genitalium-specific enzyme-linked immunosorbent assay (ELISA) free from cross-reactivity with M. pneumoniae antibodies. Using recombinant fragments of the C-terminal part of MgPa (rMgPa), we developed....... genitalium strains were isolated (J. S. Jensen, H. T. Hansen, and K. Lind, J. Clin. Microbiol. 34:286-291, 1996). The objective of this study was to characterize immunogenic proteins of M. genitalium by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting by using a hyperimmune rabbit...

  18. Immunogenicity of an HPV-16 L2 DNA vaccine

    Science.gov (United States)

    Hitzeroth, Inga I.; Passmore, Jo-Ann S.; Shephard, Enid; Stewart, Debbie; Müller, Martin; Williamson, Anna-Lise; Rybicki, Edward P.; Kast, W. Martin

    2009-01-01

    The ability to elicit cross-neutralizing antibodies makes human papillomavirus (HPV) L2 capsid protein a possible HPV vaccine. We examined and compared the humoral response of mice immunised with a HPV-16 L2 DNA vaccine or with HPV-16 L2 protein. The L2 DNA vaccine elicited a non-neutralising antibody response unlike the L2 protein. L2 DNA vaccination suppressed the growth of L2-expressing C3 tumor cells, which is a T cell mediated effect, demonstrating that the lack of non-neutralizing antibody induction by L2 DNA was not caused by lack of T cell immunogenicity of the construct. PMID:19559114

  19. Synthesis of an oxytetracyline-tolidin-BSA immunogen and antibodies production of anti-oxytetracyline developed for oxytetracyline residue detection with enzyme-linked immunosorbent assays technique

    Directory of Open Access Journals (Sweden)

    Widiastuti R

    2013-06-01

    Full Text Available An oxytetracycline-tolidin-bovine serum albumin (OTC-tolidin-BSA-conjugate was synthezed as immunogen for producing specific antibodies in immunized rabbits that would be used as reagent for development of OTC residue detection with enzym-linked immunoassays technique. The immunogen was prepared through diazotization tolidin and subsequently reacted with OTC. The red purple immunogen of OTC-tolidin-BSA absorbed at wave lengths of 277 nm and 488 nm under UV screening absorbances and confirmation with the high performance liquid chromatography (HPLC showed the absence of peak at retention time of 3.46 minutes. Characaterized result with SDS-PAGE showed the molecular weight of the OTC-tolidin-BSA at 69.79 kDA. Subsequently, the immunogen was immunized into New Zealand rabbits in order to produce the polyclonal antibodies. The antibodies were purified using a protein A sepharose column. The OD optimum responses of 0.92 to 1.20 were obtained from the second fractionation at dilution of 1/1000 by titrating the antibodies and OTC-tolidin-BSA coating antigen at concentration of 10 µg/mL on several bleeding times.

  20. Long term results of total lymphoid irradiation in the treatment of cardiac allograft rejection

    International Nuclear Information System (INIS)

    Wolden, Suzanne L.; Tate, David J.; Hunt, Sharon A.; Strober, Samuel; Hoppe, Richard T.

    1996-01-01

    radiation. Two malignancies were reported during the follow-up period. One was prostate cancer in a 57 year old man which was probably unrelated to treatment. The other was a non-Hodgkin's lymphoma in a 7 year old boy who had also received multiple courses of OKT3. Three year actuarial survival after irradiation was 60% and 70% for the intractable rejection cohort and prophylactic groups respectively. Most deaths occurred within 2 years of TLI and were caused in equal proportions by rejection, infection and other medical problems. Conclusion: TLI is an effective and durable treatment for control of chronic, intractable cardiac rejection as demonstrated in long-term follow up of up to 9.1 years. A possible mechanism of action is long term alteration in T-lymphocyte subsets. Patients experience transient bone marrow suppression but no increase in infection or bleeding. They may be permanently maintained on lower doses of steroids and the risk of radiation induced malignancy is low. TLI is not recommended as induction therapy because of the high risk of rejection when azathioprine is withheld during irradiation in the immediate post-transplant period

  1. Non-immunogenicity of overlapping gag peptides pulsed on autologous cells after vaccination of HIV infected individuals.

    Directory of Open Access Journals (Sweden)

    Henrik N Kløverpris

    several Macaca nemestrina studies using this approach, OPAL-HIV-Gag(c was not significantly immunogenic in humans and improved methods of generating high-frequency Gag-specific T-cell responses are required.ClinicalTrials.gov, Registry number: NCT01123915, URL trial registry database: http://www.clinicaltrials.gov/ct2/results?term=OPAL-HIV-1001&Search=Search.

  2. Transcriptomes and pathways associated with infectivity, survival and immunogenicity in Brugia malayi L3

    Directory of Open Access Journals (Sweden)

    Spiro David

    2009-06-01

    Full Text Available Abstract Background Filarial nematode parasites cause serious diseases such as elephantiasis and river blindness in humans, and heartworm infections in dogs. Third stage filarial larvae (L3 are a critical stage in the life cycle of filarial parasites, because this is the stage that is transmitted by arthropod vectors to initiate infections in mammals. Improved understanding of molecular mechanisms associated with this transition may provide important leads for development of new therapies and vaccines to prevent filarial infections. This study explores changes in gene expression associated with the transition of Brugia malayi third stage larvae (BmL3 from mosquitoes into mammalian hosts and how these changes are affected by radiation. Radiation effects are especially interesting because irradiated L3 induce partial immunity to filarial infections. The underlying molecular mechanisms responsible for the efficacy of such vaccines are unkown. Results Expression profiles were obtained using a new filarial microarray with 18, 104 64-mer elements. 771 genes were identified as differentially expressed in two-way comparative analyses of the three L3 types. 353 genes were up-regulated in mosquito L3 (L3i relative to cultured L3 (L3c. These genes are important for establishment of filarial infections in mammalian hosts. Other genes were up-regulated in L3c relative to L3i (234 or irradiated L3 (L3ir (22. These culture-induced transcripts include key molecules required for growth and development. 165 genes were up-regulated in L3ir relative to L3c; these genes encode highly immunogenic proteins and proteins involved in radiation repair. L3ir and L3i have similar transcription profiles for genes that encode highly immunogenic proteins, antioxidants and cuticle components. Conclusion Changes in gene expression that normally occur during culture under conditions that support L3 development and molting are prevented or delayed by radiation. This may explain

  3. The effect of gamma-irradiation conditions on the immunogenicity of whole-inactivated Influenza A virus vaccine.

    Science.gov (United States)

    David, Shannon C; Lau, Josyane; Singleton, Eve V; Babb, Rachelle; Davies, Justin; Hirst, Timothy R; McColl, Shaun R; Paton, James C; Alsharifi, Mohammed

    2017-02-15

    Gamma-irradiation, particularly an irradiation dose of 50kGy, has been utilised widely to sterilise highly pathogenic agents such as Ebola, Marburg Virus, and Avian Influenza H5N1. We have reported previously that intranasal vaccination with a gamma-irradiated Influenza A virus vaccine (γ-Flu) results in cross-protective immunity. Considering the possible inclusion of highly pathogenic Influenza strains in future clinical development of γ-Flu, an irradiation dose of 50kGy may be used to enhance vaccine safety beyond the internationally accepted Sterility Assurance Level (SAL). Thus, we investigated the effect of irradiation conditions, including high irradiation doses, on the immunogenicity of γ-Flu. Our data confirm that irradiation at low temperatures (using dry-ice) is associated with reduced damage to viral structure compared with irradiation at room temperature. In addition, a single intranasal vaccination with γ-Flu irradiated on dry-ice with either 25 or 50kGy induced seroconversion and provided complete protection against lethal Influenza A challenge. Considering that low temperature is expected to reduce the protein damage associated with exposure to high irradiation doses, we titrated the vaccine dose to verify the efficacy of 50kGy γ-Flu. Our data demonstrate that exposure to 50kGy on dry-ice is associated with limited effect on vaccine immunogenicity, apparent only when using very low vaccine doses. Overall, our data highlight the immunogenicity of influenza virus irradiated at 50kGy for induction of high titre antibody and cytotoxic T-cell responses. This suggests these conditions are suitable for development of γ-Flu vaccines based on highly pathogenic Influenza A viruses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Development of a transgenic mouse model to study the immunogenicity of recombinant human insulin

    NARCIS (Netherlands)

    Torosantucci, Riccardo; Brinks, Vera; Kijanka, Grzegorz; Halim, Liem Andhyk; Sauerborn, Melody; Schellekens, Huub; Jiskoot, Wim

    2014-01-01

    Mouse models are commonly used to assess the immunogenicity of therapeutic proteins and to investigate the immunological processes leading to antidrug antibodies. The aim of this work was to develop a transgenic (TG) Balb/c mouse model for evaluating the immunogenicity of recombinant human insulin

  5. Microsporidial infection masquerading as graft rejection post-Descemet's stripping automated endothelial keratoplasty

    Directory of Open Access Journals (Sweden)

    Lumbini Devi

    2017-01-01

    Full Text Available A 51-year-old immunocompetent male with a history of Fuchs' endothelial dystrophy and immature cataract who underwent Descemet's stripping automated endothelial keratoplasty with intraocular lens implantation in both eyes presented with redness and defective vision of 1-day duration in his left eye. Slit lamp examination revealed coarse superficial punctate lesions with graft edema. He was diagnosed with acute graft rejection and treated with topical steroids. Two days later, symptoms worsened in his left eye with the involvement of his right eye showing a similar clinical picture. An infectious etiology was suspected and in vivo confocal microscopy ordered, which revealed hyperreflective dots, highly suggestive of microsporidial spores. The patient was prescribed topical fluconazole 0.3% in both eyes. This unique presentation of bilateral graft edema following microsporidial keratoconjunctivitis in postgraft patients requires a high index of suspicion as it can be easily be mistaken for and mismanaged as acute graft rejection.

  6. Phenomenology’s Rejects: Religion after Derrida’s Denegations

    Directory of Open Access Journals (Sweden)

    Alvis Jason W.

    2017-10-01

    Full Text Available Religion, as well as any individuals’ volitionally chosen ‟worldview,” generally get conceived solely in affirmative terms of value. ‟Religion” has been conceptualized almost solely on the terms of axiology: as the experience of ‟the greatest” holiness (Otto, the purely valuable sacred (Eliade; the most ‟ultimate concern” (Tillich; the symbols accepted to order life (Geertz, or the binding of oneself to deep value (Müller. Yet there are limitations of such axiomatic thinking, limitations that can be exemplified through an interpretation of Derrida’s ‟globolatinization,” which he described as a system of thought that promotes a universalism of pseudo or petit-valuations, and punishes those resistant and inflexible to them in the name of toleration. This essay investigates what happens when this ‟axiomatic” register (i.e. a reduction to a set of values gets displaced in order to conceptualize religion also in terms of the nonvaluable or ‟rejected.” Rejection entails the paradox that what is rejected often speaks to a deeper reality of what in fact is desired. Thus, what we reject usually says infinitely more about us than what we claim to value and affirm. This essay interprets Derrida’s essay ‟How to Avoid Speaking: Denials” alongside his ‟Faith and Knowledge” in order to offer a Derridean conception of religion on the terms of a rejection that amounts to a double-affirmation or de-negation.

  7. Safety, Tolerability, and Immunogenicity of Interferons

    Directory of Open Access Journals (Sweden)

    Michael G. Tovey

    2010-04-01

    Full Text Available Interferons (IFNs are class II cytokines that are key components of the innate immune response to virus infection. Three IFN sub-families, type I, II, and III IFNs have been identified in man, Recombinant analogues of type I IFNs, in particular IFNα2 and IFNβ1, have found wide application for the treatment of chronic viral hepatitis and remitting relapsing multiple sclerosis respectively. Type II IFN, or IFN gamma, is used principally for the treatment of chronic granulomatous disease, while the recently discovered type III IFNs, also known as IFN lambda or IL-28/29, are currently being evaluated for the treatment of chronic viral hepatitis. IFNs are in general well tolerated and the most common adverse events observed with IFNα or IFNβ therapy are “flu-like” symptoms such as fever, headache, chills, and myalgia. Prolonged treatment is associated with more serious adverse events including leucopenia, thrombocytopenia, increased hepatic transaminases, and neuropsychiatric effects. Type I IFNs bind to high-affinity cell surface receptors, composed of two transmembrane polypeptides IFNAR1 and IFNAR2, resulting in activation of the Janus kinases Jak1 and Tyk2, phosphorylation and activation of the latent cytoplasmic signal transducers and activators of transcription (STAT1 and STAT2, formation of a transcription complex together with IRF9, and activation of a specific set of genes that encode the effector molecules responsible for mediating the biological activities of type I IFNs. Systemic administration of type I IFN results in activation of IFN receptors present on essentially all types of nucleated cells, including neurons and hematopoietic stem cells, in addition to target cells. This may well explain the wide spectrum of IFN associated toxicities. Recent reports suggest that certain polymorphisms in type I IFN signaling molecules are associated with IFN-induced neutropenia and thrombocytopenia in patients with chronic hepatitis C. IFN

  8. Immunogenicity and ecotoxicity of engineered nanoparticles

    Science.gov (United States)

    Maurer-Jones, Melissa Ann

    -induced oxidative stress. The generalizability of the mechanism of TiO2 toxicity, as detailed in Chapter Two and Three, is explored in Chapter Four in a bacteria model, Shewanella oneidensis, studying the functions of biofilm formation using a quartz crystal microbalance (QCM) and flavin secretion using high performance liquid chromatography (HPLC). This study revealed that the proximity of the TiO 2 nanoparticles to S. oneidensis caused changes in gene expression resulting in an observed delay in biofilm growth and increase in riboflavin secretion. Chapter Five works to develop an in situ Ag nanoparticle characterization tool using fluorous-phase ion selective electrodes to measure dissolved Ag+, with preliminary investigation into the toxicity of Ag nanoparticles and Ag+ ions to S. oneidensis, resulting in one of the first in situ characterization tools for nanoparticles during toxicity assessments. Moving beyond laboratory work, Chapter Six examines bench scientists' perspective on the regulation of nanotherapies moving from pre-clinical to first-in-human trials and the ethical considerations for the implementation of nanotechnology. Finally, Chapter Seven details the development of a 3-day nanotoxicity laboratory for introductory chemistry classes to introduce students to interdisciplinary science and the cutting edge research field of nanotoxicology. In total, my project has considered the scientific, ethical, and educational implications for nanotoxicology and has ultimately contributed to a better understanding of the nanoparticle-cell interaction.

  9. Long-term experience of plasmapheresis in antibody-mediated rejection in renal transplantation.

    LENUS (Irish Health Repository)

    Brown, C M

    2009-11-01

    Antibody-mediated rejection (AMR) continues to pose a serious challenge in renal transplantation with potentially devastating consequences. Treatment options for this condition include plasmapheresis, high-dose intravenous immunoglobulin (IVIG), plasmapheresis with low-dose IVIG, and the use of rituximab (anti-CD20 chimeric antibody). We previously reported on the short-term outcome of plasmapheresis as a rescue therapy for AMR in our centre. We now report on the long-term follow up.

  10. Acute Liver Allograft Antibody-Mediated Rejection: an inter-institutional study of routine histopathological features

    OpenAIRE

    O'Leary, Jacqueline G.; Shiller, S. Michelle; Bellamy, Christopher; Nalesnik, Michael A.; Kaneku, Hugo; Terasaki, Paul I.; Klintmalm, Göran B.; Demetris, Anthony J.

    2014-01-01

    Acute antibody-mediated rejection (AMR) occurs in a minority of sensitized liver transplant recipients. Although histopathologic characteristics have been described, a generalizable scoring system used to trigger a more in-depth analysis is needed to screen for this rare but important finding. Toward this goal, we created a training and validation cohort from 3 high volume liver transplant programs of putative acute AMR and control cases that were evaluated blindly by 4 independent transplant...

  11. Novel Vaccine Against Mycoplasma Hyosynoviae: The Immunogenic Effect of Iscom-Based Vaccines in Swine

    DEFF Research Database (Denmark)

    Lauritsen, Klara Tølbøll; Vinther Heydenreich, Annette; Riber, Ulla

    Arthritis in swine is frequently caused by Mycoplasma hyosynoviae (Mhs). For the development of an effective vaccine we investigated the immunogenic effect of three vaccine preparations with the ISCOM adjuvant Posintro™ from Nordic Vaccine. A: formalin fixed whole-cells Mhs (300 µg/dose) mixed...... with Posintro, B: Deoxycholate extracted lipoproteins from Mhs organisms (DOC-antigen, 300 μg/dose) in Posintro and C: DOC-antigen (50 μg/dose) in Posintro. Each vaccine-group contained three pigs. Vaccinations (i.m.) were performed at 12 and 15 weeks of age. The development of specific IgG and secretion...... of IFNγ were measured. Three weeks after the second vaccination, pigs were euthanised and autopsied. Vaccine B induced a high level of specific serum IgG in all pigs a week after boost. Vaccine C gave a variable response after boost, with two pigs seroconverting, while no response was seen by vaccine A...

  12. Immunogenicity of the hTERT540-548 peptide in cancer

    DEFF Research Database (Denmark)

    Wenandy, L.; Sorensen, R.B.; Sengelov, L.

    2008-01-01

    Human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, is an attractive target antigen for cancer immunotherapy due to its expression in the vast majority of human tumors. The first immunogenic peptide described from hTERT was the HLA-A2-restricted peptide hTERT540...... in a peptide-specific, HLA-A2-restricted fashion. Furthermore, it was described that vaccination of cancer patients with hTERT540 introduced functional antitumor CD8(+) Tcells in patients. More recently, it was described that most patients with cancer have circulating hTERT540-specific CD8(+) T lymphocytes....... In contrast, several other studies have concluded that hTERT540 is not presented on the surface of tumor cells and that immunization of cancer patients with hTERT540 leads to the introduction of specificTcells that do not recognize tumor cells in vivo. In the present commentary, we summarize these highly...

  13. A review of immunogenicity and tolerability of live attenuated Hepatitis A vaccine in children

    Science.gov (United States)

    Rao, Sameer; Mao, J. S.; Motlekar, Salman; Fangcheng, Zhuang; Kadhe, Ganesh

    2016-01-01

    ABSTRACT Changing epidemiology of Hepatitis A virus (HAV) has led to an increased susceptibility of adolescents and adults to the infection. Vaccination can remarkably reduce the incidence and associated morbidity of HAV infection. This review is focused on the safety and efficacy of H2 strain derived live attenuated Hepatitis A vaccine. We found the vaccine to be highly immunogenic with minimal or negligible safety issues. Moreover, a single dose of live attenuated vaccine persists a long term immune response and can be a preferred option for developing countries. In 2014, Indian Academy of Paediatrics (IAP) also updated their recommendations for H2 vaccine as a single dose as against the previous 2 dose schedule. A focused approach to include the vaccine in national immunization program should be explored. PMID:27532370

  14. Composition of gut microbiota and its influence on the immunogenicity of oral rotavirus vaccines.

    Science.gov (United States)

    Magwira, Cliff A; Taylor, Maureen B

    2018-05-08

    The introduction of oral rotavirus vaccines (ORVVs) has led to a reduction in number of hospitalisations and deaths due to rotavirus (RV) infection. However, the efficacy of the vaccines has been varied with low-income countries showing significantly lower efficacy as compared to high-income countries. The reasons for the disparity are not fully understood but are thought to be multi-factorial. In this review article, we discuss the concept that the disparity in the efficacy of oral rotavirus vaccines between the higher and lower socio-economical countries could be due the nature of the bacteria that colonises and establishes in the gut early in life. We further discuss recent studies that has demonstrated significant correlations between the composition of the gut bacteria and the immunogenicity of oral vaccines, and their implications in the development of novel oral RV vaccines or redesigning the current ones for maximum impact. Copyright © 2018. Published by Elsevier Ltd.

  15. The Effect of Irradiation on the Immunogenity of Brucella Abortus

    International Nuclear Information System (INIS)

    Arifin, M.; Tuasikal, Boky J.; Endhang Pudjiastuti; Ernawati Yulia

    2004-01-01

    An experiment was carried out to study the effect of irradiation on the immunogenity of B. abortus. The B. abortus were irradiated by Gamma Cells ( 60 Co). An experiment were divided into four groups. The first group (V1) was inoculated by irradiated B. abortus with the dose of 0.25 kGy. The second group (V2) was inoculated by irradiated B. abortus with the dose of 0.50 kGy. The third group (V3) was inoculated by irradiated B. abortus with the dose of 0.75 kGy. The fourth group (V4) was inoculated by Brucella vaccine 8.19. The observation respectively were included purely test, safety test, RBT serological test, diffusion test, development the colony of B. abortus in lien, and pathology anatomic inspection. The results obtained showed that 0.25 kGy was the expectantly dose of irradiation which could not only decreasing the infectivity of B. abortus but also has the ability to become a good immunogen for stimulating the immune response in the experiment animals. (author)

  16. Cytokines in immunogenic cell death: Applications for cancer immunotherapy.

    Science.gov (United States)

    Showalter, Anne; Limaye, Arati; Oyer, Jeremiah L; Igarashi, Robert; Kittipatarin, Christina; Copik, Alicja J; Khaled, Annette R

    2017-09-01

    Despite advances in treatments like chemotherapy and radiotherapy, metastatic cancer remains a leading cause of death for cancer patients. While many chemotherapeutic agents can efficiently eliminate cancer cells, long-term protection against cancer is not achieved and many patients experience cancer recurrence. Mobilizing and stimulating the immune system against tumor cells is one of the most effective ways to protect against cancers that recur and/or metastasize. Activated tumor specific cytotoxic T lymphocytes (CTLs) can seek out and destroy metastatic tumor cells and reduce tumor lesions. Natural Killer (NK) cells are a front-line defense against drug-resistant tumors and can provide tumoricidal activity to enhance tumor immune surveillance. Cytokines like IFN-γ or TNF play a crucial role in creating an immunogenic microenvironment and therefore are key players in the fight against metastatic cancer. To this end, a group of anthracyclines or treatments like photodynamic therapy (PDT) exert their effects on cancer cells in a manner that activates the immune system. This process, known as immunogenic cell death (ICD), is characterized by the release of membrane-bound and soluble factors that boost the function of immune cells. This review will explore different types of ICD inducers, some in clinical trials, to demonstrate that optimizing the cytokine response brought about by treatments with ICD-inducing agents is central to promoting anti-cancer immunity that provides long-lasting protection against disease recurrence and metastasis. Copyright © 2017. Published by Elsevier Ltd.

  17. Influences of obesity on the immunogenicity of Hepatitis B vaccine.

    Science.gov (United States)

    Liu, Fang; Guo, Zhirong; Dong, Chen

    2017-05-04

    Hepatitis B vaccine is regarded as the most effective method for the prevention of hepatitis B virus (HBV) infection. However, several factors such as age, body mass index and immunocompetent state have been reported to be associated with reduced immunization responses. The present commentary was aimed to discuss the influences of obesity on the immunogenicity of hepatitis B vaccines. Available peer-reviewed literatures, practice guidelines, and statistics published on hepatitis B vaccine in obesity between 1973 and 2015. Obesity was significantly associated with non-response to hepatitis B vaccine immunization. The risk of nonresponsiveness of hepatitis B vaccine among obese people increased with BMI. Moreover, the obesity might lead to an increased risk of HBV vaccine-escape mutations. The mechanism responsible for decreased immunization responses in obesity included leptin-induced systemic and B cell intrinsic inflammation, impaired T cell responses and lymphocyte division and proliferation. Therefore, more studies should be performed to analyze the influences of obesity on the immunogenicity of hepatitis B vaccines to improve the immunoprotecive effect of hepatitis B vaccines in future.

  18. Size, Shape, and Sequence-Dependent Immunogenicity of RNA Nanoparticles.

    Science.gov (United States)

    Guo, Sijin; Li, Hui; Ma, Mengshi; Fu, Jian; Dong, Yizhou; Guo, Peixuan

    2017-12-15

    RNA molecules have emerged as promising therapeutics. Like all other drugs, the safety profile and immune response are important criteria for drug evaluation. However, the literature on RNA immunogenicity has been controversial. Here, we used the approach of RNA nanotechnology to demonstrate that the immune response of RNA nanoparticles is size, shape, and sequence dependent. RNA triangle, square, pentagon, and tetrahedron with same shape but different sizes, or same size but different shapes were used as models to investigate the immune response. The levels of pro-inflammatory cytokines induced by these RNA nanoarchitectures were assessed in macrophage-like cells and animals. It was found that RNA polygons without extension at the vertexes were immune inert. However, when single-stranded RNA with a specific sequence was extended from the vertexes of RNA polygons, strong immune responses were detected. These immunostimulations are sequence specific, because some other extended sequences induced little or no immune response. Additionally, larger-size RNA square induced stronger cytokine secretion. 3D RNA tetrahedron showed stronger immunostimulation than planar RNA triangle. These results suggest that the immunogenicity of RNA nanoparticles is tunable to produce either a minimal immune response that can serve as safe therapeutic vectors, or a strong immune response for cancer immunotherapy or vaccine adjuvants. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Size, Shape, and Sequence-Dependent Immunogenicity of RNA Nanoparticles

    Directory of Open Access Journals (Sweden)

    Sijin Guo

    2017-12-01

    Full Text Available RNA molecules have emerged as promising therapeutics. Like all other drugs, the safety profile and immune response are important criteria for drug evaluation. However, the literature on RNA immunogenicity has been controversial. Here, we used the approach of RNA nanotechnology to demonstrate that the immune response of RNA nanoparticles is size, shape, and sequence dependent. RNA triangle, square, pentagon, and tetrahedron with same shape but different sizes, or same size but different shapes were used as models to investigate the immune response. The levels of pro-inflammatory cytokines induced by these RNA nanoarchitectures were assessed in macrophage-like cells and animals. It was found that RNA polygons without extension at the vertexes were immune inert. However, when single-stranded RNA with a specific sequence was extended from the vertexes of RNA polygons, strong immune responses were detected. These immunostimulations are sequence specific, because some other extended sequences induced little or no immune response. Additionally, larger-size RNA square induced stronger cytokine secretion. 3D RNA tetrahedron showed stronger immunostimulation than planar RNA triangle. These results suggest that the immunogenicity of RNA nanoparticles is tunable to produce either a minimal immune response that can serve as safe therapeutic vectors, or a strong immune response for cancer immunotherapy or vaccine adjuvants.

  20. Immunogenicity to Biotherapeutics – the role of Anti-drug Immune complexes

    Directory of Open Access Journals (Sweden)

    Murli eKrishna

    2016-02-01

    Full Text Available AbstractBiologic molecules are increasingly becoming a part of the therapeutics portfolio that has been either recently approved for marketing or those that are in the pipeline of several biotech and pharmaceutical companies. This is largely based on their ability to be highly specific relative to small molecules. However by virtue of being a large protein, and having a complex structure with structural variability arising from production using recombinant gene technology in cell lines, such therapeutics run the risk of being recognized as foreign by a host immune system. Given the range of immune mediated adverse effects that have been documented to biologic drugs thus far, including infusion reactions, and the evolving therapeutic platforms in the pipeline that engineer different functional modules in a biotherapeutic, it is critical to understand the interplay of the adaptive and innate immune responses, the pathophysiology of immunogenicity to biologic drugs in instances where there have been immune mediated adverse clinical sequelae and address technical approaches for their laboratory evaluation. The current paradigm in immunogenicity evaluation has a tiered approach to the detection and characterization of anti-drug antibodies (ADAs elicited in vivo to a biotherapeutic; alongside with the structural, biophysical and molecular information of the therapeutic, these analytical assessments form the core of the immunogenicity risk assessment. However many of the immune mediated adverse effects attributed to ADAs require the formation of a drug/ADA immune complex intermediate (ICs that can have a variety of downstream effects. This review will focus on the activation of potential immunopathological pathways arising as a consequence of circulating as well as cell surface bound drug bearing-ICs, risk factors that are either intrinsic to the therapeutic molecule or to the host which might predispose to IC mediated effects, and review the recent

  1. Integrated Kidney Exosome Analysis for the Detection of Kidney Transplant Rejection.

    Science.gov (United States)

    Park, Jongmin; Lin, Hsing-Ying; Assaker, Jean Pierre; Jeong, Sangmoo; Huang, Chen-Han; Kurdi, A; Lee, Kyungheon; Fraser, Kyle; Min, Changwook; Eskandari, Siawosh; Routray, Sujit; Tannous, Bakhos; Abdi, Reza; Riella, Leonardo; Chandraker, Anil; Castro, Cesar M; Weissleder, Ralph; Lee, Hakho; Azzi, Jamil R

    2017-11-28

    Kidney transplant patients require life-long surveillance to detect allograft rejection. Repeated biopsy, albeit the clinical gold standard, is an invasive procedure with the risk of complications and comparatively high cost. Conversely, serum creatinine or urinary proteins are noninvasive alternatives but are late markers with low specificity. We report a urine-based platform to detect kidney transplant rejection. Termed iKEA (integrated kidney exosome analysis), the approach detects extracellular vesicles (EVs) released by immune cells into urine; we reasoned that T cells, attacking kidney allografts, would shed EVs, which in turn can be used as a surrogate marker for inflammation. We optimized iKEA to detect T-cell-derived EVs and implemented a portable sensing system. When applied to clinical urine samples, iKEA revealed high level of CD3-positive EVs in kidney rejection patients and achieved high detection accuracy (91.1%). Fast, noninvasive, and cost-effective, iKEA could offer new opportunities in managing transplant recipients, perhaps even in a home setting.

  2. Marginality and Social Rejection in Amiri Baraka's Slave Ship

    Directory of Open Access Journals (Sweden)

    Hamid Hammad Abed

    2016-11-01

    Full Text Available Marginality and social rejection are the most influential matters exploited by Baraka to intentionally criticize the American society.  More often than not, these two matters have become the scenes of major or minor acts of humiliation and dehumanization that threaten to violate the ethical rules of living. This paper aims at investigating the impact of marginality and social rejection on a number of black characters in Baraka's Slave Ship who are brought to America to be sold as commodities. It is divided into two sections and conclusion. Section one deals with Amiri Baraka’s dramatic thought and experience of marginality within the American society. The textual analysis of Slave Ship is investigated in section two. The significance of the study lies in its textual exploration of the impact of marginality and social rejection in subverting the American dream of democracy, freedom, and equality in Baraka’s Slave Ship.

  3. Acute Hepatic Allograft Rejection in Pediatric Recipients: Effective Factors.

    Science.gov (United States)

    Dehghani, S M; Shahramian, I; Afshari, M; Bahmanyar, M; Ataollahi, M; Sargazi, A

    2018-01-01

    Acute cellular rejection (ACR), a reversible process, can affect the graft survival. To evaluate the relation between ACR and clinical factors in recipients of allograft liver transplantation. 47 recipients of liver were consecutively enrolled in a retrospective study. Their information were retrieved from their medical records and analyzed. Of the 47 recipients, 38 (81%) experienced acute rejection during 24 months of the transplantation. None of the studied factors for occurring transplant rejection, i.e ., blood groups, sex, age, familial history of disease, receiving drugs and blood products, type of donor, Child score, and Child class, was not found to be significant. During a limited follow-up period, we did not find any association between ACR and suspected risk factors.

  4. Prostanoids modulate inflammation and alloimmune responses during graft rejection

    Directory of Open Access Journals (Sweden)

    P.N. Rocha

    2005-12-01

    Full Text Available Acute rejection of a transplanted organ is characterized by intense inflammation within the graft. Yet, for many years transplant researchers have overlooked the role of classic mediators of inflammation such as prostaglandins and thromboxane (prostanoids in alloimmune responses. It has been demonstrated that local production of prostanoids within the allograft is increased during an episode of acute rejection and that these molecules are able to interfere with graft function by modulating vascular tone, capillary permeability, and platelet aggregation. Experimental data also suggest that prostanoids may participate in alloimmune responses by directly modulating T lymphocyte and antigen-presenting cell function. In the present paper, we provide a brief overview of the alloimmune response, of prostanoid biology, and discuss the available evidence for the role of prostaglandin E2 and thromboxane A2 in graft rejection.

  5. Graft rejection by cytolytic T cells. Specificity of the effector mechanism in the rejection of allogeneic marrow

    International Nuclear Information System (INIS)

    Nakamura, H.; Gress, R.E.

    1990-01-01

    Cellular effector mechanisms of allograft rejection remain incompletely described. Characterizing the rejection of foreign-marrow allografts rather than solid-organ grafts has the advantage that the cellular composition of the marrow graft, as a single cell suspension, can be altered to include cellular components with differing antigen expression. Rejection of marrow grafts is sensitive to lethal doses of radiation in the mouse but resistant to sublethal levels of radiation. In an effort to identify cells mediating host resistance, lymphocytes were isolated and cloned from spleens of mice 7 days after sublethal TBI (650 cGy) and inoculation with allogeneic marrow. All clones isolated were cytolytic with specificity for MHC encoded gene products of the allogeneic marrow donor. When cloned cells were transferred in vivo into lethally irradiated (1025 cGy) recipients unable to reject allogeneic marrow, results utilizing splenic 125IUdR uptake indicated that these MHC-specific cytotoxic clones could suppress marrow proliferation. In order to characterize the effector mechanism and the ability of the clones to affect final engraftment, double donor chimeras were constructed so that 2 target cell populations differing at the MHC from each other and from the host were present in the same marrow allograft. Results directly demonstrated an ability of CTL of host MHC type to mediate graft rejection and characterized the effector mechanism as one with specificity for MHC gene products

  6. A Longitudinal Study of Rejecting and Autonomy-Restrictive Parenting, Rejection Sensitivity, and Socioemotional Symptoms in Early Adolescents.

    Science.gov (United States)

    Rowe, Susan L; Gembeck, Melanie J Zimmer; Rudolph, Julia; Nesdale, Drew

    2015-08-01

    Rejection sensitivity (RS) has been defined as the tendency to readily perceive and overreact to interpersonal rejection. The primary aim of this study was to test key propositions of RS theory, namely that rejecting experiences in relationships with parents are antecedents of early adolescents' future RS and symptomatology. We also expanded this to consider autonomy-restrictive parenting, given the importance of autonomy in early adolescence. Participants were 601 early adolescents (age 9 to 13 years old, 51% boys) from three schools in Australia. Students completed questionnaires at school about parent and peer relationships, RS, loneliness, social anxiety, and depression at two times with a 14-month lag between assessments. Parents also reported on adolescents' difficulties at Time 1 (T1). It was anticipated that more experience of parental rejection, coercion, and psychological control would be associated with adolescents' escalating RS and symptoms over time, even after accounting for peer victimisation, and that RS would mediate associations between parenting and symptoms. Structural equation modelling supported these hypotheses. Parent coercion was associated with adolescents' increasing symptoms of social anxiety and RS over time, and parent psychological control was associated with increasing depressive symptoms over time. Indirect effects via RS were also found, with parent rejection and psychological control linked to higher T1 RS, which was then associated with increasing loneliness and RS. Lastly, in a separate model, peer victimisation and RS, but not parenting practices, were positively associated with concurrent parent reports of adolescents' difficulties.

  7. Analysis of Turbine Load Rejection for APR1400 using SPACE

    International Nuclear Information System (INIS)

    Kim, Sang Jin; Park, Chan Eok; Choi, Jong Ho; Lee, Gyu Cheon

    2016-01-01

    Turbine Load Rejection event is one of the Performance Related Design Basis Event (PRDBE) that can be stabilized using plant control systems without any safety system actuation. The initiation of the event is turbine load rejection from 100% to 5% in 0.019 seconds. The NSSS control systems of APR1400 is composed of the Power Control System (PCS) and the Process-Component Control System (P-CCS). The PCS includes Reactor Regulating System (RRS), Reactor Power Cutback System (RPCS) and Digital Rod Control System (DRCS). The P-CCS includes the Pressurizer Pressure Control System (PPCS), the Pressurizer Level Control System (PLCS), the Feedwater Control System (FWCS) and the Steam Bypass Control System (SBCS). Turbine load rejection results in the increase of secondary pressure due to sudden blocking of steam flow to turbine. Then the Reactor Coolant System (RCS) cooling through steam generators is decreased rapidly and the RCS temperature will be increased. Turbine load rejection is a typical event to test NSSS control systems since it requires the automatic response of all major NSSS control systems. It is shown that the NSSS control systems of APR1400 have the capability to stabilize the plant without any safety system actuation for turbine load rejection event. This analysis results show that SPACE code has the capability to analyze the turbine load rejection event. However, further validation is necessary for other PRDBEs such as Two Main Feedwater Pumps Trip, Turbine Load Step Change and Turbine Load Ramp Down (5%/min) to verify the capability of SPACE for the full range of performance analyses

  8. Analysis of Turbine Load Rejection for APR1400 using SPACE

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Jin; Park, Chan Eok; Choi, Jong Ho; Lee, Gyu Cheon [KEPCO Engineering and Construction Co. Ltd., Deajeon (Korea, Republic of)

    2016-10-15

    Turbine Load Rejection event is one of the Performance Related Design Basis Event (PRDBE) that can be stabilized using plant control systems without any safety system actuation. The initiation of the event is turbine load rejection from 100% to 5% in 0.019 seconds. The NSSS control systems of APR1400 is composed of the Power Control System (PCS) and the Process-Component Control System (P-CCS). The PCS includes Reactor Regulating System (RRS), Reactor Power Cutback System (RPCS) and Digital Rod Control System (DRCS). The P-CCS includes the Pressurizer Pressure Control System (PPCS), the Pressurizer Level Control System (PLCS), the Feedwater Control System (FWCS) and the Steam Bypass Control System (SBCS). Turbine load rejection results in the increase of secondary pressure due to sudden blocking of steam flow to turbine. Then the Reactor Coolant System (RCS) cooling through steam generators is decreased rapidly and the RCS temperature will be increased. Turbine load rejection is a typical event to test NSSS control systems since it requires the automatic response of all major NSSS control systems. It is shown that the NSSS control systems of APR1400 have the capability to stabilize the plant without any safety system actuation for turbine load rejection event. This analysis results show that SPACE code has the capability to analyze the turbine load rejection event. However, further validation is necessary for other PRDBEs such as Two Main Feedwater Pumps Trip, Turbine Load Step Change and Turbine Load Ramp Down (5%/min) to verify the capability of SPACE for the full range of performance analyses.

  9. Kidney graft rejection studies with labeled platelets and lymphocytes

    International Nuclear Information System (INIS)

    Martin-Comin, J.

    1986-01-01

    The usefulness of In-111-labelled platelets and lymphocyte scintigraphy in acute kidney graft rejection is evaluated in 155 patients. Blood cells were labelled with 100-150 uCi of In-111-oxine and reinjected. Subsequently patients were scanned once daily from 2 hours post-reinjection up to a week. The graft/contralateral area activity ratio was calculated in all scans. It is concluded that In-111-labelled platelets scintigraphy is nowadays the method of choice for acute kidney graft rejection diagnosis, especially in patients under cyclosporine immunosuppression. (author)

  10. Rechazo y retrasplante corneal Corneal rejection and re-transplantation

    Directory of Open Access Journals (Sweden)

    Miguel O Mokey Castellanos

    2007-06-01

    Full Text Available Se efectuó una investigación observacional análítica retrospectiva, sobre los transplantes corneales efectuados en el Servicio de Oftalmología del Hospital "Hermanos Ameijeiras. Rechazaron 76 pacientes, que se compararon con un control de 89 pacientes, que en un período similar no tuvieron rechazo. El queratocono fue la afección corneal que predominó. El primer lugar en los rechazos correspondió a queratoherpes (43,5 %. El menor índice de rechazo fue para el queratocono (8,8 %. Se analizó la multiplicidad de rechazos; y fue frecuente que se presentara un solo rechazo, aunque sí hubo congruencia entre el número de rechazos y la necesidad de retrasplantes. Se encontró que los resultados de la conducta médica o quirúrgica se relacionaban con la causa. Se calcula un índice de supervivencia (Kaplan-Meier, que concluye que en los primeros dos años existe menos posibilidad de aparición de rechazoAn retrospective observational analytical research was conducted on corneal transplants performed at Ophthalmological Service in “Hermanos Ameijeiras” hospital . Seventy six patients had graft rejection and were compared to a control group of 89 patients that did not present rejection in the same period of time. Keratoconus was the prevailing corneal problem. The highest rejection rate corresponded to keratoherpes (43,5% whereas the lowest rate was for keratoconus (8,8%. Multiplicity of rejections was analyzed and it was found that mostly one graft rejection occured, but number of rejections was associated with the need of re-transplantation. It was found that the results of medical or surgical performance were related to the cause of graft rejection. A survival index (Kaplan-Meier was estimated, which showed that occurence of graf rejection is less probable in the first two years

  11. What next after the rejection of Swiss electricity market legislation?

    International Nuclear Information System (INIS)

    Miolo, A.; Rechsteiner, S.

    2002-01-01

    This article discusses the situation in Switzerland after the rejection of new legislation on the liberalisation of the Swiss electricity market (Electricity Market Law, EMG) in a public vote in September 2002. The problems thus posed and the possibilities for further action available to those involved and affected are discussed. The legal situation after the rejection of the EMG is discussed with respect to Swiss regional structures and cantonal regulations. Three possible scenarios are discussed - the status quo, a solution to be provided by the electricity business or a Federal decree. The possibilities open to electricity enterprises for optimisation and the realisation of synergies to increase efficiency and competitiveness are discussed

  12. Self-error-rejecting photonic qubit transmission in polarization-spatial modes with linear optical elements

    Science.gov (United States)

    Jiang, YuXiao; Guo, PengLiang; Gao, ChengYan; Wang, HaiBo; Alzahrani, Faris; Hobiny, Aatef; Deng, FuGuo

    2017-12-01

    We present an original self-error-rejecting photonic qubit transmission scheme for both the polarization and spatial states of photon systems transmitted over collective noise channels. In our scheme, we use simple linear-optical elements, including half-wave plates, 50:50 beam splitters, and polarization beam splitters, to convert spatial-polarization modes into different time bins. By using postselection in different time bins, the success probability of obtaining the uncorrupted states approaches 1/4 for single-photon transmission, which is not influenced by the coefficients of noisy channels. Our self-error-rejecting transmission scheme can be generalized to hyperentangled n-photon systems and is useful in practical high-capacity quantum communications with photon systems in two degrees of freedom.

  13. Automatic Stabilization of a Riderless Bicycle using the Active Disturbance Rejection Control Approach

    Directory of Open Access Journals (Sweden)

    Mauro Baquero-Suárez

    2017-12-01

    Full Text Available This work proposes an ADRC (Active Disturbance Rejection Control strategy by disturbance extended observers to stabilize a moving riderless bicycle with a variant forward speed. Although the bicycle has an unstable and non-linear dynamics when in its upright position, which can be modeled as a LPV (Linear-Parameter-Varying system that depends on the forward speed, a simplified time-invariant and lumped-parameter model, with an nominal constant forward speed is used in the controller design. ADRC scheme groups discrepancies between the simplified model and the plant, with external disturbances into an equivalent additive unified disturbance signal at input, which is estimated via the observer and rejected through a linear control law. The effectiveness of this strategy is validated by a co-simulation between ADAMS and MATLAB, which exhibits a high performance and robustness in a virtual dynamic model of the bicycle, submitted to severe external disturbances and parameter variations.

  14. Scanning light-sheet microscopy in the whole mouse brain with HiLo background rejection

    Science.gov (United States)

    Mertz, Jerome; Kim, Jinhyun

    2010-01-01

    It is well known that light-sheet illumination can enable optically sectioned wide-field imaging of macroscopic samples. However, the optical sectioning capacity of a light-sheet macroscope is undermined by sample-induced scattering or aberrations that broaden the thickness of the sheet illumination. We present a technique to enhance the optical sectioning capacity of a scanning light-sheet microscope by out-of-focus background rejection. The technique, called HiLo microscopy, makes use of two images sequentially acquired with uniform and structured sheet illumination. An optically sectioned image is then synthesized by fusing high and low spatial frequency information from both images. The benefits of combining light-sheet macroscopy and HiLo background rejection are demonstrated in optically cleared whole mouse brain samples, using both green fluorescent protein (GFP)-fluorescence and dark-field scattered light contrast.

  15. Diet-induced bacterial immunogens in the gastrointestinal tract of dairy cows: impacts on immunity and metabolism.

    Science.gov (United States)

    Dong, Guozhong; Liu, Shimin; Wu, Yongxia; Lei, Chunlong; Zhou, Jun; Zhang, Sen

    2011-08-09

    Dairy cows are often fed high grain diets to meet the energy demand for high milk production or simply due to a lack of forages at times. As a result, ruminal acidosis, especially subacute ruminal acidosis (SARA), occurs frequently in practical dairy production. When SARA occurs, bacterial endotoxin (or lipopolysaccharide, LPS) is released in the rumen and the large intestine in a large amount. Many other bacterial immunogens may also be released in the digestive tract following feeding dairy cows diets containing high proportions of grain. LPS can be translocated into the bloodstream across the epithelium of the digestive tract, especially the lower tract, due to possible alterations of permeability and injuries of the epithelial tissue. As a result, the concentration of blood LPS increases. Immune responses are subsequently caused by circulating LPS, and the systemic effects include increases in concentrations of neutrophils and the acute phase proteins such as serum amyloid-A (SAA), haptoglobin (Hp), LPS binding protein (LBP), and C-reactive protein (CRP) in blood. Entry of LPS into blood can also result in metabolic alterations. Blood glucose and nonesterified fatty acid concentrations are enhanced accompanying an increase of blood LPS after increasing the amount of grain in the diet, which adversely affects feed intake of dairy cows. As the proportions of grain in the diet increase, patterns of plasma β-hydroxybutyric acid, cholesterol, and minerals (Ca, Fe, and Zn) are also perturbed. The bacterial immunogens can also lead to reduced supply of nutrients for synthesis of milk components and depressed functions of the epithelial cells in the mammary gland. The immune responses and metabolic alterations caused by circulating bacterial immunogens will exert an effect on milk production. It has been demonstrated that increases in concentrations of ruminal LPS and plasma acute phase proteins (CRP, SAA, and LBP) are associated with declines in milk fat content

  16. Diet-induced bacterial immunogens in the gastrointestinal tract of dairy cows: Impacts on immunity and metabolism

    Directory of Open Access Journals (Sweden)

    Zhou Jun

    2011-08-01

    Full Text Available Abstract Dairy cows are often fed high grain diets to meet the energy demand for high milk production or simply due to a lack of forages at times. As a result, ruminal acidosis, especially subacute ruminal acidosis (SARA, occurs frequently in practical dairy production. When SARA occurs, bacterial endotoxin (or lipopolysaccharide, LPS is released in the rumen and the large intestine in a large amount. Many other bacterial immunogens may also be released in the digestive tract following feeding dairy cows diets containing high proportions of grain. LPS can be translocated into the bloodstream across the epithelium of the digestive tract, especially the lower tract, due to possible alterations of permeability and injuries of the epithelial tissue. As a result, the concentration of blood LPS increases. Immune responses are subsequently caused by circulating LPS, and the systemic effects include increases in concentrations of neutrophils and the acute phase proteins such as serum amyloid-A (SAA, haptoglobin (Hp, LPS binding protein (LBP, and C-reactive protein (CRP in blood. Entry of LPS into blood can also result in metabolic alterations. Blood glucose and nonesterified fatty acid concentrations are enhanced accompanying an increase of blood LPS after increasing the amount of grain in the diet, which adversely affects feed intake of dairy cows. As the proportions of grain in the diet increase, patterns of plasma β-hydoxybutyric acid, cholesterol, and minerals (Ca, Fe, and Zn are also perturbed. The bacterial immunogens can also lead to reduced supply of nutrients for synthesis of milk components and depressed functions of the epithelial cells in the mammary gland. The immune responses and metabolic alterations caused by circulating bacterial immunogens will exert an effect on milk production. It has been demonstrated that increases in concentrations of ruminal LPS and plasma acute phase proteins (CRP, SAA, and LBP are associated with declines in

  17. Victimization, social anxiety, and body dysmorphic concerns: appearance-based rejection sensitivity as a mediator.

    Science.gov (United States)

    Lavell, Cassie H; Zimmer-Gembeck, Melanie J; Farrell, Lara J; Webb, Haley

    2014-09-01

    Body dysmorphic disorder (BDD) is characterized by extreme preoccupation with perceived deficits in physical appearance, and sufferers experience severe impairment in functioning. Previous research has indicated that individuals with BDD are high in social anxiety, and often report being the victims of appearance-based teasing. However, there is little research into the possible mechanisms that might explain these relationships. The current study examined appearance-based rejection sensitivity as a mediator between perceived appearance-based victimization, social anxiety, and body dysmorphic symptoms in a sample of 237 Australian undergraduate psychology students. Appearance-based rejection sensitivity fully mediated the relationship between appearance-based victimization and body dysmorphic symptoms, and partially mediated the relationship between social anxiety and body dysmorphic symptoms. Findings suggest that individuals high in social anxiety or those who have a history of more appearance-based victimization may have a bias towards interpreting further appearance-based rejection, which may contribute to extreme appearance concerns such as BDD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Post-transplant soluble CD30 levels are associated with early subclinical rejection in kidney transplantation.

    Science.gov (United States)

    Grenzi, Patricia C; Campos, Érika F; Silva, Hélio T; Felipe, Claudia R; Franco, Marcelo F; Soares, Maria F; Medina-Pestana, José O; Gerbase-DeLima, Maria

    2015-03-01

    Several studies have shown association of high pre- or post-transplant levels of soluble CD30 (sCD30) with acute rejection and poor late kidney transplant outcome. Our goal was to investigate whether sCD30 levels at month-3 post-transplant are associated with subclinical rejection, presence of CD30(+) cells within the graft, and expression of immune response genes in peripheral blood mononuclear cells. The study comprised 118 adult first kidney graft recipients, transplanted at a single center, receiving tacrolimus in low concentration. All were submitted to a protocol biopsy at month-3. Subclinical rejection was identified in 10 biopsies and sCD30 levels ≥ 61.88 ng/mL (P = 0.004), younger recipient age (P = 0.030) and non-Caucasian ethnicity (P = 0.011) were independently associated with this outcome. Rare CD30(+) cells were present in only two biopsies. There was a correlation between sCD30 levels and CD30 gene expression in peripheral blood mononuclear cells (r = 0.385, P = 0.043). These results show that high sCD30 levels are independent predictors of graft dysfunction and may contribute to patient selection protocols by indicating those who could benefit from a more thorough evaluation. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Rejection of crosstalk and noise by a quasi balanced CFPI for remote ultrasound detection

    Energy Technology Data Exchange (ETDEWEB)

    Reitinger, B; Berer, T; Hornhuber, C; Burgholzer, P, E-mail: bernhard.reitinger@recendt.at [Research Center for Non Destructive Testing GmbH (Recendt), Hafenstrasse 47-51, 4020 Linz (Austria)

    2011-01-01

    In this paper we show the benefits of a quasi balanced fringe hopping CFPI (confocal Fabry-Perot interferometer) with broadband CMRR (common mode rejection ratio) for remote ultrasound detection. Ultrasonic information in general lies in the phase modulation of laser light which in this case is demodulated by using the CFPI at a certain working point on a fringe. By hopping from the positive to the negative slope on the same fringe the detected ultrasonic signals are inverted. In contrary interference signals like crosstalk from the generation, ghosts, or noise correlated to pulse laser excitation are not influenced and hence get rejected by subtracting the signals from both slopes. Hence, a minimum of two measurements is needed for common mode rejection. The fringe hopping from the positive to the negative slope is done by changing the distance of the CFPI mirrors with a precise piezoelectric-stack and a fast high resolution digital controller. As only one photo-detector with a transimpedance-amplifier is needed a high CMRR can be accomplished which is not affected by the symmetry of the fringe but only by pulse to pulse energy fluctuations of the generation laser. We show that with fringe hopping and averaging the signal to noise ratio increases much faster than with averaging without fringe hopping. This is due to the correlation of the quasi-noise with the generation cycle.

  20. Multiquadrant Subtenon Triamcinolone Injection for Acute Corneal Graft Rejection: A Case Report

    Directory of Open Access Journals (Sweden)

    Sunali Goyal

    2017-05-01

    Full Text Available Background: We report a case of reversal of an acute corneal graft rejection following multiquadrant subtenon triamcinolone injection. Case Presentation: A 19-year-old woman who had acute corneal graft rejection failed to show resolution of the graft rejection after standard treatment with systemic, intravenous, and topical steroids. The graft rejection, however, responded to injection of triamcinolone in multiple subtenon quadrants. Conclusions: For corneal graft rejection, multiquadrant subtenon triamcinolone injections may be a safe adjunct to systemic treatment.

  1. Regarding the rejection performance of a polymeric reverse osmosis membrane for the final purification of two-phase olive mill effluents previously treated by an advanced oxidation process

    International Nuclear Information System (INIS)

    Ochando-Pulido, J.M.; Martínez-Férez, A.

    2017-01-01

    In previous works on olive mill wastewater (OMW), secondary advanced oxidation treatment solved the problem related to the presence of phenolic compounds and considerable chemical oxygen demand. However, the effluent presented a significant salinity after this treatment. In this work, an adequate operation of a reverse osmosis (RO) membrane is addressed to ensure constant performance over a long period of time. In this paper, the effect of the operating parameters on the dynamic membrane rejection performance towards the target species was examined and discussed. Rejection efficiencies of all species were observed to follow a similar pattern, which consisted of slight initial improvement that further decreased over time. Rejection of both divalent ions remained constant at over 99% regardless of the operating conditions. Rejections were noticed to follow the order SO42−> Cl−> NO3− and Ca2+> Mg2+> K+> Na+, as a rule. Divalent species were moderately more highly rejected than monovalent ones, in accordance with their higher charge and molecular size, and sulfate anions were consistently rejected by over 99%. Finally, the RO membrane exiting treated effluent was depleted of the high electro conductivity initially present (above 97% rejection), permitting its re-use as good quality irrigation water (below 1 mS/cm). [es

  2. Differentiation of human umbilical cord mesenchymal stromal cells into low immunogenic hepatocyte-like cells.

    Science.gov (United States)

    Zhao, Qinjun; Ren, Hongying; Li, Xiyuan; Chen, Zhong; Zhang, Xiangyu; Gong, Wei; Liu, Yongjun; Pang, Tianxiang; Han, Zhong Chao

    2009-01-01

    Mesenchymal stromal cells (MSC) isolated from several human tissues have been known to differentiate into the hepatic lineage in vitro, but the immunogenicity of the differentiated hepatocyte-like cells (DHC) has not been reported. Umbilical cord (UC) MSC are thought to be an attractive cell source for cell therapy because of their young age and low infection rate compared with adult tissue MSC. Hepatic differentiation of UC-MSC was induced with a 2-step protocol. The expressions of hepatic markers were detected by RT-PCR and immunofluorescence staining. Albumin production and urea secretion were measured by ELISA and colorimetric assay respectively. The immunosuppressive properties of DHC was detected by mixed lymphocyte culture. After incubation with specific growth factors, including hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF), UC MSC exhibited a high hepatic differentiation ability in an adherent culture condition. The differentiated UC MSC showed hepatocyte-like morphology and expressed several liver-specific markers at gene and protein levels. Furthermore, the DHC exhibited hepatocyte-specific functions, including albumin secretion, low-density lipoprotein uptake and urea production. More importantly, DHC did not express major histocompatibility complex (MHC) II antigen and were not able to induce lymphocyte proliferation in mixed lymphocyte culture, as undifferentiated UC MSC did. Our results indicate that UC MSC are able to differentiate into functional hepatocyte-like cells that still retain their low immunogenicity in vitro. More importantly, DHC incorporated into the parenchyma of liver when transplanted into mice with CCl(4)-induced liver injury. Therefore, DHC may be an ideal source for cell therapy of liver diseases.

  3. Reject/repeat analysis and the effect prior film viewing has on a department's reject/repeat rate

    International Nuclear Information System (INIS)

    Clark, P.A.; Hogg, P.

    2003-01-01

    Purpose: Achieving cost-effectiveness within the NHS is an old initiative but one that has again been highlighted by recent government policies (The New NHS-Modern and Dependable, Stationary Office, London, 1997). It has been reiterated that it is the responsibility of individual Trusts to devise means to provide such a service. Reject/repeat analyses have long been the primary tool used to assess the cost-effectiveness of radiography departments (Quality Assurance in Diagnostic Radiology, WHO, Geneva, 1982). This research paper examines an in-house initiative (viewing patients' previous films) commonly employed in other Health Trusts in order to reduce departmental repeat/reject rates. Method: Three hundred orthopaedic patients with hip, knee and ankle prostheses were included in a reject/repeat analysis. The aim was to investigate whether or not viewing patient's previous relevant radiographs would be advantageous to the practicing radiographer. This was done through an audit cycle consisting of two audit periods each lasting for 3 months. The primary audit period recorded the baseline repeat/reject rate, with the secondary audit period recording the repeat/reject rate under an experimental condition of viewing the relevant radiographs. Results: The baseline audit revealed repeat rates of 33% in orthopaedic patients with hip, knee and ankle prostheses. The availability of prior film viewing to the radiographer reduced this repeat rate to 10.6%. Conclusion: Prior film viewing dramatically reduced the department's repeat/reject rate by 22.4%. This provides scope for significant patient dose reductions as well as reducing departmental film expenses. This is an underestimated initiative and should be used appropriately in routine clinical practice

  4. Postoperative rebound of antiblood type antibodies and antibody-mediated rejection after ABO-incompatible living-related kidney transplantation.

    Science.gov (United States)

    Ishida, Hideki; Kondo, Tsunenori; Shimizu, Tomokazu; Nozaki, Taiji; Tanabe, Kazunari

    2015-03-01

    The purpose of this study is to examine whether postoperative antiblood type antibody rebound is attributed to kidney allograft rejection in ABO blood type-incompatible (ABO-I) living-related kidney transplantation (KTx). A total of 191 ABO-I recipients who received ABO-I living-related KTx between 2001 and 2013 were divided into two groups: Group 1 consisted of low rebound [(≦1:32), N = 170] and Group 2 consisted of high rebound [(≧1:64), N = 21], according to the levels of the rebounded antiblood type antibodies within 1 year after transplantation. No prophylactic treatment for rejection was administered for elevated antiblood type antibodies, regardless of the levels of the rebounded antibodies. Within 1 year after transplantation, T-cell-mediated rejection was observed in 13 of 170 recipients (13/170, 8%) in Group 1 and in 2 of 21 recipients (2/21, 10%) in Group 2 (Groups 1 vs. 2, P = 0.432). Antibody-mediated rejection was observed in 15 of 170 recipients (15/170, 9%) and 2 of 21 recipients (2/21, 10%) in Groups 1 and 2, respectively (P = 0.898). In this study, we found no correlation between the postoperative antiblood type antibody rebound and the incidence of acute rejection. We concluded that no treatment is necessary for rebounded antiblood type antibodies. © 2014 Steunstichting ESOT.

  5. Role of TDTH and Tc populations in organ graft rejection. I. Functional analysis of graft-infiltrating T cells

    International Nuclear Information System (INIS)

    Stepkowski, S.M.; Duncan, W.R.

    1986-01-01

    To analyze the role of T cell subpopulations in the rejection of organ allografts, we developed a new model for obtaining large numbers of graft infiltrating cells (GICs). We isolated W3/25+ Th/DTH and OX8+ Ts/c from vascularized, irradiated rat spleen allografts. W3/25+ GICs obtained from spleen allografts transplanted to normal recipients were highly effective in eliciting cardiac allograft rejection when transferred to sublethally irradiated recipients, however, the OX8+ subset was incapable of eliciting rejection. On the other hand, when OX8+ GICs were obtained from spleen allografts transplanted to previously immunized recipients, they were as efficient as the W3/25+ Th/DTH subset in eliciting cardiac allograft destruction. These results indicate that the W3/25+, OX8- T cell is required for the rejection of primary organ allografts, but that the rejection of a secondary allograft by an immune recipient may be mediated, independently, by both W3/25+ and OX8+ cells

  6. Detection and surveillance of rejection reactions after heart transplant by means of a sequence of MRI of 'black blood' type

    International Nuclear Information System (INIS)

    David, N.; Escanye, J.M.; Marwan, N.S.; Marie, P.Y.; Perlot, P.; Angioi, M.; Walker, P.; Quiri, N.; Arsena, T.; Hassan, N.; Villemot, J.P.; Mattei, S.; Karcher, G.; Bertrand, A.

    1997-01-01

    A echocardiography and a MRI (Magnetic Resonance Imaging) investigation were achieved at 3 months to 7 years after heart transplant in 61 patients among whose 35 were suspected of rejection and 32 have had a myocardial biopsy. The myocardial (T 2 ) transversal relaxation time was determined by using an inversion-recovery/spin-echo upon a magnet of 0.5 T. The rejection diagnosis criteria by echography was compared with that of a anomalistic high value of T 2 : 1. the MRI was positive but the echography not in 5 cases, all having positive biopsies; 2. the echography was positive but the MRI was not in 10 cases among which all the biopsies were negative; 3. the MRI and the echography gave concordant results in 46 cases (7 positives and 39 negatives) among which an agreement with the biopsy results was observed in 91% (20/22) of cases. The 12 patients having a positive MRI have had a new examination at 2 to 15 days after the anti-rejection treatment; the T 2 values got normalized. In conclusion, the determination of the myocardial T 2 by means of a 'black blood' MRI sequence appears to be superior to an echocardiography in detecting the rejections after heart transplant and could be utilised to evaluate the efficiency of anti-rejection treatment

  7. MF/UF rejection and fouling potential of algal organic matter from bloom-forming marine and freshwater algae

    KAUST Repository

    Villacorte, Loreen O.

    2015-07-01

    Pretreatment with microfiltration (MF) or ultrafiltration (UF) membranes has been proposed for seawater reverse osmosis (SWRO) plants to address operational issues associated with algal blooms. Here, we investigated the MF/UF rejection and fouling potential of algal organic matter (AOM) released by common species of bloom-forming marine (Alexandrium tamarense and Chaetoceros affinis) and freshwater (Microcystis sp.) algae. Batch culture monitoring of the three algal species illustrated varying growth pattern, cell concentration, AOM released and membrane fouling potential. The high membrane fouling potential of the cultures can be directly associated (R2>0.85) with AOM such as transparent exopolymer particle (TEP) while no apparent relationship with algal cell concentration was observed. The AOM comprised mainly biopolymers (e.g., polysaccharides and proteins) and low molecular weight organic compounds (e.g., humic-like substances). The former were largely rejected by MF/UF membranes while the latter were poorly rejected. MF (0.4μm and 0.1μm pore size) rejected 14%-56% of biopolymers while conventional UF (100kDa) and tight UF (10kDa) rejected up to 83% and 97%, respectively. The retention of AOM resulted in a rapid increase in trans-membrane pressure (δP) over time, characterised by pore blocking followed by cake filtration with enhanced compression as illustrated by an exponential progression of δP. © 2015 Elsevier B.V.

  8. Family Rejection as a Predictor of Suicide Attempts and Substance Misuse Among Transgender and Gender Nonconforming Adults.

    Science.gov (United States)

    Klein, Augustus; Golub, Sarit A

    2016-06-01

    We examined associations between family rejection and risk of suicide attempts and substance misuse among a national sample of transgender and gender nonconforming adults. Data were drawn from the National Transgender Discrimination Survey (N = 6456). This secondary analysis was restricted to 3458 individuals who self-identified as transgender or gender nonconforming and provided complete data on study variables. We used multivariable logistic regression to examine health risks by level of reported family rejection (low/moderate/high), controlling for relevant sociodemographic characteristics. Overall, 42.3% of the sample reported a suicide attempt and 26.3% reported misusing drugs or alcohol to cope with transgender-related discrimination. After controlling for age, race/ethnicity, sex assigned at birth, binary gender identity, income, education, and employment status, family rejection was associated with increased odds of both behaviors. Odds increased significantly with increasing levels of family rejection. Family rejection related to gender identity is an understudied interpersonal stressor that may negatively affect health outcomes for transgender and gender nonconforming individuals. A better understanding of the role of close relationships in both risk and resilience for transgender individuals is critical in the development of effective public health interventions for this community.

  9. Induction of Immunogenic Cell Death with Non-Thermal Plasma for Cancer Immunotherapy

    Science.gov (United States)

    Lin, Abraham G.

    treatment, ROS immediately increased. When chemical attenuators of ROS were used, intracellular ROS was abrogated and emission of ICD markers were attenuated. This strongly suggests that plasma-induced ICD is associated with increased intracellular ROS. The gold-standard approach to evaluating whether a stimulus can elicit genuine ICD relies on a vaccination assay. CT26 colorectal cancer cells were treated at ICD-inducing regimes of plasma and injected into syngeneic Balb/c mice. One week later, mice were challenged with live CT26 cancer cells. Tumor progression was moderated in animals immunized with plasma-treated CT26 cells. Altogether, these provide strong evidence that plasma regimes can be adapted for a new application: ICD induction. Next, a study was conducted to test the potential of plasma to induce ICD in tumors in animals. Plasma treatment of subcutaneous tumors in mice elicited the emission of ecto-CRT and high mobility group box 1 (HMGB1), another marker of ICD, in the tumor and also recruited CD11c+ and CD45+ immune cells locally. This was followed by development of cancer-specific splenic T cells, indicating that a systemic anti-tumor response was elicited from localized plasma treatment of the tumor. Overall, this work demonstrates the development of non-thermal plasma as a novel method of inducing immunogenic cell death for cancer immunotherapy. The obtained results further our understanding of plasma-cellular interaction mechanisms and highlight the potential for clinical translation.

  10. From Acceptance to Rejection: Food Contamination in the Classroom.

    Science.gov (United States)

    Rajecki, D. W.

    1989-01-01

    Describes a classroom exercise to explain design and measurement principles in methodology and statistics courses. This demonstration which involves measurement of a shift from food acceptance to food rejection produces meaningful data sets. The realism of the exercise gives students a view of problems that emerge in research. (KO)

  11. Endothelial cell chimerism after renal transplantation and vascular rejection.

    NARCIS (Netherlands)

    Lagaaij, E.L.; Cramer-Knijnenburg, G.F.; Kemenade, F.J. van; Es, L.A. van; Bruijn, J.A.; Krieken, J.H.J.M. van

    2001-01-01

    BACKGROUND: The blood vessels of a transplanted organ are the interface between donor and recipient. The endothelium in the blood vessels is thought to be the major target for graft rejection. Endothelial cells of a transplanted organ are believed to remain of donor origin after transplantation. We

  12. Sonar waveforms for reverberation rejection, Part IV: Adaptive processing.

    NARCIS (Netherlands)

    IJsselmuide, S.P. van; Deruaz, L.; Been, R.; Doisy, Y.; Beerens, S.P.

    2002-01-01

    For littoral ASW, reverberation is a big problem and rejection of reverberation is of utmost importance. The influence of the transmitted signal on the signal to reverberation ratio has been presented in three preceding papers. In this paper, the influence of improved signal processing on the

  13. Facility for electrochemical dissolution of rejected fuel elements

    International Nuclear Information System (INIS)

    Deniskin, V.P.; Filatov, O.N.; Konovalov, E.A.; Kolesnikov, B.P.; Bukharin, A.D.

    2003-01-01

    A facility for electrochemical dissolution of rejected fuel elements with the stainless steel can and uranium of 90% enrichment is described. The start-adjustment works and trial-commercial tests of the facility are carried out. A s a result its technological parameters are determined [ru

  14. Peer Rejection Cues Induce Cardiac Slowing after Transition into Adolescence

    Science.gov (United States)

    Gunther Moor, Bregtje; Bos, Marieke G. N.; Crone, Eveline A.; van der Molen, Maurits W.

    2014-01-01

    The present study examined developmental and gender differences in sensitivity to peer rejection across the transition into adolescence by examining beat-by-beat heart rate responses. Children between the ages of 8 and 14 years were presented with unfamiliar faces of age-matched peers and were asked to predict whether they would be liked by the…

  15. 18 CFR 154.5 - Rejection of filings.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Rejection of filings. 154.5 Section 154.5 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... Director of the Office of Energy Market Regulation pursuant to the authority delegated to the Director in...

  16. Heat Rejection from a Variable Conductance Heat Pipe Radiator Panel

    Science.gov (United States)

    Jaworske, D. A.; Gibson, M. A.; Hervol, D. S.

    2012-01-01

    A titanium-water heat pipe radiator having an innovative proprietary evaporator configuration was evaluated in a large vacuum chamber equipped with liquid nitrogen cooled cold walls. The radiator was manufactured by Advanced Cooling Technologies, Inc. (ACT), Lancaster, PA, and delivered as part of a Small Business Innovative Research effort. The radiator panel consisted of five titanium-water heat pipes operating as thermosyphons, sandwiched between two polymer matrix composite face sheets. The five variable conductance heat pipes were purposely charged with a small amount of non-condensable gas to control heat flow through the condenser. Heat rejection was evaluated over a wide range of inlet water temperature and flow conditions, and heat rejection was calculated in real-time utilizing a data acquisition system programmed with the Stefan-Boltzmann equation. Thermography through an infra-red transparent window identified heat flow across the panel. Under nominal operation, a maximum heat rejection value of over 2200 Watts was identified. The thermal vacuum evaluation of heat rejection provided critical information on understanding the radiator s performance, and in steady state and transient scenarios provided useful information for validating current thermal models in support of the Fission Power Systems Project.

  17. Modernity rejected? Marketing schnapps gin in West Africa, 1945 ...

    African Journals Online (AJOL)

    During the 1950s and 1960s, advertising for a diverse range of products, ... why African consumers rejected the claim that schnapps gin was „modern‟, and why ... used and interpreted on a day-to-day level during the decolonisation era. ... on marketing and consumption of imported commodities in twentieth-century Africa.

  18. Developmental Differences in the Use of Recognition Memory Rejection Mechanisms

    Science.gov (United States)

    Odegard, Timothy N.; Jenkins, Kara M.; Koen, Joshua D.

    2010-01-01

    The current experiment examined the use of plausibility judgments by children to reject distractors presented on "yes/no" recognition memory tests. Participants studied two lists of word pairs that shared either a categorical or rhyme association, which constituted the global nature of the two study conditions. During the recognition memory tests,…

  19. Bone marrow-derived T lymphocytes responsible for allograft rejection

    International Nuclear Information System (INIS)

    Senjanovic, M.; Marusic, M.

    1984-01-01

    Lethally irradiated mice reconstituted with syngeneic bone marrow cells were grafted with allogeneic skin grafts 6-7 weeks after irradiation and reconstitution. Mice with intact thymuses rejected the grafts whereas the mice thymectomized before irradiation and reconstitution did not. Thymectomized irradiated mice (TIR mice) reconstituted with bone marrow cells from donors immune to the allografts rejected the grafts. Bone marrow cells from immunized donors, pretreated with Thy 1.2 antibody and C', did not confer immunity to TIR recipients. To determine the number of T lymphocytes necessary for the transfer of immunity by bone marrow cells from immunized donors, thymectomized irradiated mice were reconstituted with nonimmune bone marrow cells treated with Thy 1.2 antibody and C' and with various numbers of splenic T lymphocytes from nonimmune and immune donors. Allogeneic skin graft rejection was obtained with 10(6) nonimmune or 10(4) immune T cells. The effect of immune T cells was specific: i.e., immune T cells accelerated only rejection of the relevant skin grafts whereas against a third-party skin grafts acted as normal T lymphocytes

  20. Maternal Predictors of Rejecting Parenting and Early Adolescent Antisocial Behavior

    Science.gov (United States)

    Trentacosta, Christopher J.; Shaw, Daniel S.

    2008-01-01

    The present study examined relations among maternal psychological resources, rejecting parenting, and early adolescent antisocial behavior in a sample of 231 low-income mothers and their sons with longitudinal assessments from age 18 months to 12 years. The maternal resources examined were age at first birth, aggressive personality, and empathy.…

  1. Examining Appearance-Based Rejection Sensitivity during Early Adolescence

    Science.gov (United States)

    Bowker, Julie C.; Thomas, Katelyn K.; Spencer, Sarah V.; Park, Lora E.

    2013-01-01

    The present study of 150 adolescents ("M" age = 13.05 years) examined the associations between appearance-based rejection sensitivity (Appearance-RS) and psychological adjustment during early adolescence, and evaluated three types of other-gender peer experiences (other-gender friendship, peer acceptance, and romantic relationships) as…

  2. Evolution of silvicultural thinning: from rejection to transcendence

    Science.gov (United States)

    Boris Zeide

    2006-01-01

    Our views on a main tool of forestry, silvicultural thinning, have changed greatly since the beginning of forestry over 200 years ago. At first, thinning was rejected as something unnatural and destructive. It was believed that the densest stands were the most productive and any thinning only detracted from maximum growth produced by nature. This philosophy was still...

  3. Shape Morphing Adaptive Radiator Technology (SMART) for Variable Heat Rejection

    Science.gov (United States)

    Erickson, Lisa

    2016-01-01

    The proposed technology leverages the temperature dependent phase change of shape memory alloys (SMAs) to drive the shape of a flexible radiator panel. The opening/closing of the radiator panel, as a function of temperature, passively adapts the radiator's rate of heat rejection in response to a vehicle's needs.

  4. Biased Self-Perceptions, Peer Rejection, and Aggression in Children

    Science.gov (United States)

    White, Bradley A.; Kistner, Janet A.

    2011-01-01

    This study examined whether children's biased self-perceptions of peer acceptance are associated in a linear or curvilinear fashion with aggression, whether associations are moderated by peer rejection status, and whether associations apply uniquely to reactive aggression. Children in the 4th through 7th grades completed a self-report measure on…

  5. Increased neural response to social rejection in major depression

    NARCIS (Netherlands)

    Kumar, Poornima; Waiter, Gordon D.; Dubois, Magda; Milders, Maarten; Reid, Ian; Steele, J. Douglas

    2017-01-01

    Background: Being a part of community is critical for survival and individuals with major depressive disorder (MDD) have a greater sensitivity to interpersonal stress that makes them vulnerable to future episodes. Social rejection is a critical risk factor for depression and it is said to increase

  6. Information about radiographic films rejects of dental x-rays

    International Nuclear Information System (INIS)

    Cezimbra, M.R.; Bernarsiuk, M.E.; Bauer V, E.

    1996-01-01

    The purpose of this research was to qualify and quantify the number of dental x-ray films rejected in a Porto Alegre clinic. As we analyzed the captured data, it was concluded that, our of 1066 peri-apical films, we had a total percentage of 4.5% in relation to the total of the exams made. This 4.5% consists of the following rejects: placement, patient movement, technical errors, diaphragm, too much clarity in the result, double exposure, prolongation, shortness, darkened for not have been shot, superposed film. Because of that, the rejection, due to the bad placement of the film, is the one with the larger percentage value, i.e., 1.22% of the 4.5%. With the knowledge of the types of rejects and their causes, it was possible to correct some sources of systematic errors minimizing the repetition of the exams, saving costs, time and diminishing the ionizing radiation exposure for the patient, odontologist and his technical staff, which will be proved. (authors). 4 refs., 1 tab

  7. Fate of Manuscripts Rejected From the Red Journal

    International Nuclear Information System (INIS)

    Holliday, Emma B.; Yang, George; Jagsi, Reshma; Hoffman, Karen E.; Bennett, Katherine Egan; Grace, Calley; Zietman, Anthony L.

    2015-01-01

    Purpose: To evaluate characteristics associated with higher rates of acceptance for original manuscripts submitted for publication to the International Journal of Radiation Oncology • Biology • Physics (IJROBP) and describe the fate of rejected manuscripts. Methods and Materials: Manuscripts submitted to the IJROBP from May 1, 2010, to August 31, 2010, and May 1, 2012, to August 31, 2012, were evaluated for author demographics and acceptance status. A PubMed search was performed for each IJROBP-rejected manuscript to ascertain whether the manuscript was ultimately published elsewhere. The Impact Factor of the accepting journal and the number of citations of the published manuscript were also collected. Results: Of the 500 included manuscripts, 172 (34.4%) were accepted and 328 (65.6%) were rejected. There was no significant difference in acceptance rates according to gender or degree of the submitting author, but there were significant differences seen based on the submitting author's country, rank, and h-index. On multivariate analysis, earlier year submitted (P<.0001) and higher author h-index (P=.006) remained significantly associated with acceptance into the IJROBP. Two hundred thirty-five IJROBP-rejected manuscripts (71.7%) were ultimately published in a PubMed-listed journal as of July 2014. There were no significant differences in any submitting author characteristics. Journals accepting IJROBP-rejected manuscripts had a lower median [interquartile range] 2013 impact factor compared with the IJROBP (2.45 [1.53-3.71] vs 4.176). The IJROBP-rejected manuscripts ultimately published elsewhere had a lower median [interquartile range] number of citations (1 [0-4] vs 6 [2-11]; P<.001), which persisted on multivariate analysis. Conclusions: The acceptance rate for manuscripts submitted to the IJROBP is approximately one-third, and approximately 70% of rejected manuscripts are ultimately published in other PubMed-listed journals, but these ultimate

  8. Radiation therapy treatment of acute refractory renal allograft rejection

    International Nuclear Information System (INIS)

    Godinez, J.; Thisted, R.A.; Woodle, E.S.; Thistlethwaite, J.R.; Powers, C.; Haraf, D.

    1996-01-01

    Purpose: To evaluate the impact of the use of radiotherapy to preserve the renal graft in patients with recurrent graft rejection that failed to respond to medical treatment and identify risk factors to predict the probability of graft loss. Material and Methods: Between June 1989 and December 1995, 53 renal graft recipients were treated at our institution after experiencing several episodes of rejection. Rejection was defined as an unexplained, consecutive, daily rise in serum creatinine. Each episode was confirmed with renal biopsy. Patients who experienced rejection were initially treated with solu medrol bolus and prednisone. Patients with steroid-resistant or recurrent rejection received OKT3, polyclonal antilymphocyte antibody, FK506, or mycophenolate mofetil. Those who failed to respond to medical treatment were referred for radiotherapy. Treatment consisted of a dose of 600 cGy given in 3 or 4 fractions using 6 MV photons, AP or AP/PA. All patients underwent ultrasound kidney localization; a 2 cm margin was given around the kidney. Results: Median follow-up from the date of transplant to the last follow-up was 22 months (range 1-83 months), the median time from the date of transplant to the initiation of radiotherapy was 3 months, and the median time from the initiation of radiotherapy to the last follow up was 10 months (range 0.1 to 64 months). Of these 34 men and 19 women, median age of 3), Ninety-one percent were cadaveric transplant recipients., human leukocyte antigen matching on HLA-A and HLA-B (zero antigens in 26 patients/one or two shared antigens in 27 patients), HLA-DR locus (zero antigens in 34 patients/one or two shared antigens in 19 patients), transplant panel-reactive antibodies at transplantation (median PRA-Curr of 3% and median PRA-Max of 8%), number of acute rejection episodes, interval from the date of the transplant to the first rejection (median 1 month, range 5 days to 68 months), serum creatinine levels at the time of the first

  9. Ultraviolet irradiation in transplantation biology. Manipulation of immunity and immunogenicity

    International Nuclear Information System (INIS)

    Deeg, H.J.

    1988-01-01

    Ultraviolet irradiation, particularly in the UVB range, has profound effects on immunological mechanisms. Optimum and tolerable doses of exposure vary from species to species, and from organ to organ. As a result of limited depth penetration and possibly significant energy absorption in nontargeted cells, every model requires diligent determination of an effective nontoxic approach. Nevertheless, it is clear that UVB and UVC irradiation can abolish proliferative and stimulatory ability as well as accessory/antigen-presenting ability of leukocytes in vitro. UV treatment alters cell-surface properties, calcium mobilization, cytokine production and release, and other subcellular processes. Preliminary data suggest that these manipulations also suppress immunity and reduce immunogenicity in vivo. Exposure of solid organs and of large volumes of blood is difficult due to technical problems--in particular poor depth penetration and absorption of UV energy in generally available transfusion bags. 111 references

  10. Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics.

    Science.gov (United States)

    Garg, Abhishek D; More, Sanket; Rufo, Nicole; Mece, Odeta; Sassano, Maria Livia; Agostinis, Patrizia; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2017-01-01

    The expression "immunogenic cell death" (ICD) refers to a functionally unique form of cell death that facilitates (instead of suppressing) a T cell-dependent immune response specific for dead cell-derived antigens. ICD critically relies on the activation of adaptive responses in dying cells, culminating with the exposure or secretion of immunostimulatory molecules commonly referred to as "damage-associated molecular patterns". Only a few agents can elicit bona fide ICD, including some clinically established chemotherapeutics such as doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin. In this Trial Watch, we discuss recent progress on the development of ICD-inducing chemotherapeutic regimens, focusing on studies that evaluate clinical efficacy in conjunction with immunological biomarkers.

  11. Perceived childhood paternal acceptance-rejection among adults

    International Nuclear Information System (INIS)

    Hussain, S.; Alvi, T.; Zeeshan, A.; Nadeem, S.

    2013-01-01

    Objective: To determine the childhood perceptual difference of paternal acceptance-rejection between those having psychological disorders and non-clinical population during adulthood. Study Design: Comparative study. Place and Duration of Study: Karwan-e-Hayat, Psychiatric Care and Rehabilitation Centre, Keamari, Karachi, Pakistan, from January to August 2011. Methodology: To test our hypotheses, 69 participants were selected from Karwan-e-Hayat Psychiatric Care and Rehabilitation Centre, Karachi on the basis of purposive sampling technique and 79 from Karachi city on the basis of convenient sampling technique. To measure their perceived paternal acceptance-rejection during childhood, Adult Parental acceptance-rejection questionnaire (PARQ)/control: father-short form (Urdu translation) was administered. The statistical analysis of data was done with the predictive analytics software (PASW). Results: One hundred and forty eight (78 males and 70 females) participants with mean age of 31.28 +- 9.54 years were included. Out of them 69 (40 males and 29 females) were clinical cases of depression, mania and psychosis with mean age of 33.26 +- 9.51 years. Seventy nine (38 males and 41 females) were normal individuals with mean age of 29.54 +- 9.29 years of the demographics corresponding to the clinical population. Independent t-test revealed a significant difference in perceived childhood father acceptance-rejection between clinical and non-clinical population (p < 0.05) and significant gender difference (p < 0.05). Conclusion: The studied clinical population and male participants perceived to be more rejected by their father during their childhood than non-clinical population and female participants. (author)

  12. Implementation and rejection of industrial steam system energy efficiency measures

    International Nuclear Information System (INIS)

    Therkelsen, Peter; McKane, Aimee

    2013-01-01

    Steam systems consume approximately one third of energy applied at US industrial facilities. To reduce energy consumption, steam system energy assessments have been conducted on a wide range of industry types over the course of 5 years through the Energy Savings Assessment (ESA) program administered by the US Department of Energy (US DOE). ESA energy assessments result in energy efficiency measure recommendations that are given potential energy and energy cost savings and potential implementation cost values. Saving and cost metrics that measure the impact recommended measures will have at facilities, described as percentages of facility baseline energy and energy cost, are developed from ESA data and used in analyses. Developed savings and cost metrics are examined along with implementation and rejection rates of recommended steam system energy efficiency measures. Based on analyses, implementation of steam system energy efficiency measures is driven primarily by cost metrics: payback period and measure implementation cost as a percentage of facility baseline energy cost (implementation cost percentage). Stated reasons for rejecting recommended measures are primarily based upon economic concerns. Additionally, implementation rates of measures are not only functions of savings and cost metrics, but time as well. - Highlights: ► We examine uptake/rejection of industrial steam system energy efficiency measures. ► We examine metrics that correspond to uptake/rejection of recommended measures. ► We examine barriers hindering steam system energy efficiency measure implementation. ► Uptake/rejection of steam measures is linked to potential cost metrics. ► Increased uptake of measures and uptake of more costly measures increases with time

  13. Alpha particles induce expression of immunogenic markers on tumour cells

    International Nuclear Information System (INIS)

    Gorin, J.B.; Gouard, S.; Cherel, M.; Davodeau, F.; Gaschet, J.; Morgenstern, A.; Bruchertseifer, F.

    2013-01-01

    The full text of the publication follows. Radioimmunotherapy (RIT) is an approach aiming at targeting the radioelements to tumours, usually through the use of antibodies specific for tumour antigens. The radiations emitted by the radioelements then induce direct killing of the targeted cells as well as indirect killing through bystander effect. Interestingly, it has been shown that ionizing radiations, in some settings of external radiotherapy, can foster an immune response directed against tumour cells. Our research team is dedicated to the development of alpha RIT, i.e RIT using alpha particle emitters, we therefore decided to study the effects of such particles on tumour cells in regards to their immunogenicity. First, we studied the effects of bismuth 213, an alpha emitter, on cellular death and autophagy in six different tumour cell lines. Then, we measured the expression of 'danger' signals and MHC molecules at the cell surface to determine whether irradiation with 213 Bi could cause the tumour cells to be recognized by the immune system. Finally a co-culture of dendritic cells with irradiated tumour cells was performed to test whether it would induce dendritic cells to mature. No apoptosis was detected within 48 hours after irradiation in any cell line, however half of them exhibited signs of autophagy. No increase in membrane expression of 'danger' signals was observed after treatment with 213 Bi, but we showed an increase in expression of MHC class I and II for some cell lines. Moreover, the co-culture experiment indicated that the immunogenicity of a human adenocarcinoma cell line (LS 174T) was enhanced in vitro after irradiation with alpha rays. These preliminary data suggest that alpha particles could be of interest in raising an immune response associated to RIT. (authors)

  14. Evidence of Two Lyssavirus Phylogroups with Distinct Pathogenicity and Immunogenicity

    Science.gov (United States)

    Badrane, Hassan; Bahloul, Chokri; Perrin, Pierre; Tordo, Noël

    2001-01-01

    The genetic diversity of representative members of the Lyssavirus genus (rabies and rabies-related viruses) was evaluated using the gene encoding the transmembrane glycoprotein involved in the virus-host interaction, immunogenicity, and pathogenicity. Phylogenetic analysis distinguished seven genotypes, which could be divided into two major phylogroups having the highest bootstrap values. Phylogroup I comprises the worldwide genotype 1 (classic Rabies virus), the European bat lyssavirus (EBL) genotypes 5 (EBL1) and 6 (EBL2), the African genotype 4 (Duvenhage virus), and the Australian bat lyssavirus genotype 7. Phylogroup II comprises the divergent African genotypes 2 (Lagos bat virus) and 3 (Mokola virus). We studied immunogenic and pathogenic properties to investigate the biological significance of this phylogenetic grouping. Viruses from phylogroup I (Rabies virus and EBL1) were found to be pathogenic for mice when injected by the intracerebral or the intramuscular route, whereas viruses from phylogroup II (Mokola and Lagos bat viruses) were only pathogenic by the intracerebral route. We showed that the glycoprotein R333 residue essential for virulence was naturally replaced by a D333 in the phylogroup II viruses, likely resulting in their attenuated pathogenicity. Moreover, cross-neutralization distinguished the same phylogroups. Within each phylogroup, the amino acid sequence of the glycoprotein ectodomain was at least 74% identical, and antiglycoprotein virus-neutralizing antibodies displayed cross-neutralization. Between phylogroups, the identity was less than 64.5% and the cross-neutralization was absent, explaining why the classical rabies vaccines (phylogroup I) cannot protect against lyssaviruses from phylogroup II. Our tree-axial analysis divided lyssaviruses into two phylogroups that more closely reflect their biological characteristics than previous serotypes and genotypes. PMID:11238853

  15. Synthetic peptide vaccines: palmitoylation of peptide antigens by a thioester bond increases immunogenicity

    DEFF Research Database (Denmark)

    Beekman, N.J.C.M.; Schaaper, W.M.M.; Tesser, G.I.

    1997-01-01

    Synthetic peptides have frequently been used to immunize animals. However, peptides less than about 20 to 30 amino acids long are poor immunogens. In general, to increase its immunogenicity, the presentation of the peptide should be improved, and molecular weight needs to be increased. Many...... or an amide bond. It was found that these S-palmitoylated peptides were much more immunogenic than N-palmitoylated peptides and at least similar to KLH-conjugated peptides with respect to appearance and magnitude of induced antibodies (canine parvovirus) or immunocastration effect (gonadotropin...

  16. Immunogenicity of biotherapy used in psoriasis: the science behind the scenes.

    Science.gov (United States)

    Jullien, Denis; Prinz, Jörg C; Nestle, Frank O

    2015-01-01

    A potential limitation in the use of biologic drugs used to treat psoriasis is the development of anti-drug antibodies (ADAs). Many factors contribute to this unwanted immune response, from the product itself, to its mode of administration, the underlying disease, and patient characteristics. ADAs may decrease the efficacy of biologic drugs by neutralizing them or modifying their clearance and may account for hypersensitivity reactions. This article reviews the scientific basis of immunogenicity and the mechanisms by which it affects clinical outcomes. It also considers testing for immunogenicity and how biologic therapy of psoriasis may be tailored on the basis of immunogenicity.

  17. Excluded from social security: rejections of disability pension applications in Norway 1998-2004.

    Science.gov (United States)

    Galaasen, Anders Mølster; Bruusgaard, Dag; Claussen, Bjørgulf

    2012-03-01

    Admission to disability pension (DP) in Norway, like most other countries, requires a medical condition as the main cause of income reduction. Still, a widespread assumption is that much of the recruitment to the programme is rather due to non-medical, mainly labour market factors. In this article, we study the grey zones between acceptance and rejection of DP applications, in light of the concept of marginalisation. From the total Norwegian population, aged 18-66 in 1998, we included all first-time applications for DP between 1998 and 2004. Logistic regressions of both application and application outcome were then performed, controlling for a range of socioeconomic variables and medical diagnosis. Medical diagnosis had the strongest impact on application outcome, together with the applicant's age. High rejection risk was found among applicants with complex musculoskeletal diagnoses, and also for complex psychiatric diagnoses as compared to well-defined ones. Persons having previously received social assistance more often applied for a DP and more often were rejected. The same is true, though on a lesser scale, for people with a weak affiliation to the labour market. The DP programme in Norway is to a large degree medically oriented, not only judicially but also in practice. Nevertheless, non-medical factors have a bearing on both application rates and application outcome. The control system seems to work in a way that excludes the most marginalised applicants, thus possibly contributing to further marginalisation of already disadvantaged groups.

  18. Stress response and the adolescent transition: performance versus peer rejection stressors.

    Science.gov (United States)

    Stroud, Laura R; Foster, Elizabeth; Papandonatos, George D; Handwerger, Kathryn; Granger, Douglas A; Kivlighan, Katie T; Niaura, Raymond

    2009-01-01

    Little is known about normative variation in stress response over the adolescent transition. This study examined neuroendocrine and cardiovascular responses to performance and peer rejection stressors over the adolescent transition in a normative sample. Participants were 82 healthy children (ages 7-12 years, n = 39, 22 females) and adolescents (ages 13-17, n = 43, 20 females) recruited through community postings. Following a habituation session, participants completed a performance (public speaking, mental arithmetic, mirror tracing) or peer rejection (exclusion challenges) stress session. Salivary cortisol, salivary alpha amylase (sAA), systolic and diastolic blood pressure (SBP, DBP), and heart rate were measured throughout. Adolescents showed significantly greater cortisol, sAA, SBP, and DBP stress response relative to children. Developmental differences were most pronounced in the performance stress session for cortisol and DBP and in the peer rejection session for sAA and SBP. Heightened physiological stress responses in typical adolescents may facilitate adaptation to new challenges of adolescence and adulthood. In high-risk adolescents, this normative shift may tip the balance toward stress response dysregulation associated with depression and other psychopathology. Specificity of physiological response by stressor type highlights the importance of a multisystem approach to the psychobiology of stress and may also have implications for understanding trajectories to psychopathology.

  19. Panel reactive HLA antibodies, soluble CD30 levels, and acute rejection six months following renal transplant.

    Science.gov (United States)

    Domingues, Elizabeth M F L; Matuck, Teresa; Graciano, Miguel L; Souza, Edison; Rioja, Suzimar; Falci, Mônica C; Monteiro de Carvalho, Deise B; Porto, Luís Cristóvão

    2010-01-01

    Specific anti-human leukocyte antigen antibodies (HLA) in the post-transplant period may be present with acute rejection episodes (ARE), and high soluble CD30 (sCD30) serum levels may be a risk factor for ARE and graft loss. HLA cross-matching, panel reactive antibodies (PRA), and sCD30 levels were determined prior to transplantation in 72 patients. Soluble CD30 levels and PRA were re-assessed at day 7, 14, 21, and 28, and monthly up to the sixth.   Twenty-four subjects had a positive PRA and 17 experienced ARE. Nine of 17 ARE subjects demonstrated positive PRA and 16 had HLA mismatches. Positive PRA was more frequent in ARE subjects (p = 0.03). Eight subjects with ARE had donor-specific antibodies (DSA) in serum samples pre-transplantation, two subjects developed DSA. Three subjects without ARE had positive PRA only in post-transplantation samples. Soluble CD30 levels were higher in pre-transplant samples and ARE subjects than non-ARE subjects (p = 0.03). Post-transplant sCD30 levels were elevated in subjects who experienced rejection and were significantly higher at seven d (p = 0.0004) and six months (p = 0.03). Higher sCD30 levels following transplant were associated with ARE. Elevated sCD30 levels may represent a risk factor for acute rejection. © 2009 John Wiley & Sons A/S.

  20. Antibody-mediated rejection in kidney transplantation: a review of pathophysiology, diagnosis, and treatment options.

    Science.gov (United States)

    Kim, Miae; Martin, Spencer T; Townsend, Keri R; Gabardi, Steven

    2014-07-01

    Antibody-mediated rejection (AMR), also known as B-cell-mediated or humoral rejection, is a significant complication after kidney transplantation that carries a poor prognosis. Although fewer than 10% of kidney transplant patients experience AMR, as many as 30% of these patients experience graft loss as a consequence. Although AMR is mediated by antibodies against an allograft and results in histologic changes in allograft vasculature that differ from cellular rejection, it has not been recognized as a separate disease process until recently. With an improved understanding about the importance of the development of antibodies against allografts as well as complement activation, significant advances have occurred in the treatment of AMR. The standard of care for AMR includes plasmapheresis and intravenous immunoglobulin that remove and neutralize antibodies, respectively. Agents targeting B cells (rituximab and alemtuzumab), plasma cells (bortezomib), and the complement system (eculizumab) have also been used successfully to treat AMR in kidney transplant recipients. However, the high cost of these medications, their use for unlabeled indications, and a lack of prospective studies evaluating their efficacy and safety limit the routine use of these agents in the treatment of AMR in kidney transplant recipients. © 2014 Pharmacotherapy Publications, Inc.

  1. Application of subsurface vertical flow constructed wetlands to reject water treatment in dairy wastewater treatment plant.

    Science.gov (United States)

    Dąbrowski, Wojciech; Karolinczak, Beata; Gajewska, Magdalena; Wojciechowska, Ewa

    2017-01-01

    The paper presents the effects of applying subsurface vertical flow constructed wetlands (SS VF) for the treatment of reject water generated in the process of aerobic sewage sludge stabilization in the biggest dairy wastewater treatment plant (WWTP) in Poland. Two SS VF beds were built: bed (A) with 0.65 m depth and bed (B) with 1.0 m depth, planted with reeds. Beds were fed with reject water with hydraulic load of 0.1 m d -1 in order to establish the differences in treatment efficiency. During an eight-months research period, a high removal efficiency of predominant pollutants was shown: BOD 5 88.1% (A) and 90.5% (B); COD 84.5% (A) and 87.5% (B); TSS 87.6% (A) and 91.9% (B); TKN 82.4% (A) and 76.5% (B); N-NH 4 + 89.2% (A) and 85.7% (B); TP 30.2% (A) and 40.6% (B). There were not statistically significant differences in the removal efficiencies between bed (B) with 1.0 m depth and bed (A) with 0.65 m depth. The research indicated that SS VF beds could be successfully applied to reject water treatment in dairy WWTPs. The study proved that the use of SS VF beds in full scale in dairy WWTPs would result in a significant decrease in pollutants' load in reject water. In the analyzed case, decreasing the load of ammonia nitrogen was of greatest importance, as it constituted 58% of the total load treated in dairy WWTP and posed a hazard to the stability of the treatment process.

  2. Bortezomib-based treatment of acute antibody-mediated rejection: a case report.

    Science.gov (United States)

    Wang, Q; Li, X L; Xu, X G; Shi, B Y; Zhang, Z M; Li, Z L; Han, Y; Zhou, W Q; Chen, C Q; Cai, M; Zhang, X

    2015-12-22

    Antibody-mediated rejection (AMR) is an important factor affecting survival after renal transplantation. A highly selective proteasome inhibitor, bortezomib, clears activated plasma cells from the body and has important therapeutic effect on AMR. We investigated the effects of bortezomib on AMR in a patient after a second renal transplant. Biopsy confirmed the diagnosis of mixed cellular rejection and AMR. Bortezomib was administered on day 1 (1.3 mg/m(2)), day 4 (1.0 mg/m(2)), and day 8 (1.0 mg/m(2)). On the same days, 250 mg methylprednisolone was administered once, and cyclosporine dose (5 mg·kg(-1)·day(-1)) was reduced by 50%. Oral mycophenolate mofetil and steroid were withdrawn on day 1 of bortezomib treatment. Intermittent double-filtration plasmapheresis was also performed. We monitored parameters, including T lymphocyte subsets, CD139 and CD19 expression, panel reactive antibody (PRA), and serum creatinine concentration. At follow-up 6 months after bortezomib treatment, we observed: 1) serum creatinine stabilized at 130 μM from a peak level of 337 μM; 2) PRA decreased from a maximum of 66.7 to 0%; 3) blood plasma cell percentage rebounded after significantly decreasing following the first dose of bortezomib; 4) in renal allograft biopsy, immunohistochemical staining for C4d shifted from strongly positive to negative, and cellular rejection shifted from type IIA to borderline; and 5) adverse effects such as platelet suppression, hypotension, and grade 3 peripheral neuropathy emerged. Bortezomib effectively treated antibody-mediated renal transplantation rejection in this case study, but clinical trials with large sample sizes are still needed to explore clinical safety and tolerability.

  3. On the wind power rejection in the islands of Crete and Rhodes

    International Nuclear Information System (INIS)

    Katsaprakakis, Dimitris Al.; Papadakis, Nikos; Christakis, Dimitris G.; Zervos, Arthouros

    2007-01-01

    Crete and Rhodes represent the two biggest isolated power systems in Greece. The energy production in both islands is based on thermal power plants. The annual wind energy rejection percentage is calculated for Crete and Rhodes in this paper. The rejected wind energy is defined as the electric energy produced by the wind turbines and not absorbed by the utility network, mainly due to power production system's stability and dynamic security reasons. A parametric calculation of the annual wind energy rejection percentage, in terms of the installed wind power, the power demand and the maximum allowed wind power instant penetration percentage, is accomplished. The methodology takes into account (i) the wind power penetration probability, restricted by the thermal generators technical minima and the maximum allowed wind power instant penetration percentage over the instant power demand; and (ii) the wind power production probability, derived by the islands' wind potential. The present paper indicates that isolated power systems which are based on thermal power plants have a limited wind power installation capacity - in order to achieve and maintain an adequate level of system stability. For a maximum wind power instant penetration percentage of 30% of the power demand, in order to ensure an annual wind energy rejection percentage less than 10%, the total installed wind power should not exceed the 40% of the mean annual power demand. The results of this paper are applicable to medium and great size isolated power systems, with particular features: (i) the power production is based on thermal power plants; (ii) the power demand exhibits intensive seasonal variations and is uncorrelated to the wind data; (iii) the mean annual power demand is greater than 10MW; and (iv) a high wind potential, presenting mean annual wind velocity values greater than 7.5ms-1, is recorded. (Author)

  4. 21 CFR 111.170 - What requirements apply to rejected components, packaging, and labels, and to rejected products...

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What requirements apply to rejected components... supplement? 111.170 Section 111.170 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

  5. Attenuated Human Parainfluenza Virus Type 1 Expressing Ebola Virus Glycoprotein GP Administered Intranasally Is Immunogenic in African Green Monkeys.

    Science.gov (United States)

    Lingemann, Matthias; Liu, Xueqiao; Surman, Sonja; Liang, Bo; Herbert, Richard; Hackenberg, Ashley D; Buchholz, Ursula J; Collins, Peter L; Munir, Shirin

    2017-05-15

    The recent 2014-2016 Ebola virus (EBOV) outbreak prompted increased efforts to develop vaccines against EBOV disease. We describe the development and preclinical evaluation of an attenuated recombinant human parainfluenza virus type 1 (rHPIV1) expressing the membrane-anchored form of EBOV glycoprotein GP, as an intranasal (i.n.) EBOV vaccine. GP was codon optimized and expressed either as a full-length protein or as an engineered chimeric form in which its transmembrane and cytoplasmic tail (TMCT) domains were replaced with those of the HPIV1 F protein in an effort to enhance packaging into the vector particle and immunogenicity. GP was inserted either preceding the N gene (pre-N) or between the N and P genes (N-P) of rHPIV1 bearing a stabilized attenuating mutation in the P/C gene (C Δ170 ). The constructs grew to high titers and efficiently and stably expressed GP. Viruses were attenuated, replicating at low titers over several days, in the respiratory tract of African green monkeys (AGMs). Two doses of candidates expressing GP from the pre-N position elicited higher GP neutralizing serum antibody titers than the N-P viruses, and unmodified GP induced higher levels than its TMCT counterpart. Unmodified EBOV GP was packaged into the HPIV1 particle, and the TMCT modification did not increase packaging or immunogenicity but rather reduced the stability of GP expression during in vivo replication. In conclusion, we identified an attenuated and immunogenic i.n. vaccine candidate expressing GP from the pre-N position. It is expected to be well tolerated in humans and is available for clinical evaluation. IMPORTANCE EBOV hemorrhagic fever is one of the most lethal viral infections and lacks a licensed vaccine. Contact of fluids from infected individuals, including droplets or aerosols, with mucosal surfaces is an important route of EBOV spread during a natural outbreak, and aerosols also might be exploited for intentional virus spread. Therefore, vaccines that protect

  6. The Neural Basis of Recollection Rejection: Increases in Hippocampal-Prefrontal Connectivity in the Absence of a Shared Recall-to-Reject and Target Recollection Network.

    Science.gov (United States)

    Bowman, Caitlin R; Dennis, Nancy A

    2016-08-01

    Recollection rejection or "recall-to-reject" is a mechanism that has been posited to help maintain accurate memory by preventing the occurrence of false memories. Recollection rejection occurs when the presentation of a new item during recognition triggers recall of an associated target, a mismatch in features between the new and old items is registered, and the lure is correctly rejected. Critically, this characterization of recollection rejection involves a recall signal that is conceptually similar to recollection as elicited by a target. However, previous neuroimaging studies have not evaluated the extent to which recollection rejection and target recollection rely on a common neural signal but have instead focused on recollection rejection as a postretrieval monitoring process. This study utilized a false memory paradigm in conjunction with an adapted remember-know-new response paradigm that separated "new" responses based on recollection rejection from those that were based on a lack of familiarity with the item. This procedure allowed for parallel recollection rejection and target recollection contrasts to be computed. Results revealed that, contrary to predictions from theoretical and behavioral literature, there was virtually no evidence of a common retrieval mechanism supporting recollection rejection and target recollection. Instead of the typical target recollection network, recollection rejection recruited a network of lateral prefrontal and bilateral parietal regions that is consistent with the retrieval monitoring network identified in previous neuroimaging studies of recollection rejection. However, a functional connectivity analysis revealed a component of the frontoparietal rejection network that showed increased coupling with the right hippocampus during recollection rejection responses. As such, we demonstrate a possible link between PFC monitoring network and basic retrieval mechanisms within the hippocampus that was not revealed with

  7. In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity

    KAUST Repository

    Pahil, Sapna

    2017-08-02

    Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp. This approach led to the identification of many immunogenic peptides. The five most promising peptides based on MHC binding efficiency were a putative lipoprotein (EL PGI I), a putative heat shock protein (EL PGI II), Spa32 (EL PGI III), IcsB (EL PGI IV) and a hypothetical protein (EL PGI V). These peptides were synthesized and the immunogenicity was evaluated in BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP) and the hypothetical protein elicited good humoral response, whereas putative lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by increased IFN-γ and TNF-α cytokine levels. The patient sera from confirmed cases of shigellosis were also evaluated for the presence of peptide specific antibodies with significant IgG and IgA antibodies against the HSP and the hypothetical protein, bestowing them as potential future vaccine candidates. The antigens reported in this study are novel and have not been tested as vaccine candidates against Shigella. This study offers time and cost-effective way of identifying unprecedented immunogenic antigens to be used as potential vaccine candidates. Moreover, this approach should easily be extendable to find new potential vaccine candidates for other pathogenic bacteria.

  8. Immunogenicity and safety of investigational vaccine formulations against meningococcal serogroups A, B, C, W, and Y in healthy adolescents.

    Science.gov (United States)

    Saez-Llorens, Xavier; Aguilera Vaca, Diana Catalina; Abarca, Katia; Maho, Emmanuelle; Graña, Maria Gabriela; Heijnen, Esther; Smolenov, Igor; Dull, Peter M

    2015-01-01

    This phase 2 study assessed the immunogenicity, safety, and reactogenicity of investigational formulations of meningococcal ABCWY vaccines, consisting of recombinant proteins (rMenB) and outer membrane vesicle (OMV) components of a licensed serogroup B vaccine, combined with components of a licensed quadrivalent meningococcal glycoconjugate vaccine (MenACWY-CRM). A total of 495 healthy adolescents were randomized to 6 groups to receive 2 doses (Months 0, 2) of one of 4 formulations of rMenB antigens, with or without OMV, combined with MenACWY-CRM, or 2 doses of rMenB alone or one dose of MenACWY-CRM then a placebo. Immunogenicity was assessed by serum bactericidal assay with human complement (hSBA) against serogroups ACWY and serogroup B test strains; solicited reactions and any adverse events (AEs) were assessed. Two MenABCWY vaccinations elicited robust ACWY immune responses, with higher seroresponse rates than one dose of MenACWY-CRM. Bactericidal antibody responses against the rMenB antigens and OMV components were highest in subjects who received 2 doses of OMV-containing MenABCWY formulations, with ≥68% of subjects achieving hSBA titers ≥5 against each of the serogroup B test strains. After the first dose, solicited local reaction rates were higher in the MenABCWY or rMenB groups than the MenACWY-CRM group, but similar across groups after the second dose, consisting mainly of transient injection site pain. Fever (≥38.0°C) was rare and there were no vaccine-related serious AEs. In conclusion, investigational MenABCWY formulations containing OMV components elicited highly immunogenic responses against meningococcal serogroups ACWY, as well as serogroup B test strains, with an acceptable safety profile. [NCT01210885].

  9. Immunogenicity of a killed bivalent (O1 and O139 whole cell oral cholera vaccine, Shanchol, in Haiti.

    Directory of Open Access Journals (Sweden)

    Richelle C Charles

    2014-05-01

    Full Text Available Studies of the immunogenicity of the killed bivalent whole cell oral cholera vaccine, Shanchol, have been performed in historically cholera-endemic areas of Asia. There is a need to assess the immunogenicity of the vaccine in Haiti and other populations without historical exposure to Vibrio cholerae.We measured immune responses after administration of Shanchol, in 25 adults, 51 older children (6-17 years, and 47 younger children (1-5 years in Haiti, where cholera was introduced in 2010. A≥4-fold increase in vibriocidal antibody titer against V. cholerae O1 Ogawa was observed in 91% of adults, 74% of older children, and 73% of younger children after two doses of Shanchol; similar responses were observed against the Inaba serotype. A≥2-fold increase in serum O-antigen specific polysaccharide IgA antibody levels against V. cholerae O1 Ogawa was observed in 59% of adults, 45% of older children, and 61% of younger children; similar responses were observed against the Inaba serotype. We compared immune responses in Haitian individuals with age- and blood group-matched individuals from Bangladesh, a historically cholera-endemic area. The geometric mean vibriocidal titers after the first dose of vaccine were lower in Haitian than in Bangladeshi vaccinees. However, the mean vibriocidal titers did not differ between the two groups after the second dose of the vaccine.A killed bivalent whole cell oral cholera vaccine, Shanchol, is highly immunogenic in Haitian adults and children. A two-dose regimen may be important in Haiti, and other populations lacking previous repeated exposures to V. cholerae.

  10. Safety, immunogenicity, and protective efficacy of two doses of RIX4414 live attenuated human rotavirus vaccine in healthy infants.

    Science.gov (United States)

    Araujo, Eliete C; Clemens, Sue Ann C; Oliveira, Consuelo S; Justino, Maria Cleonice A; Rubio, Pilar; Gabbay, Yvone B; da Silva, Veronilce B; Mascarenhas, Joana D P; Noronha, Vânia L; Clemens, Ralf; Gusmão, Rosa Helena P; Sanchez, Nervo; Monteiro, Talita Antônia F; Linhares, Alexandre C

    2007-01-01

    To determine the safety, immunogenicity and efficacy of two doses of rotavirus vaccine in healthy Brazilian infants. A randomized, multicenter, double-blind, placebo-controlled trial was conducted in Brazil, Mexico and Venezuela. Infants received two oral doses of vaccine or placebo at 2 and 4 months of age, concurrently with routine immunizations, except for oral poliomyelitis vaccine (OPV). This paper reports results from Belém, Brazil, where the number of subjects per group and the viral vaccine titers were: 194 (10(4.7) focus forming units - FFU), 196 (10(5.2) FFU), 194 (10(5.8) FFU) and 194 (placebo). Anti-rotavirus (anti-RV) antibody response was assessed in 307 subjects. Clinical severity of gastroenteritis episodes was measured using a 20-point scoring system with a score of >or= 11 defined as severe GE. The rates of solicited general symptoms were similar in vaccine and placebo recipients. At 2 months after the second dose, a serum IgA response to RV occurred in 54.7 to 74.4% of vaccinees. No interference was seen in the immunogenicity of routine vaccines. Vaccine efficacy against any rotavirus gastroenteritis (RVGE) was 63.5% (95%CI 20.8-84.4) for the highest concentration (10(5.8) FFU). Efficacy was 81.5% (95%CI 44.5-95.4) against severe RVGE. At its highest concentration (10(5.8) FFU), RIX4414 provided 79.8% (95%CI 26.4-96.3) protection against severe RVGE by G9 strain. RIX4414 was highly immunogenic with a low reactogenicity profile and did not interfere with seroresponse to diphtheria, tetanus, pertussis, hepatitis B and Hib antigens. Two doses of RIX4414 provided significant protection against severe GE caused by RV.

  11. In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity

    KAUST Repository

    Pahil, Sapna; Taneja, Neelam; Ansari, Hifzur Rahman; Raghava, G. P. S.

    2017-01-01

    Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp. This approach led to the identification of many immunogenic peptides. The five most promising peptides based on MHC binding efficiency were a putative lipoprotein (EL PGI I), a putative heat shock protein (EL PGI II), Spa32 (EL PGI III), IcsB (EL PGI IV) and a hypothetical protein (EL PGI V). These peptides were synthesized and the immunogenicity was evaluated in BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP) and the hypothetical protein elicited good humoral response, whereas putative lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by increased IFN-γ and TNF-α cytokine levels. The patient sera from confirmed cases of shigellosis were also evaluated for the presence of peptide specific antibodies with significant IgG and IgA antibodies against the HSP and the hypothetical protein, bestowing them as potential future vaccine candidates. The antigens reported in this study are novel and have not been tested as vaccine candidates against Shigella. This study offers time and cost-effective way of identifying unprecedented immunogenic antigens to be used as potential vaccine candidates. Moreover, this approach should easily be extendable to find new potential vaccine candidates for other pathogenic bacteria.

  12. In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity.

    Science.gov (United States)

    Pahil, Sapna; Taneja, Neelam; Ansari, Hifzur Rahman; Raghava, G P S

    2017-01-01

    Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp. This approach led to the identification of many immunogenic peptides. The five most promising peptides based on MHC binding efficiency were a putative lipoprotein (EL PGI I), a putative heat shock protein (EL PGI II), Spa32 (EL PGI III), IcsB (EL PGI IV) and a hypothetical protein (EL PGI V). These peptides were synthesized and the immunogenicity was evaluated in BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP) and the hypothetical protein elicited good humoral response, whereas putative lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by increased IFN-γ and TNF-α cytokine levels. The patient sera from confirmed cases of shigellosis were also evaluated for the presence of peptide specific antibodies with significant IgG and IgA antibodies against the HSP and the hypothetical protein, bestowing them as potential future vaccine candidates. The antigens reported in this study are novel and have not been tested as vaccine candidates against Shigella. This study offers time and cost-effective way of identifying unprecedented immunogenic antigens to be used as potential vaccine candidates. Moreover, this approach should easily be extendable to find new potential vaccine candidates for other pathogenic bacteria.

  13. In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity.

    Directory of Open Access Journals (Sweden)

    Sapna Pahil

    Full Text Available Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp. This approach led to the identification of many immunogenic peptides. The five most promising peptides based on MHC binding efficiency were a putative lipoprotein (EL PGI I, a putative heat shock protein (EL PGI II, Spa32 (EL PGI III, IcsB (EL PGI IV and a hypothetical protein (EL PGI V. These peptides were synthesized and the immunogenicity was evaluated in BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP and the hypothetical protein elicited good humoral response, whereas putative lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by increased IFN-γ and TNF-α cytokine levels. The patient sera from confirmed cases of shigellosis were also evaluated for the presence of peptide specific antibodies with significant IgG and IgA antibodies against the HSP and the hypothetical protein, bestowing them as potential future vaccine candidates. The antigens reported in this study are novel and have not been tested as vaccine candidates against Shigella. This study offers time and cost-effective way of identifying unprecedented immunogenic antigens to be used as potential vaccine candidates. Moreover, this approach should easily be extendable to find new potential vaccine candidates for other pathogenic bacteria.

  14. Incremental Nonlinear Dynamic Inversion and Multihole Pressure Probes for Disturbance Rejection Control of Fixed-wing Micro Air Vehicles

    NARCIS (Netherlands)

    Smeur, E.J.J.; Remes, B.D.W.; de Wagter, C.; Chu